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Gangliosides as neurotrophic agents: studies on the mechanism of action. During the normal course of neuronal differentiation gangliosides undergo marked changes in both quantity and quality. These changes, i.e. several-fold increase in concentration and appearance of the gangliotetraose family, have been observed both in vivo and in neuronal cell cultures. In addition to these naturally occurring (endogenous) manifestations, exogenously administered gangliosides have been observed to exert neuritogenic and/or neuronotrophic effects on a variety of neuroblastoma cell lines and primary neuronal culture systems. Unlike the endogenous effects, which appear to require gangliotetraose structures, the structural specificity of the exogenous effect is quite broad. Thus, all of 11 different gangliosides proved neuritogenic with neuro-2A neuroblastoma cells. Furthermore, synthetic sialoglycolipids possessing a beta-ketosidic sialic acid linkage and/or a glyceride-like moiety in place of ceramide all caused enhanced neurite outgrowth in neuro-2A, PC12, and embryonic chick dorsal root ganglia. A derivative of GM1 lacking the negative charge was also active in the same 3 systems. These results point to general perturbation of the membrane, probably a physical-chemical effect, in a manner which triggers intracellular events leading to differentiation. In contrast to these in vitro results, use of the above GM1 derivative in two in vivo models proved ineffective in maintaining the level of cholinergic markers that were preserved by GM1 in lesioned brains. These results point to fundamentally different mechanism for the trophic effects of administered gangliosides in vivo and in vitro. | 16 |
Two functionally distinct anti-tumor effector cells isolated from primary murine sarcoma virus-induced tumors. The ability of cells from primary MSV-induced tumors to function as effector cells in vitro was evaluated. Host cells were isolated by enzymatic disaggregation of the tumor and fractionated by sedimentation velocity at unit gravity on a Ficoll gradient. Characterization of these cells indicated that 30 to 40 % were T lymphocytes, about 50% were macrophages and less than 5% were B lymphocytes. Two different functional activities were mediated by these cells: cytolysis, as measured by the CRA, and inhibition of proliferation, as measured by the GIA. The effector cells in the CRA were T cells with sedimentation velocities of 3.5 to 4.0 mm/hr, whereas those cells which mediated the GIA were presumably macrophages and displayed a heterogeneity in size two peak sedimentation velocities, one at 4.0 mm/hr and another at 6.0 mm/hr. Activity by the effector cells in the CRA was antigen specific in contrast to the activity in the GIA which was directed against cells which did not carry detectable cross-reacting antigens. | 18 |
Pharmacotherapy for self-injurious behavior: preliminary tests of the D1 hypothesis. 1. The D1 dopamine hypersensitivity model of self-injurious behavior leads to a testable clinical hypothesis: that the mixed D1/D2 dopamine antagonist fluphenazine may improve the symptoms of self-injurious patients. 2. The hypothesis was tested in an open pilot trial in six patients and a partially controlled trial in nine patients. 3. Some degree of clinical improvement was observed in eleven of the fifteen. 4. The trials represent a partial affirmation of the D1 hypothesis. However, it is also clear that conventional methodology for psychopharmacologic research is inappropriate for the proper clinical evaluation of self-injurious patients. The proper method should include the following elements: i) An epidemiologically representative sample ii) A naturalistic study environment iii) A longitudinal design with long-term follow-up iv) Concurrent behavioral ratings using direct observations and a reliable, treatment-sensitive rating scale. 5. Before subjects enter a clinical trial of an experimental medication, a neuropsychiatric differential diagnosis should be applied to limit the diversity of the sample. | 13 |
Polyclonal B cell activation of IgG2a and IgG2b production by infection of mice with lactate dehydrogenase-elevating virus is partly dependent on CD4+ lymphocytes. Concentrations of IgM and IgG isotypes were determined by capture ELISA in plasma of Swiss, BALB/c and C58/M mice. Plasma IgG isotype concentrations, especially of IgM, IgG1 and IgG2a, varied considerably between mouse strains, batches of mice of the same strain and individual mice and as a function of age. Infection of the mice with LDV, which is known to replicate primarily in a subpopulation of macrophages, consistently resulted in a rapid elevation of plasma IgG2a (or of IgG2b in some Swiss nu/+ mice), but no plasma IgG increases were observed in mice immunized with inactivated LDV. Plasma IgG2a elevation after LDV infection was greatly delayed and reduced by depletion of the mice of CD4+, but not of CD8+, T cells by administration of protein-G-purified anti-CD4 or anti-CD8 mAbs, and completely inhibited by repeated treatment of the mice with cyclophosphamide. Treatment with anti-CD4 mAbs, or cyclophosphamide also greatly reduced the production of anti-LDV antibodies, while not significantly affecting the replication of LDV in these mice. Nude Swiss mice also failed to produce anti-LDV antibodies, though supporting normal LDV replication. Plasma IgM, IgG1, IgG2a and IgG2b levels increased in LDV-infected nu/nu mice, but similar changes were observed in uninfected mice. The results indicate that the LDV-induced polyclonal activation of B cells requires productive LDV infection of mice and is, at least partly, dependent on functioning CD4+ cells. They suggest that productive infection of the LDV-permissive subpopulation of macrophages leads to the activation of CD4+ T lymphocytes of subset 1 and their Spleen cells from 5-day LDV-infected BALB/c mice incorporated [3H]thymidine 2-3 times more rapidly in vitro than spleen cells from companion uninfected mice, whereas their responses to concanavalin A and lipopolysaccharide were reduced 60-70%. | 20 |
Federal, state, and local partnerships in providing primary care: one urban health department's endeavor with a state university medical center. We describe how the federal government, the City of Chicago, and the State of Illinois worked together to increase the availability and accessibility of health care services on Chicago's underserved west side by reopening a bankrupt, federally-funded community health center. The federal government made the building available to the City which then contracted with a state university medical center to be the provider of services. This partnering has allowed the Chicago Department of Health to offer services in a previously underserved area. The University has gained an opportunity for community-based primary care teaching, as well as community relations. Patients have increased access to a wide variety of specialty and inpatient care. If public health providers are to be successful in this financial climate, they must look to new partners and new ways of delivering services to increase availability of services at a time when they are greatly needed. | 17 |
Combined simian hemorrhagic fever and Ebola virus infection in cynomolgus monkeys. Simian hemorrhagic fever (SHF) virus and a new strain of Ebola virus were isolated concurrently in recently imported cynomolgus monkeys (Macaca fascicularis) being maintained in a quarantine facility. Ebola virus had never been isolated in the U.S. previously and was presumed to be highly pathogenic for humans. A chronology of events including measures taken to address the public health concerns is presented. The clinicopathologic features of the disease were abrupt anorexia, splenomegaly, marked elevations of lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, with less prominent elevations of blood urea nitrogen, creatinine, and other serum chemistry parameters. Histologically, fibrin deposition, hemorrhage, and necrosis of lymphoid cells and reticular mononuclear phagocytes were present in the spleens of SHF and of Ebola virus-infected animals. Intravascular fibrin thrombi and hemorrhage were also present in the renal medulla and multifocally in the gastrointestinal tract. Necrosis of lymphoid and epithelial cells was occasionally noted in the gastrointestinal tract. The histopathologic findings considered specific for Ebola virus infection include hepatocellular necrosis, necrosis of the zona glomerulosa of the adrenal cortex, and interstitial pneumonia, all of which were generally associated with the presence of 1 to 4 mu intracytoplasmic amphophilic inclusion bodies. The disease spread within rooms despite discontinuation of all direct contact with animals, and droplet or aerosol transmission was suspected. Antibody to Ebola virus developed in animal handlers but no clinical disease was noted, suggesting a less virulent strain of virus.(ABSTRACT TRUNCATED AT 250 WORDS) | 18 |
Group G streptococcal lymphadenitis in rats. Group G streptococci which have been isolated from the oral flora of rats are also normal inhabitants of the human skin, oropharynx, gastrointestinal tract, and female genital tract. This group of streptococci can cause a wide variety of clinical diseases in humans, including septicemia, pharyngitis, endocarditis, pneumonia, and meningitis. Ten days after oral gavage with 7,12-dimethylbenz[a]anthracene, 12 of 22 two-month-old, female, outbred, viral-antibody-free rats presented with red ocular and nasal discharges and marked swelling of the cervical region. Various degrees of firm, nonpitting edema in the region of the cervical lymph nodes and salivary glands as well as pale mucous membranes and dehydration were observed. Pure cultures of beta-hemolytic streptococci were obtained from the cervical lymph nodes of three rats that were necropsied. A rapid latex test system identified the isolates to have group G-specific antigen. These streptococcal isolates fermented trehalose and lactose but not sorbitol and inulin and did not hydrolize sodium hippurate or bile esculin. A Voges-Proskauer test was negative for all six isolates. Serologic tests to detect the presence of immunoglobulin G antibody to rat viral pathogens and Mycoplasma pulmonis were negative. Histopathologic changes included acute necrotizing inflammation of the cervical lymph nodes with multiple large colonies of coccoid bacteria at the perimeter of the necrotiz zone. To our knowledge, this is the first report of naturally occurring disease attributed to group G streptococci in rats. | 16 |
[Various activities of the nucleolus organizer region in normal and leukemic bone marrow cells: semiquantitative data and computer- assisted image analysis by silver staining]. A cytochemical technique with silver nitrate staining was used to study the nucleolar organizer activity in metaphase spread of bone marrow cells from 13 patients with acute lymphocytic leukemia (ALL), 11 patients with chronic myelogenous leukemia (CML), 7 patients with acute myelogenous leukemia (AML), and 4 normal persons. Additionally, computer-assisted image analysis was used to quantitate the amount of silver staining in interphase nuclei of bone marrow cells from 6 untreated ALL patients, 3 normal subjects and 1 bone-marrow-transplant recipient. The results obtained have indicated that the nucleolar organizer reactivity (NOR) is significantly lower in the control group than that in ALL patients. NOR activity level is significantly lower in both CML patients in chronic phase, and AML patients than in the ALL group, and is similar to that in the control group. When the data obtained for the interphase nuclei were compared with those obtained for the metaphase spread, a strong correlation was recorded between the fraction of bone-marrow metaphases stained positively with silver, the average number of silver-positive nucleolar organizer regions per metaphase, and the amount of silver staining in the interphase nuclei. Silver staining used for the detection of these disease-related differences in NOR activity can serve as a diagnostic procedure in evaluating human leukemias. The computer-assisted image analysis of bone marrow cell interphase nuclei would be useful for more accurate resolving biological and medical problems. | 21 |
Applying tribological principles to improve the performance of the Hoffmann external fixator's universal joint. As part of a continuing investigation of sources of slippage in the universal joints of external fixation devices, a study was conducted to determine if selected interfaces of the Hoffmann external fixator (rod/clip torsional, cheek/bowl and clip/cheek) could be improved by moving the point of contact between the wing-nut clamp and cheek closer to the centre of the wing-nut clamp. It was felt that the movement of the point of contact would reduce the magnitude of the frictional torque resisting the tightening of the wing-nut clamp. The point of contact was changed by the addition of a Belleville washer between the interface of the wing-nut clamp and the cheek. Increased slippage torques of approximately 100 per cent were noted in all interfaces at low values of tightening torque (6 and 8 N m) of the wing-nut clamp and improvements of not less than 50 per cent were obtained at higher tightening torques (10 and 12 N m) on the wing-nut clamp. | 20 |
Macromolecular structure of reassembled neurofilaments as revealed by the quick-freeze deep-etch mica method: difference between NF-M and NF-H subunits in their ability to form cross-bridges. Neurofilament (NF) structure and ability to form cross-bridges were examined by quick-freeze deep-etch mica and low-angle rotary-shadow electron microscopy in NFs purified from bovine spinal cord and reassembled in various combinations of NF subunits. When NFs were reassembled from triplet proteins, NF-L, NF-M and NF-H, they were oriented randomly and often fragmented, but their elongated filaments (12-15 nm wide) and the cross-bridges (4-5 nm wide) connecting them were similar in appearance to those of isolated bovine NFs or in vivo rat NFs. Projections extended from the wall of the core filament in almost the same pattern as the cross-bridges and were the same in width and interval (minimum interval, 20-25 nm) as the cross-bridges. Projections were more conspicuous when core filaments were separated by 60 to 80 nm or more, while cross-bridges were more conspicuous when core filaments were close to each other. Projections or cross-bridges extended bilaterally at intervals of 20 to 25 nm where core filaments expanded and formed a network between filaments which were far from one another. When NFs were reconstructed from NF-L alone, only core filaments appeared, the same width as the filaments of triplet NFs. The core filaments were occasionally in almost direct contact with each other, with no projection or cross-bridge. When NFs were reassembled from NF-M alone or NF-L + NF-M, although NF-M core filaments were shorter and slightly thinner than NF-L + NF-M core filaments, both had projections, and both had cross-bridges, but cross-bridges were less evident. Cross-bridges were almost the same in width as those of triplet NFs, but significantly shorter and much less frequent although the minimum interval was the same, and core filaments were not attached to each other. In contrast, when NFs were reconstituted from NF-H alone or NF-L + NF-H, both had conspicuous projections and cross-bridges, similar to those of triplet NFs. Thus, when NFs contained NF-H, they formed frequent cross-bridges and long projections with extensive peripheral branching. When NFs contained NF-M but no NF-H, they tended to form cross-bridges, and to form projections that were shorter and straighter and without peripheral branching. That is, there appears to be a significant difference between NF-M and NF-H in ability to form cross-bridges and thus in interaction with adjacent NFs. | 17 |
Critical appraisal of therapeutic endoscopy in biliary tract diseases. Endoscopic treatment (by sphincterotomy) is now the preferred method for patients with retained or recurrent bile duct stones after surgery. It is also applicable to many acutely ill or high-risk patients who have not undergone cholecystectomy. Endoscopic stenting is preferable to the percutaneous transhepatic method for palliation of malignant biliary obstruction in patients unfit or unsuitable for surgery. Balloon dilatation and stenting can be used for management of postoperative bile duct trauma and biliary fistulae, and in patients with dominant strictures in sclerosing cholangitis. Papillary stenosis and sphincter of Oddi dysfunction can be treated by sphincterotomy after careful patient selection. Endoscopy is a new and simpler form of surgery. A team approach including endoscopists, surgeons, and radiologists is essential for appropriate patient care and for objective evaluation of new methods. | 16 |
A transient acidification linked to intracellular Ca2+ in anti-mu-stimulated human B-lymphocytes. Mitogen-induced cellular proliferation is in many cell types preceded by rapid changes in intracellular pH and free Ca2+ concentration. We studied the patterns of pH and Ca2+ changes in normal resting human B-lymphocytes after exposure to anti-mu antibodies and the monoclonal antibody IF5, reactive with the CD20 antigen, both able to activate resting B-lymphocytes to enter the G1 phase of the cell cycle. Monitoring intracellular pH with the pH-sensitive, fluorescent dye, 2',7'-bis(carboxyethyl)-5,6-carboxy-fluorescein, we demonstrated that poly- and monoclonal anti-mu antibodies induced a rapid (maximum change within 2 min) intracellular acidification of 0.06 pH units followed by a slower (10-15 min) alkalinization towards, or slightly above, the resting pH of 6.88. The acidification response was amiloride-resistant, whereas the return to baseline was sensitive. Intracellular free Ca2+ was measured by using the fluorescent Ca2+ dye, indo-I. Exposure of cells to anti-mu resulted in a rapid increase (maximum change within 2 min) in cytoplasmic Ca2+ of 340 nM and a slower decline in fluorescence back to baseline of about 180 nM. In contrast to anti-mu, IF5 caused no change in cytoplasmic Ca2+ and pH. However, the Ca2+ ionophore ionomycin at low concentrations mimicked the Ca2+ response as well as the pH response to anti-mu. In Ca2(+)-free solutions the intracellular Ca2+ stores are usually rapidly depleted and, indeed, the Ca2+ and pH responses to anti-mu were reduced after 5 min and almost abolished after 35 min under such conditions.(ABSTRACT TRUNCATED AT 250 WORDS) | 16 |
Hep G2 cell line as a human model for sulphate conjugation of drugs. 1. The objective of this study was to examine the usefulness of the hepatoma cell line Hep G2 as a model for human sulphoconjugation of drugs, in particular stereoselective conjugation. 2. Using the substrates p-nitrophenol and dopamine, we found sulphation activities consistent with the presence of both the phenol (P) and the monoamine (M) form of the human phenolsulphotransferases in these cells. 3. The Kmapp was 3.0 microM for the sulphation of p-nitrophenol. This activity was inhibited selectively by 2,6-dichloro-4-nitrophenol, IC50 6 microM. The Kmapp was 39 microM for the sulphation of dopamine. This activity was selectively inhibited by elevated temperature. 4. The chiral adrenergic drugs (+/-)-terbutaline and (+/-)-4-hydroxypropranolol were both sulphated stereoselectively with Kmapp and Vmaxapp values for each enantiomer virtually identical to previous observations with human liver cytosol. 5. In a direct comparison, the estimated activity of the P form of phenolsulphotransferase in the Hep G2 cell line was 30% of that in human liver, whereas, surprisingly, the activity of the M form of phenolsulphotransferase was 4.5 times higher in the Hep G2 cells than in the liver. | 11 |
Central serotonin receptors and delayed gastric emptying in non-ulcer dyspepsia. To determine whether central serotonin receptors are involved in the pathophysiology of non-ulcer dyspepsia. Between subjects study of solid phase gastric emptying and prolactin response to buspirone challenge. 12 patients fulfilling criteria for non-ulcer dyspepsia and 12 age and sex matched controls. Solid phase gastric emptying measured by scintigraphic assessment of the movement of a standard meal labelled with technetium-99m and indium-111; responsiveness of central serotonin 1A receptors measured by the prolactin release following challenge with oral buspirone 60 mg. Solid phase gastric emptying was significantly delayed in the patients with non-ulcer dyspepsia (t 1/2 = 90.6 (SD 14.5) minutes in patients and 54.6 (10.7) minutes in controls; 95% confidence interval 24.7 to 46.7 minutes, p < 0.001). Prolactin release was significantly greater in patients compared with controls (1272.7 (1039.9) mU/l v 292.9 (136.1) mU/l; 352.1 to 1607.5 mU/l, p < 0.01). Gastric emptying and prolactin release were significantly correlated (r = 0.59, p = 0.04) in the patients but not in the controls (r = 0.23). Central serotonin 1A receptors may have a role in the pathophysiology of non-ulcer dyspepsia of the dysmotility subtype. | 15 |
Er:YAG laser ablation of enamel and dentin of human teeth: determination of ablation rates at various fluences and pulse repetition rates. A pulsed Er:YAG laser (2.94 microns) was used to determine ablation depths per pulse of laser energy at 2 Hz and 5 Hz in human teeth cross sections of enamel and dentin. Ablation depths per pulse at 2 Hz in enamel of intact human teeth were measured and compared to ablation depths per pulse determined in enamel cross sections at 2 Hz. Close correlation was observed for ablation depths per pulse of laser energy between teeth cross sections and intact teeth for enamel. Photographs of lased holes at 2 Hz and 5 Hz indicated minimal thermal effects in enamel at fluences below 80 J/cm2. Minimal thermal effects in dentin were noted below 74 J/cm2. Scanning Electron Microscopy (SEM) pictures of lased dentin showed an irregular serrated surface. Results of this study suggest that the Er:YAG laser can effectively ablate enamel and dentin with minimal thermal effects at 2 Hz and 5 Hz. | 14 |
[The clinical evaluation of tactile sensation in entrapment neuropathy using detection threshold of vibrotactile stimuli]. Two mechanoreceptive units, the rapidly adapting unit (RA unit) and the Pacinian corpuscle unit (PC unit), play an important role in the sensibility of the hand. It has been shown that detection thresholds of vibrotactile stimuli directly reflect the neural activity of the RA unit (in cases of stimulation below 50 Hz) and the PC unit (in cases of stimulation above 50 Hz). We applied this psychophysical approach to a clinical evaluation of tactile sensation in entrapment neuropathy. The detection thresholds of sinusoidal stimuli (25, 50, 100, 200, 300 Hz) were measured in 11 cases of carpal tunnel and 8 cases of cubital tunnel syndrome. By comparing the threshold curve of affected fingers with that of normal ones we were able to determine the severity of sensory disturbance. It was assumed that the PC unit was selectively disturbed in the early stages of the disease and that the RA unit was also disturbed in advanced stages. | 17 |
The ATP-sensitive K+ channel mediates hypotension in endotoxemia and hypoxic lactic acidosis in dog. Endotoxemia causes hypotension characterized by vasodilation and resistance to vasopressor agents. The molecular mechanisms responsible for these changes are unclear. The ATP-regulated K+ (K+ATP) channel has recently been found to be an important modulator of vascular smooth muscle tone which may transduce local metabolic changes into alterations of vascular flow. We report here that in endotoxic hypotension, the sulfonylurea glyburide, a specific inhibitor for the K+ATP channel, caused vasoconstriction and restoration of blood pressure. Glyburide also induced vasoconstriction and restoration of blood pressure in the vasodilatory hypotension caused by hypoxic lactic acidosis, while it was ineffective in the hypotension induced by sodium nitroprusside. Thus, vasodilation and hypotension in septic shock are, at least in part, due to activation of the K+ATP channel in vascular smooth muscle, and anaerobic metabolism with acidosis is a sufficient stimulus for channel activation. Because anaerobic metabolism and acidosis are common features in shock of any etiology, sulfonylureas may be effective therapeutic agents in the treatment of shock. | 18 |
Roles of active oxygen species in glomerular epithelial cell injury in vitro caused by puromycin aminonucleoside. The mechanism of puromycin aminonucleoside (PAN)-induced nephrosis has not yet been well defined. In the present study, we examined the protective effect of active oxygen scavengers on the PAN-induced injury of cultured rat glomerular epithelial cells (GECs) and the generation of active oxygen species in PAN-treated GECs. When exposed to PAN (greater than or equal to 25 micrograms/ml), cellular damage occurred in a time- and dose-dependent manner as evaluated by both the LDH release and MTT colorimetric assays. Concomitant addition of either the hydrogen peroxide (H2O2) scavenger, catalase, or the iron chelating agent, deferoxamine, to the culture medium caused a striking reduction of cellular injury. This suggested a role for H2O2 and for hydroxyl radicals (OH.) generated via the iron-catalyzed breakdown of H2O2 in PAN nephrosis. Using the scopoletin fluorescence assay, the release of H2O2 into the culture medium by GECs exposed to PAN (greater than or equal to 50 micrograms/ml) was shown to increase dose-dependently (greater than or equal to 57 +/- 11 pmol/4.4 x 10(6) cells per h, P less than 0.01) as compared with control cells (14 +/- 2 pmol/4.4 x 10(6) cells per h). These results strongly suggested that active oxygen species, especially H2O2 and OH., might play an important role in PAN-induced GEC injury in vitro as well as in vivo. | 18 |
Gene targeting using a mouse HPRT minigene/HPRT-deficient embryonic stem cell system: inactivation of the mouse ERCC-1 gene. A convenient system for gene targeting that uses hypoxanthine phosphoribosyltransferase (HPRT) minigenes as the selectable marker in HPRT-deficient mouse embryonic stem (ES) cells is described. Improvements to the expression of HPRT minigenes in ES cells were achieved by promoter substitution and the provision of a strong translational initiation signal. The use of minigenes in the positive-negative selection strategy for gene targeting was evaluated and the smaller minigenes were found to be as effective as a more conventional marker--the herpes simplex virus thymidine kinase gene. Minigenes were used to target the DNA repair gene ERCC-1 in ES cells. A new HPRT-deficient ES cell line was developed that contributes with high frequency to the germ line of chimeric animals. The ability to select for and against HPRT minigene expression in the new HPRT-deficient ES cell line will make this system useful for a range of gene-targeting applications. | 16 |
Tectopontine pathway in the cat: laminar distribution of cells of origin and visual properties of target cells in dorsolateral pontine nucleus. 1. The superior colliculus projects to the dorsolateral nucleus of the pons. Retrograde transport of horseradish peroxidase (HRP) revealed that cells in the superior colliculus, which send their axons to the pons, lie in both superficial (III) and deep (IV--VII) layers. Superficial cells outnumbered deep cells. The inferior colliculus also projects heavily to the dorsolateral pontine nucleus. 2. Dorsolateral pontine visual cells were activated only by visual stimulation. Cells responsive to somatic or auditory stimulation were also found in the dorsolateral nucleus, and they too responded to only one sense modality. 3. Of the dorsolateral pontine visual cells, 69% were directionally selective. 4. Dorsolateral pontine visual cells were responsive to moving targets over a wide range of stimulus velocities. Velocities between 25 and 100 degrees/s were the most effective. No cells responded to a stationary stimulus. 5. Single-spot targets were the most effective stimuli. Stimulus size was a more important parameter than stimulus configuration. Many cells had inhibitory regions outside of their excitatory fields. 6. The excitatory receptive fields of dorsolateral pontine cells were very large (median, 1,100 deg2). 7. Nearly all receptive fields were centered in the contralateral visual hemifield, and 91% of the dorsolateral visual cells were activated from either eye. 8. We conclude that the visual cells in the dorsolateral nucleus have receptive-field properties that are similar to those of cells in the superior colliculus. The preference of dorsolateral cells for single-spot targets contrasts strongly with the multiple-spot preference of medial pontine cells, which receive their input from visual cortex. | 10 |
The effects of rubidium, caesium and quinine on 5-HT-mediated behaviour in rat and mouse--2. Caesium. Rats and mice were given either CsCl (3 mmol/kg, s.c.) or saline (as control), twice daily for 3 days. The administration of tranylcypromine (TCP) (15 mg/kg, i.p.) to rats pretreated with CsCl produced the 5-HT behavioural syndrome. Pretreatment with CsCl also enhanced the syndrome induced by p-chloroamphetamine (3 mg/kg, i.p.) or by TCP (15 mg/kg, i.p.) plus L-tryptophan (50 mg/kg, i.p.). p-Chlorophenylalanine (300 mg/kg, i.p., daily on 2 consecutive days) or (-)-propranolol (20 mg/kg, i.p.), pindolol (4 mg/kg, i.p.) and ritanserin (0.4 mg/kg, s.c.), all prevented the behavioural syndrome induced by CsCl and TCP in rats. Pretreatment of rats with CsCl potentiated the 5-HT syndrome, elicited by the 5-HT agonists, 8-OH-DPAT (0.5 mg/kg, s.c.), 5-MeODMT (2 mg/kg, s.c.) and quipazine (25 mg/kg, i.p.). Pretreatment with CsCl potentiated the 5-HT2-mediated head-twitches in the mouse but had no effects on hypothermia in the mouse induced by 8-OH-DPAT (0.5 mg/kg, s.c.). The rate of synthesis of 5-HT in the whole brain (excluding cerebellum) was enhanced by pretreatment with CsCl. The enhancement of 5-HT neuronal function by caesium may be related to its ability to block K(+)-channels in neuronal membranes. | 10 |
Duration of hepatitis B surface antigenemia (HBs Ag) in hemodialysis patients. Follow-up studies were done on 231 hemodialysis patients during a period of from one to 48 months to determine the natural history of hepatitis B surface antigenemia (HBs Ag). Of those studied, 113 (49%) exhibited HBs Ag. The probability of remaining HBs Ag positive over the mean follow-up period of 14.4 months was 62%. All of the 38 patients whose HBs Ag reverted to negative did so within ten months. Those patients whose HBs Ag reverted to negative had SGOT levels that were less frequently elevated than the patients with persistent antigenemia. Of hemodialysis patients with HBs Ag, 60% showed e antigen (HBe Ag). | 12 |
Diarylamidine derivatives with one or both of the aryl moieties consisting of an indole or indole-like ring. Inhibitors of arginine-specific esteroproteases. A series of 62 diarylamidine derivatives was evaluated for their antiproteolytic activity. In all but two of the compounds one or both of the amidino-substituted aryl moieties was either an indole or an indole-like ring. The latter included indene, benzimidazole, benzofuran, benzol[beta]thiophene, and several other related nitrogen-containing heterocycles. Several of the compounds exhibited considerable inhibitory potency against thrombin, trypsin, and pancreatic kallikrein. An outstanding inhibitor of trypsin was found in bis(5-amidino-2-benzimidazolyl)methane (compound 42) with a Ki value of 1.7 X 10(-8) M(pH. 8.1, 37 degrees C). Another derivative, 1,2-di(4-amidino-2-benzofuranyl)ethane (compound 21), proved to be a highly effective inhibitor of the overall blood clotting process. From a general structure-activity standpoint these compounds demonstrate that minor structural variations of low-molecular-weight inhibitors can result in significant changes in specificity and potency with regard to antiproteolytic activity. | 15 |
Varicella in children with cancer: Seventy-seven cases. The purpose of this study was to characterize varicella in childhood cancer patients. Seventeen of the 77 patients reviewed were in remission and off all therapy for 3 to 22 months. No one in this group died from varicella or had evidence of visceral dissemination. Among the remaining 60 patients, all of whom were receiving anticancer theapy when they developed varicella, 19 (32%) had visceral dissemination and 4 died, for a mortality rate of 7%. Each of the deaths was associated with primary varicella pneumonitis, with or without acute encephalitis. Visceral dissemination was not related to type or status of malignancy or to duration of specific anticancer therapy. Varicella was more likely to disseminate in children with absolute lymphopenia, less than 500 cells per cubic millimeter, than in patients with higher lymphocyte counts. Cessation of anticancer theapy prior to the onset of lesions appeared to lessen the risk of dissemination. These results show that varicella is more severe in cancer patients on therapy than the general population or in patients who have completed therapy, but is not highly fatal. | 14 |
Identification of a plant-derived mollicute as a strain of an avian pathogen, Mycoplasma iowae, and its implications for mollicute taxonomy. Strain PPAV, a filamentous but nonhelical mollicute, was isolated from aborted apple seeds in France in late 1979. This organism grew well in SP-4 broth, fermented glucose, and required sterol for growth, and most of its properties suggested that it belonged to the genus Mycoplasma. However, it was serologically distinct; in addition, unlike other Mycoplasma species, genome measurements consistently yielded values of about 1,000 MDa (ca. 1,500 kbp), and the organism had a growth temperature optimum of 43 degrees C. A comparison of strain PPAV 16S rRNA sequences with those of other mollicutes revealed a high degree of sequence similarity to a strain of Mycoplasma iowae, which is commonly encountered in poultry. This relationship was confirmed by performing a restriction endonuclease pattern analysis and DNA-DNA hybridization tests. The genome size of type strain 695 of M. iowae was determined to be about 1,000 MDa (1,500 kbp) by renaturation kinetics, a value which is much higher than any other value known in the genus. Additional measurements by pulsed-field gel electrophoresis yielded values of 1,300 kbp for both strain PPAV and M. iowae. Subsequent phenotypic comparisons supported this relationship. Serologic tests with strain PPAV and other strains of M. iowae confirmed the findings of other investigators that this species is serologically heterogeneous. The high optimum temperature for growth of strain PPAV was also shared by a number of M. iowae isolates. Genome size is an inappropriate character for taxonomic assignment to the family Mycoplasmataceae because strain PPAV and other established species in this family are now known to have genomes ranging in size from 1,000 to 1,400 kbp. | 16 |
A pneumatic reduction device for gastroschisis and omphalocele. A new preformed pneumatic reduction device is available in two sizes, and it is recommended that a set be available for emergency use in any hospital which deals with the definitive emergency therapy of the newborn. The devices can be washed and flash sterilized as needed and, if properly cared for, can be reused repeatedly. The bag has facilitated the early care of newborns with omphalocele and gastroschisis and has allowed the rapid and effective reduction of eviscerated intestines. These bags can also be used for the controlled ventral hernias necessary in the treatment of infants born with large diaphragmatic hernias. It is hoped that the search for better techniques and materials will be continued, since the dramatic improvement in the survival rate of infants with gastroschisis and omphalocele has occurred not from a better understanding of the defects but by the application of improved techniques and materials in their treatment. | 19 |
[Inter-arterial anastomosis in dextral position of the aortic arch in patients with tetralogy of Fallot]. The article discusses the results of formation of inter-arterial anastomoses in 58 (12.7%) patients with a severe form of Fallot's tetralogy in dextra-position of the arch of the aorta. The specific features of the course and diagnosis of dextra-position of the aortic arch in Fallot's tetralogy are analysed, and the significance of radiologic and echocardiographic examination in the choice of the position and type of interarterial anastomoses is determined. It is proved that Blalock-Taussig's anastomoses must be formed on the side opposite to the aortic arch, while shunting operations must be carried out on the side on which the arch of the aorta is located. | 19 |
Outcome analysis in 654 surgically treated lumbar disc herniations. This article reports the outcomes of 654 consecutive patients treated during a 4.5-year period. Patients had a microdiscectomy, a laminectomy plus microdiscectomy, or a decompressive laminectomy with a microdiscectomy. The causes of ruptured discs were lifting (31.4%), falls (10.2%), and sports (10.0%). Almost all patients had complained of leg pain (99%), and 79% had radicular pain in a dermatomal distribution. Thirty-three percent of the patients had been involved in industrial accidents, and 6% had legal claims pending during the surgical period. Almost 11% of the patients had complications, and there was one death caused by abdominal arterial bleeding. Patients were also rated according to the Prolo Functional-Economic Outcome Rating Scale to improve the ability to compare series in the future. Almost 80% of the patients had good outcomes as defined by scores on this scale of 8 (16.2%), 9 (33.2%), and 10 (26.9%). Several conclusions can be drawn from the results of this series: 1) most patients had good outcomes; 2) patients with nonindustrial injuries had better outcomes than did patients with industrial injuries; 3) professionals with legal concerns and laborers with industrial insurance had good outcomes; and 4) the Functional-Economic Outcome Rating Scale appears to be a useful tool for comparing different procedures more objectively and for comparing the outcomes across series. | 14 |
The isolation and characterization of a calmodulin-encoding gene (CMD1) from the dimorphic fungus Candida albicans. Candida albicans is a dimorphic, opportunistic pathogen of humans, and calcium and calmodulin have been implicated in its morphogenic transition. The C. albicans calmodulin-encoding gene, CMD1, was isolated from cDNA and genomic phage lambda libraries using the Saccharomyces cerevisiae CMD gene as a hybridization probe. Southern-blot hybridization analysis of genomic DNA suggests the existence of only one type of calmodulin gene in C. albicans. Comparison of cDNA and genomic sequences identified a 222-bp intron located immediately after the Met start codon. The predicted amino acid sequence was 60% identical with yeast CMD and 70% identical with CMDs of filamentous fungi and vertebrates. We have localized the CMD1 gene to chromosome 3 using the contour-clamped homogeneous electric field gel electrophoresis. The CMD1 gene hybridized to a single 650-nucleotide transcript which was present in equivalent amounts in both the yeast and hyphal forms of the organism. | 16 |
[The autotransplantation of hematopoietic stem cells from the peripheral blood]. The authors discuss the existence of polypotent hemopoietic stem cells in the peripheral blood as well as a possibility of restoring hemopoiesis by means of the given cells after the lethal myelotoxic exposure. In 5 patients with hemoblastoses, suspension of mononuclear leukocytes in an amount of 0.5 X 10(9) per kg bw was obtained using short-interval leukocytapheresis on blood cell separator. After carrying out different schemes of pretransplantation preparation the defrosted suspension of mononuclear cells was injected without wash out to the patients' central vein. The recovery of the peripheral blood indicators was attained on days 10-30 after the autotransplantation of stem blood cells. | 17 |
Liposomal amphotericin B (AmBisome) in the treatment of fungal infections in neutropenic patients. The use of high-dose chemotherapy and the subsequent prolonged neutropenia in patients with haematological diseases has resulted in an increased incidence of fungal infections. The diagnosis and treatment of these infections in neutropenic patients pose major therapeutic problems. The only drug with proven efficacy in the treatment of deep-seated fungal infections, including invasive aspergillosis, is amphotericin B. Unfortunately, this drug has adverse side effects, most importantly dose-dependent nephrotoxicity; furthermore, some patients fail to show a response to amphotericin B. We have treated 20 patients undergoing myeloablative chemotherapy and/or bone marrow transplantation for haematological diseases with liposomal amphotericin (AmBisome) for proven or suspected aspergillosis. Eighteen patients had diffuse interstitial pneumonitis and two patients had suspected fungal liver abscesses. Five patients had mycologically proven fungal infection and of these, three patients (60%) showed a complete response to liposomal amphotericin. Eleven patients received liposomal amphotericin because of the failure of conventional amphotericin B to eradicate proven or suspected fungal infection. Five of these 11 patients (45%) showed a complete clinical response to liposomal amphotericin. Eight patients received liposomal amphotericin because of pre-existing renal impairment or nephrotoxicity caused by conventional amphotericin B. Four of these patients (50%) showed a response to liposomal amphotericin. Recovery from probable fungal infection in this group of patients occurred when there was complete remission of underlying disease and recovery of neutrophil counts, when they were concurrently treated with liposomal amphotericin. | 17 |
Enhanced fluoride uptake in enamel with a fluoride-impregnated prophylactic cup. A series of in vitro studies have been performed to study the release of tin and fluoride from an experimental prophylactic cup and the influence of this release on the fluoride content of enamel. It has been found that the release of fluoride from the prophy cup during a simulated prophylaxis results in a significant increase in the fluoride content of the treated enamel. It has also been observed that in those instances in which the fluoride-containing paste has a pH of less than about 3.8 this effect is partially additive to the increase in the fluoride content of enamel associated with the use of fluoride-containing prophylactic pastes. Collectively, these findings suggest that this prophylactic cup merits further investigation as a practical means of increasing the value of the prophylaxis phase of a multiple-fluoride treatment program for the partial control of dental caries. | 18 |
[Kidney involvement in infectious endocarditis (hematuria)]. As many as 113 patients suffering from infectious endocarditis (IE) were placed under observation. Renal damage was discovered in 28 patients (24.7%). Hematuria was the common laboratory sign of renal damage. 15% of patients showed microhematuria, 9.7 had macrohematuria. In 15% of patients with IE, hematuria was due to diffuse glomerulonephritis, in 5.3% to renal infarction, and in 4.4% to focal glomerulonephritis. In 3.5% of patients, the nephrotic syndrome developed at the disease onset, it was attended by hematuria and was thus a cause of erroneous diagnoses. The appearance of hematuria at the IE onset, attesting to involvement of the kidneys into the pathological process, complicates the diagnosis and early treatment institution. Detection of the hematuric syndrome in patients with a verified diagnosis of IE requires specification of the character of renal damage. The latter one contributes to a graver and prognostically unfavourable course of IE. In 2 out of 8 patients with associated IE and renal damage, the death was caused by progressive chronic renal failure. Postmortem examination confirmed mesangioproliferative glomerulonephritis in all the subjects; in 4, it was coupled with renal infarction. 14.1% of the patients manifested complete and 3.5% partial disappearance of hematuria under the influence of adequate antibacterial therapy of IE. | 13 |
Nephritogenicity of the lprcg gene on the MRL background. The novel lymphoproliferative and autoimmune lprcg gene, originally discovered in the CBA/K1Jms (CBA) strain of mice, was transferred onto the MRL/MpJ (MRL) strain background, and the resultant partially congenic MRL-lprcg/lprcg carrying 93% or more MRL genomes on average were examined for immune-complex glomerulonephritis and serological aberrations. Ordinary histological studies revealed that MRL-lprcg/lprcg mice developed glomerulonephritis histologically indistinguishable from that in MRL-lpr/lpr but at a lower frequency than in MRL-lpr/lpr mice. Glomerular immune complex deposition was almost the same in MRL-lprcg/lprcg and MRL-lpr/lpr mice. The levels of serum Ig, circulating immune complexes and autoantibodies in MRL-lprcg/lprcg were comparable to or even higher than those in MRL-lpr/lpr mice. Comparison of the serological abnormalities between MRL-lprcg/lprcg with glomerulonephritis and CBA-lprcg/lprcg without it evidenced the enhanced class switch from IgM to IgG responses in both class-specific autoantibody responses and serum Ig levels in MRL-lprcg/lprcg as in MRL-lpr/lpr mice. These results taken together indicate that the lprcg gene functions in much the same manner as lpr in induction of glomerulonephritis and serological abnormalities on the MRL background as expected from the allelism between the two mutant genes. | 18 |
Diagnostic cytology and electron microscopy of fine needle aspirates of retroperitoneal lymph nodes in the diagnosis of metastatic pelvic neoplasms. Ten patients with abnormal pelvic lymphangiograms underwent fluoroscopically directed percutaneous fine needle aspiration biopsy of retroperitoneal lymph nodes. In all cases, the primary diagnosis had already been established by biopsy or resection. In nine cases, aspiration cytology was positive for the same cell type identified in the primary neoplasm. In one of these nine cases, electron microscopy was utilized to further study the malignant cells in the aspirate. In the tenth case, the aspirate was negative for tumor, and the patient continues to be followed. Cytologic confirmation of lymphangiographically positive or suggestive nodes is useful in pelvic neoplasms and may obviate exploratory surgery in assessing the extent of disease and aid in planning therapy. | 17 |
Studies of the lipid phase transitions of Escherichia coli by high sensitivity differential scanning calorimetry. High sensitivity adiabatic differential scanning calorimetry was performed on lipids, membrane vesicles, and whole cells of Escherichia coli enriched in particular unsaturated fatty acids by genetic means. Information concerning the shape of the transition is discussed. Transitions with an asymmetric shape reminiscient of a second order transition were observed. Comparison between the lipid transition observed in whole cells, membrane vesicles, and extracted lipids enriched in elaidate reveal some basic similarities. Studies of synthetic lipids were undertaken in an attempt to interpret the shapes of these transitions as a function of the lipid components of the membrane. | 16 |
A group of scs elements function as domain boundaries in an enhancer-blocking assay. Chromosomes of higher eukaryotes are thought to be organized into a series of discrete and topologically independent higher-order domains. In addition to providing a mechanism for chromatin compaction, these higher-order domains are thought to define independent units of gene activity. Implicit in most models for the folding of the chromatin fiber are special nucleoprotein structures, the domain boundaries, which serve to delimit each higher-order chromosomal domain. We have used an "enhancer-blocking assay" to test putative domain boundaries for boundary function in vivo. This assay is based on the notion that in delimiting independent units of gene activity, domain boundaries should be able to restrict the scope of activity of enhancer elements to genes which reside within the same domain. In this case, interposing a boundary between an enhancer and a promoter should block the action of the enhancer. In the experiments reported here, we have used the yolk protein-1 enhancer element and an hsp70 promoter:lacZ fusion gene to test putative boundary DNA segments for enhancer-blocking activity. We have found that several scs-like elements are capable of blocking the action of the yp-1 enhancer when placed between it and the hsp70 promoter. In contrast, a MAR/SAR DNA segment and another spacer DNA segment had no apparent effect on enhancer activity. | 16 |
An ultrastructural and biochemical analysis of the epithelial-mesenchymal interface of the ruminal mucosa during development. The ultrastructure of fetal and adult bovine epithelial-mesenchymal interface of the ruminal mucosa was described and then correlated to the biochemical analysis for glycosaminoglycans (GAGs). During development a progressive undulation of the basement membrane, increase of connective tissue filamentous material, and folding of the cellular membrane of the basal epithelial cells were observed. Coincidently, a decrease in the relative composition of hyaluronic acid and an increase in chondroitin sulfate was observed. These results suggest a correlation between glycosaminoglycans composition and the expression of some cellular events resulting in morphological changes which operate during ruminal morphogenesis. | 20 |
Differentiation of biologically distinct cucumber mosaic virus isolates by PAGE of double-stranded RNA. Electrophoresis on 5% polyacrylamide was used to analyze dsRNAs of 26 cucumber mosaic virus isolates propagated in Nicotiana tabacum. There was variation between isolates in the migration of each of the dsRNAs 1, 2, and 3. Comparison of the dsRNA profiles enabled each isolate to be allocated to 1 of 7 distinct dsRNA profile types. Two distinct and readily distinguishable isolates were mixed in planta and dsRNA from these infected plants compared with in vitro mixtures of them. All bands from both types were present, indicating that the differences were real and reproducible. This method is of value as a means of classifying cucumber mosaic virus isolates, as it more closely reflects a range of biological characteristics than do other methods currently used. | 15 |
Distribution of a nuclear envelope antigen during the syncytial mitoses of the early Drosophila embryo as revealed by laser scanning confocal microscopy. The changing distribution of a nuclear envelope antigen recognized by a monoclonal antibody raised against human fibroblast vimentin during the syncytial mitoses of the Drosophila embryo has been studied with a confocal laser scanning microscope. The antigen appears very early as irregular aggregates in the peripheral cytoplasm of the preblastoderm embryo. As the first nuclei reach the periplasm the antigen is localized on the nuclear envelope and the cytoplasmic staining decreases. In addition to the perinuclear labeling we observed intense midzone and polar staining during the mitotic cycle. A possible relationship between polar localization of the antigen and centrosome position is discussed. | 18 |
Relationship between establishment of persistent infection of haemagglutinating virus of Japan and the properties of the virus. The infectious virus (HVJ-pi) obtained from BHK cells persistently infected with haemagglutinating virus of Japan was found to be temperature-sensitive as well as causing little or no cytopathic effect (c.p.e.) and leading to establishment of carrier cultures in several cell lines at both permissive (32 degrees C) and non-permissive (38 degrees C) temperature. In order to obtain information about the role of HVJ-pi in the establishment of persistent infection, comparative studies were made of some phenotypic properties of HVJ-pi and HVJ-38 which was obtained by passing wild-type HVJ in eggs at 38 degrees C and was proved to be highly cytopathic. HVJ-pi differed from HVJ-38 in (1) temperature sensitivity in its ability to produce virus progeny, (2) infectivity for embryonated eggs, (3) neuraminidase activity, (4) the thermal stability of HA and neuraminidase activity, and (5) the polypeptide composition of BHK-grown viruses. B cells infected with HVJ-pi release haemagglutinin more efficiently, and less HA was accumulated on the cell membrane. In considering these results, it was concluded that the difference of envelope proteins might be involved in the striking difference in c.p.e. between HJV-pi and HVJ-38. | 18 |
Reinnervation of partially denervated rat soleus muscle. The reinnervation of partially denervated rat soleus muscles by their interrupted, regenerating motor axons has been examined in adult white rats. If reinnervation occurred after the remaining, intact motor axons had sprouted to their full, maximal extent, then the regenerating axons formed synapses preferentially with denervated muscle fibers and not with fibers innervated by sprouts. The sprouted motor units retained their size as if no reinnervation had occurred. On the other hand, if reinnervation occurred early during the sprouting process, the sprouting motor units were never able to attain their maximal size. Further, some muscle fibers became innervated by both sprouted and regenerating axons. These "hyperinnervated" fibers lost their dual innervation within a few weeks. The sprouted axons seemed to be the nerve fibers preferentially eliminated from these hyperinnervated fibers, since during the loss of hyperinnervation the sprouted motor units decreased in size while the motor units formed by the regenerating axons did not change in size. It is proposed that the occurrence of hyperinnervation is influenced by the amount of time sprouting axons have to consolidate their synapses with muscle fibers. Further, it is proposed that on muscle fibers which can become hyperinnervated, the sprouted motor neurons are at a disadvantage in the competition for maintenance because of their larger unit sizes. | 15 |
Effects of hyperthermia and stimulation of the hypothalamus on the activity of the phrenic nerve in hypo- normo- and hypercapnic rabbits. Experiments were carried out on male rabbits, anesthetized with urethane, bilaterally vagotomized, paralysed and artificially ventilated. The preoptic area (POA) was stimulated at three different levels of CO2: in hypo- normo- and hypercapnia under normothermia, moderate hyperthermia and hyperthermia. Changes in central respiratory activity (monitored by phrenic nerve activity) due to CO2 levels, stimulation of the POA during normothermia and progressively increased body temperature were investigated. Results showed that: (i) When body temperature was raised and during stimulation of the POA, the frequency of phrenic nerve volleys, tidal volume eq. and minute ventilation eq. were increased. (ii). The acceleration of the respiratory rhythm was reached by shortening of both respiratory phases, inspiratory and expiratory. However, the expiratory phase changed more than the inspiratory one and there was a close proportional relationship between inspiratory and expiratory durations. (iii) Together with the increase in the respiratory drive resulting in the combination of influences of both factors, the temperature and CO2, the effects of POA stimulation diminished gradually. | 15 |
Coexpression of CD4 and CD8 on peripheral blood T cells and lamina propria T cells in inflammatory bowel disease by two colour immunofluorescence and flow cytometric analysis. Using two colour immunofluorescence with fluorescein isothiocyanate and phycoerythrin labelled monoclonal antibodies and multiparameter flow cytometry, we investigated the coexpression of CD4 and CD8 antigens on peripheral blood lymphocytes and lamina propria lymphocytes of patients with ulcerative colitis and Crohn's disease and normal control subjects. Both the absolute number and the proportion of peripheral blood CD4+, CD8+ cells in inflammatory bowel disease were small but significantly increased compared with those in normal control subjects. Peripheral blood lymphocytes activated with phytohaemagglutinin showed appreciably increased coexpression of CD4+, CD8+. These CD4, CD8 positive cells were large and granular. Thus the increased number of peripheral blood CD4+, CD8+ cells in inflammatory bowel disease suggests that chronic immune activation occurs not only in the active state of the disease but also in remission. The proportion of CD4+, CD8+ cells in the lamina propria was greater than in peripheral blood in normal subjects, suggesting chronic immune stimulation of the local immune system. This was also seen in patients with Crohn's disease or inactive ulcerative colitis. The proportion of CD4+, CD8+ cells was, however, significantly less in the lamina propria of patients with active ulcerative colitis. Whether this implies a possible defect in mucosal immunoregulation in active ulcerative colitis cannot be determined from these results. | 18 |
Model systems for the coordination chemistry of cytochrome P-450. Studies on model complexes have supported the presence of a mercaptide as the fifth ligand of cytochrome P-450 monooxygenases. When alcohol or thiol ligands are added to the sixth coordination position of a five-coordinated 4-nitrobenzene thiolate complex of FeIII protoporphyrin IX dimethyl ester chloride low spin complexes with optical and EPR-spectra very similar to cytochrome P-450 are obtained. From a comparison with all ligands of cytochrome P-450 and the model complexes it is concluded that a hard ligands must occupy the sixth coordination position of cytochrome P-450. An imidazole group is less likely, also in view of the ligand field parameters. The significance of the fifth and sixth ligand of cytochrome P-450 is discussed with respect to the monooxygenase mechanism. | 16 |
Effect of alpha-fetoprotein and other serum factors derived from hepatoma-bearing rats on the mixed lymphocyte response. Serum alpha-globulin fractions isolated by physiocochemical techniques from normal adult Buffalo rats suppressed lymphocyte proliferation in vitro. The factors responsible for mixed lymphocyte culture suppression appeared to be strain specific since they were not demonstrable in the same fractions from normal LBN rat serum. Similar fractionation of the serum from Buffalo rats bearing the Morris Hepatoma 7777 obtained from two different sources also yielded suppressive protein fractions that differed both chemically and functionally. Both variants of this hepatoma produced high serum concentrations of alpha-fetoprotein (AFP), providing an opportunity to study the possible immunoregulatory role of their fetal-associated globulins. Fractions rich in AFP that lacked other serum alpha-globulins were obtained by gel filtration chromatography and were devoid of any in vitro immunosuppressive activity. When AFP that was further purified by immunoabsorption was added to mixed lymphocyte cultures, no effect was observed at doses below 400 mug/ml. The MLC response was augmented with higher doses, similar to albumin purified by the same methods. | 17 |
The effect of allopurinol on the kynurenine formation in humans following a tryptophan load. The effect of allopurinol on the kynurenine formation in three manic depressive patients, two in remission and on in depression, has been studied during long-term treatment with L-tryptophan. The patients were loaded with 100 mg L-tryptophan per Kg body weight prior to and after one week on allopurinol, 300 to 500 mg per day. The area under curve (AUC) of plasma total and free tryptophan increased slightly in the patients in remission but not in the depressive. The former showed no change in the AUC of plasma kynurenine whereas an increase was seen in the depressive. The results suggest that allopurinol does not inhibit the human tryptophan pyrrolase definitely during loadings with L-tryptophan. | 13 |
Interaction among mu-opioid receptors and alpha 2-adrenoceptors on SH-SY5Y human neuroblastoma cells. The clonal human neuroblastoma cell line SK-N-SH-SY5Y was previously shown to express mu-opioid and alpha 2-adrenoceptors which are both negatively coupled to adenylyl cyclase. Because of the potential use of alpha 2-agonists in the treatment of narcotic dependence, we tested the interactions among he alpha 2-agonists, clonidine and norepinephrine, and morphine on AC in SH-SY5Y cells. Pretreatment with retinoic acid resulting in partial neuronal differentiation greatly enhanced the cells' sensitivity towards adenylyl cyclase stimulation by prostaglandin E1, and its inhibition by morphine and alpha 2-agonists. Norepinephrine (EC50 = 69 nM) maximally inhibited prostaglandin E1-stimulated cAMP accumulation (by approximately 83%), and the alpha 2-agonist yohimbine reversed these effects. Clonidine (EC50 = 32 nM) was a partial agonist, with 50 to 60% maximal inhibition. The combined effects of morphine (maximum approximately 70% inhibition) and norepinephrine exceeded the effect of either agent alone, yielding more than 90% inhibition of prostaglandin E1-stimulated cAMP accumulation. As previously reported for morphine, only a partial tolerance was observed for adenylyl cyclase inhibition by norepinephrine. Further, no cross-tolerance was observed between clonidine and morphine. The combined results indicate that mu-opioid receptors and an alpha 2-adrenoceptor subtype are colocalized on the same cells in SH-SY5Y culture, which hence serves as a model to study opioid-alpha 2-adrenergic interactions. | 19 |
Poly-maleic acid anhydride (PMA) coupled cortisol antibody in routine determination of urinary free cortisol. Antibodies against cortisol-21-hemisuccinate conjugated to bovine serum albumin was raised in rabbits and conjugated with poly-maleic acid anhydride. The conjugate was used in a solid phase radioimmunoassay to measure the urinary excretion of unconjugated cortisol. Cortisol was extracted with methylene chloride, the extract purified by chromatography on Sephadex LH-20, and the cortisol content measured with the radioimmunoassay. The intra-assay variation of the method was 6 per cent and the interassay variation 10 per cent. In 95 normal adult persons the excretion of free cortisol was 11--70, mean 30 micrograms/24 h. No sex or age difference was found. In 8 children aged 7--14 years the excretion was 8--46 micrograms/24 h. | 15 |
Influence of myectomy, ileal valve, and ileal reservoir on the ecology of the ileum. Fecal bacteriology, fecal volatile fatty acids, and ileal mucosal morphology were studied in dogs after ileoanal anastomosis alone, ileoanal anastomosis and myectomy, ileoanal anastomosis and myectomy with ileoileal valve, and ileoanal anastomosis with duplicated (J) ileal reservoir. The ratio of anaerobes to aerobes was significantly less in stool from dogs which had undergone ileoanal anastomosis compared with each of the other three groups (P less than 0.01). The numbers of streptococci and clostridia both were significantly less in stool from dogs with ileoanal anastomosis alone than in any other group. The concentrations of fecal acetic and propionic acids were significantly less in dogs with ileoanal anastomosis alone than in any other group (P less than 0.05), but there were no significant differences in the concentrations of fecal butyric or valeric acids. The severity of mucosal inflammation and degree of villous atrophy were more marked in the ileum of J reservoirs (P less than 0.01), and the percentage of stool retained after defecation was greater (P less than 0.05) in dogs with J reservoirs than in any other group. Therefore, the use of myectomy resulted in significant changes in the ecology of the distal ileum although changes typical of pouchitis were seen only in dogs with J reservoirs. | 21 |
Permeability lesions in male Escherichia coli infected with bacteriophage T7. The abortive development of bacteriophage T7 in E. coli cells carrying F factors has previously been attributed to a lack of virus-directed modification of ribosomes in such cells. We find it unnecessary to postulate such translational control to explain the failure of T7 development. Instead, there is a general cessation of macromolecular syntheses around 8 min after T7 infection of F' cells. This cessation is correlated with a sudden outflow of the entire acid-soluble pool of phosphorus-containing compounds and loss of the ability to accumulate amino acids. Manifestation of these defects requires expression of at least one T7 gene and one episomal gene. | 14 |
Computed tomography in primary reticulum cell sarcoma of the brain. The CT findings in 16 patients with histologically proved primary central nervous system (CNS) reticulum cell sarcoma (RCS) showed this malignancy to have predilection for the basal ganglia and thalamus, the periventricular white matter, the corpus callosum, and the vermis cerebelli. In 43% of patients with untreated tumor it presented as multifocal lesions; in each of these patients the basal ganglia were involved in conjuction with another site. In the other 57% of patients with untreated tumor presenting as solitary lesions the basal ganglia, the corpus callosum, and the frontal lobe were sites of predilection. Such solitary lesions may be indistinguishable from other tumors. Contrast enhancement of RCS was characteristically homogeneous with rare lucency, even in very large lesions. | 16 |
Signature pattern analysis: a method for assessing viral sequence relatedness. Signature pattern analysis identifies particular sites in amino acid or nucleic acid alignments of variable sequences that are distinctly representative of a query set of sequences relative to a background set. We explore the merits of using signature patterns for analysis of HIV-1 (human immunodeficiency virus type 1) sequences in cases of epidemiological linkage and potential superinfection. For these purposes, query sets are viral sequences that are all derived from one HIV-1 infected individual, hence the signature pattern is the array of sites that are characteristic of the range of viral variants obtained from that person. Once a signature pattern has been objectively defined, it can be used to examine other viral sequences from other individuals for evidence of genetic relatedness. A computer program to facilitate this analysis, VESPA, is described and applied to sequence data gathered during the investigation of HIV-1 transmission in a dental practice. The implications of signature polymorphisms seen within an infected individual, and shared polymorphisms between linked individuals, are also considered. VESPA may also be applied to the molecular analysis of biological phenotypes. | 18 |
The effect of time of exposure on fluoride uptake by human enamel from acidulated fluoride solutions in vitro. Fluoride uptake on and in enamel during topical application of acidulated solutions was studied. The variables were different time intervals and different pH levels of the treatment solutions. The experiment was carried out with human enamel exposed to 2% NaF solutions, pH 3.5 and 5.5, for 30 sec, 60 sec, 5 min, and 60 min. The amounts of fluoride formed on (as calcium fluoride) and in (as fluorapatite) enamel were determined by chemical assessments, and scanning electron microscopy provided the visualization of the deposits on the surface. It could be demonstrated that the two pH levels caused deposition of large amounts of calcium fluoride and that almost twice as much was deposited at pH 3.5 as at 5.5. The amount of deposit increased rapidly with time of exposure in both situations compared with similar experiments with neutral fluoride solutions. Firmly bound fluoride was incorporated in the enamel only during the 60-min incubation. | 15 |
Clinical reasoning in manual therapy. Clinical reasoning refers to the cognitive process or thinking used in the evaluation and management of a patient. In this article, clinical reasoning research and expert-novice studies are examined to provide insight into the growing understanding of clinical reasoning and the nature of expertise. Although hypothetico-deductive methods of reasoning are used by clinicians at all levels of experience, experts appear to possess a superior organization of knowledge. Experts often reach a diagnosis based on pure pattern recognition of clinical patterns. With an atypical problem, however, the expert, like the novice, appears to rely more on hypothetico-deductive clinical reasoning. Five categories of hypotheses are proposed for physical therapists using a hypothetico-deductive method of clinical reasoning. A model of the clinical reasoning process for physical therapists is presented to bring attention to the hypothesis generation, testing, and modification that I feel should take place through all aspects of the patient encounter. Examples of common errors in clinical reasoning are highlighted, and suggestions for facilitating clinical reasoning in our students are made. | 17 |
Muscular reflex stimuli to the cardiovascular system during isometric contractions of muscle groups of different mass. 1. The cardiovascular responses to voluntary isometric contractions performed by human subjects are determined by the proportion of maximal tension achieved by the muscles contracting, and not by the mass of the contracting muscles, nor by the absolute tension achieved (Lind & McNicol, 1967; confirmed here). When two or more muscle groups contract simultaneously at different relative tensions, the increments in heart rate and blood pressure are the same as when the muscle group at the higher relative tension contracts alone at that tension (Lind & McNicol, 1967). It is known that there are both central and reflex stimuli to the cardiovascular system in exercise, and the present study examines whether the muscular reflex stimuli are related to the proportion of maximal tension achieved or to the mass of contracting muscle. 2. Isometric hind-limb contractions were induced in anaesthetized dogs and cats by stimulation of spinal ventral roots. Pressor responses to contraction of both hind limbs were greater than responses to contractions of either hind limb alone. No differences were observed between heart rate responses to single or combined hind-limb contractions. 3. When human subjects perform isometric contractions, a pressor response can be maintained beyond the conclusion of the exercise by occluding muscle blood flow. This response is generally attributed to a reflex set up in the muscle by the action of chemical factors on afferent nerves. When comparable pressor responses were evoked by comparable proportional efforts with either the whole hand or the little finger, it was found here that the pressor responses remaining during the period of post-exercise occlusion were greater when the greater mass of muscle had been exercised. 4. It is concluded that the muscular reflex drive in isometric exercise is related to the bulk of contracting muscle. | 14 |
Rapid turnover serum proteins in fulminant hepatitis. An attempt was made to find reliable indices for early diagnosis of fatal cases of acute viral hepatitis, using the values of serum proteins with rapid turnover. Of the subfractions of serum protein, prealbumin, alpha2-HS-glycoprotein and Normotest were measured simultaneously before the appearance of hepatic coma/or gastrointestinal bleeding in 78 cases of acute viral hepatitis, verified by biopsy or necropsy. The mean value of prealbumin with a very short half-life of one or two days, was 6.0 mg/dl in fatal cases, 7.4 mg/dl in surviving ones of subacute form of fulminant hepatitis. The difference between fatal and surviving cases was not statistically significant. In contrast to this, the values alpha2-HS-glycoprotein with a comparatively short halflife of four to six days, showed statistically significant difference between fatal (21.9 mg/dl) and surviving cases (37.4 mg/dl). Normotest was also depressed in fatal (10.7%) and surviving cases (45.3%). The difference was statistically significant. The present results indicate the possibility of differentiating fatal cases from surviving ones at an early stage, using the reduction of alpha2-HS-glycoprotein and the value of Normotest. | 15 |
[Glutamine metabolism by rumen microorganisms: effect of monensin]. Transformation of glutamine of mixed population of microorganisms-symbionts is demonstrated. Protection of glutamine and its intermediates (glutamate and pyroglutamate) under the influence of ionophore (monensin) is found. It is accompanied by the reduced (by 30-70 per cent and more) levels of ammonia formation, total VFA, acetate, butyrate, pH, alpha-ketoglutarate dehydrogenase and glutamine synthetase at parallel increase of L-aspartate and L-alanine: 2-oxoglutarate, aminotransferase activity, redox potential of stability of protein content. It is suggested that the rapid change of Eh level on the 24th hour of incubation reflects the main stage of pyroglutamate formation being one of the final products of glutamine degradation when monensin is used. Ionophore affects first of all the inhibition of metabolic processes in gram-positive rumen microorganisms. | 18 |
Defective particles in alphavirus infections. This article summarizes our studies with defective-interfering particles of Sindbis virus obtained by high multiplicity passaging of the virus in BHK cells. Cells infected with these defective passages accumulate a species of RNA (20S) at the expense of 26S RNA--the mRNA coding for the viral structural proteins. Although the structure of the RNA in defective particles remains undefined, our studies of replicative forms and replicative intermediates suggest that it is larger than the intracellular 20S RNA. The defective particles are unable to synthesize detectable amounts of viral structural proteins when they infect a cell in the absence of standard virus and they do not contribute to the stimulation of intracellular viral RNA synthesis. We have proposed a model for the mechanism of interference by these defective particles in which standard and defective RNAs compete for a limited amount of viral-specific replicase. | 18 |
Modulation of human alveolar macrophage properties by ozone exposure in vitro. We have investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3) (0.1-1.0 ppm for 2-4 hr). The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2 (PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O3, we found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O2-) production in response to phorbol ester was reduced after exposure of HAM to O3 while the basal O2- release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3. However, compared to controls, O3- exposed HAM produced significantly lower levels of these cytokines when stimulated with bacterial lipopolysaccharide (LPS). Two-dimensional gel electrophoretic analysis of proteins made by HAM following in vitro exposure to O3 identified 11 proteins whose rate of synthesis was significantly altered. Thus, these studies show that exposure to O3 alters the functional competence of HAM. While there is a minimal effect on protein expression or synthesis, the responses of HAM to particulate immune complexes, to bacterial LPS, and to PMA are impaired. The release of arachidonic acid and PGE2 suggest that the effect of O3 is primarily targeted to the HAM cell membrane. These changes may ultimately result in increased susceptibility to inhaled infectious agents in the O3-exposed individual. | 16 |
Identification of heparin-binding proteins in bovine seminal plasma. A group of four similar proteins, BSP-A1, BSP-A2, BSP-A3, and BSP-30-kDa, represent the major acidic proteins found in bovine seminal plasma (BSP). These proteins are secretory products of the seminal vesicles; they bind to spermatozoa upon ejaculation and could represent decapacitation factors. It has been shown that the glycosaminoglycans present in the female reproductive tract are involved in the capacitation of spermatozoa. Therefore, it was of interest to investigate whether BSP-A1, -A2, -A3, and -30-kDa proteins of bovine seminal fluid interact with heparin. Chromatography of alcohol precipitates of bovine seminal fluid on a heparin-Sepharose column resolved these proteins into three peaks. Peaks 1 and 2 (retarded proteins) were eluted upon extensive washing of the column with 0.05 M phosphate buffer, pH 7.4 (equilibrating buffer), and accounted for approximately 25% of the applied proteins. Proteins in peak 3 represented adsorbed proteins and were eluted with phosphate buffer containing 1 M NaCl. Proteins in each peak were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. Peak 1 contained proteins with molecular weights ranging from 8 to 350 kDa, peak 2 contained a single protein with a molecular weight of 14 kDa, and peak 3 contained proteins with molecular weights of 15.5, 16, 25, and 30 kDa. The proteins in peak 3 were further resolved into unadsorbed (peak 4) and adsorbed (peak 5) proteins on a gelatin-Agarose column. Separation of the proteins of peak 3 and peak 5 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and reducing agents followed by transfer to nitrocellulose and probing with antibodies against the previously well-characterized BSP proteins indicated the presence of BSP-A1, BSP-A2, BSP-A3, and BSP-30-kDa proteins.(ABSTRACT TRUNCATED AT 250 WORDS) | 16 |
MMPI criteria for diagnosing schizophrenia. An attempt was made to find a combination of MMPI scale relationships which were highly discriminating of schizophrenia. Through the use of a standardized structured interview and a diagnostic system for schizophrenia based on the use of discriminant function analysis with nonpathognomonic symptom combinations, a reliable and valid system was used to establish the criterion diagnosis. Approximately 72% of patients reliably diagnosed as schizophrenics were detected on the MMPI via a set of standard criteria (T score on Sc greater than or equal to 80 less than or equal to 100; total raw score on Sc consisted of no more than 35% K items; T score on F greater than or equal to 75 less than or equal to 95; T score on Pt less than or equal to Sc). Only 5.5% of nonschizophrenics obtained all these standard criteria on the MMPI. The assets and liabilities of these MMPI criteria to diagnose schizophrenia are discussed. | 17 |
Spectrophotometric pH titrations and nitration with tetranitromethane of the tyrosyl residues in yeast phosphoglycerate kinase. Spectrophotometric pH titrations of phosphoglycerate kinase (EC 2.7.2.3) reveal seven tyrosyl residues. In the native state one tyrosyl residue has pKapp equal to 9.3, another has pKapp of about 12.9, and five have pKapp values close to 11.0. Titration above pH 10 causes concomitant reduction of the catalytic activity. Reactivation of the enzyme occurs during storage at pH 7.8. In 6 M guanidine - HCl seven tyrosyl residues with pKapp values equal to 10.0 appear. Nitration of three tyrosyl residues occurs easily when tetranitromethane is used in excess. Four tyrosyl residues appear to be masked or buried. The tyrosyl residue having pKapp equal to 9.3 can be selectively nitrated. Simultaneously the enzyme loses 40% of its catalytic activity. No change in the Km value for one or the other of the two substrates, MgATP or 3-phospho-D-glycerate, was observed in the mononitrated enzyme. On the other hand MgATP protects the tyrosyl residue from nitration whereas 3-phospho-D-glycerate at corresponding condition appears harmless. These results suggest the low ionizing tyrosyl residue to be situated close to the binding site of MgATP, possibly in a pocket just behind. Circular dichroism measurements indicated that minor successive changes occur in the secondary structure, mainly the beta-structure, when the enzyme is being nitrated. It is reasonable to think that these structural changes, possible in combination with steric hindrance, are responsible for the decrease in catalytic activity. Dimerization of the enzyme occurs if the single thiol group is not masked before the tetranitromethane treatment. | 13 |
IgM M-protein in a patient with sensory-dominant neuropathy binds preferentially to polysialogangliosides. A 77-year-old man presented sensory-dominant neuropathy associated with IgM M-protein reacting with various gangliosides. The M-protein bound to gangliosides with polysialosyl residue, such as GD1b, GD3, GT1b, GT3, GQ1b, and GQ1c. In addition, GD1a, GM3 and LM1, having a terminal monosialosyl epitope, were also recognized. Previously, Ilyas et al. described a similar case in which sensory symptoms were associated with IgM M-protein reacting with gangliosides containing a disialosyl group, such as GD3, GD1b, and GT1b, but not GM3 and GD1a. It is suggested that the reactivity of IgM M-protein with polysialogangliosides may be associated with the pathogenesis of sensory-dominant neuropathy. | 13 |
Differences in the impact and management of heart disease between older women and men. Findings are presented from an exploratory study of differences in the impact and management of heart disease between men and women aged 60 and over (N = 323). The sample consisted of ambulatory, non-institutionalized, cardiac patients who had agreed to participate in a self-management intervention study. Differences between men and women were found regarding symptom experience, physical functioning, exercise compliance, use of prescribed drugs, and physician/clinic visits. Differences in emotional well-being and psychosocial functioning were not found; however, women reported more stress and limitation in the area of household management. Implications for future research and practice are discussed. | 15 |
Lipophilic O-antigens containing D-glycero-D-mannoheptose as the sole neutral sugar in Rhodopseudomonas gelatinosa. Lipopolysaccharides (LPS, O-antigens) of 12 strains of the photosynthetic bacterium Rhodopseudomonas gelatinosa were obtained by the phenol/chloroform/petroleum ether method, recommended for extracting lipophilic glycolipids of enterobacterial R-mutants. All R. gelatinosa LPS have essentially the same chemical composition. Similar to LPS of Salmonella R-mutants of chemotypes Rd1 and Rd2, the sole neutral sugar constituent is an aldoheptose. The heptose of R. gelatinosa LPS has the D-glycero-D-manno- configuration, in contrast to the L-glycero-D-mannoheptose of enterobacterial LPS. 2-Keto-3-deoxyoctonate forms the acid-labile linkage between the lipid moiety (lipid A) and the oligosaccharide moiety of R. gelatinosa LPS. Like enterobacterial lipid A, lipid A of this species contains phosphate and D-glucosamine as the sole amino sugar. The fatty acid spectrum conprises beta-hydroxycapric, lauric, and myristic acids. Beta-Hydroxymyristic acid, the typical fatty acid of enterobacterial LPS, is lacking. The R. gelatinosa LPS show O-antigenic acitivity; passive hemagglutinations with untreated or heat-treated (not well alkali-treated) LPS and antisera prepared against heat-killed cells yield high titers. According to the serological cross-reactions observed, the LPS of the 12 strains could be arranged into two different serotypes: serotype I comprising strains 29/1, 29/2, 25/2, and serotype II comprising strains 44/K/6, 3/1, IS/10, 39/2, Dr2, 2150, P8P9, K32, P18f3.1. No serological cross-reactions were observed between LPS of these two different serotypes in passive hemagglutinations. | 16 |
Temperature dependence of thermal expansion coefficient for palladium-based binary alloy. Temperature dependencies of thermal expansion coefficients for the alloys of Pd-Ag, Pd-Cu and Pd-Co binary systems were measured at temperatures up to 900 degrees C, with heating and cooling rates of 5 degrees C/min. The coefficient of thermal expansion of alloys with no transformation in the temperature range of interest in porcelain firing was well approximated by a linear equation of temperature. The constants in the equation were shown as a function of the weight for the added element. Thermal expansion of the palladium-based alloy with no transformation was well estimated at any temperature range and at any composition by using the constants represented here. The coefficients of thermal expansion before and after order-disorder transformation and magnetic transformation were measured in Pd-Cu and Pd-Co alloys, respectively. The results suggest that transient and residual stresses in porcelain-fused-to-metal restorations can be effectively controlled by making use of transformation of the alloy. | 17 |
The effect of urea on the aggregate state and elastase inhibitor activity of the water-insoluble fraction from bovine and human lens. Preparations of alpha-crystallin from bovine and human lens exhibited elastase inhibitor activity with a specific activity of 100-250 U mg-1 protein. A washed water-insoluble fraction from bovine, human and cataractous lens nuclei, when solubilized by sonication, gave specific activities of 910, 950 and 1270 U mg-1, respectively. Disaggregation of these water-insoluble fractions in 8.0 M urea, with subsequent reaggregation by urea removal, resulted in a decrease in inhibitor activity. Agarose A-5m gel filtration chromatography after the urea treatment resolved a residual high molecular weight (HMW) fraction and a peak which eluted at the position of water soluble alpha-crystallin. Assays showed that the urea-induced 'alpha-crystallin' peaks from all three preparations had specific activities, equivalent to native alpha-crystallin, whereas the HMW fractions retained their original high specific activity. We conclude that the increased elastase inhibitor activity of the water-insoluble fraction is a property of the aggregate state of the component alpha-crystallin molecules, which is lost upon reaggregation to an 800-kDa alpha-crystallin. Amino acid analysis of the bovine water-insoluble fraction suggested a content of 85-90% alpha-crystallin and 10-15% beta H-crystallin, which was confirmed by SDS-PAGE.(ABSTRACT TRUNCATED AT 250 WORDS) | 18 |
TSH-receptor and adhesion molecules in autoimmune thyroid disease. Using a human TSH receptor (TSH-R) cDNA probe we investigated TSH-R expression levels in 20 human thyroid fragments by Northern blot analysis: 14 Graves' disease, 2 Hashimoto's disease, 3 endemic goiter and 1 healthy thyroid gland. TSH-R expression was low in those thyroids where expression of the major histocompatibility complex class I (MHC I), class II (MHC II) and intercellular adhesion molecule 1 (ICAM-1) was high, whereas expression of the endothelial leukocyte adhesion molecule 1 (ELAM-1) bore no relation to TSH-R expression. In situ hybridization showed that next to lymphocytes (MHC II), thyroid cells (MHC II, ICAM-1) and endothelial cells (ICAM-1, ELAM-1) were the source of transcripts of these T-cell activating antigens. We conclude that next to MHC I and II, the expression of additional T-cell activating antigens such as ICAM-1 and ELAM-1 play a role in the initiation of auto-immune thyroid disease. | 19 |
Phylogenetic analysis of 48 papillomavirus types and 28 subtypes and variants: a showcase for the molecular evolution of DNA viruses. Papillomaviruses are attractive models for studying the molecular evolution of DNA viruses because of the large number of isolates that exhibit genomic diversity and host species and tissue specificity. To examine their relationship, we selected two amino acid sequences, one of 52 residues within the early gene E1 and the other of 44 residues within the late gene L1, which allowed insertion- and deletion-free alignment of all accessible papillomavirus sequences. We constructed phylogenetic trees from the amino acid and corresponding nucleotide sequences from 28 published and 20 newly determined animal and human papillomavirus (HPV) genomic sequences by using distance matrix, maximum-likelihood, and parsimony methods. The trees agreed in all important topological aspects. One major branch with two clearly separated clusters contained 11 HPV types associated with epidermodysplasia verruciformis. A second major branch had all the papillomaviruses involved in genital neoplasia and, in distant relationship, the cutaneous papillomaviruses HPV type 2a (HPV-2a), HPV-3, and HPV-10 as well as the "butcher's" papillomavirus HPV-7 and two simian papillomaviruses. Four artiodactyl (even-toed hoofed mammal) papillomaviruses, the cottontail rabbit papillomavirus, and avian (chaffinch) papillomavirus type 1 formed a third major branch. Last, four papillomaviruses exhibited little affinity to any of these three branches; these were the cutaneous types HPV-1a, HPV-4, and HPV-41 and B-group bovine papillomavirus type 4. The phylogeny suggests that some branches of papillomavirus evolution are restricted to particular target tissues and that a general process of long-term papillomavirus-host coevolution has occurred. This latter hypothesis is still conjectural because of bias in the current data base for human types and the paucity of animal papillomavirus sequences. The comparison of evolutionary distances for the most closely related types with those of 28 subtypes and variants of HPV-2, HPV-5, HPV-6, HPV-16, and HPV-18 supports the type as a natural taxonomic unit, with subtypes and variants being expressions of minor intratype genomic diversity similar to that found in the natural populations of all biological species. An exception to this seems to be HPV-2c, which has an evolutionary distance from HPV-2a of the intertype magnitude and may eventually have to be regarded as a distinct type. We describe an experimental approach that estimates the taxonomic and phylogenetic positions of newly identified papillomaviruses without viral isolation and complete genomic sequencing.(ABSTRACT TRUNCATED AT 400 WORDS) | 19 |
[Diagnostic accuracy of fine needle aspiration cytology guided by ultrasonography in intra-abdominal and retroperitoneal lesions]. Evaluation of the fine needle aspiration cytology guided by ultrasonography in the diagnosis of abdominal and retroperitoneal tumors. Transversal study of diagnostic standard-criterion test. Ultrasonographic Unity Digestive Disease Department. Hospital Oncológico Padre Machado. 98 patients with intraabdominal and retroperitoneal lesions. Fine needle aspiration cytology guided by Ultrasonography. INDICE TEST: Laparoscopy and/or laparotomy. Estimation of sensibility (S), Specificity (E), Efficacy (Ef), positive predictive value (VPP), negative predictive value (VPN), measure of false positives (TFP) and measure of false negatives (TFN) by diagnosis method. VP: 81%; VN: 12%; FP: 1%; FN: 6%; S: 93%; E: 92.3%; Ef.: 97%; VPP: 98.7%; VPN: 66%; TFP: 1.25%; Benign lesions: 22.5%; Malignancy lesions: 65.5%; non lesions: 12%; complications: severe: 1%, non significance: 5%. Fine needle aspiration cytology guided by ultrasound has high sensibility, specificity, efficacy, with low value of false positive. However, it has high incidence of false negatives and negative predictive value. We recommend diagnostic procedures when the suspicion of tumor is high did the cytology is negative. | 12 |
The modification of gastrointestinal tolerance and responses to abdominal irradiation by chemotherapeutic agents. Groups of male DBA/2 mice were irradiated with partial abdominal exposures of x radiation ranging from 100 to 1,600 rads. Concomitant with radiation exposure and at 1 or 4 hours prior to, and at 1, 6, 24, or 48 hours after irradiation, various chemotherapeutic agents were administered, i.e., methotrexate, Cytoxan, adriamycin and BCNU. The results suggest that excessive gastrointestinal toxicity may result if aggressive chemotherapy is closely spaced with radiation exposure for the treatment of abdominal neoplasms. However, adjustment of dose and time patterns based on the proliferative responses of the mucosa may circumvent such toxicity to a large extent. | 18 |
Effects of family environment on negative symptoms and quality of life of psychotic patients. This study tested the hypothesis that negative symptoms and quality of life for patients with functional psychoses are associated with family environment. Fifty-seven first-admission patients with functional psychoses were assessed at hospital admission for severity of psychopathology and premorbid adjustment. Relatives residing with patients rated the family environment at admission and one month after discharge on the Family Environment Scale. Patients made the same ratings after discharge. Six months later, patients were reassessed on severity of psychopathology, negative symptoms, and quality of life. Multiple regression analyses showed that higher levels of positive emotional expressiveness in the family predicted milder and fewer negative symptoms and better quality of life at follow-up. The prediction was statistically independent of the initial severity of psychopathology or premorbid adjustment. | 17 |
Clinicopathologic correlation of xenon arc and argon laser photocoagulation. Procedure in human diabetic eyes. Xenon arc and argon laser lesions applied as scatter treatment to two diabetic patients were studied clinically and histopathologically. Seventy-one burns were grouped as very severe, severe, and moderately severe, according to pigmentation and diameter of the retinal scar. All lesions except half of the moderately severe ones showed full-thickness retinal involvement. In very severe xenon burns, whether xenon or argon, only proliferated retinal pigment epithelium provided a thin retinal scar, corresponding to an ophthalmoscopic appearance of "bare sclera". In the center of severe and moderately severe lesions, both glial cells and pigment epithelium bridged the retinal defect, forming a thick pigmented scar that contained pigment-laden macrophages. Rephotocoagulation over such thick scars may be less hazardous than is generally assumed. Nonvascular preretinal membranes were frequently present over very severe xenon lesions but rarely over very severe argon burns. | 14 |
Preserved neurotransmitter receptor binding following ischemia in preconditioned gerbil brain. Preconditioning the brain with sublethal ischemia induces tolerance to subsequent ischemic insult. Using [3H]quinuclidinyl benzilate (QNB), [3H]MK 801, [3H]cyclohexyladenosine, [3H]muscimol, and [3H]PN200-110, we investigated the alterations in neurotransmitter receptor and calcium channel binding in the gerbil hippocampus following ischemia with or without preconditioning. Two-minute forebrain ischemia, which produced no neuronal damage, resulted in no alterations in binding except for a slight reduction in [3H]QNB binding in the CA1 subfield. Three-minute ischemia destroyed the majority of CA1 pyramidal cells and caused, in CA1, reductions in binding of all ligands used. Preconditioning with 2-min ischemia followed by 4 days of reperfusion protected against CA1 neuronal damage and prevented the reductions in binding although [3H]QNB and [3H]PN200-110 binding transiently decreased in the early reperfusion period, suggesting down-regulation. Thus, preconditioning protects against damage to the neurotransmission system as well as histopathological neuronal death. | 19 |
Clinical utility and monitoring of breast cancer by circulating immune complexes. Circulating immune complexes (CIC) were estimated in 22 patients of breast carcinoma, 25 healthy control volunteers and 10 follow-up cases after mastectomy by polyethylene glycol precipitation (PEG pptn) test and Latex agglutination inhibition (LAI) test. CIC levels increased with advancing stage of breast carcinoma. Significant increase in CIC levels was observed in stage II (p < 0.01), followed by highly significant increase in stage III and IV (p < 0.01) as compared to the control group. Sharp decrease in CIC levels was observed three months after radical surgery in 9 post-operative patients. One patient remained seropositive by both tests, followed by a fatal outcome after four months follow-up. Seropositivity for CIC by PEG pptn test in patients of breast carcinoma was 72.72 percent as compared to 81.81 percent by LAI test. Combination of both tests increased total CIC positivity by 90.9 percent. Clinical utility and prognostic significance of CIC in monitoring breast carcinoma patients has been demonstrated by our study. | 14 |
Interfering passages of Sindbis virus: concomitant appearance of interference, morphological variants, and trucated viral RNA. Serial passage of Sindbis at high multiplicities of infection resulted in cyclical variations in virus titer. Decreases in virus titer were correlated with the appearance of smaller-sized virions, interference and truncated viral RNA. The smaller particles were 37 nm in diameter, exclusive of the hemagglutinin spikes as compared with a diameter of 50 nm for standard virions. Passages which contained 37-nm partilces also interfered with infectious center formation by standard, plaque-purified virus. Polyacrylamide gel analysis of RNA isolated from virions present in interfering passages demonstrated the sequential appearance of three RNA species smaller than standard RNA with approximate molecular weights of 3.3 X 106, 2.7 X 106, and 2.2 X 106. The 3.3 X 106 RNA was evident in passage 5, by passage 8 both the 3.3 X 106 and 2.7 X 106 RNAs were present, and by passage 13 all three were present with the 2.2 X 106 RNA predominating. | 16 |
Modulation of GABA transport in synaptosomes by histamine. We have examined the effects of exogenous and intrasynaptosomal histamine on the GABA transport in rat brain synaptosomes. Exogenous histamine had no effect on GABA uptake, but inhibited veratridine-evoked GABA release. GABA uptake was susceptible to the modification of histamine synthesis in synaptosomes. The increase of synaptosomal histamine level by incubation under conditions favouring histamine synthesis from 2.6 to 5.2 pmole/mg protein, decreased the GABA uptake by about 75%. As demonstrated in experiments with an inhibitor of histidine decarboxylase--semicarbazide, this effect comprised 15% inhibition evoked by the histamine precursor--histidine, whereas the remaining 60% inhibition could be ascribed to the effect of newly synthesized histamine. | 17 |
Superoxide dismutase activity, lipid peroxide production and corpus luteum steroidogenesis during natural luteolysis and regression induced by oestradiol deprivation of the ovary in pseudopregnant rabbits. The relationship of oxygen free radicals to corpus luteum function in rabbits was explored during various stages of pseudopregnancy, including natural and induced luteal regression. Induced luteolysis was achieved during mid-pseudopregnancy by removal of an oestradiol capsule placed at the onset of pseudopregnancy, which suppressed ovarian oestradiol production. Activity of manganese superoxide dismutase (Mn SOD) was significantly and positively correlated with ovarian progesterone production (P < 0.01) throughout pseudopregnancy and during natural regression. Oestradiol deprivation for 12, 24 or 72 h resulted in declines in Mn SOD activity and progesterone secretion, although Mn SOD rose and corpus luteum steroidogenesis was restored to normal when the capsule was replaced for 48 h before assessment, having been removed for 24 h. Lipid peroxide and progesterone concentrations were not correlated, although a significant rise in lipid peroxides in the luteal tissue was detected after deprivation of oestradiol for 72 h. Changes in progesterone production and Mn SOD activity were not associated with alterations in concentration of prostaglandin F metabolite. These data suggest that Mn SOD may be involved in regulating function of the corpus luteum during pseudopregnancy in rabbits and that oxygen free radicals may play a role in regression of corpus luteum in this species. | 28 |
A comparison of the effects of antitumor agents upon normal human epidermal keratinocytes and human squamous cell carcinoma. The pharmacologic responses of normal and malignant epidermal cells to chemotherapeutic agents were examined in a system which consists of a serum-free "defined" medium. The effects of methotrexate (MTX), fluorodeoxyuridine (FUDR), and hydroxyurea upon cell growth, DNA synthesis, thymidylate synthase activity, and dihydrofolate reductase (DHFR) activity were compared in normal human epidermal keratinocytes (NHEK), newborn epidermal cells (NEC), human squamous cell carcinoma (SCC-25), and a methotrexate-resistant human squamous cell carcinoma (SCC-15R). Normal keratinocytes were found to be 10(3) to 10(4) times less sensitive to the effects of MTX and FUDR than the malignant cells with respect to growth and DNA synthesis. The differential sensitivity to MTX and FUDR was not due to differences in growth media, increased target enzyme activity, e.g., DHFR and thymidylate synthase, or impaired transport of these drugs. The results indicate that the mechanism for the increased sensitivity of the squamous cell carcinoma to MTX and FUDR must involve a process which is distal to the de novo synthesis of dTMP. | 20 |
Hematologic toxicity of AZT and ddC administered as single agents and in combination to rats and mice. Toxicity studies of 3'-azido-2',3'-dideoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC) were conducted in F344/N rats and B6C3F1 mice. The drugs were administered as single agents and in combination. In all studies, animals were treated by oral gavage twice a day, 7 days a week. In studies of the individual compounds, each was administered for 13 weeks at the following concentrations: AZT in rats, 0, 125, 250, 500, 1000 mg/kg and in mice, 0, 25, 50, 100, 400, 1000 mg/kg; ddC in rats and mice, 0, 250, 1000, 2000 mg/kg. Additional male rats and female mice that were treated with 0, 250, 1000, or 2000 mg/kg ddC and male and female mice treated with 0, 50, 400, 1000 mg/kg AZT were maintained for 30 days after treatment was stopped (at 94 days) to evaluate the reversibility of toxic effects. Hematologic variables were measured on Days 5, 23, and 94 (last day of dosing), and on Day 123 (after a 30-day period without treatment). AZT and ddC produced dose-related, poorly regenerative, macrocytic anemias as evidenced by decreases in erythrocyte counts, hematocrits, and hemoglobin concentrations and increases in mean corpuscular hemoglobin and mean corpuscular volume. Bone marrow samples in rats treated with AZT were hyperplastic whereas those in mice treated with AZT and rats and mice treated with ddC were hypoplastic. The hematologic toxicity of AZT was more severe than that of ddC. Generally, toxic effects of either chemical were greater in mice than in rats and more pronounced in female than in male animals. After 30 days without dosing, hematologic effects either resolved or dramatically improved. In studies in which ddC and AZT were administered in combination for 4 weeks at concentrations of 0/0, 0/500, 500/0, 10/500, 100/500, 500/500, and 500/1000 mg/kg ddC/AZT, there was macrocytic anemia in animals in the lower doses and marked microcytic anemia in surviving male mice in higher dose groups. Most female mice died in the 500/500 and 500/1000 mg/kg ddC/AZT dose groups. At lower concentrations (100/500, 500/1000 mg/kg ddC/AZT), effects of the two drugs were similar to those in the single drug studies. At higher concentrations (500/500 and 500/1000 mg/kg ddC/AZT), the combination treatment produced enhanced hematopoietic toxicity. These studies demonstrated the early and progressive time course of toxicity of AZT and ddC, species differences in sensitivities and responses, and reversibility of effects after termination of treatment. Based on these findings, a chronic toxicity study is being conducted with AZT in mice. | 14 |
Sexual activity and attitudes toward contraception among women seeking termination of pregnancy in Zaria, northern Nigeria. One hundred and eight (108) women seeking termination of pregnancy in Zaria were studied during a period of 3 months (October to December 1985). The mean age was 21.8 years (range 15-38); 35.6% were below the age of 20 years and 57% were students. The three major tribes engage in illegal termination of pregnancy and Yorubas were in the majority; 53.3% had history of previous induced abortion. Sixty-three percent had had sexual experience by the age of 18 years. The major reasons for seeking termination of pregnancy were "still in school" and "not married." Although 88.8% had knowledge of contraception, less than half actually used any method. Of the 60 patients who volunteered information on their views on legalization of abortion, 21 (35%) were against legalization of abortion for various reasons. Family health education in schools and contraceptive counseling among the adolescents will reduce the prevalence of illegal abortions and its disastrous consequences. | 14 |
[Morphologic studies on the effect of acrylnitrile in subchronic intoxication experiments in the white rat]. 100 female and male white rats were treated with acrylnitrile using 4 various dosages. It was our practice to give orally acrylnitrile in physiological sodium chloride solution by probang, and the treatment was continued for 69 days from Monday to Friday in the week. After the treatment with acrylnitrile from the 70th day the animals were killed in intervals. Blood of orbital venous plexus was analysed by electrophoresis for determination of serum proteins, and organs were investigated histologically. It has been shown that of all organs the greatest alterations have been found in livers, kidneys and lungs. Taking by surprise our studies indicated that the application of 1/16 LD50 acrylnitrile dosage cause greater morphological damages in liver than those applications of higher concentrations in other groups. | 14 |
Lack of physiological adaptation of the atrioventricular interval to heart rate in patients chronically paced in the AAIR mode. Seventeen consecutive patients, aged 56 +/- 12, were chronically paced in the AAIR mode for a symptomatic sinus node disease with atrial chronotropic incompetence defined by a peak exercise heart rate (HR) less than 75% of the maximal predicted heart rate (MPHR) mean = 65 +/- 10%). Sensors used were activity sensing (n = 7), minute ventilation (n = 6), or respiratory rate (n = 4). Basic pacing rate was programmed at 71 +/- 5 beats/min and the maximal sensor rate at approximately 85% MPHR (143 +/- 10); other sensor parameters were programmed individually. Six months after implant, two standardized and symptom limited exercise tests were performed in random order, AAI and AAIR modes, respectively. AAIR pacing significantly improved peak exercise HR (139 +/- 14 vs 112 +/- 30 beats/min; P less than 0.01), maximal sustained workload (132 +/- 42 vs 110 +/- 38 watts; P less than 0.02), and total exercise duration (724 +/- 299 vs 594 +/- 245 sec; p less than 0.02) compared to the AAI mode. In all 17 patients, HR was continuously sensor driven in the AAIR mode, making it possible to precisely study the adaptation of the stimulus-R interval and of the stimulus-R:RR ratio during exercise. Six patients normally adapted with a progressive shortening. Six others did not adapt at all without any variation of interval. Five patients paradoxically increased their stimulus-R interval (286 +/- 10 msec at peak E vs 220 +/- 19 msec at rest) and their stimulus-R:RR ratio (67 +/- 20% vs 29 +/- 4%), producing P waves occurring immediately after, or even within the R wave of the preceding cycle; two patients complained of severe exercise related symptoms corresponding to the so-called "AAIR pacemaker syndrome." The principal factors involved in the nonadaptation of AV interval to HR were related to the patient (organic heart disease, with the particular problem of the denervated heart; the bradytachy syndrome; and the use of drugs, especially beta blockers and Class I antiarrhythmic drugs) or to the pacemaker ("overstimulation" phenomenon). These observations constitute an additional argument for wider indications of implanting DDDR units in these patients. | 19 |
[Water intake, pH and ammonia levels in the ruminal contents of sheep fed pelleted feed]. Wethers were studied for the effect of the complete pelleted feed ration on the intake of water and concentration of pH and ammonia in the rumen. The animals consumed daily 1300 g of dry matter of the diet containing 41.81% of meadow hay, 25.8% of barley, 15.37% of sawdust, 14.98% of molasses, 1.32% of urea and 1.24% of vitamin mineral supplement. This feed was given to them for six months. The pelleted diet increased the intake of water (the dry matter consumption remaining the same in the control and experimental group), reduced pH concentration (6.0--6.2) and slightly increased the level of ammonia in the first hour after feeding; this was probably due to a rapid release of nitrogen compounds from the feed and to intensive rumen fermentation. | 16 |
Nucleic acid and protein differences in Volvox carteri cell types. Nucleic acids in Volvox carteri have different radioactive labelling patterns in the two cell types, reproductive (gonidia) and somatic. Incorporation of 32P into DNA is maximum during gonidial division in both whole spheroids and isolated somatic and reproductive cells. The most active period of radioactive incorporation into the rRNA of gonidia and somatic cells is during spheroid enlargement, after which the terminally differentiated somatic cells show a steady, continuous decline. Incorporation into the gonidial rRNA declines markedly during late stages of gonidial division but increases during daughter spheroid growth. Polyarylamide gel electrophoresis profiles of cellular proteins are distinctive for spheroids at different developmental stages and also for the isolated cell types. | 17 |
Light-induced infrared light scattering signal in the retina: effect of phosphodiesterase inhibitors. Visible light changes IR light scatter through a toad retina. This signal presents three components: at low light intensity (100-400 bleached rhodopsins/rod) an early decrease in IR light scatter, of small amplitude, with time to peak of 1-6 s; at intermediate light intensity (1200-16,000 bleached rhodopsins/rod) a slow increase in IR light scatter, with time to peak of 10-30 s; at high light intensity (50,000-160,000 bleached rhodopsins/rod) a last increase in IR light scatter, with time to peak of 1 min. Light sensitivity, amplitude and time to peak of the last two components are increased by inhibitors (3-isobutyl-1-methyl-xanthine and papaverine) of the cyclic 3'5' guanosine monophosphate phosphodiesterase. | 19 |
[Chemotaxis, phagocytosis and metabolic activation of leukocytes in patients with acute pneumonia]. The authors describe changes in functional activity of peripheral blood leukocytes, namely in the absorptive capacity, metabolic activation, chemotaxis in vivo and in vitro in patients with grave acute pneumonia (n-102) and destructive pneumonia (n-16). At the stage of active inflammation, the patients with acute pneumonia showed a decrease in leukocyte function (chemotaxis and phagocytosis) and metabolic activation of that cell type, related to the growth of the output of the toxic forms of oxygen. The changes revealed were found to be dependent on the activity of inflammation and volume of infiltration in the pulmonary tissue. The functional changes in leukocytes discovered in patients suffering from acute pneumonia, particularly in those with destruction confirm the possibility that those cells are involved into the pathogenesis of the destructive process. | 21 |
No change in spontaneous behavior of rats after acute oral doses of aspartame, phenylalanine, and tyrosine. Spontaneous behavior subsequent to acute oral administration of high doses of aspartame, phenylalanine, or tyrosine was analyzed using a computer pattern recognition system. Sprague-Dawley male rats (250-300 g) were dosed orally with aspartame (500 or 1000 mg/kg), phenylalanine (281 or 562 mg/kg), or tyrosine (309 or 618 mg/kg), and their behavior was analyzed 1 hr after dosing. The computer pattern recognition system recorded and classified 13 different behavioral acts performed by the animals during the first 15-min exploration of a novel environment. Three measures that provide independent information concerning motor output from the central nervous system were taken: the number of behavioral initiations, total time, and time structure. These results were compared with the effects induced by d-amphetamine. Plasma concentrations of phenylalanine and tyrosine were determined from blood samples taken immediately after behavioral examination. Data analysis revealed that these doses of aspartame, phenylalanine, and tyrosine did not induce any significant changes in spontaneous behavior. Unlike low doses of amphetamine and despite high plasma concentrations of phenylalanine and tyrosine, no behavioral alteration was detected by the computer pattern recognition system. Absence of behavioral changes in this study using an objective analysis of behavior raises questions concerning the relationship between amino acid precursor loading and purported anecdotal changes in behavior following aspartame administration. | 19 |
Malignant behavior and resistance to cisplatin of human ovarian carcinoma xenografts established from the same patient at different stages of the disease. Three human ovarian carcinoma lines (HOC8) derived from the same patient before (P-HOC8) and after (R-HOC8 and Y-HOC8) cycles of chemotherapy were established i.p. in nude mice. The biological characterization showed that these tumor lines had various features in common. Cytological and histopathological characteristics and the expression of tumor-associated antigens OC125 and MOV18 were maintained in the three variants and were comparable to the patient's primary tumor. The HOC8 variants were aneuploid with a chromosome mode number of 80-81. All three tumor lines grew better i.p. than s.c. in nude mice. After i.p. injection the HOC8 lines produced ascites in all the mice, infiltration of pancreas, liver, diaphragm, and lung metastases. The sensitivity to cisplatin was evaluated for HOC8 lines growing in nude mice and mirrored the clinical development of resistance. Treatment with cisplatin of mice transplanted i.p. with P-HOC8 (obtained before the patient received chemotherapy) resulted in a significant increase in survival time; the R-HOC8 and Y-HOC8 lines (obtained after chemotherapy) were less sensitive. HOC8 xenografts, which represent the course of a single patient's disease, are a useful model for investigating the development of drug resistance in ovarian carcinoma. | 13 |
Pathology of acute ischemic myocardium. Special references to (I) evaluation of morphological methods for detection of early myocardial infarcts, and (II) lipid metabolism in infarcted myocardium. Morphological changes of early myocardial infarction within 24 hours after the onset of the acute attack were described together with a review of the literatures. For the practical purpose in detecting very early infarcts, enzymatic histochemistry is the most reliable method. Other methods previously reported such as wavy pattern of the muscle fibers and fuchsinophilia are still controvertial. Lipid metabolism in the infarcted myocardium of dogs was studied both morphologically and biochemically. Up to 3 hours, after the coronary ligation, the tissue lipids accumulated in the necrotic areas with a rise of triglyceride, but later than 6 hours the lipids decreased and were lost from the necrotic tissue, while the surrounding living cells were accumulated with neutral lipids. Serum free fatty acids were elevated in the coronary sinus blood in 6 hours after the ligation. Linolic acids were contained in high proportion in both coronary venous blood after 6 hours, and normal myocardial phospholipid. These results may lead to another possible factor in addition to catecholamine activity to elevate serum FFA in acute myocardial infarction that fatty acids may be released partly from tissue phospholipid and once ever accumulated triglyceride. | 17 |
Influence of breed, number of suckling lambs, and stage of lactation on ewe milk production and lamb growth under range conditions. Milk production and lamb growth were characterized in 118 multiparous, 3- to 7-yr-old Rambouillet, Columbia, Polypay, and Suffolk ewes under spring sage range and high mountain meadow grazing from 28 to 98 d postpartum. Daily milk yield as measured by the lamb suckling weight differential technique did not differ (P greater than .05) among breeds, although milk production of Suffolk ewes tended to be higher than that of the other three breeds. Within the Rambouillet, Columbia, and Polypay breeds, total estimated yield of ewes with twins was 13 to 17% higher than that of ewes with singles, whereas in the Suffolk breed, suckling twins increased total milk yield 61% over that of ewes with singles. Twin lambs induced a larger differential in dam milk production in late lactation (70 to 98 d) than in earlier lactation (28 to 70 d). Number of lambs did not influence milk protein, Ca, or P content (P greater than .05). Fat levels in colostrum and 4-d milk were elevated 14 and 20%, respectively, in ewes suckling twins compared with ewes suckling singles. Under range conditions, Suffolk ewes suckling single or twin lambs lost more BW (12 and 21% of 4-d postpartum body weight, respectively) than Rambouillet (4 and 7%), Columbia (5 and 8%), or Polypay (8 and 8%) ewes. Correlation coefficients of milk production and lamb growth rate were positive and significant (P less than .05) up to 56 d of age. Growth rate was less closely associated with milk production for twin than for single lambs. | 15 |
A sensitive enzyme-linked immunosorbent assay for human interleukin-8. In order to quantify human interleukin-8 (IL-8), which is chemotactic for T cells and basophils as well as neutrophils, we developed an enzyme-linked immunosorbent assay (ELISA). Since binding inhibition tests indicated that three monoclonal antibodies (mAbs; BS-1, WS-4, WS-6) blocked the binding of 125I-labelled IL-8 to neutrophils, we tested an ELISA using these mAbs as primary antibodies, rabbit anti-IL-8 Ab as the secondary antibody, and alkaline phosphatase-labelled goat anti-rabbit Ab as the conjugate. Among the three mAbs tested, WS-4 was the most sensitive with a detection limit of 16 pg/ml. Several other cytokines, including monocyte chemotactic and activating factor (MCAF), which is structurally related to IL-8, showed no cross-reactivity in this system, indicating that this ELISA is specific for IL-8. The coefficients of variation for the intra- and interassays were below 10%. Furthermore, this ELISA also detected natural IL-8 (including both 72 and 77 amino acid forms) produced by cultured human cells and cell lines stimulated with IL-1, suggesting that this system will be useful in the detection of natural IL-8 in various body fluids. | 20 |
Occupational exposure to hexachlorocyclopentadiene. How safe is sewage? In March 1977, a large volume of the industrial chemical hexachlorocyclopentadiene (HCCPD) was dumped into a municipal sewage system in Kentucky. We evaluated the health effects of exposure to HCCPD in 145 sewage treatment plant workers. We found that 85 (59%) had noted eye irritation, 65 (45%) had headaches, and 39 (27%) had throat irritation. Symptoms occurred throughout the plant; however, highest attack rates occurred in primary sewage treatment areas. Medical examination of 41 employees three days after the plant was closed showed proteinuria and elevation of serum lactic dehydrogenase levels; these findings were not present three weeks later. This episode demonstrates the toxicity of HCCPD and emphasizes the vulnerability of sewage workers to chemical toxins in wastewater systems. | 12 |
[Electron microscopy as a method of classification of hematopoietic-system tumors]. 83 biopsies of lymph nodes and 35 specimens of blood in different types of haematopoietic system oncological involvement were examined electronoptically with a view to finding distinguishing features such as would prove to be better than other methods used in diagnosing the above tumours. In the granulocytic series these proved to be granules though there was a loss of their formation in most of the poorly diagnosable processes. However, it proved to be relatively easy to make use of tests for phagocytosis in myelomonocytes. In the histiocytic series the defining features (phagocytosis and proteosynthesis) proved to be too general in nature to find any relevant use in oncological diagnosis. On the other hand, the rod-like granules of Langerhans' cells proved to be a reliable guide in diagnosing histiocytosis X similarly as the Weibel-Palade granules did in diagnosing endotheliosis. In the lymphocytic series, B series diagnosis can be facilitated by the presence of spatially arranged interdigitations; in the T series interdigitations are either missing or else are arranged in a single plane only. The erythrocytic series is defined by the presence of ferritin while megakaryocytes are defined by the phenomenon of fissure-like communications.--All those features were merely supplementary in nature and could not be used as an independent diagnostic method particularly in view of the small volume of the processed specimens as these did not always contain representative material or else supplied it in a hardly classifiable mixture. | 21 |
Usefulness of the hypo-osmotic swelling test for evaluation of human sperm fertilization. We examined spermatozoa from 135 male patients consulting for infertility to evaluate the usefulness of the hypo-osmotic swelling (HOS) test of sperm fertility for the swim-up washing method. HOS test values significantly improved following the treatment of spermatozoa using the swim-up washing method. There were no differences in the rate of sperm motility between the normal group and the oligozoospermic group following treatment, but the HOS test identified significant differences in swelling rates in both groups before and after treatment. The results of the HOS test following swim-up washing were higher during fertilization attempts for 11 cases of successful intra-uterine insemination (IUI) than during unsuccessful IUI attempts; there were no significant differences between the control group and the successful IUI cases. Moreover, using the lower-normal limits for overall sperm swelling (52%) and g-type sperm swelling (30%) obtained from a normal control group, we found that swelling rates were higher when IUI was successful. These findings indicate that the HOS test is an effective measure of sperm fertilizing function when the swim-up washing method is used for sperm treatment. The score of g-type sperm swelling can be used as a substitute for overall sperm swelling. | 16 |
Frequencies of centromeric heteromorphisms of human chromosomes 3 and 4 as detected by QFQ technique: can they be identified by RFA technique? One hundred normal Caucasians were studied by sequential QFQ and RFA banding techniques in order to estimate the type and frequency of heteromorphisms in the centromeric regions of chromosome 3 and 4. Intensity variants were classified into 1 of 5 levels of QFQ banding. QFQ intensity heteromorphisms (greater than or equal to level 3) for chromosomes 3 and 4 were 62 and 15 percent respectively. The interrelationship between QFQ and RFA variants were also examined. When the centromere was brilliant by QFQ, it was found that it was deep red by RFA; when it was pale by QFQ, it was light red by RFA. Neverthless, a blind coded study could not pick up these color variants by RFA. QFQ banding showed variations of the centromeric regions of chromosomes 3 and 4 while RFA banding failed to demonstrate it. It was concluded that QFQ is the most useful technique in detecting the different intensity levels in the centromeric regions of chromsomes 3 and 4. | 13 |
[3H]rauwolscine behaves as an agonist for the 5-HT1A receptors in human frontal cortex membranes. The alpha 2 adrenergic antagonist [3H]rauwolscine binds with comparable nanomolar affinity to alpha 2 adrenoceptors and the nonadrenergic 5-HT1A receptors sites in human frontal cortex membranes. Addition of 0.5 mM GTP into the incubation medium produces a significant decrease in the amount of [3H]rauwolscine binding sites (Bmax = 230 +/- 16 and 115 +/- 11 fmol/mg protein in the absence and presence of GTP, respectively). The affinity for [3H]rauwolscine remains unchanged (i.e. KD = 40 +/- 0.9 nM and 4.1 +/- 1 nM). This effect of GTP can be attributed to decreased binding of the radioligand to the 5-HT1A receptors. GTP decreases binding of [3H]rauwolscine to nearly the same level as the one corresponding to the alpha 2 adrenoceptors in membranes from both the human frontal cortex and hippocampus. The venom of the marine cone snail, Conus tessulatus, preferentially inhibits [3H]rauwolscine binding to 5-HT1A receptors as compared with the alpha 2 adrenoceptors. Following complete masking of the 5-HT1A receptors by this venom. GTP no longer affects the saturation binding characteristics of [3H]rauwolscine for the remaining alpha 2 adrenoceptors. Nucleotides decrease the binding of [3H]rauwolscine to the 5-HT1A receptors with an order of potencies (i.e. GTP gamma S greater than GPP(NH)P much greater than GDP greater than GTP much greater than ATP) that is typical for nucleotide-mediated receptor-G protein dissociation. This suggests that [3H]rauwolscine is a 5-HT1A receptor agonist and this conclusion is compatible with earlier functional studies, indicating that rauwolscine (as well as yohimbine) has agonistic properties at the level of 5-HT autoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS) | 14 |
Mycobacteria and human heat shock protein-specific cytotoxic T lymphocytes in rheumatoid synovial inflammation. To study the cytotoxic capacity of mycobacteria-specific T lymphocyte lines and clones from sites of inflammation in patients with rheumatoid arthritis (RA). We also studied antigen specificity, surface phenotype, expression of T cell receptors (TCR), and HLA restriction. Autologous macrophages (M phi) from the synovial membrane (SM), synovial fluid (SF), or peripheral blood (PB) were used as target cells in cytotoxicity assays. All SM and SF cell lines tested thus far have shown specific lysis of the autologous M phi from SM or PB that had been pulsed with BCG (bacillus Calmette-Guerin), but no cytotoxicity when the targets were pulsed with irrelevant antigens such as tetanus toxoid and Chlamydia. Both CD4+ and CD8+ cells were shown to be involved in the specific cytolysis. The majority of the cytotoxic T lymphocyte (CTL) lines were TCR alpha/beta + cells. However, both TCR alpha/beta + and TCR gamma/delta + clones (TCR delta 1+) from one RA patient showed antigen-specific lysis. Antigen-specific recognition by a number of CTL lines and clones generated from SF and SM was restricted by HLA-DR molecules. Two Mycobacterium bovis 65-kd heat shock protein (HSP)-specific TCR alpha/beta + SF T cell clones also lysed M phi that had been pulsed with a recombinant human 65-kd HSP. Joint inflammation and destruction might be partly attributable to a cross-reaction of mycobacteria-induced cytotoxic T cells with self HSP. | 15 |
Photolytic inhibition and labeling of proteins with aryl diazonium compounds. In the course of preparing aryl azide derivatives for use as photoprobes, we have observed significant light sensitivity in the precursor aryl diazonium compounds. The photosensitive properties of this class of compounds are of interest since they will seek out cationic binding sites in biological targets, and can be employed to inhibit complementary targets at acid pH. The relationship between photolytic change in the structure of diazonium compounds and the corresponding change in function of a biological target are presented. Experiments are described in which the dark and light sensitive properties of a model diazonium compound, diazobenzene sulfonate (DBS), were determined. The ultraviolet spectra were used to evaluate the dark stability and light sensitivity of DBS. Chymotrypsin and trypsin served as functioning targets for further evaluation of the photochemical properties. Both enzymes are stable to the probe in the dark at acid pH. A rapid loss of enzyme activity was observed following flash photolysis of DBS-enzyme solutions. Photolytic incorporation of radioactive DBS into chymotrypsin was observed. Aryl diazonium salts can be employed to probe the availability of complementary sites in biological targets at different acid pH values. | 15 |
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