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Cell cycle-dependent variations in deoxyribonucleotide metabolism among Chinese hamster cell lines bearing the Thy- mutator phenotype. Deoxyribonucleotide pool imbalances are frequently mutagenic. We have studied two Chinese hamster ovary cell lines, Thy- 49 and Thy- 303, that were originally characterized by M. Meuth (Mol. Cell. Biol. 1:652-660, 1981). In comparison with wild-type CHO cells, both lines have elevated dCTP/dTTP ratios, resulting from loss of feedback control of CTP synthetase. While asynchronous cultures of both cell lines contain nearly identical deoxyribonucleoside triphosphate (dNTP) pools and both display elevated spontaneous mutation frequencies, the mutation frequencies between the two cell lines differ by as much as 10-fold. We asked whether differences in dNTP pools could be seen in extracts of rapidly isolated nuclei. Small differences, probably not large enough to account for the differences in mutation frequencies, were seen. However, when synchronized S-phase-enriched cell populations were examined, substantial differences were seen, both in whole-cell extracts and in nuclear extracts. Thy- 303 cells, which have higher mutation frequencies than do Thy- 49 cells, also showed the more aberrant dNTP pools. These data indicate that the Thy- 303 line contains a second mutation in addition to the mutation affecting CTP synthetase control. Evidence suggests that this putative second mutation affects an allosteric regulatory site of ribonucleotide reductase. The data on intranuclear dNTP pools in synchronized S-phase cells indicate that higher proportions of cellular dATP and dGTP are found in the nucleus than are corresponding amounts of dCTP and dGTP. Thus, despite the porous nature of the nuclear membrane, there are conditions under which the distributions of deoxyribonucleotides across this membrane are not random.
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An immunohistochemical study of mesothelial cell seeding for knitted Dacron. Six greyhounds underwent bilateral femoral artery replacement with knitted Dacron, one side seeded with omental digest at graft preclotting, the other acting as an unseeded control. Grafts were removed at 24 hours and two months. Tissue was examined using a monoclonal antibody (MNF116) directed against a broad range of human cytokeratins to differentiate mesothelial cells (MC) from microvascular endothelial cells (MEC), which stained only with a polyclonal antibody directed against von Willebrand Factor (anti-vWF). Cells released from omentum by collagenase stained with MNF116 and reacted poorly with anti-vWF. Identical cells were observed to be within the interstices of seeded but not control knitted Dacron. Few remained in seeded grafts (n = 2) removed at 24 hours and none at two months (n = 4).
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[Acute disseminated histiocytosis X (Langerhans cell histiocytosis) with fatal course in an adult]. Histiocytosis X is very rare in late adulthood, usually taking a benign course with a good prognosis. A 56-year-old patient developed acute disseminated histiocytosis X with multiorgan involvement. Despite extensive diagnostic work-up the diagnosis could only be established on the grounds of a skin biopsy. Histiocytosis X cells are S 100 protein-positive and express the membrane antigens CD 1, CD 4 and HLA-DR. Electron microscopy reveals Birbeck granules. On static cytophotometry, histiocytosis X cells exhibited normal DNS content without aneuploidy. One year after the onset of disease the patient's condition deteriorated rapidly despite aggressive polychemotherapy (CHOP), and he died of multiorgan failure due to histiocytosis X.
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[Plasma lipids in respiratory insufficiency: relation with hypercapnia and hypoxaemia (author's transl)]. A study of plasma lipids in a group of 111 patients with chronic lung disease has been carried out and compared with a reference group of 37 normal subjects. In decompensated patients, a decrease in beta-lipoproteins, cholesterol, triglycerids, total lipids, and in the beta-lipoproteins cholesterol/total cholesterol ratio (Cb-Ct) was observed. These changes were not in correlation with PaCO2 values, neither with the presence or absence of cor pulmonale, but seemed to be related with the degree of hypoxaemia. The distribution of patients in two groups according to PaO2 (below or above 50 mmHg) revealed statistically significant difference. The follow-up of 23 of these patients showed a good correlation of clinical evolution with dyslipemia.
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Computerized topographical analysis of functionally homogeneous neuronal sets. A computer-assisted analysis of the spatial distribution of neurons having homogeneous characteristics is described in this paper. The camera lucida drawings of sections of a brain nucleus and the points representing the neurons labeled on the basis of a specific behavior of discharge rates were digitized on a personal computer Amiga 2000 or IBM compatible. Our software provided: a) the computerized, stereotaxically oriented reconstruction of the stored sections and of the plotted neurons; b) the identification within each section of the mass center (MC) of the units sharing a given behavior and of the area where the density of such neurons was maximal (MDA). The routine was tested on the spatial distribution of neuronal responses to serotonin in the lateral vestibular nucleus.
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[Transmission of impulse trains by nerve fibers upon near-threshold stimulation]. Impulse trains evoked by stimulation of the hindlimb nerves were studied in group A fibres at the lumbar level of spinal cord in anesthetized cats. Random (Poissonian) trains fo stimuli and trains with modified structure were used. With suprathreshold stimulation the impulse trains in the nerve fibres differed from the stimulus trains only by the absence of the shortest (less than 1.0 divided by 1.5 ms) intervals caused by refracteriness. Substantial differencies between the impulse and stimulus trains occurred when the stimulus intensity was decreased to a near-threshold level and mean frequency of stimulation was higher than 10 per second. Differences were found in interval histograms, intensity functions, correlation coefficients for successive intervals. Afterdischarge processes in the nerve fibres are supposed to be the main reason of changes in the impulse train structure.
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Distinct functional roles of two active site thiols in UDPglucose 4-epimerase from Kluyveromyces fragilis. UDPglucose 4-epimerase from Kluyveromyces fragilis was earlier shown to have two conformationally vicinal thiols at the active site. Upon treatment with diamide, these thiols form a disulfide linkage across the subunits that results in coordinated loss of catalytic activity and coenzyme fluorescence (Ray, M., and Bhaduri, A. (1980) J. Biol. Chem. 255, 10777-10786). Employing a number of thiol-specific reagents, we now suggest discriminatory and nonidentical roles for these two thiols. Kinetic and statistical analysis of 5,5'-dithiobis-(2-nitrobenzoic acid) and N-ethylmaleimide modification reaction of epimerase show that only one thiol is essential for activity. Consecutive modification experiments clearly show that the same active thiol is modified in both cases. However, significant differences are observed when the reactivity of these reagents is monitored in terms of coenzyme fluorescence. Treatment with N-ethylmaleimide leads to a form of inactive enzyme that fully retains its fluorescent properties whereas modification with 5,5'-dithiobis-(2-nitrobenzoic acid), on the other hand, results in the loss of both activity and fluorescence. The closely spaced nonessential second thiol, which is not modified by N-ethylmaleimide is therefore involved in generating and maintaining the coenzyme fluorescence. Modification studies with a series of spin-labeled maleimide shows that only 3-(maleimidomethyl)proxyl causes partial quenching of coenzyme fluorescence. This suggests that the active thiol is situated at a distance of 4.5 A approximately from the coenzyme fluorophore.
14
Cancer incidence in Norwegian Seventh-Day Adventists 1961 to 1986. Is the cancer-life-style association overestimated? Standardized incidence ratio for cancer in Norwegian Seventh-Day Adventists compared with the general population was not significantly different from unity (men 91, women 97). Persons converting late in life had a higher incidence than those converting at an earlier age. Respiratory cancers (standardized incidence ratio [SIR] 59, 95% CI = 36 to 91) and cancers with an unspecified site (SIR 53, 95% CI = 25 to 97) were rarer and cancer of the uterine corpus (SIR 164, 95% CI = 109 to 237) was more common in Seventh-Day Adventists before the age of 75 years. Inclusion of all registered Seventh-Day Adventists regardless of religious activity and the relatively low cancer incidence rates in the Norwegian population could contribute to the nonsignificant result with regard to total cancer. Main etiologic factors in cancer development in Norway should be sought in areas where Seventh-Day Adventists do not differ from the general population.
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On fantasies of self-creation. The authors present a psychoanalytic study of fantasies of self-creation. These fantasies constitute important mental structures shaping the lives of many individuals. Although hitherto unreported in the clinical literature, artists have made rich use of self-creation fantasies, and we therefore begin our investigation with representative portraits of self-creators by Milton, Goethe, and two modernists, Luigi Pirandello and F. Scott Fitzgerald. We then describe the psychoanalyses of two men whose lives were shaped and organized by self-creation fantasies, showing the clinical value of uncovering and analyzing these fantasies. We offer some preliminary observations on the cultural significance of self-creation fantasies and their impact on the analyst and the analytic enterprise.
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Islet cell antibody reactivity with human fetal pancreatic islets. To evaluate the possibility of autoimmune processes against pancreatic islets in fetal life, we tested islet cell antibody (ICA) reactivity with 14 fetal pancreata obtained after abortion at the 15th up to the 19th week of gestation. Pancreatic islets positive for a monoclonal proinsulin antibody but non-reactive with ICA negative control serum were found in 9/14 pancreata and all (9/9) of them showed a positive reaction with the ICA standard. It is concluded that ICA reactivity may be detected in fetal human pancreata. Further studies on fetal islet cell antibody reactivity in the development of insulin dependent diabetes mellitus (IDDM) are warranted.
17
Cloning and complete nucleotide sequence of the gene for the main component of hemagglutinin produced by Clostridium botulinum type C. In Clostridium botulinum types C and D, phage conversion to toxin and hemagglutinin (HA) production has been reported. DNA was extracted from a converting type C Stockholm phage, c-st, and a fragment (7.8 kilobase pairs) coding for the parts of both toxin and HA was cloned. The gene for HA was recloned, and the complete nucleotide sequence was determined. The molecular mass of this gene product was 33 kilodaltons, and it showed HA activity. The HA preparation partially purified from a type C Stockholm culture demonstrated two major bands (33 and 53 kilodaltons) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with or without reducing agent. The amino acid sequence of the N terminus of the 33-kilodalton component of the native HA preparation, which was determined by a direct protein microsequencing procedure, was identical to that deduced from the nucleotide sequence of cloned HA gene. These data indicate that the cloned gene product (33 kilodaltons) is an important component of HA.
17
Serum lipids, lipoproteins, and apolipoproteins during postmenopausal estrogen replacement therapy combined with either 19-nortestosterone derivatives or 17-hydroxyprogesterone derivatives. To study the influence of combined hormone replacement therapy on levels of serum lipids, lipoproteins, and apolipoproteins. One hundred thirty-nine healthy early postmenopausal women selected by means of a questionnaire, a medical examination, and a laboratory screening procedure to be a representative sample of postmenopausal Danish women aged 45 to 55 years old were randomized to four treatment and two placebo groups. The four groups receiving hormone replacement therapy were given 2 mg estradiol valerate equivalents (E), either sequentially combined with 75 micrograms levonorgestrel (E/LNG), 10 mg medroxyprogesterone acetate (E/MPA), or 150 micrograms desogestrel (E/DG), or continuously combined with 1 mg cyproterone acetate (E/CPA). Serum lipids, lipoproteins, and apolipoproteins were measured before institution of hormone replacement therapy and at nine well-defined times during the following 84 days. Total response and cyclical variations were calculated. All active treatment regimens reduced serum low-density lipoprotein cholesterol (LDL-C) significantly: E/CPA, 6% (95% confidence limits 0.3% to 11.3%); E/LNG, 10.9% (4.9% to 16.6%); E/MPA, 14.4% (7.4% to 20.9%); E/DG, 10.7% (3.3% to 17.6%). The changes in serum total cholesterol and apolipoprotein B were similar but smaller than those in LDL-C. None of these treatment regimens induced significant overall changes in serum high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A1 (Apo A1). The sequentially combined hormone treatments induced significant cyclical variations in HDL-C, with an increase during estrogen therapy and a decrease during combined therapy: E/LNG, 13.3% (7.4% to 19.4%); E/MPA, 6.9% (1.6% to 12.6%); E/DG, 10.3% (5.8% to 14.9%). No cyclical changes in HDL-C were found in the group receiving continuously combined hormone replacement therapy (E/CPA). The changes in Apo A1 parallel those in HDL-C. All the treatment regimens produced changes in levels of serum lipids, lipoproteins, and apolipoproteins that may be considered favorable in terms of cardiovascular disease.
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The value of ultrasound in predicting non-visualization of the gall-bladder on OCG: implications for imaging strategies in patient selection for non-surgical therapy of gallstones. Gall-bladder visualization on oral cholecystography (OCG) is required for most non-surgical therapies of gallstones. In this study we attempted to establish sonographic criteria which will predict non-visualization of the gall-bladder on OCG. For this purpose we compared the results of ultrasound (US) and OCG in 171 patients with gallstones being assessed for non-surgical therapy. Sonographic criteria for non-visualization were a contracted gall-bladder and stone impaction in the gall-bladder neck or cystic duct. In detecting findings which predict non-visualization on OCG, US had a sensitivity of 78.3% and a specificity of 97.6%. The predictive values were: positive findings 92.3% and negative findings 92.4%. The overall accuracy was 92.4%. We conclude that US can be used as a first step in selecting patients for non-surgical therapy and if US indicates a contracted gall-bladder, 11% of the patients can be excluded from further diagnostic imaging.
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The effect of visual feedback and self-scaling on plaque control behavior. Psychological factors are involved in inducing patients to practice the plaque control necessary for periodontal health. It is suggested that oral hygiene behavior can be modified by increasing visual feedback by means of optical devices, and by giving patients the task of scaling their own teeth. The optical devices used for intraoral inspection must be specifically designed for this task. A pilot study was undertaken to test the modification in plaque control behavior in patients using a specially-designed optical system and performing self-scaling. Twelve patients participated in the study; six were given optical devices and taught self-scaling and plaque control, whereas the other six acted as controls, received a scaling from a hygienist, and were taught plaque control. All subjects received 3 hours of chairside time. Before treatment both groups had mean PHP indiced (plaque) of 3.2. Five months after the completion of treatment, the experimental group had a mean PHP index of 0.7, whereas the control group had a score of 1.9. The patients performing self-scaling demonstrated that they could remove supragingival calculus and extrinsic stains as effectively as a trained hygienist.
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Single lung transplantation for severe emphysema. Lung transplantation is effective therapy for patients with severe obstructive lung disease. We reviewed seven patients with severe emphysema (age, 48 +/- 5 years; forced expiratory volume in 1 second [FEV1] 0.76 +/- 0.26 liters) who received single-lung transplants (SLT) at our institution between August 1989 and September 1990. Studies to assess the adequacy of cardiac function before transplantation showed moderately reduced right ventricular function (by multiple gated acquisition, 34 +/- 6%), moderately elevated pulmonary artery pressure (25 +/- 3 mm Hg), and normal left ventricular function (by multiple gated acquisition 65% +/- 12%) and coronary arteriograms. Time on the waiting list before transplantation was reduced compared with heart-lung transplant (HLT) recipients (waiting time, 2.9 +/- 1.5 months for SLT, 9.6 +/- 10.2 months for HLT). Six of the SLT recipients are currently alive (after transplantation interval, 17 +/- 5 months); the remaining recipient died of pulmonary embolism 21 days after SLT. Number of ventilator days, intensive care unit days, and days to hospital discharge after transplantation did not differ significantly from HLT recipients. Cardiopulmonary bypass was necessary in four SLT recipients. Pulmonary function was markedly improved after SLT (FEV1, 1.78 +/- 0.73 L/min after SLT versus 0.75 +/- 0.3 L/min before SLT; p less than 0.01), and functional status is correspondingly improved. SLT constitutes effective therapy for patients with severe emphysema, including those with moderate reduction of right ventricular function; and SLT offers distinct advantages over HLT, including decreased waiting time before transplantation, improved donor organ utilization, and less frequent need for cardiopulmonary bypass.
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Plasma-vitamin E and low plasma lipoprotein levels in sickle cell anemia patients. Increasing evidence suggests that in vivo lipid peroxidation may be an important factor in sickle cell anemia (HbSS). Vitamin E is the major lipid-soluble antioxidant in plasma, and this vitamin, as well as cholesterol, is transported in plasma almost exclusively by lipoproteins. The purpose of this investigation was to determine if vitamin E and plasma lipoprotein-cholesterol levels in sickle cell anemia (SCA) patients are interrelated. We found that low plasma-vitamin E levels in SCA patients were accompanied by low levels of plasma-cholesterol. The mean plasma-vitamin E/plasma-cholesterol ratio was similar in 12 SCA patients (6.1 +/- 0.7 micrograms vitamin E per mg plasma-cholesterol) and 21 controls (6.5 +/- 0.7 micrograms/mg). Our results suggest that the low levels of plasma-vitamin E in SCA patients may be related to decreased levels of lipoprotein carriers. The low plasma-cholesterol levels in SCA patients (139.1 +/- 9.9 mg/dL) were due to low levels of both high density lipoprotein-cholesterol (HDL-cholesterol of 35.0 +/- 1.0 mg/dL) and low density lipoprotein-cholesterol (LDL-cholesterol of 97.8 +/- 9.2 mg/dL). The "atherogenic index," defined as LDL-cholesterol/HDL-cholesterol, was similar in the SCA patients (2.9 +/- 0.2) and the controls (3.0 +/- 0.4).
15
Does GABA act through dopaminergic/cholinergic interaction in the regulation of higher environmental temperature-induced change in body temperature? Acute exposure of adult male albino rats to higher ambient temperature (40 degrees C) for 2 h significantly increased body temperature (BT). Administration of either bicuculline (1 mg/kg, i.p.), a GABA antagonist, or physostigmine (0.1 mg/kg, i.p.), an inhibitor of acetylcholinesterase, significantly increased BT of normal and heat-exposed rats. Treatment with muscimol (1 mg/kg, i.p.), a GABA agonist, produced hypothermia in normal rats and prevented an increase in BT of heat-exposed rats. The dopamine agonist, L-dopa (100 mg/kg, p.o.) along with carbidopa (10 mg/kg, p.o.) reduced BT of normal rats. Further, the bicuculline-or physostigmine-induced enhancement of BT in normal and heat-exposed rats was potentiated when both drugs were administered concomitantly. But this potentiating effect remained unaltered when dopamine antagonist haloperidol (1 mg/kg, i.p.) was administered along with bicuculline and physostigmine. Treatment with atropine (5 mg/kg, i.p.), a cholinergic antagonist, abolished the hyperthermic effect of bicuculline but potentiated the hypothermic effect of muscimol either at 28 degrees C or at 40 degrees C. Bicuculline-induced hyperthermia was attenuated at normal or higher temperature by pretreatment with L-dopa + carbidopa. The administration of L-dopa + carbidopa either abolished or reduced the hyperthermic effect of physostigmine at room temperature or at higher ambient temperature. These results suggest that (a) GABAergic, cholinergic and dopaminergic systems are involved in thermoregulation, (b) exposure to high environmental temperature may inhibit central GABAergic activity which activates the cholinergic system without affecting the dopaminergic system and raises BT, (c) central dopaminergic and GABAergic systems act independently through the modulation of cholinergic activity in the regulation of BT under normal ambient temperature.
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Effect of manipulation of plasma lactate on integrated EMG during cycling. This investigation was undertaken to record electromyographic activity of the vastus lateralis muscle during incremental cycling exercise and to determine whether it would be sensitive to altered dynamics of plasma lactate increases seen with intense exercise. Trained cyclists (N = 6) performed two progressive, stepwise exercise tests (23.5 W.min-1) to fatigue on a cycle ergometer at 90 rpm. One of the exercise tests was preceded by arm ergometer exercise in an attempt to elevate the circulating plasma lactate levels prior to starting the criterion exercise test. The starting mean plasma lactate values were 4.59 and 26.69 mmol lactate.-1 for the two exercise sessions. Cardiorespiratory values did not differ significantly between exercise sessions completed in the absence and presence of increased circulating plasma lactate. The no-arm trial (i.e., nonelevated plasma lactate condition) was associated with a plasma lactate inflection point (Tlac) at 72.6% VO2max. Previous arm exercise elevated the lactate such that during the criterion exercise plasma lactate values were decreasing with increasing power output at lower exercise intensities. As exercise intensity increased lactate values also increased beginning at a power output of about 76% VO2 max. Mean per cycle integrated EMG (CIEMG) increased linearly with increased power output in both exercise sessions. The slopes of the EMG-power output curve were not significantly different (P less than 0.05). There were no inflection points in these curves. The absence of an inflection point show that surface EMG does not provide an indication of Tlac.
14
Overexpression of virD1 and virD2 genes in Agrobacterium tumefaciens enhances T-complex formation and plant transformation. The VirD1 and VirD2 proteins encoded by an inducible locus of the virulence (vir) region of the Agrobacterium tumefaciens Ti plasmid are required for site-specific nicking at T-DNA border sites. We have determined the nucleotide sequence of a 3.6-kilobase-pair fragment carrying the virD locus from nopaline Ti plasmid pTiC58. In contrast to the previous report (Hagiya et al., Proc. Natl. Acad. Sci. USA 82:2669-2673, 1985), we found that the first three open reading frames were capable of encoding polypeptides of 16.1, 49.7, and 21.4 kilodaltons. Deletion analysis demonstrated that the N-terminal conserved domain of VirD2 was absolutely essential for its endonuclease activity. When extra copies of the virD1 and virD2 genes were present in an A. tumefaciens strain carrying a Ti plasmid, increased amounts of T-strand and nicked molecules could be detected at early stages of vir induction. Such strains possessed the ability to transform plants with higher efficiency.
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How T cells talk to target cells. T cell defects are very often involved in haematological diseases and occur even more frequently as a consequence of our therapeutic interventions. T cells play a central role in the immune defence of the organism. To perform this function, they move around the body to achieve a particular stage of development and in search for antigenic insult. In the course of this, they have to communicate and cooperate with various cells. T cells carry a high number of structurally and functionally defined and even more as yet undefined surface structures. The variability and functional pleitropism of these molecules and as a consequence that of their interactions with surface structures of other cells is infinite. This paper will be limited to discuss briefly the following subjects: the presentation of antigens to T cells, structure and function of the T cell receptor (TCR) and its interactions with the antigen, presenting major histocompatibility complex (MHC) molecule, accessory molecules and other modulating surface structures, the role of carbohydrates, pitfalls of inferences on interacting cell surface structures.
15
Treatment of acute nonlymphoblastic leukemia in adults with daunorubicin-DNA complex: a preliminary report. Forty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1 + ARA-C on days 1--5; R 2 = courses of daunorubicin on days 1 and 2 + ARA-C on days 4--8; R 3 = courses of daunorubicin-DNA complex on days 1--2 + ARA-C on days 4--8. Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.
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Closely linked lesions in a region of the X chromosome affect central and peripheral steps in gustatory processing in Drosophila. We have analyzed a set of closely linked mutations on the X chromosome of Drosophila that lead to defects in gustatory behavior. The mutations map to a small region of the X chromosome between 10E1-4. Two distinct complementation groups, gustB and gustD, map to the ends of this region. These groups show complex complementation patterns with the mutations gustC and GT-1, which also map to this region. We describe the behavioral and electrophysiological properties of the mutants. These mutations affect peripheral receptor properties as well as more central processing steps in the gustatory pathway.
12
Stimulation and inhibition with LH and other hormones of female mammalian meiosis in vitro. Utilizing some known physiological preovulatory hormone levels and specific cytological end-points, experiments were carried out with two different media to obtain a clearer understanding of meiotic maturation in vitro of ewe, cow, monkey and human oocytes. In the first series of experiments, it was shown that, in McCoy's medium, ovine LH, prostaglandin E1 and ovine prolactin increased the percentage of divisions of ewe oocytes, without cAMP as a demonstrable intermediate. Monkey oocytes incubated in McCoy's medium with fetal calf serum were stimulated by ovine LH, prostaglandin E2 or cAMP. Human oocytes were stimulated to divide in Diploid medium by ovine LH, oestradiol-17 beta with LH added later, or prostaglandin E1. Diploid medium containing added sheep serum markedly inhibited the meiotic activity of ewe oocytes when ovine LH, HCG, cAMP, prostaglandin E1 and E2 of prolactin were added. This effect was studied by separating the contained fetal calf and sheep sera. It was noted that when LH, HCG, or prostaglandins E1 and E2 were added to a system utilizing fetal calf serum, only spontaneous resumption of meiosis occurred: stimulated and spontaneous activity were reduced when cAMP or prolactin were added. The inhibition of ewe oocyte maturation in Diploid medium with sheep serum and additives was also seen with cow oocytes incubated in Diploid medium containing fetal calf serum and LH, HCG, cAMP or prostaglandin E1 and E2. Cow oocytes incubated in McCoy's medium with equivalent fetal calf serum and added LH were sharply inhibited but spontaneous maturation persisted in the presence of added HCG, cAMP or bovine prolactin.
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Particulate myocardial perfusion scintigraphy: its clinical usefulness in evaluation of coronary artery disease. The determination of myocardial viability is a crucial parameter in the evaluation of a patient with coronary artery disease. Particulate myocardial perfusion scintigraphy (PMPS) is one of several methods available for this determination. A brief comparison between PMPS and two other commonly used methods is described in this review. The technique and analysis are described and applied to 194 patients with 366 surgically bypassed regions. The patients are analyzed for postoperative regional wall function and for total ventricular function as expressed by ejection fraction. PMPS is a highly accurate and unique study for clinically predicting myocardial viability.
16
Carbon-13 nuclear magnetic resonance study of the alpha- and beta- isomers of methadol and acetylmethadol hydrochlorides. The 13C-NMR spectra reported in these studies give direct evidence for the presence of two contributing conformers for alpha-methadol hydrochloride, alpha-acetylmethadol hydrochloride and beta-acetylmethadol hydrochloride. Indirect evidence is also available for the presence of more than one conformer for beta-methadol hydrochloride. However, in order to be more descriptive about the structures of the conformers, it is necessary to obtain 13C-NMR spectra that have a higher degree of resolution than is available from our present NMR system. Such systems are available, and plans are currently in progress to obtain 13C-NMR spectra or these compounds at high enough magnetic fields and low enough temperatures to give us the necessary data.
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Naturally occurring persistent feline oncornavirus infections in the absence of disease. Healthy feline leukemia virus (FeLV)-infected cats from leukemia cluster environments were followed for up to 23 months for development of disease and evidence of alteration in the hemogram. The incidence of disease development in FeLV-postive cats was more than fivefold higher than the incidence for FeLV-negative cats. Ten cases of leukemia developed in 69 infected cats, whereas one case of leukemia occurred in 59 uninfected cats. The incidence for development of diseases other than leukemia was 30.4 percent for FeLV-infected cats as opposed to 6.8 per cent for uninfected cats. This could be a result of the immunosuppressive effects of FeLV. Felv-infected cats had no evidence of subclinical anemia. Mean packed cell volumes and total leukocyte counts were about the same for infected and uninfected animals. The only variation seen in healthy FeLV-infected cats was a decreased mean lymphocyte count. The difference between mean lymphocyte count for FeLV-infected and uninfected animals was significant at the 0.999 level. These findings suggest that the incubation period for feline leukemia may be very prolonged under natural conditions and that an increased susceptibility to unrelated infectious diseases exists during this period. This increased susceptibility was apparently not associated with anemia or depressed total leukocyte counts.
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Protein antigens of mycobacteria studied by quantitative immunologic techniques. Crossed immunoelectrophoresis has great resolving power in the demonstration of immunogenic constituents of mycobacteria. The pattern with multiple precipitate lines is highly reproducible and allows precise identification of components. After the isolation of individual proteins, immunologic specificity combined with molecular weight determination and N-terminal amino acid sequencing should be used to ensure consistent identification in different laboratories. Simultaneous quantification of individual proteins in sonicates of washed bacilli and culture fluids permits the determination of a localization index, which indicates whether the proteins are cytoplasmic constituents or actively secreted. Several "new," actively secreted proteins have recently been defined, and the role of these proteins in the interaction between the bacilli and the infected host is discussed.
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Interventions related to respiratory care. Nursing interventions provide the link between nursing diagnosis and patient outcomes. The validation of nursing interventions is the starting point for a standardized nursing language. This study adapted a method for the validation process for nursing interventions and identified interventions that nursing experts believe are vital to the care of respiratory patients. The study served as the pilot for further surveys by the Iowa classification project. Based on the results of this study, the group made modifications in the survey process. Specifically, national samples of nurses were used, definitions were included in the surveys, and standard deviations were calculated for each activity. The subsequent articles in this issue demonstrate these changes.
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Interference with the glycosylation of Semliki Forest virus proteins. It has been shown that under defined conditions the multiplication of SFV can be inhibited by specific interference with the production of viral glycoproteins. These conditions are: a) Either 0.2 mM dGlc or 2 mM glucosamine in glucose-containing medium, b) lack of any sugar or energy source in the culture medium, c) pyruvate as energy source, late in the infectious cycle. Under these conditions underglycosylated glycoproteins occur, which cannot be used to form physical or infectious particles. It is not yet clear whether the appearance of a heterogeneous population of molecules in the molecular weight range between 50 and 63,000 is due exclusively to different lengths of the carbohydrate side chains, or also due to wrong splitting or partial degradation of the precursor molecules by cellular proteases. Glucosamine seems to act via the accumulation of UDP-N-acetylglucosamine (or a derivative of it), while dGlc is metabolized along the pathway of mannose and acts mainly as an antimetabolite of mannose.
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[A pathogenesis of chronic subdural hematoma; it's relationship to subdural membrane]. Our report concerns 112 cases of chronic subdural hematoma (CSH). M:F ratio is 3.5:1. (Fig. 1). The etiology of CSH is as follows; mild head injury (71 pts.), post-craniotomy (3 pts.), post-V-P shunt (1 pt.) and unknown (37 pts.). All patients are diagnosed by CT scan. Twenty patients were followed up after the subdural space was expressed as low density on CT (Fig.2). 14 of these were found to have extremely thin subdural fluid collection without compression of the brain. Cisternography by using radioisotope and/or metrizamide was carried out in seven patients in whom the subdural fluid collection was found on CT, and in five of whom the dye flowing into the subdural space was retained for 24-48 hours (Fig. 3 a). For treatment, burr holes and irrigation of the hematoma was carried out and then a drain was inserted into the subdural space. The inner membrane of the chronic subdural hematoma was looked at in 19 patients during surgery. All but one showed the inner membrane totally covering the brain surface. However, in one patient the inner membrane didn't entirely cover the brain surface, suggesting that this was the condition just before the entire encapsulation of the hematoma (Fig. 4 b). It used to be considered that a blood clot in the subdural space is needed to develop a chronic subdural hematoma. However, since the introduction of CT scan, there have been many reports suggesting that chronic subdural hematoma has developed from subdural fluid collection without apparent evidence of blood clot after head injury. Therefore, it has been controversial whether the blood clot is absolutely essential to develop into the chronic subdural hematoma or not.(ABSTRACT TRUNCATED AT 250 WORDS)
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Evaluations by three graduating classes of a required community health project. The authors analyzed seniors' evaluations of the first three years of an intensive community health project at the Bowman Gray School of Medicine of Wake Forest University in 1988-89, 1989-90, and 1990-91. The project was designed to provide a public health perspective by having the students select, study, and propose solutions to a community health problem. Of 285 seniors, 240 (84%) completed evaluation questionnaires, using a five-point scale. The students' perceptions of the value of the project became steadily more favorable with each subsequent class; the classes of 1990 and 1991 rated the value of the project as being greater than that of most other experiences in their medical education. The project was more positively evaluated by the 106 responding students (44%) who planned to enter primary care specialties. The students who invested more time in the project also perceived its value to be greater.
14
Partial apolipoprotein E-beta-galactosidase fusion protein expressed in Escherichia coli retains binding activity to the LDL(B/E) receptor. A partial rat apo E-beta-galactosidase fusion protein was produced in Escherichia coli Y1089 infected with recombinant lambda GT11 obtained by immunoscreening of a rat liver cDNA library with an anti-rat LDL antiserum. Partial cDNA overlapped the apo E mRNA sequence coding for apo E binding domain towards the LDL(B/E) receptor up to codon for Arg-139. Fusion protein specifically bound to human fibroblasts. The high-affinity component exhibited a Kd of 5 x 10(-8) M and 4.1 x 10(5) sites per cell. Fusion protein binding to fibroblasts was mediated by their apo E moiety and not by beta-galactosidase since: (1) specific binding of fusion protein was competed out by human LDL; (2) beta-galactosidase did not compete with fusion protein binding; and (3) human fibroblasts from a patient with familial hypercholesterolemia, deficient in LDL(B/E) receptor, bound fusion protein 10-times lower than control fibroblasts. It was demonstrated that partial fusion protein retained the functional activity of the native apo E. However, compared to full-length native or engineered apo E, fusion protein was able to bind fibroblasts without being complexed with phospholipids. Fusion proteins might be a useful tool for studying the functional efficiency of the LDL(B/E) receptor and for mapping residues and domains involved in the binding process.
19
Acquisition and performance difference between normal and mentally handicapped adults on a complex assembly task. Several single studies concerned with work training with the mentally handicapped have been reported in the literature (Bitter & Bolanovich, 1966; Huddle, 1967; Gold, 1969; Screven, Straka & Lafond, 1971). Most have been concerned with issues of acquisition and motivation to perform. No studies have been reported which focus on the evaluation of different techniques of training or which assess rate of acquisition against that of non-handicapped controls. The aim of this experiment is twofold. It uses a complex task, analysed by MTM-2, to enable comparison between the performances of mentally handicapped adults and adults from a 'normal' population, in the acquisition of new work skills. Various strategies of training were compared and the increase in the rate and quality of performance following acquisition was measured for both, in terms of speed and accuracy of production. Results add further support for the notion that the potential of mentally handicapped individuals is commonly underestimated. It is hoped that the findings provide a basis from which further experiments can be developed and evaluated.
15
Mechanism of heparin and serum lipoprotein interaction: effects of calcium, phosphorylcholine, and a serum fraction. The mechanism of formation of an insoluble complex between heparin and rat serum lipoprotein has been studied. Optical density changes during the reaction, counting of the fatty acid labelled lipoproteins in the precipitates, and complexing of [14C]palmitate-labelled lipoprotein with heparin-CNBr-Sepharose were used to quantitatively determine the formation of insoluble complexes. The maximal heparin--lipoprotein complex formation requires 25--30 mM of Ca2+, but with micromolar amounts of phosphorylcholine, the reaction was saturated at only 10 mM of Ca2+. The effect of phosphorylcholine in promoting the reaction was lost when purified chylomicrons or very low density lipoproteins were used. The effect of phosphorylcholine in promoting the interaction between heparin and pure chylomicrons or very low density lipoproteins was regained when a crude serum protein factor of unwashed chylomicrons was added to the system, suggesting that rat serum contains a protein factor(s) which normally inhibits the heparin--lipoprotein interaction by raising the requirement of Ca2+. Phosphorylcholine counteracted the effect of this protein, thereby favouring the precipitation reaction in the presence of much lower concentration of Ca2+. The results have been discussed with special reference to the possibility of a relationship between mucopolysaccharides, Ca2+, lipoproteins, and arterial phospholipids in the pathogenesis of atherosclerosis.
20
The spinal cervical way of afferent innervation of the tongue motor apparatus. An experimental investigation in the dog. The studies were performed on 24 young, adult dogs. In 16 of the animals sections were made of the descending ramus of the hypoglossal nerve and of the stem of the hypoglossal nerve at various levels: at the base of the skull (superior hypoglossectomy), proximally from the descending ramus (middle hypoglosectomy), and at the entrance to the tongue (inferior hypoglossectomy). Phantom operations were performed in 4 animals and material from 4 others (not operated on) was used for control purposes. The post-operative survival rate ranged from 10 to 29 days. In all 4 cases rostral spinal cervical ganglia were collected. In half of the cases the materials were stained with cresyl violet and further quantitative and qualitative studies of retrograde neuronal changes were performed. The remaining half of the material, prepared with Gomori method on acid phosphatase, was subject to statistical analysis of the degree of acid phosphatase activity. The increase or decrease in number of neurons of definite degree of activity was taken as an index of the increase or decrease of enzymatic activity. As a result of transection of the hypoglossal nerve and its descending ramus, in cresyl violet material, qualitative and quantitative degenerative changes were found in dorsal root ganglia C1 to C3 on the operated side. It was also found that corresponding to the tigrolytic changes in the neurons of the above mentioned ganglia there was an increase of activity for acid phosphatase. The same kinds of changes were found in the spinal ganglia C2 and C3 after transection of the hypoglossal nerve at the entrance to the muscles of the tongue. These results lead the authors to suggest that the tongue motor apparatus receives afferent innervation from neurons locates homolaterally in spinal ganglia C2 and C3.
15
Living arrangements and survival among middle-aged and older adults in the NHANES I epidemiologic follow-up study. There is concern about but little information on how living alone affects the health and survival of older adults. We examined the association between living arrangements (living alone, with a spouse, or with someone other than a spouse) and survival among 7651 adults, aged 45 to 74 years in the National Health and Nutrition Examination Survey (NHANES I) (1971-1975) and traced at the NHANES I Follow-up Study (1982-1984), to see whether certain sociodemographic factors (race, education, income, and employment), health behaviors (alcohol, smoking, physical activity, and obesity), or chronic medical conditions were influential in the association. We found a stronger association of living arrangements with survival for men than for women, and for middle-aged men than for older men. For men, those living alone and those living with someone other than a spouse were equally disadvantaged in terms of survival. Income, race, employment, and physical activity influenced the association of living arrangements and survival, but their impact varied by age, gender, and living arrangement. Living arrangements had a weak impact on survival among men, but had no effect among women.
18
Evidence for a precursor-product relationship between intracytoplasmic A particles and mouse mammary tumour virus cores. This report presents evidence which supports a relationship between intracytoplasmic A particles (CAP) and mouse mammary tumour virus (MMTV). Three MMTV-specific antigenic determinants in CAP (MMTV p27, p14 and p10) uere detected by immunodiffusion. No structural proteins of comparable mol. wt. were found in CAP; however, exposure of CAP to trypsin resulted in the cleavage of the CAP structural proteins to MMTV-like polypeptides. This process was accompanied by the preservation of MMTV-specific antigen determinants. Disulphide bonds were necessary for the structural maintenance of CAP. Reducing agents destroyed the organized structure of CAP, whereupon processing of CAP proteins to MMTV-like polypeptides by trypsin was prevented. CAP p82, possessed only MMTV p27 antigenic determinants, while CAP polypeptides p20--18 possessed p10 antigenic determinants. Following processing of CAP structural proteins by trypsin, MMTV-specific p27 antigenic determinants were shifted from CAP p82 to CAP p27; MMTV-p10 antigenic determinants were found with CAP p15--10. These results suggest a model wherein CAP structural proteins are modified by protease during maturation, resulting in the shift of their proteins to sizes consistent with those which have been currently identified as the major internal components of the virion and that this phenomenon is largely predicated on the folding of CAP proteins into the morphologically intact A particle.
15
Miconazole: a review of its antifungal activity and therapeutic efficacy. Miconazole2, a synthetic imidazole derivative, is a new topical antifungal agent for use in the local treatment of vaginal, and skin and nail infections due to yeasts and dermatophytes. It is particularly active against Candida spp., Trichophyton spp., Epidermophyton spp., Microsporum spp. and Pityrosporon orbiculare (Malassezia furfur), but also possesses some activity against Gram-positive bacteria. In vaginal candidiasis, miconazole vaginal cream has produced higher cure rates than conventional nystatin vaginal tablets or amphotericin B vaginal cream. There have been no published comparisons with nystatin vaginal cream or foaming vaginal tablets - the nystatin dosage form preferred by some clinicians. The vaginal cream has also achieved a cure where previous nystatin or natamycin therapy had failed. Miconazole has proved equally effective in both Candida and dermatophyte infections of the skin, but as yet there have been no published comparisons with other antifungal agents. However, it has been successfully used in chronic skin infections which had not responded satisfactorily to other agents such as natamycin and pecilocin. Preliminary experience with oral and intravenous miconazole therapy in systemic candidiasis is promising. Miconazole preparations are well accepted and tolerated.
17
In situ hybridization analysis of the FMRFamide neuropeptide gene in Drosophila. II. Constancy in the cellular pattern of expression during metamorphosis. We have studied changes in the pattern of specific neuropeptide gene expression during the metamorphosis of the Drosophila nervous system. Prior to metamorphosis, the Drosophila FMRFamide gene is expressed exclusively within the central nervous system in a stereotyped pattern that comprises roughly 60 neurons (Schneider et al., '91). Using in situ hybridization, we found that the FMRFamide gene was continuously expressed throughout all stages examined: at each of 15 stages of adult development and through at least the first 10 days of adult life. There were no differences between the results observed with 2 exon-specific hybridization probes, thus indicating little if any alternative splicing during postembryonic development. Despite many changes in the positions of individual hybridization signals due to the large-scale reorganization of the nervous system, the continuous pattern of gene expression through adult development permitted many adult signals to be identified as larval signals. We concluded that the adult pattern of FMRFamide gene expression was largely derived from persistent larval neurons. Adult-specific hybridization signals in the brain and ventral ganglion were also detected and these corresponded to many of the approximately 40 adult-specific FMRFamide-immunoreactive neurons. One specific larval signal was lost during adult development and the intensities of other signals fluctuated in reproducible manners. These stereotyped differences in hybridization signal intensity resemble similar observations made in larval stages (Schneider et al., '91) and support the hypothesis that the steady-state levels of FMRFamide transcripts are differentially regulated among the diverse neurons that express the gene.
16
Effect of fenbendazole and ivermectin on development of strongylate nematode eggs and larvae in calf feces. Thirty-nine weaned steer calves (mean weight 284 kg) were maintained under dry-lot conditions and assigned (based on fecal nematode egg count) to one of three treatment groups of 13 animals each as follows: control (no treatment), fenbendazole (5 mg kg-1), and ivermectin (0.2 mg kg-1). Fecal samples were collected 12 h before treatment, at treatment, and 12, 24, 48 and 72 h after treatment for determination of nematode eggs per gram, and (after culture) infective larvae per gram and population distribution. The effect of treatment on egg development was observed in feces collected 12 and 24 h after treatment. There was essentially no difference in efficacy, based on egg counts, of fenbendazole and ivermectin. Egg count was reduced 100% by both anthelmintics at 72 h after treatment. Viability, based on percent of eggs reaching the infective larval stage, of developing stages at 12, 24, and 48 h after fenbendazole treatment was 0.1%, 1.1%, and 0%; after ivermectin treatment the corresponding values were 23.7%, 30.1%, and 28.6%, respectively. Fenbendazole treatment resulted in little or no development of eggs and/or larvae in feces deposited 12 and 24 h after treatment, whereas development proceeded normally (compared with the control group) in ivermectin treated feces. Population distribution of infective larvae was predominantly Haemonchus and Cooperia with some Ostertagia and Oesophagostomum.
17
Identification of individual prokaryotic cells by using enzyme-labeled, rRNA-targeted oligonucleotide probes. A method to microscopically detect and identify individual cells of members of the domains Bacteria and Archaea is presented. rRNA-targeted oligonucleotides were 5' end labeled with the enzyme horseradish peroxidase and used for whole-cell hybridization. Specifically bound probe was visualized by the enzymatic formation of an intracellular precipitate from the substrate diaminobenzidine. Permeation of the enzyme-labeled probe into whole fixed cells of gram-negative bacteria required their pretreatment with lysozyme-EDTA, whereas permeability of some archaebacterial cells was improved by addition of detergent to the hybridization buffer. Hitherto we had not achieved penetration of enzyme-labeled probe into gram-positive bacteria and yeast cells. This method should be a valuable tool for identification of suitable prokaryotic cells in environments with elevated background fluorescence or in situations in which an epifluorescence microscope is not available.
18
Single dose cabergoline versus bromocriptine in inhibition of puerperal lactation: randomised, double blind, multicentre study. European Multicentre Study Group for Cabergoline in Lactation Inhibition. To compare the efficacy and safety of a single dose of 1 mg of cabergoline with that of bromocriptine 2.5 mg twice daily for 14 days in the inhibition of puerperal lactation. Prospective, randomised, double blind, parallel group, multicentre study. University of hospital departments of obstetrics and gynaecology in different European countries. 272 puerperal women not wishing to lactate (136 randomised to each drug). Women randomised to cabergoline received two 0.5 mg tablets of cabergoline and one placebo tablet within 27 hours after delivery and then placebo twice daily for 14 days. Those randomised to bromocriptine received 2.5 mg of bromocriptine and two placebo tablets within 27 hours and then 2.5 mg of bromocriptine twice daily for 14 days. Success of treatment (complete or partial) according to milk secretion, breast engorgement, and breast pain; rebound symptomatology; serum prolactin concentrations; and number of adverse events. Complete success was achieved in 106 of 136 women randomised to cabergoline and in 94 of 136 randomised to bromocriptine and partial success in 21 and 33 women respectively. Rebound breast symptomatology occurred respectively in five and 23 women with complete success up to day 15 (p less than 0.0001). Serum prolactin concentrations dropped considerably with both drugs from day 2 to day 15; a prolactin secretion rebound effect was observed in women treated with bromocriptine. cabergoline and 36 receiving bromocriptine (p = 0.054), occurring most during the first treatment day. A single 1 mg dose of cabergoline is at least as effective as bromocriptine 2.5 mg twice daily for 14 days in preventing puerperal lactation. Because of the considerably lower rate of rebound breast activity and adverse events and the simpler administration schedule cabergoline should be the drug of choice for lactation inhibition.
15
A comparison by 220-MHz NMR of histidine hydronium ion titrations in porcine pancreatic ribonuclease and an extensively deglycosylated derivative. 220-MHz NMR was used to observe the titration behavior of the 5 histidine residues in porcine pancreatic ribonuclease (ribonucleate pyrimidine-nucleotido-2'-transferase (cyclizing), EC 3.1.4.22) and a derivative prepared by removal of 80% of the attached carbohydrate from this glycoprotein. Resonances due to histidine C-2 protons were observed over the full pH range for 3 of the residues; such resonances for the remaining 2 histidine residues broadened out as the pH was increased. Resonances due to histidine C-4 protons were also observed for 2 of the residues. The titration curves for both proteins were identical within experimental error. Resonances were assigned by comparison with histidine NMR titrations in ribonucleases from other species. Histidine 105, immediately adjacent to the site of attachment of a heterosaccharide side chain, has a C-2 proton chemical shift and pK that are insensitive to the large alteration in the bulk of the carbohydrate side chain. The chemical shifts of the C-2 proton of histidine 48 and of the C-4 proton of histidine 80, histidine residues that are close to one another and to another heterosaccharide side chain, show a similar insensitivity. The observations are direct evidence in support of the thesis that the heterosaccharides in porcine ribonuclease project away from the surface of the protein into the solution environment.
19
Myocardial conducting system dysfunctions from thoracic impact. An analysis of electrocardiograms (ECG lead II) obtained following blunt thoracic impacts conducted on 12 anesthetized pigs indicated that all animals developed some degree of trauma to the heart conducting system: sino-atrial nodal disturbances, atrio-ventricular junctional dysfunction, intraventricular conduction defects (e.g., bundle branch blocks), or ventricular fibrillation. The induced ventricular fibrillation proceeded rapidly to the demise of four animals in this study. A comparison of the occurrence of ventricular fibrillation with measured biomechanical response parameters indicated a significant correlation of ventricular dysfunction with high levels of sternal acceleration (930 g) and impact velocity (10.7 m/s). The initiation of ventricular fibrillation did not correlate with typical biomechanical thoracic injury "indicators" (i.i., level of normalized thoracic deflection, cumulative AIS, peak spinal acceleration, or applied force). An injury severity classification (MCD) was subsequently developed for the evaluation of myocardial conducting system dysfunctions.
23
Effects of Eimeria mitis on egg production of single-comb White Leghorn hens. Single-comb white leghorn hens infected with either B4 or C2 strain of Eimeria mitis produced watery droppings as early as day 5 PI. E. mitis infection did not affect egg weight. However, specific gravities of the eggs produced by the hens infected with E. mitis were lower than those produced by the controls. Egg production was significantly reduced temporarily, but most birds returned to production within 14 days. Many of the birds that ceased to lay went through a complete-body molt (56% of the C2-infected hens and 20% of the B4-infected hens). Hens that ceased to lay regained considerable amounts of pigment in their skin, beaks, and shanks.
11
[Behaviour of urinary excretion of lysozyme in renal diseases and in urinary tract infections (author's transl)]. Urinary excretion of lysozyme was investigated in a group of 66 patients with various renal diseases, nephrolitiasis and urinary tract infections. The results obtained demonstrate that the amount of the enzyme excreted is related to the entity of tubular damage whereas is not with glomerular damage. No correlation was found between lysozyme excretion neither to the degree of proteinuria neither to the amount of leukocytes and bacteria in the urine. In patients with urinary infections urinary lysozyme increases only when there is a tubular injury of some entity. In 90 pediatric patients with urinary infection and pyelonephritis lysozyme in the urine was found only in two cases. Therefore urinary lysozyme determination cannot be considered for the detection of early tubular injury and is not a helpful diagnostic tool in urinary tract infections.
18
The evidence for post-meiotic expression of a testis-specific isoform of a regulatory subunit of calcineurin using a monoclonal antibody. The expression of a regulatory subunit of calcineurin (CaN beta) during rat spermatogenesis was examined in rat testes using a monoclonal antibody Va1. Results showed that a testis-specific isoform of CaN beta was expressed only 3 weeks after birth, when meiosis begins, and increased in amount depending on the maturation of spermatogenesis. The matured sperm, which consists of only post-meiotic cells, is most likely to have only the testis-specific isoform of CaN beta. The brain type isoform of CaN beta was not detected in rat sperm. Immunoblot analysis of testes from different rodent species by a monoclonal antibody Va1 showed that all rodent species examined had their own homologues corresponding to a testis-specific isoform of CaN beta in rats, although they showed distinctively different molecular weights on SDS-PAGE compared to the testis-specific isoform in rats. Each homologue was shown to be specifically expressed in post-meiotic phase of spermatogenesis, as was seen in rats.
19
The development of a sunscreen. Australians generally admire an evenly tanned skin, and the ability to acquire such a tan without much or any discomfort due to burning, is widely prized and envied. Various topical sunscreens have been introduced in order to facilitate the attainment of such a state, and this paper describes the stages in the development of such a product. The final product must obviously contain an active ingredient with the necessary selective filtering properties. This ingredient, and the vehicle in which it is presented, must be free of sensitising properties and must not cause acute or chronic toxic effects. Finally, it must be shown, under various typical conditions of use, to possess overall efficacy in terms of protecting from burning while permitting tanning.
15
[CDP-choline improves the postoperative rehabilitation of patients with cerebral risk]. To evaluate the efficacy of CDP-choline to prevent from brain damages after surgery for high risk patients, 210 patients receiving pre and post operative parenteral CDP-choline were compared to 204 controls (mean age 73 years) in a multicenter open randomised study. Quality and delay of anesthetic recovery were assessed. Cognitive screening test and self-control scale (simplified Mini Mental Status test and Barthel Index) were performed the day before and the first and fourth day after surgery. CDP-choline does not enhance quality or delay of anesthetic recovery but increases the percentage of subjects with a better fourth post-operative than preoperative cognitive and self-control test (p less than 0.05).
16
Speech pattern hearing aids for the profoundly hearing impaired: speech perception and auditory abilities. A family of prototype speech pattern hearing aids for the profoundly hearing impaired has been compared to amplification. These aids are designed to extract acoustic speech patterns that convey essential phonetic contrasts, and to match this information to residual receptive abilities. In the first study, the presentation of voice fundamental frequency information from a wearable SiVo (sinusoidal voice) aid was compared to amplification in 11 profoundly deafened adults. Intonation reception was often better, and never worse, with fundamental frequency information. Four subjects scored more highly in audio-visual consonant identification with fundamental frequency information, five performed better with amplified speech, and two performed similarly under these two conditions. Five of the 11 subjects continued use of the SiVo aid after the tests were complete. A second study examined a laboratory prototype compound speech pattern aid, which encoded voice fundamental frequency, amplitude envelope, and the presence of voiceless excitation. In five profoundly deafened adults, performance was better in consonant identification when additional speech patterns were present than with fundamental frequency alone; the main advantage was derived from amplitude information. In both consonant identification and connected discourse tracking, performance with appropriately matched compound speech pattern signals was better than with amplified speech in three subjects, and similar to performance with amplified speech in the other two. In nine subjects, frequency discrimination, gap detection, and frequency selectivity were measured, and were compared to speech receptive abilities with both amplification and fundamental frequency presentation. The subjects who showed the greatest advantage from fundamental frequency presentation showed the greatest average hearing losses, and the least degree of frequency selectivity. Compound speech pattern aids appear to be more effective for some profoundly hearing-impaired listeners than conventional amplifying aids, and may be a valuable alternative to cochlear implants.
19
Blunted prolactin responses to d-fenfluramine in sociopathy. Evidence for subsensitivity of central serotonergic function. Using a neuroendocrine probe we studied nine male offenders in a forensic hospital, convicted of murder, with a diagnosis of antisocial personality disorder, who had been behaviourally 'quiescent' for varying periods and who had not recently been abusing drugs. Nine healthy age-matched men also participated. All subjects received 30 mg d-fenfluramine (d-FEN), a 5-HT releasing agent, orally, after an overnight fast, and serial samples for prolactin estimation were taken hourly for five hours. Responses were significantly impaired in the patients, suggesting a subsensitivity of certain 5-HT systems in antisocial personality disorder, regardless of recent or ongoing behavioural disturbance.
16
Gender distribution and sidedness of middle fossa arachnoid cysts: a review of cases diagnosed with computed imaging. According to earlier reports, arachnoid cysts seem to occur more frequently in males, and on the left side. The latter phenomenon could, however, be explained by a greater significance attributed to symptoms from the dominant hemisphere as a justification for invasive procedures in the pre-computed tomography era. The literature from the last third of the era of computed tomography is reviewed with respect to gender distribution and sidedness for middle fossa arachnoid cysts. Also included are a few cases of our own from the same period. It is evident from this survey of the literature, based on computed tomography studies, that there is a significant tendency for these cysts to occur in males, with a male/female ratio of nearly 3:1. This preponderance toward males could not be explained by the somewhat higher frequency of associated subdural hematomas that was found in male patients. The survey also showed that middle fossa arachnoid cysts occur or are detected significantly more frequently on the left side than on the right, with a ratio of 1.8:1.
16
Isolation and characterisation of a new hepatic bilirubin UDP-glucuronosyltransferase. Absence from Gunn rat liver. A novel UDP-glucuronosyltransferase that conjugates bilirubin IX alpha, bilirubin monoglucuronide and an arylalkanoic acid was purified to homogeneity from clofibrate treated Wistar rats. The enzyme displayed a subunit molecular mass of 54 kDa, a pI of 7.6 and was demonstrated to be N-glycosylated. Sequence analysis of peptides derived by endoproteinase Glu-C cleavage of the purified enzyme indicated that it was a new member of the recently identified UGT1 subfamily. Immunoblot analysis demonstrated that this enzyme was absent from Gunn rat liver. The molecular derivation of this enzyme and the lack of it in Gunn rats is discussed.
14
Studies on Branhamella Catarrhalis (Neisseria catarrhalis) with special reference to maxillary sinusitis. Paired sera from 97 patients with acute maxillary sinusitis were examined regarding antibodies to Branhamella catarrhalis. Precipitating antibodies were demonstrated in almost all sera both from patients and from healthy blood donors. Complement-fixing (CF) antibodies to B. catarrhalis were present in sera from 25 of the 97 patients and in one of 20 healthy blood donors. The titres were low and the titre changes when present were of a small magnitude. CF antibodies were most commonly demonstrated in the younger age groups. The patients with demonstrable CF antibodies to B. catarrhalis did not differ from patients without antibodies regarding radiological appearance or healing during therapy. Strains of B. catarrhalis were all rapidly killed by normal human serum but not in heated sera. The strains could not multiplicate significantly at an oxygen tension corresponding to about half the atmospheric value. The possible significance of the serological and bacteriological findings is discussed.
13
Pulmonary eosinophilia with systemic features: therapy and prognosis. Of 65 patients presenting with pulmonary eosinophilia to one Respiratory Unit during a 20-year period, 12 (18%) had systemic features associated with their pulmonary disease. Eleven had fever, three night sweats, three arthralgia, three vasculitic rashes and two weight loss. Anaemia, myalgia, peripheral neuropathy, mononeuritis, pericardial effusion and photosensitivity rash were each recorded in single patients. None had evidence of hypersensitivity to drugs, helminthes or other allergens. Ten of the 12 patients could be classified as cryptogenic pulmonary eosinophilia and two as Churg Strauss syndrome. Ten were female. The maximum recorded eosinophil counts were higher in the 12 patients with systemic features compared with the remaining 53 patients [mean (SD) 5613 (3883) vs. 2359 (3046) x 10(6) 1(-1), P < 0.02], whereas both asthma and recurrent episodes of eosinophilia were significantly less common. Steroid therapy achieved a good clinical response and radiological clearing in the majority of patients. All 12 patients were treated with prolonged duration oral prednisolone [mean (SEM) dose 8.5 (3.8) mg day-1 duration 5.5 (1.3) years]. The two patients with Churg Strauss syndrome required azathioprine in addition to long-term prednisolone. There were no deaths and currently four patients are off all steroids and six receive less than 5 mg day-1. During a median follow-up period of 11 years, there was no significant decline in FEV1 or VC, measured as percent predicted values. Persistent radiographic abnormalities consistent with fibrosis or bronchiectasis were not seen.(ABSTRACT TRUNCATED AT 250 WORDS)
13
Psoriasis vulgaris, fetal growth, and genomic imprinting. We report on 2 independent lines of evidence suggesting genomic imprinting of a major gene for psoriasis vulgaris. First, the birth weight of children from psoriatics is influenced by the sex of the psoriatic parent. Children from fathers with psoriasis are considerably (270 g) heavier than children from mothers with psoriasis (P less than 0.004). Second, the disease manifestation (penetrance) depends in part on the sex of the psoriatic parent. Offspring from fathers with psoriasis and male "gene carriers" are significantly (P less than 0.015 and P less than 0.007) more often affected than offspring from mothers with psoriasis and female "gene carriers." Of 91 grandchildren with psoriasis 59 (65%) have an affected grandfather and 32 (35%) a psoriatic grandmother. This deviation from the expected distribution is significant (P less than 0.04). Genomic imprinting is considered a special case of epigenetic modification. We propose that epigenetic modifications of a major predisposing gene in somatic tissues could cause differences in disease activity of psoriasis and could account for the often unpredictable clinical course the disease takes.
14
Structure and serological specificity of the K13-antigenic polysaccharide (K13 antigen) of urinary tract-infective Escherichia coli. The primary structure of the K13-antigenic polysaccharide (K13 antigen) of Escherichia coli O6:K13:H1 was elucidated by composition, periodate oxidation, Smith degradation, and methylation analysis. The polysaccharide consists of a repeating sequence of 3-linked ribofuranose and 7-linked 3-deoxymannooctulosonic acid (KDO). About 50% of the KDO residues are O-acetylated at position 4 or 5. Measurement of the optical rotary dispersion indicated that in aqueous solution the K13 polysaccharide assumes a secondary structure in which the carboxyl groups of KDO are engaged. The serological specificity of the K13 polysaccharide is expressed through KDO and its O-acetyl substituent, the ribose unit being antigenically silent. There are two populations of anti-K13 antibodies one directed against the charged region of the KDO and the other against the O-acetyl groups.
17
Lomefloxacin and temafloxacin: two new fluoroquinolone antimicrobials. The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, safety, drug interactions, and dosage and administration of lomefloxacin and temafloxacin, two new antimicrobials, are presented. Lomefloxacin and temafloxacin exhibit activity comparable to that of ciprofloxacin against the Enterobacteriaceae. Lomefloxacin has only modest activity against common gram-positive organisms. Temafloxacin exhibits increased activity against the streptococci and moderate activity against many anaerobes, as compared with ciprofloxacin. Lomefloxacin and temafloxacin have only moderate antipseudomonal activity. Their elimination half-lives are 6-10 hours and they have good oral absorption, excellent penetration into many tissues and fluids, and a better drug-interaction profile than other similar agents. Lomefloxacin has demonstrated comparable efficacy to other therapies in the treatment of lower respiratory-tract infections and urinary-tract infections (UTIs) and for prophylaxis before surgical procedures in the urinary tract. Temafloxacin has been shown to be effective in the treatment of lower respiratory-tract infections, infections of the skin and associated structures, uncomplicated and complicated UTIs, bacterial prostatitis, and gonococcal and non-gonococcal urethritis and cervicitis. The most frequent adverse effects with lomefloxacin are gastrointestinal upset and headache; with temafloxacin, gastrointestinal complaints. Lomefloxacin's dosage is 400 mg p.o. daily for 10 days for treatment of acute bacterial exacerbations in chronic bronchitis or simple cystitis and for 14 days for treatment of complicated UTIs. Lomefloxacin is a new oral fluoroquinolone that is indicated for the treatment of various bacterial infections. Temafloxacin, another new fluoroquinolone, appeared to have some favourable characteristics but was withdrawn from the market.
18
Management of thrombophlebitis in the prepartum period. A case report. The case of a 30-year-old female who presented with acute onset of ileofemoral thrombophlebitis during the 37th week of pregnancy is presented. Treatment with intravenous infusion of heparin was initiated on the day of admission. The following day, the patient went into active labor. Heparin was stopped, and a Greenfield filter was placed in the suprarenal inferior vena cava. Six hours later, the patient had a normal vaginal delivery. Fifteen hours after delivery, heparin was restarted. The patient was discharged eight days later on therapeutic levels of Coumadin. Anticoagulation was maintained for six months and at one year she was asymptomatic.
10
Search for an adenine photoproduct in DNA. Poly(d[14C]A), p(dA)2, and [14C]adenosine-labeled DNA were irradiated at 254 nm with fluences up to 50 J/m2, and then following formic acid hydrolysis at 170 degrees C WERE SUBJECTED TO PAPER CHROMAtography using a butanol:water:acetic acid (80:30:12) solvent system. For poly(dA), up to 25% of the radioactivity appeared as fluorescent material located in the Rf 0.21-0.29 region. The hydrolysate of the purified photoproduct, p(dA)2, isolated from irradiated p(dA)2 by DEAE chromatography also had an Rf of 0.29 as well as an absorbance maximum at 310 nm. In all cases studied, however, the photoproduct yield in the Rf 0.29 region for native DNA was less than 2%. Denaturation of the DNA appeared to enhance the yield slightly, although no pronounced peak in this region of the chromatogram was discerned. Mechanistic studies indicate that the yield of the adenine photoproduct in poly(dA) is favored by base stacking, has a singlet excimer as a precursor, and is quenched by hydrogen bonding to a pyrimidine. It is concluded that the yield of the adenine photoproduct in both native and denatured DNA is considerably less than in poly (dA) and in all probability does not represent a biologically significant product.
17
Entry of [3H]norepinephrine, [125I]albumin and Evans blue from blood into brain following unilateral osmotic opening of the blood-brain barrier. The blood-brain barrier in adult rats was opened unilaterally by infusing 1.58 M L (+)-arabinose in 0.9% NaCl solution into the internal carotid artery, via a catheter in the external carotid. The common carotid remained patent during the procedure. Osmotic barrier opening allowed entry into the brain of three intravascularly administered tracers--a visual tracer Evans blue (pulsely injected) and radioactive tracers [3H]norepinephrine (continuously infused) and [125I]albumin (pulsely injected). In osmotically perfused brain tissue, uptake of both 3H and 125I from blood was increased 2-5-fold above control, with maximal increases observed in the caudate nucleus, hippocampus and thalamus. In control brain regions, Evans blue and albumin remained intravascular, whereas norepinephrine was taken up, possibly by sympathetic nerve endings in cerebral vessels, as a function of blood plasma concentration and duration of exposure. The barrier closed within 4 h after intracarotid arabinose infusion, and barrier opening was not associated with edema as measured two days after infusion.
21
Latex glove allergy. A survey of the US Army Dental Corps. To assess the prevalence of latex glove allergy in a population of health care providers (dentists) with a high occupational exposure to latex gloves. A survey instrument was distributed to all active-duty dental officers in the US Army (n = 1628). The survey was designed to identify those individuals who had symptoms of allergy to latex gloves. US Army dental facilities worldwide. The response rate to the survey was 64% (n = 1043). There were 143 (13.7%) responses indicating latex glove allergy. If nonrespondents were assumed to be allergy-free, the prevalence rate would be 8.8%. Latex allergy, as ascertained by self-report in this survey, appears to have a substantial prevalence in this health care provider population.
10
Gastrointestinal implications in the rat of wheat bran, oat bran and pea fibre. The gastrointestinal (GI) effects of three different dietary fibre (DF) sources: wheat bran (WB), oat bran (OB) and pea fibre (PF), were compared with a low-fibre diet in a 4-week trial with rats (initial bodyweight 210 g). The DF sources varied widely in chemical composition, solubility and water-holding properties, and particle size. The DF sources were mixed into diets to comprise the same amount of non-starch polysaccharides (NSP; 135 g/kg dry matter (DM)). Compared with the control diet, all fibre-containing diets reduced apparent digestibility of DM, energy, and protein significantly but to different extents. The ranking order of faecal DM bulking followed that of NSP recovery in the faeces: WB > OB > PF > control. The elongating effect of the diets on the GI tract was most pronounced in the rats fed on the OB diet. The mean transit time (MTT) of the OB diet was similar to that of the control diet (approximately 37 h), which was significantly slower than the MTT of the WB and PF diets (approximately 23 h). The study confirms that no simple cause and effect relationship exists between chemical composition, physical properties, and physiological effects of dietary fibre and their effects along the GI tract.
14
The California Psychological Inventory and the Semantic Differential dimensions. The feasibility of describing first order factors and scales of the California Psychological Inventory (CPI) by using the factors of the semantic differential and rated adjustment and introversion-extraversion was investigated in samples of 150 male and 80 female college students. Results indicated that both the semantic differential and the ratings significantly overlapped with the CPI, but that the degree of the relationship was not large enough to support the contention that the semantic differential factors are sufficient to describe completely what is being measured by the CPI. The relationships did prove useful, however, in further clarifying the nature of the CPI.
19
"Asthma Alley": a space clustering study of asthma in Brooklyn, New York City. A certain section of the borough of Brooklyn has sometimes been referred to as "Asthma Alley," expressing a feeling that this area in Brooklyn shows a markedly higher rate of asthma than adjacent areas. This study describes an epidemiologic method developed to determine whether the popular perception of spatial clustering of cases reflects reality. The spatial distribution of respiratory visits to the emergency room is taken as a reference against which clustering of asthma visits is compared, on the assumption that it is a good measure of the proportion of people in that area that make use of the emergency room facilities. From approximately 9,000 visits for asthma during the study period we were able to show that: (1) the differences in distribution of asthma cases among the health areas of Brooklyn are statistically significant; and (2) the health areas that show an excess of asthma visits lie along a belt east of the two hospitals and coincide with the popular impression of the location of "Asthma Alley."
21
Relation of glenoid fossa morphology to mandibulofacial asymmetry, studied in dry human Lapp skulls. Asymmetry in the shape and location of the temporomandibular joint and its associations with mandibulofacial asymmetry were studied in 40 Lapp skulls by a method in which the configuration of the fossa is clearly defined. The results show a general directional temporomandibular asymmetry. The glenoid fossa on the right was on average more laterally and distally placed than on the left when studied in the axial view. The mandible was more often longer on the left than on the right in the frontal view. The temporomandibular asymmetry found here was associated with skull base characteristics and left-right differences in mandibular length. The basic reason for the asymmetric relationships may lie in the reciprocal interaction between the developmental aspects of the skull base and impaired directional function.
14
Oxygen protects rat brain from ischaemic injury. Interruption of the oxygen supply to the brain promotes functional and structural damage of the brain, such as oedema and swelling. The most prominent cellular reaction to this type of damage has been found to be trophic or proliferative changes in glial cells. We examined dynamic changes in glial cells adjacent to the infarcted tissue in response to oxygenation. Results showed that astrocyte proliferation was seen more at 3 than at 7 days after middle cerebral artery occlusion, while their numbers with and without oxygenation were almost the same. The proliferation of microglia, however, was seen more with than without oxygenation. However, microglia seem to be able to secrete an angiogenetic factor under hypoxic conditions, and are active in terms of superoxide dismutase (SOD). Cerebral blood flow is directly related to tissue oxygen content and its autoregulatory capacity has been found to be greater as the volume contracts. As a result, we suggest that the application of oxygen-treated microglia to ischaemic tissue could diminish tissue damage, and that the most effective oxygenation can be achieved by the withdrawal of blood and reduction of the intracranial pressure.
15
A case of clinically diagnosed pure septal infarction. Interventricular septal involvement in myocardial infarction is usually associated with infarction of the left ventricular anterior free wall, as the obstruction is at the major portion of the left anterior descending coronary artery. Acute myocardial infarction with obstruction only of the first septal branch is rare. We describe here a case of pure septal infarction. The case was diagnosed by emergency coronary arteriogram (CAG). Although the patient had a large first septal branch, his global left ventricular function was preserved. Abnormal findings were localized in only septal region as determined by left ventriculography (LVG), two-dimensional echocardiography (2DE), and 99mtechnetium pyrophosphate (99m Tc-PYP) and 201thallium (201Tl) myocardial scintigraphy.
15
Mice housed in a cage with a maze learn the maze without explicit training. Mice were housed in a cage with a maze. A water tap was placed at the entrance of the maze. The exit of the maze connected with another cage (home cage). Food was placed in the home cage. Three different multiple mazes (types 1-3) were placed. 1) Mice were housed for 10 h a day in the apparatus and then removed to a normal cage for fasting. One trial per day was carried out after fasting for 13 h. In each trial, a mouse was put at the entrance of the maze and then the number of errors and the time till it reached the home cage was counted. Mice reached a learning criterion at Trial 2. 2) Administering scopolamine (0.125-0.5 mg/kg) 30 min before Trial four disturbed the maze work dose dependently in a type 3 maze, the most complex maze among the three, but did not in type 1 and 2 mazes. 3) Administering scopolamine (0.25-1.0 mg/kg) 30 min before Trial 11 to the mouse of the type 3 maze did not disturb the maze work. These results show that a mouse housed in a cage with a maze learns the maze without explicit training and scopolamine can differentially effect performance based upon the degree of training.
9
Biogenesis of mitochondria. XLII. Genetic analysis of the control of cellular mitochondrial DNA levels in Saccharomyces cerevisiae. The proportion of total cell DNA which is mitochondrial DNA was measured in haploid, diploid and tetraploid strains of S. cerevisiae grown under a standard set of conditions. For all strains tested the mitochondrial DNA level was in the range 16%-25% of total cell DNA. Repeated measurements of the cellular level of mitochondrial DNA in two haploid strains showed that these strains have measurably different cellular mitochondrial DNA levels (17% and 24% of total DNA, respectively) under our conditions. These two grande strains were used to investigate the role of the mitochondrial and nuclear genomes in the regulation of the mitochondrial DNA level. We have shown by genetic analysis that the difference between these two strains is determined by at least two nuclear genes. The mitochondrial genome is not involved in the regulation of cellular mitochondrial DNA levels. A number of purified petite clones derived from independent spontaneous petite isolates of the grande strain which contained 24% mitochondrial DNA were also studied. The mitochondrial DNA levels in all but one of these petites fell in the range 20-25% of total cell DNA. From these results we conclude that, in general, the mitochondrial DNA level in petite strains is controlled by the same mechanism as operates in grande strains. We propose a general model for the control of the cellular mitochondrial DNA level, in which the amount of mitochondrial DNA per cell is determined by regulation of the number of mitochondrial DNA molecules per cell. This regulation is mediated through the availability of a set of nuclear coded components, possibly a mitochondrial membrane site, which are required for the replication of mitochondrial DNA.
15
Drug research, development and expenditure - what about the future? Drug research and development today is an undertaking requiring special skills and understanding, formidable financial resources and the closely co-ordinated co-operation of everyone concerned with the drug programme in all its aspects. Incorrect results, wrong deductions or decisions and unrealistic delays due to bureaucratic obstructions, all have an adverse effect in the final analysis. The price (financially and otherwise) we have to pay for the end-product is invariably intimately related to what happened during the entire development process. Everyone connected with drug development, in whatever capacity, has a moral obligation to ensure that the development programme follows a path which is as smooth as possible.
17
Field trial of live attenuated influenza A/B ("Alice"/R-75) vaccine. The reactogenicity, immunogenicity and protection effecacy of a serum inhibitor-resistant live attenuated influenza A/B ("Alice"/R-75) vaccine was determined in a group of health young volunteers. The influenza A component was derived from A/England/42/72 (H3N2) strain, and the B component from B/Hong Kong/5/72 strain. Sixty-eight subjects had hemagglutination inhibition (HAI) antibody titers to influenza A hemagglutinin (HA) antigen of less than or equal to 1:8 ("low A" group) and 75 had similarly low antibody titers to B HA antigen ("low B" group). Two inocula given 14 days apart consisted of vaccine in two doses (VV); one dose of vaccine followed by placebo (VP); or two doses of placebo (PP). The reactogenicity of the vaccine was low, with approximately 25% of subjects in both the immunized and placebo categories having symptoms mainly of respiratory nature. The A component of the vaccine was immunogenic with 90.9% of the subjects in the low A group VV category showing seroconversion. By contrast, only 20% of VV subjects in the low B group seroconverted to B antigen. The vaccine afforded significant protection againndergone a slight antigenic drift. There was no difference in protection afforded either by one or two doses of the vaccine. Thus the overall protection efficacy following at least one dose of the vaccine was 80.0% (p = .01), and in the low A group subjects it was 85.5% (p = .01).
15
Normal and neoplastic human plasma cells express bcl-2 antigen. The bcl-2 (B-cell leukaemia/lymphoma 2) proto-oncogene is associated with the 14;18 translocation in follicular lymphoma juxtaposing bcl-2 with the immunoglobulin heavy chain region. bcl-2 has been cloned and sequenced and a monoclonal antibody to amino acids 41 to 54 of the bcl-2 protein has been raised. The expression of bcl-2 in follicular lymphoma has been demonstrated by immunohistological staining and also in normal lymphocytes. The presence of the bcl-2 onco-protein has been demonstrated by immunofluorescence using conventional and confocal microscopy in normal and malignant plasma cells from myeloma patients and myeloma cell lines. Plasma cells from 8/8 normal donors were positive, although the proportion of positive cells and the intensity of staining varied. Eight of 10 patients with myeloma or plasma cell leukaemia had positive plasma cells, and 6/11 plasma cell lines and one lymphoma cell line also expressed the onco-protein. bcl-2 expression is a feature of normal plasma cells and data from the cell lines confirm that expression is not dependent on the presence of the 14;18 translocation.
16
Pharmacokinetics of methohexital during cardiovascular surgery with cardiopulmonary bypass. The pharmacokinetics of methohexital after intravenous bolus administration was studied during cardiovascular surgery with cardiopulmonary bypass. The effect of body temperature (normothermia and hypothermia) during cardiopulmonary bypass on methohexital pharmacokinetics was investigated. The pharmacokinetic data obtained were compared with those from vascular surgery without cardiopulmonary bypass. A marked decrease in plasma methohexital concentrations and therefore in area under curve and a significant increase in clearance and in volume of distribution were observed in the cardiopulmonary bypass groups compared to the vascular surgery group without cardiopulmonary bypass. However, the elimination half-life and the mean residence time were similar in the 2 groups. Furthermore, the study shows that body temperature during cardiopulmonary bypass does not influence methohexital pharmacokinetics.
18
Family therapy outcome research: a trial for families, therapists, and researchers. This article describes the process of an evolving research project. Initially conceived as a study investigating outcome measures and their sensitivity to change after a course of family therapy, the project soon changed its focus. As unexpected results were recorded, the clinical research team became destabilized and the individual team members responded by making their own "sense" of the data, reflecting their respective clinical and scientific positions. As clinicians and researchers began to challenge each other's belief systems, the project entered a new stage. The interactions within the team became of increasing interest and themselves objects of research. The recursive nature of re-search was demonstrated, and the act of writing this report completed the circle, as the various authors tried to achieve a balance between reporting the content and the process of this project.
15
[Effects of male sex hormones on specific uptake and release of 3H-serotonin in the rat hypothalamus in vitro]. With the use of "isotopic method" a study was made of the main parameters of functional activity of serotoninergic elements of hypothalamus--the specific uptake and release of 5-OT. The animals used were sexually mature rats castrated on the first postnatal day. In sexually mature intact males the specific uptake of 3H-5-OT by serotoninergic structures of the anterior hypothalamus was significantly lower than in females. Castration of animals on the first day of life resulted in the increase of specific 5-OT uptake in sexually mature males up to that observed in females. There were no differences between the sexes in the rate of spontaneous release of 5-OT. However, response to K(+)-depolarization in the anterior hypothalamus of intact males was significantly lower than that in females. In the hypothalamus of males castrated neonatally the amplitude of the response to the effect of the depolarizing agent was increase up to the level observed in females. By the results obtained it is indicated that elimination of the effect of male hormones on the first postnatal day results in the increase of 5-OT uptake and release in the hypothalamus of sexually mature rat males.
16
Duplex Doppler sonography of the umbilical arteries: predictive value in IUGR and correlation with birth weight. Forty-three women with either clinically high-risk singleton pregnancies or a predicted fetal weight less than the 10th percentile were studied in their third trimester by duplex Doppler sonography of the free umbilical artery to assess the associations between umbilical arterial flow resistance and intrauterine growth retardation (IUGR) and birth weight. Test criteria included: the greatest (GRI), mean (MRI), and least (LRI) resistive index. The criterion with the strongest association with IUGR (p = 0.001) was the parameter of the LRI predicting IUGR). Linear regression analysis showed a nonsignificant correlation between RI and percentile birth weight, with r2 = 0.05 and p = 0.131. While significant associations can be shown between RI and IUGR, the clinical use of the results of this test should reflect the imprecise nature of these correlations.
17
Mutagenic and recombinogenic effects of the antitumor antibiotic anthramycin. Anthramycin, one of the pyrrolo(1,4)benzodiazepine antibiotics with potent antitumor activity, was tested for its effects on a number of genetic parameters. The results show that this antibiotic is nonmutagenic in the Ames strains of Salmonella typhimurium while mutagenic in only one and antimutagenic in the rest of the genes tested in the eukaryotic organism Saccharomyces cerevisiae. The antibiotic is, however, a potent recombinogen inasmuch as it induced mitotic crossing over, mitotic gene conversion, and possibly other chromosomal alterations in a diploid strain of S. cerevisiae. These studies emphasize the need for a battery of test systems including eukaryotic organisms to detect the genetic activity of certain antitumor drugs. The importance of considering data distinguishing between highly mutagenic and poorly mutagenic cancer chemotherapeutic agents is also discussed.
20
GABA-immunoreactive terminals synapse on primate spinothalamic tract cells. Gamma-aminobutyric acid (GABA) is a putative inhibitory neurotransmitter in the vertebrate nervous system. Several lines of evidence suggest that GABA plays an important role in the processing and modulation of sensory input in the spinal cord dorsal horn. In the present study, the relationship between GABA-immunoreactive (GABA-IR) terminals and spinothalamic tract (STT) cells in the monkey lumbar cord was investigated. Physiologically characterized STT cells, one located in lamina V and two located in lateral lamina IV, were intracellularly injected with horseradish peroxidase (HRP). A fourth STT cell, located in lamina I, was retrogradely labeled following injection of HRP into the contralateral thalamus. Immunogold labeling of ultrathin sections through the cell bodies and proximal dendrites of the STT neurons demonstrated that the percentage of the GABA-IR terminals in contact with these profiles was 24.7% and 36%, respectively. The average STT surface length contacted by GABA-IR terminals for cell bodies and proximal dendrites was 18.2% and 26.7%, respectively. For the lamina I cell, 7 out of 35 (20%) of the terminals were GABA-IR and they covered 9.6% of the surface analyzed. These data demonstrate that GABA-IR terminals synapse directly on STT cells, constituting a substantial proportion of the terminal population on these cells. Furthermore, compared to the cell bodies, a greater percentage of the input on the proximal dendrites is GABAergic. These anatomical data are consistent with the findings of a previously published iontophoretic study that demonstrated that GABA can exert a strong inhibitory influence on STT cells. These findings are discussed in relation to GABAergic involvement in tonic and phasic inhibition of STT neurons.
16
Does the choice of suture material affect the incidence of wound infection? A comparison of dexon (polyglycolic acid) sutures with other commonly used sutures in an accident and emergency department. One hundred and four patients with superficial lacerations were sutured with either Dexon (polyglycolic acid), silk, polyethylene or nylon sutures. The incidence of postoperative tissue reaction and wound infection was compared. There were few complications and these occurred with almost the same frequency in each suture group, although there were slightly more cases of infection in the patients who were sutured with silk. Dexon was seen to possess certain advantages in that it caused as little tissue reaction as the other sutures but did not have to be removed subsequently. This could clearly be of benefit to the patients and hospital staff alike.
13
Inert gas a-A differences: a direct reflection of V/Q distribution. A computer model was developed to study the relationship between ventilation-to-perfusion (V/Q) mismatch and the development of inert gas arterial-to-alveolar partial pressure differences (a-A differences). Increasing inhomogeneity of V/Q ratio is revealed directly as an increase in the a-A difference of each gas. The quantitative relationships between the Q vs. V/Q distribution and the fractional a-A difference solubility plot (a-A difference plot) were studied and described. These studies demonstrated that for log normally distributed V/Q ratios, the area under the a-A difference plot is linearly related to the log variance of the V/Q distribution and can be estimated directly from the values obtained from six gases. The maximum a-A difference occurs for a gas whose solubility is numerically equal to the mean V/Q. The effects of departure from log normality and multimodality are discussed. We conclude from these studies that quantitative information regarding the degree of inhomogeneity of V/Q for log normal distribution is available from direct calculations of inert gas retention and excretion data. Qualitative information is also available indicating the departure from log normality and the region toward which the distribution is skewed.
17
Hypothermic effects of alkylxanthines: evidence for a calcium-independent phosphodiesterase action. Caffeine induces a dose-dependent decrease in core body temperature in mice and the hypothermia induced by a 100 mg/kg dose of caffeine was seen to persist for greater than 160 min. Other alkylxanthines including theophylline, enprophylline, isbutylmethylxanthine and 1,3-dipropyl-7-methylxanthine also showed dose-dependent reductions in body temperature. The dose of these drugs required to reduce body temperature by 2 degrees C was calculated and correlated with the affinities for the compounds at adenosine A1 and A2 receptors and their activities in inhibiting calcium dependent and independent phosphodiesterases. Significant relationships were found between the 2 degrees C hypothermic dose (HD2) and soluble and membrane calcium-independent phosphodiesterase inhibiting activity (r2s = 0.950 and 0.940, respectively). No significant relationship was seen between HD2 and soluble calcium-dependent phosphodiesterase inhibiting activity or with A2 adenosine receptor affinity. The relationship between HD2 and A1 adenosine receptor affinity (r2 = 0.739) did however almost reach statistical significance. These results would suggest that phosphodiesterase inhibition, instead of or in addition to adenosine receptor blockade, may play an important role in the effects of alkylxanthines on body temperature.
19
The pedynograph: a clinical tool for force measurement and gait analysis in lower extremity amputees. The pedynograph is a simple, inexpensive piece of equipment which can be used in the clinical setting to monitor amputee gait. Strain gauges applied to the pylon of a modular prosthesis and incorporated in an appropriate electrical circuit provide measurements of axial load which are displayed on an oscilloscope during ambulation. Preliminary experience with the described equipment has shown that it is of value in monitoring and regulating weight bearing in patients with healing or maturing stumps or impairment of stump sensation. Gait and prosthetic problems can be analyzed, their correction documented and a permanent record of amputee performance provided.
19
Effects of antioxidants on oxygen toxicity in vivo and lipid peroxidation in vitro. Convulsions and pulmonary damage result when animals are exposed to hyperbaric oxygen at pressures above about 300 kPa. Several hydroxyl radical scavengers (namely dimethylsulphoxide, dimethylthiourea and mannitol), the iron chelator desferrioxamine and the lipid antioxidant butylated hydroxytoluene were tested for possible protection against such hyperbaric oxygen toxicity. Dimethylthiourea and dimethylsulphoxide prolonged the latency to the first convulsion, but, surprisingly, dimethylthiourea very significantly increased pulmonary damage at both pressures used (515 and 585 kPa). Desferrioxamine also slightly increased lung damage at 585 kPa. Other antioxidants did not alter neurotoxicity or pulmonary toxicity induced by hyperbaric oxygen at 515 or 585 kPa. The antioxidants were also tested for their ability to inhibit lipid peroxidation (TBARS formation) in vitro. Desferrioxamine (5 and 50 microM), and butylated hydroxytoluene (0.1 mM and 1 mM) greatly inhibited TBARS formation in brain and lung homogenates incubated at 37 degrees. None of the hydroxyl radical scavengers affected TBARS levels in homogenates. There was no correlation between in vitro inhibition of lipid peroxidation and in vivo protection against oxygen toxicity.
18
HLA-A, B and C polymorphisms in three major populations living in South Africa. The HLA class I antigen gene and haplotype frequencies of three major population groups living in the Transvaal province of South Africa were determined. The HLA-A, B and C antigens were tested in 877 South African Negroids, 381 Coloured and 771 Caucasoids. Differences in gene and haplotype frequencies between the various populations were observed. HLA-A11 appears with a low frequency in the Negroids (gf = 0.004) and the Caucasoids revealed an absence of HLA-Bw70. The frequencies of the HLA antigens in the Coloured population were generally intermediate between those of the other two groups. The most frequent haplotypes were A3, B7; A30, B8 and A2, B58 in the Caucasoids, Negroids and Coloured respectively. Genetic distance analysis reveals that Negroids and Caucasoids are distinct groups and the Coloured occupy an intermediate position.
13
The measurement of dynamic latent variables in longitudinal aging research: quantifying adult development. Dynamic latent variables involve systematic intraindividual change over time. Although it seems natural to apply traditional measurement theory to dynamic latent variables, in fact this is often inappropriate. Traditional measurement theory is based on the idea of static latent variables and offers little guidance to the researcher who wishes to measure a dynamic latent variable with a high degree of accuracy and validity. It is the contention of this article that measurement of a dynamic latent variable must start from a clearly defined substantive theory about human development. Two approaches that take this perspective are presented: the longitudinal Guttman simplex (LGS), a measurement model for dynamic latent variables undergoing irreversible cumulative, unitary development; and latent transition analysis (LTA), a more general latent class measurement model.
19
P-glycoprotein expression during tumor progression in the rat liver. P-Glycoprotein (Pgp) has been shown to mediate multidrug resistance in tumor cell lines. Overexpression of Pgp has been detected in clinical cancer samples of many histological types. The basis and biological significance of such increases in Pgp expression are not well understood. In this study, the expression of Pgp during stepwise progression to rat liver cancer was examined to investigate the possible role of Pgp in carcinogenesis. An immunohistochemical technique was used to detect Pgp at the single-cell level, in a large number of liver nodules, hepatocellular carcinoma, and in distant metastases of the carcinomas. The results showed that distinct changes in Pgp expression occurred during stepwise liver carcinogenesis and that these changes were closely associated with the microscopic anatomy of the lesions. In contrast to gamma-glutamyl transpeptidase and glutathione S-transferase-7.7, whose expression appeared to correlate with the early steps of liver carcinogenesis, Pgp expression was higher in the large hyperplastic nodules and in hepatocellular carcinomas than in the early microscopic lesions. A particularly striking finding was the consistent expression of Pgp in the lung metastases. These findings suggested that Pgp was associated with a more progressed malignant phenotype in liver carcinogenesis.
16
Autoreactive T cell clones isolated from normal and autoimmune-susceptible mice exhibit lymphokine secretory and functional properties of both Th1 and Th2 cells. Recent studies have suggested the existence of two mutually exclusive subpopulations of T helper (Th) cells in the murine immune system, called Th1 which produces interleukin (IL)-2 and interferon (IFN)-gamma but not IL-4 and Th2 which secretes IL-4 and IL-5 but not IL-2. Also, functionally, Th1 cells generally activate the macrophages and mediate delayed-type hypersensitivity whereas Th2 cells provide help efficiently to B cells. In the present study, we investigated the lymphokine secretory properties of two well-characterized autoreactive (self-Ia reactive) T cell clones isolated from normal DBA/2 mice and autoimmune-susceptible MRL-lpr/lpr mice. It was observed that both the autoreactive T cell clones, following activation, produced IL-2, IL-4, and IFN-gamma. They induced hyper-Ia expression and cell proliferation in syngeneic B cells as well as activated the macrophages to exhibit tumoristatic properties. Both clones could also induce T-T network interaction in which syngeneic naive CD4+ T cells responded directly to stimulation with autoreactive T cell clones. The T-T interaction was demonstrable in 1-month-old MRL-lpr/lpr mice prior to the onset of the autoimmune disease but not in 6-month-old mice having lymphadenopathy and autoimmune disease. Unlike Th1 and Th2 cells which upon antigenic stimulation respond to exogenous IL-2 and IL-4, the autoreactive T cell clones responded only to IL-2 but not to IL-4. Our data suggest the existence of a unique subset of immunoregulatory CD4+ Th cells having the lymphokine secretory and functional properties of both the murine Th1 and Th2 subsets.
18
Aneurysms arising from the proximal (A1) segment of the anterior cerebral artery. A study of 38 cases. This study reviews aneurysms of the proximal segment (A1) of the anterior cerebral artery in 38 patients (23 men and 15 women) and their surgical, angiographic, and clinical management. Thirty-seven aneurysms were saccular and one was fusiform. The incidence of A1 aneurysms among a total of 4295 aneurysm cases treated was 0.88%. Multiple aneurysms occurred in 17 patients (44.7%) of the 38 cases; in 10 (58.8%), there was bleeding from the A1 aneurysm. The aneurysms were classified into five categories according to the mode of origin of the aneurysm in relation to the A1 segment: in 21 cases, aneurysms originated from the junction of the A1 segment and a perforating artery; in eight, from the A1 segment directly; in six, from the proximal end of the A1 fenestration; and in two, from the junction of the A1 segment and the cortical branch. One patient had a fusiform aneurysm. Computerized tomography (CT) of these aneurysms revealed bleeding extending to the septum pellucidum similar to that of anterior communicating artery aneurysms. When performing radical surgery it is very important to recognize the characteristics of A1 aneurysms, including multiplicity, a high incidence of vascular anomalies (especially A1 fenestration), and their similarity to anterior communicating artery aneurysms on CT.
17
The mechanism of Ca2+ stimulation of citrulline and N-acetylglutamate synthesis by mitochondria. ATP-driven citrulline synthesis by mitochondria treated with oligomycin, uncoupler and Ca2+ ionophore is stimulated more than 2-fold by an increase in extramitochondrial free [Ca2+] in the range 1-5 microM. Stimulation increases with the length of preincubation of mitochondria with Ca2+. EGTA prevents stimulation if added at the start of the preincubation period, but is without effect if added at the end, suggesting that Ca2+ acts indirectly on citrulline synthesis via the accumulation of an intermediate. Neither carbamoyl-phosphate synthase (ammonia) nor ornithine carbamoyltransferase are stimulated by up to 50 microM free Ca2+ in mitochondrial extracts, but N-acetylglutamate synthase is stimulated about 30% by 10 microM free Ca2+. We propose that an increase in the activity of N-acetylglutamate synthase in response to an increase in free [Ca2+] in the mitochondrial matrix may contribute to hormonal stimulation of the urea cycle.
18
[Orbital, osseous, meningeal and cerebral findings in oculodermal melanocytosis (nevus of Ota). Clinico-histopathologic correlation in 2 patients]. In two patients suffering from congenital oculodermal melanocytosis (nevus of Ota) orbital, osseous, meningeal, and cerebral manifestations are documented. In a 38-year-old European with a nevus of Ota on the right side an ipsilateral orbital tumor was diagnosed and surgically removed. The histological examination revealed a primary spindle shaped malignant melanoma of the orbit. In addition, many benign melanocytes were found in the optic nerve, in the extraocular muscles, in the orbital fat tissue, and in the dura of the sphenoid. In a 17-year-old Ethiopian with a nevus of Ota of the right side an increase in size of the pigmented process was observed during puberty in the orbital fat tissue, in the extraocular muscles, in the optic nerve, in the periorbital bones, in the temporal muscle, and in the cortex of the frontal brain lobe. A deep excision from the lower eye lid revealed a histologically benign oculo-orbito-dermal melanocytosis. An irradiation was performed because of growth again after segmental excision, however without success. In the ipsilateral eye a secondary open-angle glaucoma was diagnosed. In the nevus of Ota an involvement of the orbit and of the meningo-cerebral tissue must be considered.
15
Scanning electron microscopy of normal human scar tissue and keloids. The fibrous architecture of 5 normal human scars between 1 week and 1 year old and 4 keloid scars has been studied by scanning electron microscopy. In normal wounds, significant changes in fibril and fibre orientations and mode of aggregation take place as the scars mature, indicating that remodelling carries on for many months. There are also major differences between the edge and centre of the wound. These changes can be related to the stresses placed on the fibroblasts which have responded by laying down collagen aligned in such a way as to resist these forces. It is suggested that keloid fibroblasts may lack this ability to respond appropriately to orientational stress.
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Studies on the mechanism of lysis of Echinococcus granulosus protoscoleces incubated in normal serum. Brood capsules were obtained from freshly collected cysts of equine and ovine strains of Echinococcus granulosus. Protoscoleces were freed from brood capsules either by mechanical disruption or pepsin-HCI digestion. Preparations of protoscoleces studied included: mechanically released protoscoleces without further treatment, or incubated either in HCI pH 2.0 or in evaginating solution (containing Na taurocholate) for 24 h; pepsin-HCI released protoscoleces without further treatment or incubated in evaginating solution for 24 h or 7 days. Half of each preparation of ovine protoscoleces was fixed in absolute methanol. All fresh preparations of protoscoleces lysed rapidly when incubated in normal human serum. Studies with a fluorescein isothiocyanate (FITC) labelled sheep anti-human C3 antiserum revealed the presence of C3 on the surface of lysing protoscoleces. Antibody could not be detected on the surface of any of the preparations of fresh or methanol-fixed protoscoleces using direct or indirect fluorescent antibody tests suggesting that the classical pathway of complement activation was not involved in the lytic process. Strong evidence for lysis by the alternate pathway of complement activation was the lysis of protoscoleces which had been treated with pepsin-HCI and lysis of protoscoleces in guinea-pig serum deficient in C4 component of complement.
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Separate medullary pathways mediatiating reflex vagal bradycardia to stimulation of buffer nerves in the cat. In this investigation of medullary pathways mediating reflex vagal bradycardia to stimulation of buffer nerves, four series of experiments were done in 37 cats anesthetized with chloralose, paralyzed and artificially ventilated. In the first series using animals in which the contralateral vagus was sectioned and the spinal cord was transected at C2, simultaneous stimulation of the aortic depressor (ADN) and carotid sinus (CSN) nerves elicited a bradycardia of magnitude not significantly different from the algebraic sum of the responses elicited by stimulation of the two buffer nerves separately, suggesting the existence of two separate central pathways mediating vagal bradycardia. In the second series, in spinal unilaterally vagotomized animals, lesions of the nucleus ambiguus (AMB) selectively attenuated the ADN reflex vagal bradycardia but not the CSN response; on the other hand, lesions of the external cuneate nucleus (ECN) attenuated the reflex vagal bradycardia elicited by stimulation of the CSN, but did not alter the ADN response. In the third series of experiments, 153 spontaneously firing single units in the region of the AMB and 98 in the region of the ECN were tested for responses to ADN and CSN stimulation. In the AMB 42% of the responsive units were excited only by stimulation of the ADN, 25% were activated only by stimulation of the CSN and 33% were activated by stimulation of both buffer nerves. Of the single units in the ECN region 85% were excited only by stimulation of the CSN, 15% during stimulation of both the CSN and ADN and none responded to stimulation of only the ADN. In the final series, electrical stimulation of the ECN evoked antidromic compound action potentials in the CSN but not in the ADN. Electrical stimulation of the AMB did not evoke antidromic activity in either the CSN or ADN. These studies provide evidence for the existence of two separate medullary pathways mediating the vagal reflex bradycardia to stimulation of the ADN and CSN.
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Acute respiratory failure and obesity with normal ventilatory response to carbon dioxide and absent hypoxic ventilatory drive. We measured hypoxic and hypercapnic ventilatory drive in a 64 year old woman with acute respiratory failure, congestive heart failure and obesity when she was in remission. She had a ventilatory response to carbon dioxide (CO2) comparable to that in six obese women without hypoventilation but no ventilatory response to hypoxia or to vital capacity breaths of 15 per cent CO2 in N2. Following weight loss, her ventilatory response to CO2 increased but hypoxic ventilatory response to CO2 increased but hypoxic ventilatory drive remained absent. These findings indicate that attenuation of hypoxic ventilatory drive caused by loss of peripheral chemoreceptor function can be a predisposing factor in the development of acute respiratory failure associated with obesity.
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[Eosinophilia-myalgia syndrome associated with 5-OH-tryptophan. Description of a case]. The Authors report a case of eosinophilia-myalgia syndrome in a patient with a history of alcohol abuse, treated with a 5-OH-tryptophan containing drug. As regards the pathogenesis of this "new" clinical syndrome, three major hypotheses can be considered: a) autoimmune, according to which tryptophan could act as an "immunogenic" stimulus, thus evoking a cell-mediated reaction against neuromuscular structures; b) dysmetabolic, that is to say, related to neurotoxic metabolites of tryptophan, which in certain conditions could be degraded by an "alternate" pathway that is normally less operating; c) toxic, which is the most accredited nowadays, according to which there is a toxic factor, perhaps similar to aniline, linked to the process of manufacture and purification of L-tryptophan. In our patient, the drug withdrawal and a therapy with steroids led to the remission of the syndrome.
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In vivo and in vitro studies of quinine sensitivity of Plasmodium falciparum in Thailand. Forty-four patients with falciparum malaria were studied. Nine patients were given quinine orally at a daily dose of 1.5 gm base for a period of 14 days. The mean parasite clearance in all 9 patients was 3.3 days, and none had recrudescence in follow-up examinations for 31 days. The in vivo study of these 9 patients showed sensitivity to quinine which correlated with the in vitro test, with concentration of quinine base 2.5-5.8 microgram/ml of blood that inhibited the maturation of Plasmodium falciparum parasites. The results of the in vitro test of 35 patients showed concentrations of quinine base 2.1-5.4 microgram/ml of blood were able to inhibit the maturation of P. falciparum parasites. Therefore, these studies indicate that Plasmodium falciparum are still sensitive to quinine and quinine remains to be the drug of choice for the treatment of falciparum malaria in Thailand.
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Visuo-perceptual impairment and cerebral lesions in spastic diplegia with preterm birth. Eighteen cases of spastic diplegia (SD) ranging in age from 5 year 4 month to 9 year 5 month with preterm birth were studied to clarify the relationship between visuo-perceptual impairment and their cerebral lesions. All underwent neuropsychological examinations including the Frostig developmental test of visual perception, Tanaka-Binet or Suzuki-Binet intelligence test, and MRI examination. Cerebral lesions were detected in all subjects, and the volume of the peritrigonal white matter of the parietal and occipital lobes was significantly correlated with the visuo-perceptual impairment (r = 0.74, in the axial plane; r = 0.64, in the coronal plane). We propose that visuo-perceptual impairment is caused by cerebral lesions and that the measurement of peritrigonal white matter by MRI is useful for detecting potential visuo-perceptual impairment at an early age.
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Oxytocin attenuates the cocaine-induced exploratory hyperactivity in mice. The effects of pimozide, a dopamine-receptor blocker and oxytocin, a neurohypophyseal neuropeptide were investigated in mice on the cocaine-induced exploratory hyperactivity. The action of oxytocin on changes of dopaminergic neurotransmission induced by cocaine was also measured. Cocaine-induced exploratory hyperactivity could be blocked by pimozide (1 mg kg-1, s.c.). Oxytocin (0.05-1.0 micrograms) inhibited the cocaine-induced hyperactivity in an U-shaped dose-response manner. In the nucleus accumbens, oxytocin antagonized the increased dopamine disappearance, elicited by cocaine, but not in the nucleus caudatus. The data suggest that oxytocin may influence the behavioural effect of cocaine by modulating dopaminergic neurotransmission in mesolimbic dopaminergic terminal region of the brain.
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Regulation of hepatic protein synthesis in chronic inflammation and sepsis. The regulation of protein synthesis was determined in livers from control, sterile inflammatory, and septic animals. Total liver protein was increased in both sterile inflammation and sepsis. The rate of protein synthesis in vivo was measured by the incorporation of [3H]phenylalanine into liver proteins in a chronic (5 day) intra-abdominal abscess model. Both sterile inflammation and sepsis increased total hepatic protein synthesis approximately twofold. Perfused liver studies demonstrated that the increased protein synthesis rate in vivo resulted from a stimulation in the synthesis of both secreted and nonsecreted proteins. The total hepatic RNA content was increased 40% only in sterile inflammation, whereas the translational efficiency was increased twofold only in sepsis. The increase in translational efficiency was accompanied by decreases in the amount of free 40S and 60S ribosomal subunits in sepsis. Rates of peptide-chain elongation in vivo were increased 40% in both sterile inflammation and sepsis. These results demonstrate that sepsis induces changes in the regulation of hepatic protein synthesis that are independent of the general inflammatory response. In sterile inflammation, the increase in protein synthesis occurs by a combination of increased capacity and translational efficiency, while in sepsis, the mechanism responsible for accelerated protein synthesis is an increased translational efficiency.
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