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Prognosis after recovery from myocardial infarction: the relative importance of cardiac dilatation and coronary stenoses. In order to further define clinical and angiocardiographic predictors of long-term survival after myocardial infarction we followed 616 consecutive male patients under 60 years of age, survivors of a first (N = 455) or recurrent (N = 161) myocardial infarction, for 8.8 +/- 2.9 years. Patients had angiocardiography at 4-8 weeks after infarction; none had thrombolysis, but 33% had cardiac surgery, 14% on a clinical trial basis. Left ventricular end-systolic volume was the most powerful predictor of cardiac mortality; ejection fraction and end-diastolic volume added no further information. Myocardial score, a measure of the severity of coronary stenoses in relation to the amount of myocardium supplied, was of only borderline predictive value on multivariate analysis, possibly because any effect had been negated by coronary surgery. Administration of beta-blocker drugs had an independent effect of improving prognosis, while continued cigarette smoking worsened it. Age, status of index infarction (first or recurrent) and serum cholesterol did not affect survival. A trial of surgery, carried out in a subset of 200 of these patients who were relatively asymptomatic but had severe coronary disease, showed no survival advantage for intended surgical over non-surgical management. We conclude that a high left ventricular end-systolic volume remains the most important adverse prognostic factor after recovery from myocardial infarction.
| 19 |
Central neurocytoma: immunohistochemical and ultrastructural study. Eight cases of central neurocytomas were studied by immunohistochemistry and electron microscopy. Seven tumors were located in the lateral ventricles and one in the subependymal region. All but one patient had a favorable postoperative course. The tumors were composed of small uniform cells possessing amitotic round nuclei with frequent perinuclear halos, a few Homer Wright rosettes and no ganglion cells; an appearance resembling that of oligodendroglioma. Immunohistochemical studies disclosed neuron-specific enolase and Leu-7 positivity in all tumors, S-100 protein-positive cells were found in six, while glial fibrillary acidic protein--and vimentin-positive cells were confined to the blood vessels. Myelin basic protein as well as neurofilament were not detected in the tumors. Synaptophysin-positive areas were seen in one tumor. Ultrastructural examination showed distinctive neuronal tumor cells which had a cytoplasm with sparse dense-core vesicles and thin cell processes containing parallel microtubules. They were classified into three different types of tumor cells according to the extent of differentiation. The most consistent finding for histological diagnosis was the presence of typical or abortive synapses with clear and dense-core vesicles. Additionally, synaptophysin may be a specific marker for some central neurocytomas.
| 14 |
Break points in human chromosomes. Break points of structural rearrangements of human chromosomes can be identified by banding techniques. The present study attempts to analyze the randomness and the distribution of the reported spontaneous break points in the human genome. Reports of break points in structural rearrangements of human chromosomes from the published sources up to October 1976 were analyzed. Based on the assumption that each unit length of band has an equal chance of being broken, chi2 tests show that positions of breakage are highly non-random; that is, breaks are more frequent in the negative band areas and in the centromeric and terminal regions. In double-break rearrangements the same band types tend to rejoin. The distribution of breaks is not proportional to the chromosome length. The longer chromosomes (i.e., 1--12, X) have a lower number of breaks per unit length, while the shorter chromosomes (i.e., 13--22, Y) have a greater number of breaks per unit length with the exception of chromosomes 4, 9, 10, 16, 17, 19, 20 and X. Out of the whole genome, chromosomes 9, 13, 18, 21, 22 and Y have the most breaks per unit length and chromosomes 16, 6, 2, 3 and 19 have the fewest. 18p11, 21q22 and Yp11 are the three bands with most frequent breaks. There are 53 bands where no breaks have been reported.
| 11 |
Effects of asbestos and beryllium on release of alveolar macrophage enzymes. Rabbit alveolar macrophages were exposed in culture medium to asbestos, beryllium sulfate, and beryllium oxide. The specific activities of the lysosomal hydrolases, acid phosphatase beta-N-acetylglucosaminidase and beta-glucuronidase plus the glycolytic enzyme, phosphohexose isomerase were determined in the medium, whole-cell homogenates, mitochondrial fractions, and supernatant. These hydrolases increased significantly in the medium but not in the mitochondrial fraction of cells exposed to dusts. Asbestos and beryllium sulfate were highly cytotoxic for alveolar macrophages in vitro and the data suggested that these agents were not associated with an increase in enzyme synthesis but rather a direct cytotoxic effect at the macrophage membrane level. For induction of enzyme release in vitro, a higher concentration of beryllium oxide was needed when compared with asbestos and beryllium sulfate. The cytotoxicity and enzyme release induced by these agents may represent an important nonspecific mechanism by which they induce inflammation and perhaps local proliferation of fibroblasts.
| 19 |
Posterior iliac osteotomy for fixed pelvic obliquity. In nine children with a myelomeningocele and fixed pelvic obliquity due to uncorrectable lumbosacral scoliosis, a bilateral posterior iliac osteotomy was done and a wedge of bone was transferred form the low side to the high side of the pelvis. This produced a mean correction of 14 degrees (41 per cent) of the pelvic obliquity and a mean correction of the trunk list from the midline of seven centimeters (69 per cent). Two to seven-year follow-ups showed that the correction was permanent, without tendency for the obliquity to return as long as the scoliosis did not progress. The procedure resulted in several complications, including fracture of the pelvis and transient sciatic-nerve palsy; however, it provided a means of correcting pelvic obliquity that could not be corrected by standard procedures.
| 18 |
Accumulation of extracellular glutamate and neuronal death in astrocyte-poor cortical cultures exposed to glutamine. The function of astrocytes in cerebral cortex may be studied by comparing the properties of conventional, astrocyte-rich cultures with astrocyte-poor cultures in which astrocyte proliferation has been stringently suppressed. Exposure of astrocyte-poor, but not astrocyte-rich, cultures to fresh medium containing 2 mM glutamine resulted in the death of most neurons within 24 h. This study was undertaken to understand the basis for the apparent toxicity of glutamine in astrocyte-poor cultures. The toxicity of glutamine was found to be mediated by glutamate, which demonstrated an LD50 as a neurotoxin in astrocyte-poor cultures of 2 microM. Exposure of astrocyte-poor (but not astrocyte-rich) cultures to fresh medium containing glutamine for 17.5-24 h resulted in the accumulation of substantial quantities of glutamate (255 +/- 158 microM; mean +/- standard deviation) coincident with the death of neurons in the cultures. Exposure of astrocyte-poor cultures to glutamate in the absence of glutamine did not result in the accumulation of extracellular glutamate. Both the neuronal death and the extracellular glutamate accumulation in astrocyte-poor cultures exposed to glutamine could be blocked by N-methyl-D-aspartate (NMDA) antagonists. These observations suggest that astrocytes as well as glutamine may play an important role in the pathogenesis of glutamate neurotoxicity in the central nervous system.
| 20 |
Role of water-soluble dietary fiber in the management of elevated plasma cholesterol in healthy subjects. Guidelines for the use of water-soluble dietary fibers (WSDF) in the dietary management of elevated plasma cholesterol are not well-established. Consequently, 4 studies were conducted to explore the plasma lipid-lowering effects of a variety of WSDF. Studies were randomized, double-blind, placebo-controlled trials involving healthy men and women (plasma cholesterol greater than 5.17 mmol/liter; greater than 200 mg/dl). Study duration ranged from 4 to 12 weeks. The WSDF acacia gum yields a low viscosity, palatable beverage when mixed in water. However, despite its WSDF classification, acacia gum consumed for 4 weeks as the sole WSDF source (15 g of WSDF/day) or primary source in a WSDF mixture (17.2 g of WSDF/day; 56% derived from acacia gum) did not produce a significant lipid-lowering effect versus placebo. When 15 g of WSDF/day consisting of psyllium hust, pectin, and guar and locust bean gums (medium viscosity) was consumed for 4 weeks, significant reductions in cholesterol resulted (total cholesterol 8.3%, low-density lipoprotein cholesterol 12.4%; p less than 0.001) that were comparable to changes achieved with 10 g of WSDF/day from high-viscosity guar gum. The magnitude of the lipid-lowering effect was related to intake of WSDF ranging from 5 to 15 g/day (low-density lipoprotein cholesterol +0.8% [placebo], -5.6% [5 g/day], -6.8% [10 g/day], -14.9% [15 g/day]; p less than 0.01 for trend). The effects of WSDF on plasma lipids were similar for men and women. A diet rich in selected WSDF may be a useful adjunct to the dietary management of elevated plasma cholesterol.
| 16 |
Dimorphic male brains and alternative reproductive tactics in a vocalizing fish. Brains and types of behavior among sexually mature vertebrates are portrayed as having two phenotypic states: male and female. However, mating systems and the behavioral tactics employed by the two sexes are far more diverse than conveyed by this simple intersexual dichotomy. For example, in many species, sexually mature males may practice one of two alternative mating tactics. Recent studies of a sound-producing teleost fish now show that intrasexual dimorphism of vocal motor phenotypes among males accompanies the intrasexual divergence of types of reproductive behavior. Thus, one group of males, like females and juveniles, lacks the behavioral, neurophysiological and morphological traits typical of the sexually differentiated vocal motor pathway of the second group. The results are an explicit demonstration that for any one species: (1) alternative mating tactics can be paralleled by alternative phenotypes for the neurons that determine tactic-specific types of behavior, and (2) reproductive maturation is not obligatorily linked to the expression of neuronal secondary sex characteristics.
| 19 |
The treatment of avoidance behaviour following severe brain injury by satiation through negative practice. Brain-injured patients may frequently develop behaviour disorders in order to avoid participating in rehabilitation activities. In recent years, the use of behaviour modification techniques, particularly the use of positive reinforcement and time-out, has been increasingly reported in the literature as a means of remediating behaviour disturbance in this population. However, reward- or extinction-based programmes are generally not effective in the treatment of avoidance behaviours as they may be ineffective or, at worst, encourage further avoidance of rehabilitation activities. This paper, describes the use of satiation through negative practice in the successful treatment of a severely brain-injured patient whose behaviour, in the form of prolonged shouting, had previously not responded to the range of behavioural techniques used previously with this population. Two successive treatment programmes that were used in an attempt to satiate shouting are presented. Significant reductions in both the frequency and duration of shouting were found, enabling physical and functional gains to be made through successful participation in previously avoided rehabilitation activities. The validity of the use of this technique in the treatment of avoidance behaviour in brain-injured patients is discussed.
| 20 |
Bovine kidney alkaline phosphatase. Purification, subunit structure, and metalloenzyme properties. Kidney alkaline phosphatase was purified to homogeneity. It is a glycoprotein of about 172,000 molecular weight. Analyses of the subunit structure by sedimentation equilibrium in 6 M guanidine hydrochloride and by gel electrophoresis in sodium dodecyl sulfate indicate that the alkaline phosphatase is a dimer comprising two very similar or identical subunits of about 87,000 molecular weight. The native enzyme contains 4.5 +/- 0.2 g atoms of zinc per mol of protein. Reconstitution experiments from the apophosphatase show that binding of 4 Zn2+ per mol of dimer is essential for full activity. The kinetic data of Zn2+ binding to the apoprotein require at least a two-step mechanism, in which one of the steps corresponds to a conformational change within the enzyme. This paper also presents data concerning amino acid composition, sugar content, enzyme stability, absorbance index, and sedimentation velocity.
| 14 |
Germ cell-specific expression of a gene encoding eukaryotic translation elongation factor 1 alpha (eEF-1 alpha) and generation of eEF-1 alpha retropseudogenes in Xenopus laevis. We have studied by in situ hybridization the expression of the genes encoding the somatic form and the oocyte form of Xenopus laevis eEF-1 alpha. The somatic form of eEF-1 alpha (eEF-1 alpha S) mRNA is virtually undetectable in male and female germ cells of the adult gonad but is very abundant in embryonic cells after the neurula stage. In contrast, another form of eEF-1 alpha (eEF-1 alpha O) mRNA is highly concentrated in oogonia and in previtellogenic oocytes but is undetectable in eggs and embryos. eEF-1 alpha O mRNA is also present in spermatogonia and spermatocytes of adult testis. The latter finding identifies eEF-1 alpha O mRNA as a germ cell-specific gene product. Although germ cells contain very little eEF-1 alpha S mRNA, several eEF-1 alpha S retropseudogenes exist in X. laevis chromosomes. These genes are thought to arise in germ cells from reverse transcription of mRNA and subsequent integration of the cDNA copies into chromosomal DNA. We suggest that eEF-1 alpha S pseudogenes are generated in primordial germ cells of the embryo before they differentiate into oogonia or spermatogonia.
| 15 |
Free-operant comparisons of wild and domestic Norway rats. Wild and domestic rats (Rattus norvegicus) were compared on nondifferential appetitive variable interval responding, discrimination, and discrimination reversal procedures. The effects of strain, sex, deprivation, preexperimental handling, and sessions on response rate were examined. Performances during the 60 days of variable interval training showed prolonged increases over that period for all strain-sex groupings, with domestic subjects responding at higher rates than wild. Males also tended to respond at higher rates than females. During the discrimination procedure wild subjects showed more resistance to extinction than did the domestic subjects, although these differences generally diminished after the 30 days of training. During the discrimination reversal procedure domestic subjects reversed their responding pattern more readily than did the wild subjects, and domestic females reached criterion significantly sooner than domestic males. The effects of deprivation and handling were not significant during the experimental procedures.
| 17 |
Relationship of air temperature to various chemical, haematological, and haemostatic variables. Results for biochemical and haematological variables have been correlated with data on atmospheric temperature in order to identify possible mechanisms through which low environmental temperature may increase mortality from myocardial infarction and cerebrovascular disease. With the exception of cholesterol, there were no associations in the case of several clinical chemistry variables, or of haemoglobin and related indices. With varying degrees of consistency among the sex and age groups studied, temperature was positively correlated with factor VII, antithrombin III, and cholesterol, and negatively correlated with fibrinolytic activity. The correlations were all low but may offer some clues to mechanisms whereby air temperature influences ischaemic heart and cerebrovascular disease mortality.
| 22 |
Refractory anemia with excess of blast cells: prognostic factors and effect of treatment with androgens or cytosine arabinoside. Results of a prospective trial in 58 patients. Cooperative Group for the Study of Aplastic and Refractory Anemias. The results of a prospective study of 58 patients with refractory anemia and partial blastic infiltration of the bone marrow lead to the following conclusions. The median survival (12 months from diagnosis) is shorter and the rate of acute leukemia as cause of death (60%) higher than in other retrospective series. This group of patients, however, appears to be a "continuum" of preleukemic states with more or less rapid evolution, so that the exclusion of the most severe cases appears unjustified. Based on the degree of bone marrow blastosis, and also on the degree of blood cytopenias, the anomalies of 59 Fe incorporation kinetics and the bone marrow stem-cell cultures, it is possible to derive a plausible prognosis for individual patients, which could aid the choice of therapy. Androgen therapy does not accelerate leukemic evolution, but does not improve the bone marrow insufficiency. Cytosine-arabinoside at low dosage exhibited no toxicity, but did not delay the appearance of overt leukemia.
| 15 |
Isolated hepatic lipocytes and Kupffer cells from normal human liver: morphological and functional characteristics in primary culture. The development of techniques for isolating hepatic lipocytes (Ito, stellate or fat-storing cells) from rodents has been instrumental in defining their role in hepatic vitamin A storage and fibrogenesis. In this study, we developed a method for the purification of lipocytes and Kupffer cell from wedge sections of normal human liver and examined their properties in primary culture. Sections of donor liver (400 to 600 gm) harvested but not used for transplantation were perfused in situ with University of Wisconsin solution and used for lipocyte isolation within 48 hr. Cells were isolated by catheter perfusion of the wedge through several large vessels with L-15 salts, Pronase and collagenase, followed by Larex density gradient centrifugation. Lipocytes were plated on either uncoated plastic or a basement membrane-like gel. Lipocyte and Kupffer cell yields were 2.3 +/- 0.6 x 10(5) and 8.6 +/- 1.4 x 10(5) cells, respectively, per gram of liver (n = 5). Lipocyte purity was 91% as assessed by vitamin A autofluorescence, and Kupffer cell purity was 83% as determined by uptake of fluorescinated staphylococci. Lipocytes cultured on the plastic spread within 48 to 72 hr, displaying slightly more heterogeneous retinoid droplet size than comparable rat cells; on a basement-membrane gel, the cells remained aggregated and spherical with occasional spindlelike extensions. Lipocytes on plastic expressed procollagens I and III, collagen IV and laminin by immunocytochemistry, and types I, III and IV procollagen messenger RNAs by RNAse protection. Northern blot and polymerase chain reaction, respectively. Transmission electron microscopy of lipocytes at 7 days demonstrated a prominent rough endoplasmic reticulum and contractile filaments. Scanning electron microscopy revealed a smooth cell surface with perinuclear droplets beneath the cell membrane. With continued primary culture on plastic (more than 7 days), cells appeared "activated" (i.e., increased spreading and diminished retinoid droplets) and began proliferating as assessed by nuclear autoradiography and [3H]thymidine incorporation. Kupffer cells observed by scanning electron microscopy in early primary culture displayed prominent membrane ruffling and lamellipodia. In summary, we have established a reproducible method for the isolation and primary culture of human lipocytes and Kupffer cells.
| 18 |
Fetal development of the urethral sphincter. A morphological study was carried out on 25 human embryos (3-60 mm CR) and 20 human fetuses (15-40 weeks). The anatomical analysis was completed by immunocytochemical studies of different markers of muscle differentiation (vimentin, desmin, titin and isoforms of the myosin heavy chains). A mesenchymal condensation forms around the urethra after the division of the cloaca (E.H. 12-15 mm CR). The m. pubo-rectalis appears in 20-30 mm CR embryos, following the opening of the anal membrane. Striated muscle fibers can be clearly differentiated at 15 weeks. At this time, the smooth muscle layer also becomes thicker at the level of the bladder neck and forms the inner part of the urethral musculature. The urethral sphincter is a functional unit composed of central smooth muscle fibers and peripheral striated muscle fibers. In the human fetus, this musculature mainly develops in the anterior wall of the urethra. We analysed the expression of smooth and skeletal markers as an original approach to the muscular development in this region.
| 12 |
Pseudomonas aeruginosa. Vaccines and immunotherapy. Among opportunistic infections with gram-negative bacilli, those caused by Pseudomonas aeruginosa are associated with particularly high mortalities. Accordingly, considerable interest exists to develop immunotherapeutic or immunoprophylactic agents for this pathogen. In vitro as well as in vivo studies in animal models have demonstrated that LPS serotype-specific antibodies against P. aeruginosa confer protection. Thus, cell wall-derived LPS P. aeruginosa vaccines have been developed for active immunization. Toxic side effects from LPS and relatively slow immune response to active immunization in patients needing rapid protection have led to the development of high-titered anti-P. aeruginosa immunoglobulin G preparations. Passive immunotherapy with these polyclonal antibody preparations has shown promising results in animal models and in clinical pilot studies. More recently, murine and human monoclonal antibodies against P. aeruginosa have been developed. These preparations offer the potential advantage over polyclonal globulin preparations of low protein dosages and virtually unlimited supply.
| 16 |
Demonstration of cellular and humoral immunity to transplantable carcinomas derived from the respiratory tract of rats. Previous studies with respiratory tract tumors in mice have suggested that such tumors are not immunogenic or are only weakly so. To determine whether this is a general characteristic of neoplasias found in the airways of rodents, we investigated seven transplantable carcinomas in rats, six of which originated from tracheal epithelium and one of which orginated from the distal lung. These carcinomas were all of the squamous type and were induced by three different carcinogenic polycyclic hydrocarbons. All of the tumors were shown to be immunogenic, capable of mobilizing cellular and humoral immune responses in isogenic hosts upon immunization. This was demonstrated by induction of transplantation resistance, by Winn's neutralization test, and by the detection of antibodies in the sera of tumor-immune hosts by two independent methods (antibody-dependent cytotoxicity and antibody-binding test). The degree of immunogenicity varied among the tumor lines. The most metastatic tumor was clearly the least immunogenic. The relationship between carcinogenic insult and immunogenicity, as well as the possible nature of the tumor-associated antigens involved, is discussed.
| 17 |
Visual suppression test. Visual suppression of caloric nystagmus was studied in normal adults and in 98 clinical cases in order to justify the application of the procedure as a clinical test. The maximum slow phase velocity during ten seconds in darkness and the slow phase velocity during ten seconds in light were taken from the recordings and measured. The mean values of these slow phase velocities were calculated and the mean slow phase velocity in darkness was assigned a value of 100%. The value which the slow phase velocity in light subtracts from the slow phase velocity in darkness, represents the visual suppression. It was determined that visual suppression of the slow phase velocity of caloric nystagmus was 48 +/- 10% in 22 normal adults. This was caused by the visual fixation mechanisms. Cases in which lesions were diagnosed in the cerebellum, such as spinocerebellar degeneration and cerebelitis, showed reduced or abolished visual suppression. The lesion side can be determined by this test. Compensation following unilateral sudden loss of inner ear function can be measured by the visual suppression test.
| 13 |
DNA bioprints: simple nonisotopic DNA fingerprints with biotinylated probes. The discovery of multilocal DNA fingerprinting represented a revolution in criminal identification and paternity testing. However, for routine use in clinical laboratories, the standard DNA fingerprint methodology is too complex. We have been successful in the development of a simplified DNA nonisotopic fingerprinting system using biotin-labeled probes which we have called DNA bioprints. To achieve this we explored three main technical features: utilization of biotinylated nonradioactive probes as a simpler substitute for 32P-labeled probes, utilization of oligonucleotide probes as a simpler substitute for recombinant probes, and direct hybridization in the dried agarose gel as a simpler substitute for Southern blots. In this article we review our results in the development of DNA bioprints.
| 17 |
Lipoprotein synthesis in Escherichia coli spheroplasts: accumulation of lipoprotein in cytoplasmic membrane. Synthesis of cell envelope proteins was studied in ethylenediaminetetraacetic acid-lysozyme spheroplasts of Escherichia coli ML30. The rate of incorporation of [3H]arginine into proteins in spheroplasts was about 30% of that of intact cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins synthesized in spheroplasts revealed the preferential synthesis of five polypeptides, one of which has been identified as the free form of murein lipoprotein. Lipoprotein synthesized in spheroplasts was found to be of same molecular size as that of mature lipoprotein. No prolipoprotein was observed even with a short pulse-labeling with [3H]arginine. On the other hand, significant accumulation of newly synthesized lipoprotein in the cytoplasmic membrane fraction of spheroplasts was observed. These results suggest that the processing of prolipoprotein occurs in the cytoplasmic membrane fraction of the cell envelope.
| 16 |
Global in vivo replacement of choline by N-aminodeanol. Testing a hypothesis about progressive degenerative dementia: II. Physiological and behavioral effects. We have examined the progressive effects of replacement of dietary choline with NADe for a period of 120 days on a broad spectrum of behavioral and physiological functions known to involve the cholinergic system. The magnitudes of these effects tended to increase with time on the NADe diet, but those related to learning and memory were largely confined to the 60-120-day period. Neurochemical effects were concomitant with the replacement of Ch by NADe, being consistent with a hypocholinergic state as found in such progressive degenerative dementias as Alzheimer's disease. As cholinergic functioning was progressively impaired, basic physiological ("vegetative") processes appeared not to be affected. Apparently the rate at which the hypofunctional state developed was sufficiently slow for adjustments to occur, allowing the animal to adapt at a survival level to neurochemical changes. More complex behavioral functions were affected progressively, cognitive processes (e.g., learning and memory) being most sensitive and showing the least adaptability. We propose that the syndrome generated by NADe replacement of Ch represents an experimental model of progressive degenerative dementia.
| 16 |
[Lower toxicity with the topical low-dose BCG therapy of superficial bladder carcinoma?]. Twelve patients with superficial bladder cancer and carcinoma in situ of the bladder were treated with intravesically instilled BCG solution. As suggested by Pagano's group, we used BCG in a lower dose than usual hitherto (75 mg, strain Pasteur Paris). Complete tumor remission was obtained in all patients except the two whose treatment had to be discontinued at an early stage because of severe side effects. None of our patients was free of symptoms; pain or micturition, pollakiuria, gross hematuria, fever, swollen lymph nodes, and epididymitis occurred. We think, therefore, that low-dose therapy with BCG is as effective as full-dose therapy but the side effects are no less severe.
| 14 |
Predicting the profitability of alfalfa silage and pasture feeding systems for Holstein steers. Data from two research trials were used as inputs to a model to project the return to capital of two-phase alfalfa silage and pasture feeding systems for Holstein steers. This approach presents a methodology for applying research data over widely varying conditions. Cattle received a 40% (High = H), 22% (Medium = M), or 8% (Low = L) alfalfa silage diet or grazed an orchardgrass/ryegrass pasture (Pasture = P) during Period 1. During Period 2, cattle consumed a 90% concentrate diet until ultrasonic attenuation predicted that the longissimus muscle contained a small degree of marbling. All systems produced similar carcass grades, so profitability differences resulted from relationships between feed requirements, cost of feed, and cost of time. Cattle grazed on pasture yielded a higher return to capital during Period 1 and over the entire feeding system. Among the other systems, L returned more to capital during Period 1, but over the entire feeding system additional silage returned more when silage cost was less than $32 per 1.02 t (as fed). Above this cost, the continuous 90% concentrate diet yielded a higher return. Cattle implanted with trenbolone acetate and estradiol returned $60 in Trial 1 and $86 in Trial 2 more per animal than did unimplanted steers.
| 14 |
Metabolism of 3-(2', 4', 5'-triethoxybenzoyl) propionic acid, a new biliary smooth muscle relaxant with choleretic activity. II. Metabolism after repeated dosing in rats, in relation to choleretic activity. 1. Accumulation and possible induction in the metabolism of triethoxybenzoylpropionate were studied in rats in relation to the choleretic effect of the drug. Daily oral administration of [14 C] triethoxybenzoylpropionate showed no accumulation of drug or metabolites. Pre-treatment of rats with the drug did not induce its own metabolism or the metabolism of aminopyrine, p-nitroanisole, hexobarbital or zoxazolamine. 2. Choleresis in rats induced by triethoxybenzoylpropionate resulted from enhanced formation of the bile acid-independent fraction of canalicular origin, presumably mediated by the increased transfer of sodium into the canaliculi. This was not altered by repeated pre-treatment with the drug, in accordance with the metabolic findings.
| 14 |
Association of amyloidosis with erythema nodosum leprosum reactions and recurrent neutrophil leucocytosis in leprosy. Rectal biopsy in 190 inpatients at a leprosy hospital in the Highlands of Papua New Guinea disclosed 16 patients with secondary amyloidosis. This represented 20% of the patients who had had polar lepromatous leprosy (L.L.) for more than 2 years. Patients with amyloidosis characteristically had either a history of recurrent attacks of erythema nodosum leprosum (E.NH) reactions or chronic trophic ulcers. Levels of the serum component (protein SAA) antigenically related to the amyloid fibril protein AA were monitored, at varying intervals for three months, in lepromatous patients with E.N.L. reaction. The SAA levels rose during E.N.L. reactions in parallel with the neutrophil count. SAA occurred with greatest frequency among patients with LH, while most non-lepromatous patients with detectable SAA had chronic trophic ulcers. The correlation between raised neutrophil count and elevated SAA concentration, observed in this and other studies, suggests that neutrophils are associated with the production of SAA.
| 13 |
Nonoliguric acute renal failure. The course of nonoliguric acute renal failure (ARF) in 11 patients was analyzed. The possible etiology of the renal failure was multiple in all cases and did not differ from that seen in oliguric acute tubular necrosis (ATN). Other than the urine volume, which ranged from 510 to 2,325 ml/day, there was no major clinical or biochemical difference between these cases of nonliguric ARF and those described for oliguric ATN. Creatinine clearance, however, was higher than anticipated in oliguric ATN and ranged from 2.8 to 15.0 ml/min. There was a direct relationship between creatinine clearance and daily urine volume. The essential difference between oliguric and nonoliguric renal failure appears to be the lesser degree of renal damage in the nonoliguric form.
| 12 |
The de facto US mental health services system: a public health perspective. The President's Commission on Mental Health has highlighted a heretofore unmet need for the linkage of data on the prevalence of mental disorder with national data on the use of mental health services. This study analyzes available epidemiological data and recent mental health services research findings to estimate the percent of the population with a mental disorder and the proportion utilizing various types of specialty mental health and general medical treatment settings. Provisional estimates indicate that at least 15% of the US population is affected by mental disorders in one year. In 1975, only one fifth of these were served in the specialty mental health sector, with about three fifths identified in the general medical (primary care) sector.
| 17 |
Arginine metabolism in benign and malignant disease of breast and colon: evidence for possible inhibition of tumor-infiltrating macrophages. L-Arginine concentrations have been measured in benign and malignant breast and colonic neoplasms and compared with the macrophage content and arginase activity within these tumors. Our study confirmed previous findings of elevated plasma arginine concentrations in malignancy and demonstrated that tissue free-arginine concentrations are substantially higher in malignant (mean 9.8 mumol/g protein) than benign (2.8 mumol/g protein) breast disease. Similarly, malignant colonic neoplasms had a higher free-arginine concentration than benign colonic polyps (14.0 vs. 7.0 mumol/g protein). The macrophage content of the malignant tumors was also significantly higher than in the benign conditions (278 vs 29/high power field in breast disease), but despite this, there was no detectable difference in the arginase activity. These findings suggest that tumor-infiltrating macrophages are not able to produce this enzyme, and/or its activity is inhibited within the tumor cell milieu. The differences observed in the arginine concentrations within these lesions has potentially important implications for the pathway of arginine metabolism and local host antitumor responses.
| 20 |
[Successes and prospects of molecular diagnosis of the most widespread inherited diseases]. Current state of molecular diagnosis of hereditary diseases most common in the former USSR such as cystic fibrosis, Duchenne muscular dystrophy, haemophilia A and B as well as phenylketonuria is reviewed. Basic results of prenatal diagnosis and carrier detection of the above mentioned diseases in St.-Petersbourg and somewhere else in Russia are presented. The urgent necessity to start an efficient molecular diagnosis of some other widespread hereditary diseases (von Willebrand's disease, Martin-Bell syndrome, polycystic kidney. Huntington chorea, myotonic dystrophy, etc.) is emphasized. Creation of new diagnostic centers dealing with most common diseases as well as complementing each other as to molecular diagnosis of more rare hereditary diseases is substantiated. Prospects of implementation of new molecular methods and novel technical approaches (preimplantation embryos, fetal cells selected from maternal blood) for more efficient diagnosis of hereditary diseases are briefly outlined.
| 16 |
Serum and erythrocyte magnesium concentrations and migraine. Most people suffering from migraine present a hypersensitivity of the cervico-facial muscles, which may be linked to magnesium deficit. This paper describes a comparative study of serum and erythrocyte magnesium levels in 79 migraine patients and 55 controls. Serum magnesium did not differ significantly in either group, but some values were quite low. On the other hand, there was a significantly greater erythrocyte magnesium deficit in persons suffering from migraine than in controls (in both female and male subjects). This fact correlates with the improved state of migraine patients (already ascertained in earlier studies) following treatment consisting of the intake of magnesium-rich water. The findings support the hypothesis of a magnesium deficit in people suffering from migraine and raise the problem of the relationship between migraine and other pathologies, including chronic magnesium deficit, latent tetany due to magnesium deficit, mitral valve prolapse, and allergy.
| 16 |
Allogeneic bone marrow transplantation in high-risk myeloid disorders using busulfan, cytosine arabinoside and cyclophosphamide (BAC). Twenty-one patients (median age = 34, range = 10-49; F:M = 7:14) received a preparative regimen consisting of busulfan 4 mg/kg/day x 4, cytosine arabinoside 2 g/m2/12 h x 4 and cyclophosphamide 60 mg/kg/day x 2 ('BAC' regimen) for allogeneic bone marrow transplantation. Out of 12 patients with acute myeloid leukemia (AML), two were in first remission, six were in second remission and four had resistant, relapsed disease or prolonged marrow aplasia after induction chemotherapy. Five of the 12 patients with AML had secondary AML. Four patients had transfusion-dependent myelodysplastic syndrome. Three patients with chronic myeloid leukemia were in the accelerated phase and two were in the blastic phase. Organ toxicities related to the preparative regimen were graded. Liver toxicity occurred in 11 patients, two of these were fatal veno-occlusive disease (VOD) (10%). Nineteen of the 21 patients had grade 2 or less diarrhea, and 13 also had mucositis. One patient developed grade 3 cardiac toxicity, and one other patient had grade 1 skin toxicity. Four patients had gross hematuria related to treatment (19%). No renal, pulmonary or CNS toxicities were encountered. Ten patients have died, two from regimen-related hepatic VOD. Of the remaining eight deaths, four were from respiratory failure in four patients (one case each of Pneumocystis pneumonia, CMV pneumonia, bronchiolitis obliterans associated with chronic graft-versus-host disease, and interstitial pneumonitis complicated pulmonary emboli), and one patient each from GI bleeding, cardiac arrhythmia, sepsis and CNS bleeding. Thus far, only one patient transplanted for secondary AML in second remission relapsed at day 230.(ABSTRACT TRUNCATED AT 250 WORDS)
| 14 |
[Comparative study of magnetic resonance and evoked potentials in patients with clinically defined multiple sclerosis]. In an attempt to establish the efficacy of the most recent diagnostic tests--magnetic resonance (MR) imaging and multimodal evoked potentials (EP), 28 patients with clinically definite multiple sclerosis (MS) (1.a Poser's categories) were studied. The MR was positive in 26 (92%) patients; the EP were altered in 23 (82%)--the visual EP in 18 (64.2%), the auditory EP in 5 (17.8%), and the somatosensory EP in 15 (53.5%). Three patients with abnormal brain stem MR had normal EP. Two patients had normal MR and altered EP. There was not any patient with normal MR and EP. The MR was the most sensitive technique for the diagnosis of MS, but only during the 3 first years of evolution. After this study we consider the convenience to have both MR and EP positive to give a patient the diagnostic of clinically definite with paraclinic support (category 1.b of Poser).
| 14 |
Soluble adenylate cyclase from thyroid membranes. Adenylate cyclase from purified beef thyroid membranes has been solubilized by the use of Triton N-101 after preactivation with guanosine 5'-(beta, gamma-imido)-triphosphate. The soluble activity passed a 0.22- micron filter, was not sedimented at 100,000 X g for 2 h, and behaved like aldolase in sucrose density gradients and on Sepharose 6B. From comparison of the sedimentation in D2O and H2O the partial specific volume was found to be like that of globular proteins (0.75 +/- 0.006), hence little detergent appeared to be bound to the enzyme. The sedimentation coefficient was 7.4 +/- 0.15, the Stokes radius 45 A, and the molecular weight 159,000. Prestimulation by thyrotropin did not survive solubilization. The stimulation produced by guanosine 5'-(beta, gamma-imido)triphosphate persisted as did the more active state resulting from pretreatment with both this nucleotide plus thyrotropin. Thyrotropin did not stimulate the solubilized enzyme. The Km for ATP, thermal stability, and inhibition by Ca2+ were identical for the membrane-bound and soluble enzyme, while the pH optimum was increased 0.5 unit in the latter. Polyanions and phenothiazines inhibited both preparations equally, whereas only membranes responded to stimulation by polylysine and ribonuclease.
| 15 |
Structure, functions, and mechanisms of substance P receptor action. Substance P is a member of a family of structurally related peptides, called tachykinins, that are involved in the regulation of many biologic processes. Diversity in the generation of multiple tachykinin peptides arises due to multiple genes encoding these peptides as well as by mechanisms of alternative RNA processing and differential posttranslational processing. The multiple peptides are neurotransmitters and/or neuromodulator substances, and they bring about their actions mainly by activating three primary types of receptors, NK-1, NK-2, and NK-3. The pharmacology and tissue locations of these receptor sites are discussed, as is their involvement in certain biologic responses. These three receptor sites have been molecularly characterized by cDNA cloning and functional expression, and all are members of the superfamily of receptors coupled to G-regulatory proteins. Second messenger systems established to be activated by tachykinin receptor stimulation include the hydrolysis of inositol containing phospholipids by a phospholipase C mechanism. The role of substance P in neurogenic inflammation and plasma extravasation is briefly discussed. The generation of new research tools recently in the tachykinin field should allow for a detailed examination of the mechanisms of peptide action, including a focus on receptor structure-function relations and regulation of receptor sensitivity.
| 19 |
The effects of suramin on human adrenocortical cells in vitro: suramin inhibits cortisol secretion and adrenocortical cell growth. Suramin, a polycyclic and polyanionic drug, has been successfully used in the therapy of inoperable adrenocortical cancer. The present study was undertaken to investigate the effects of suramin on normal human adrenocortical cells in primary monolayer cultures. The proliferation and the basal, as well as the adrenocorticotropin (ACTH)-stimulated, cortisol secretion of these cells were studied. The data show that suramin decreases basal, as well as ACTH-stimulated, cortisol secretion in a dose-dependent manner (P less than .05 from 300 mumol/L upward). At a suramin concentration of 3 mmol/L, cortisol secretion was inhibited by 70% +/- 4% in ACTH-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was also inhibited by suramin at concentrations from 300 mumol/L upward, maximal suppression (71% +/- 6%, P less than .01) being observed at a concentration of 10 mmol/L. Both inhibition of cortisol secretion and inhibition of adrenocortical cell proliferation were not due to toxicity of the compound, as could be shown by restimulation of cortisol secretion in suramin-treated cells with ACTH. Our results indicate that suramin exerts an inhibitory influence on the cortisol secretion and on the proliferation of normal human adrenocortical cells. Suramin may not only be useful in the treatment of adrenocortical cancer, but may also have an ameliorative effect on other malignant conditions with augmented steroid hormone production, resistant to conventional forms of therapy.
| 19 |
[A case of metastasis of lung cancer to renal cell carcinoma]. A 62-year-old male was admitted with abnormal shadow in chest X-P. CT and other examinations were done, and he was diagnosed left renal cell carcinoma with metastatic lung cancer. He rejected operation and was discharged. We gave him alpha-interferon injection every day. About 5 months later, he complained of fever and dyspnea, and was admitted. On the 10th day after admission, he died suddenly with massive hemoptysis. This hemoptysis was from the pulmonary artery, which was surrounded by tumors and ruptured into the trachea. Pathological diagnosis was double cancer, such a case is very rare with a primary lung cancer (oat cell carcinoma) which has metastasized into a renal cell carcinoma (common type, clear cell subtype).
| 12 |
Plasma glucagon-like immunoreactivity (GLI) in dogs. Gut glucagon-like immunoreactivity (GLI) was extracted from plasma of dogs and was compared for its molecular size and insulin releasing activity with GLI present in the intestine. Plasma was obtained from the portal vein of dogs, of which the pancreas was removed as rapidly as possible during the glucose administration into the intestine. Plasma GLI of intestinal origin was extracted by a modification of Kenny's method. The amount of GLI extractable from plasma in each dog ranged from 4.30 to 25.74 ng. The extract of plasma during glucose absorption was observed to have two peaks on gel filtration, corresponding to Peak I and Peak II of GLI extracted from the gastrointestinal tract. The intrapancreatic infusion of the Peak II GLI extractable from plasma promoted remarkable insulin release in dogs, like pancreatic glucagon. In contrast, the Peak I GLI from plasma caused an equivocal rise of insulin in the pancreatic vein. It is concluded from the experiment that gut GLI extracted from plasma shows the same elution pattern on gel filtration and the same insulin releasing activity as GLI extractable from the gut.
| 15 |
Control of developmental transcription factor sigma F by sporulation regulatory proteins SpoIIAA and SpoIIAB in Bacillus subtilis. The sporulation operon spoIIA of Bacillus subtilis consists of three cistrons called spoIIAA, spoIIAB, and spoIIAC. Little is known about the function of spoIIAA and spoIIAB, but spoIIAC encodes a sigma factor called sigma F, which is capable of directing the transcription in vitro of genes that are expressed in the forespore chamber of the developing sporangium. We now report that the products of the spoIIA operon constitute a regulatory system in which SpoIIAA is an antagonist of SpoIIAB (or otherwise counteracts the effect of SpoIIAB) and SpoIIAB is, in turn, an antagonist of SpoIIAC (sigma F). This conclusion is based on the observations that (i) overexpression of spoIIAB inhibits sigma F-directed gene expression, (ii) a mutation in spoIIAB stimulates sigma F-directed gene expression, (iii) a mutation in spoIIAA blocks sigma F-directed gene expression, and (iv) a mutation in spoIIAB relieves the block in sigma F-directed gene expression caused by a mutation in spoIIAA. The SpoIIAA/SpoIIAB/SpoIIAC regulatory system could play a role in controlling the timing of sigma F-directed gene expression and/or could be responsible for restricting sigma F-directed gene expression to the forespore chamber of the sporangium.
| 22 |
Biochemical changes in rat kidney on exposure to elemental mercury vapor: effect on biosynthesis of metallothionein. Evidence is presented that exposure of rats to elemental mercury vapor results in increased amounts of a metallothionein-like protein in kidney tissue but not in liver. After three or more daily exposures, each of 2 h duration, to elemental mercury vapor, more than 50% of the mercury in kidney tissue is bound to a protein having a molecular weight (mol. wt.) of about 10 000 as determined by Sephadex G-75 gel filtration chromatography. Cystine is incorporated into a 10 000 mol. wt. protein fraction from kidneys of rats which were injected with [U-14C] cystine after five daily 2-h exposures to mercury vapor. In contrast, no significant incorporation of [U-14C] cystine into this protein fraction was observed in kidneys of control rats or in livers of both control and mercury vapor-exposed rats. The in vivo incorporation of 109Cd into the fraction followed the same pattern as that of [14C] cystine in rats injected with tracer doses of CdCl2 labeled with radioactive 109Cd isotope. This 10 000 mol. wt. protein, newly synthesized in response to repeated exposures to mercury vapor, exhibited identical properties to metallothionein, namely in its subcellular localization, molecular weight, heat stability and isoelectric points. A significant incorporation of [U-14C]-cystine into this protein in rat kidney alone on exposure to mercury vapor confirms its induced biosynthesis in the kidney.
| 13 |
Serology, restriction fragment length polymorphism, and sequence analysis of a unique HLA class II antigen, DR5x6. We analyzed a new class II HLA haplotype, which we have designated DR5x6, by serology, restriction fragment length polymorphism (RFLP), and sequence analysis. As the name DR5x6 implies, the antigen is serologically closely related to both DR5 and DRw6. RFLP analysis of this haplotype suggests a close similarity with DRw11 haplotypes. The DNA sequences encoded by the second exon of its DRB1, DRB3, and DQB1 genes were also determined. Comparison of these sequences with those of alleles at these loci in other haplotypes suggests that this haplotype could have evolved from a DRw11 ancestor haplotype (DRw11-DRw52b (Dw25)-DQw7) by means of: (a) a gene conversion at the DRB1 locus involving DRw8 (Dw8.3) as the sequence donor, plus a point mutation or a gene conversion involving DR4-Dw4; and (b) a recombination event by which this haplotype would have acquired the DRw5a (Dw24) allele at the DRB3 locus.
| 18 |
[Chronic persistent HBsAg positive hepatitis in children. II. Effect of treatment with levamisole]. In five children affected by HBsAg positive chronic persistent hepatitis a treatment with Levamisole (LMS) modified several immunological parameters which had been found altered before treatment. In particular the percentage of E rosette forming cells increased while that of EAC decreased; B lymphocytes with SmIgG and the responsiveness to phytohaemagglutinin, which were significantly decreased and increased respectively, got normal values. Since the persistence of HBsAg was unaffected by LMS treatment and a light increase of transaminase serum levels (GPT and GOT) was observed during treatment, doubts are expressed about the opportunity of using LMS in children affected by such a form of hepatitis.
| 16 |
Effects of coronary perfusion during myocardial hypoxia. Comparison of metabolic and hemodynamic events with global ischemia and hypoxemia. The effects of metabolic accumulation on myocardial metabolism during global heart oxygen deprivation were evaluated in a working in situ swine heart preparation with controlled total coronary blood flow. Myocardial oxygen consumption was depressed to a similar extent by either reducing total coronary flow 60 per cent (ischemia, low coronary perfusion) in 10 swine or by decreasing coronary perfusate PO2 to 30 mm. Hg at normal flows (hypoxemia, high coronary perfusion) in 13 swine. Compared with findings in 13 control hearts, ischemia significantly (p less than 0.05) decreased myocardial oxygen consumption (640 to 390 mumole per hour per gram), glucose uptake (185 to 16 mumole per hour per gram), and free fatty acid consumption (32 to 17 mumole per hour per gram). ttissue levels of glycogen, creatine phosphate, and adenosine triphosphate (tatp) were significantly reduced (p less than 0.005), and tissue lactate, adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were increased (p less than 0.001). During hypoxemia, glucose uptake was increased (240 mumole per hour per gram) and free fatty acid consumption was somewhat less depressed (19 mumole per hour per gram). Creatine phosphate and ATP were higher than with ischemia (p less than 0.01), and lactate, ADP, and AMP accumulations were less (p less than 0.01). Thus, in the period immediately following myocardial oxygen deprivation, inadequate coronary perfusion caused greater metabolic buildup which inhibited myocardial substrate utilization and energy production. High coronary perfusion, even though the perfusate was unoxygenated, was associated with greater preservation of substrate utilization, higher levels of high-energy phosphates, less accumulation of metabolic products, and a longer survival. These data suggest a critical role of coronary perfusion in protecting myocardial metabolism in the immediate period following global heart hypoxia.
| 19 |
Determination of the maximum tolerated dose of idarubicin when used in a combination chemotherapy program of reinduction of childhood ALL at first marrow relapse and a preliminary assessment of toxicity compared to that of daunorubicin: a report from the Childrens Cancer Study Group. An escalating-dose trial of idarubicin, used weekly for 3 doses in combination with vincristine, prednisone, and L-asparaginase (VPLI), to reinduce remission of childhood ALL at first bone marrow relapse was conducted by the Childrens Cancer Study Group (CCSG). The maximum tolerated dose (MTD) of idarubicin, used in the manner, was determined to be 12.5 mg/m2/dose. Twelve of 16 (75%) evaluable patients in first marrow relapse of ALL treated at a dose of 10 or 12.5 mg/m2 entered a second complete remission, compared to 41 of 69 evaluable patients (59%) treated in a comparable way with daunorubicin (30 mg/m2) (VPLD). Prolonged myelosuppression was observed in both groups, but the frequency of documented bacterial sepsis and the duration of required hospitalization were greater among patients treated with idarubicin. No additional toxicity, specifically attributable to idarubicin, was observed at these doses.
| 20 |
Maximal O2 uptake of in situ dog muscle during acute hypoxemia with constant perfusion. We investigated the relationships among maximal O2 uptake (VO2max), effluent venous PO2 (PvO2), and calculated mean capillary PO2 (PCO2) in isolated dog gastrocnemius in situ as arterial PO2 (PaO2) was progressively reduced with muscle blood flow held constant. The hypothesis that VO2max is determined in part by peripheral tissue O2 diffusion predicts proportional declines in VO2max and PCO2 if the diffusing capacity of the muscle remains constant. The inspired O2 fraction was altered in each of six dogs to produce four different levels of PaO2 [22 +/- 2, 29 +/- 1, 38 +/- 1, and 79 +/- 4 (SE) Torr]. Muscle blood flow, with the circulation isolated, was held constant at 122 +/- 15 ml.100 g-1.min-1 while the muscle worked maximally (isometric twitches at 5-7 Hz) at each of the four different values of PaO2. Arterial and venous samples were taken to measure lactate, pH, PO2, PCO2, and muscle VO2. PCO2 was calculated using Fick's law of diffusion and a Bohr integration procedure. VO2max fell progressively (P less than 0.01) with decreasing PaO2. The decline in VO2max was proportional (R = 0.99) to the fall in both muscle PvO2 and calculated PCO2 while the calculated muscle diffusing capacity was not different among the four conditions. Fatigue developed more rapidly with lower PaO2, although lactate output from the muscle was not different among conditions. These results are consistent with the hypothesis that resistance to O2 diffusion in the peripheral tissue may be a principal determinant of VO2max.
| 15 |
IL-10 inhibits mitogen-induced T cell proliferation by selectively inhibiting macrophage costimulatory function. IL-10, a newly designated cytokine primarily produced by the Th2 subset of CD4+ T lymphocytes and Ly-1+ B lymphocytes, has recently been hypothesized to inhibit cytokine production by Th1 T cell clones by blocking accessory cell- (AC) dependent costimulatory function. To evaluate the effect of IL-10 on Con A-induced proliferative responses of resting murine T cells, purified T cells were cultured with different types of AC. The addition of IL-10 produced a 70 to 90% inhibition of resting T lymphocyte proliferation when purified populations of macrophages were used as AC, but had no effect on the AC function of T-depleted spleen cells, activated B cells, dendritic cells, or L cells. The inhibitory effects of IL-10 were inversely related to the concentration of mitogen and could be reversed by the addition of the neutralizing anti-IL-10 mAb, SXC1. The inhibition of macrophage AC function was not related to the induction of a suppressor cytokine as stimulation by mixtures of macrophages and limiting numbers of dendritic cells was not inhibited. The decrease in proliferative responses was primarily secondary to inhibition of IL-2 production although the failure of exogenous IL-2 to completely reconstitute the response suggested that IL-10 may also exert inhibitory effects on the induction of expression of a functional IL-2R. These results are most consistent with a model in which IL-10 inhibits the induction of expression on macrophages of a critical costimulatory molecule that may be constitutively expressed on other types of AC.
| 23 |
Coronary heart disease in the Pima Indians. Electrocardiographic findings and postmortem evidence of myocardial infarction in a population with a high prevalence of diabetes mellitus. The frequency of electrocardiographic evidence of coronary heart disease (CHD) and the rate of autopsy-proved myocardial infarction were determined in the Pima, a tribe of American Indians with a high prevalence of diabetes mellitus. The electrocardiograms of 701 Pimas, aged 40 years and over (85 per cent of the adult reservation population, 45 per cent of whom had diabetes) were read according to the Minnesota Code, and 120 postmortem examinations were reviewed for evidence of myocardial infarction. The frequency of CHD as evidenced by major Q-wave changes in the Pima (1.6/100) was about one-half that found in Tecumseh, Michigan (p less than 0.10). The relatively low rate of myocardial infarction at autopsy (15 per cent of males and 8 per cent of females aged 40 years and over) was consistent with the low prevalence of Q-wave changes. The subjects with diabetes had a higher rate of CHD than nondiabetics, both electrocardiographically and at postmortem examination, although the differences were not statistically significant. The low prevalence of CHD in the living Pima and the low rate of infarction at autopsy indicate that this tribe has a low frequency of CHD despite the extraordinarily high prevalence of diabetes mellitus.
| 19 |
The spine in osteogenesis imperfecta. A high incidence of spinal curvature, approaching 80 per cent in patients more than twelve years old, was found in a large series of patients with osteogenesis imperfecta. Curves showed early progression and a predictable pattern. In the age range between one and five years the incidence of scoliosis was 26 per cent; thereafter, it rose precipitously. The degree of curvature was greater in the older children. The Milwaukee brace was ineffective in the treatment of the scoliosis and the complications of its use were detrimental. In several patients it deformed the rib cage. It had little or no effect on the progression of the curve. The incidence and degree of curvature was related to the type of bone present. Patients with chest deformities and those who were not ambulatory seemed to have a predilection for scoliosis.
| 10 |
The clinical and health status of patients with recent-onset rheumatoid arthritis. This study was designed to document the clinical and health status of patients with recent-onset rheumatoid arthritis (RA). Three groups were studied: 108 patients who had had RA for greater than 1 year (established RA group), 313 patients who had had RA for less than or equal to 1 year (recent-onset RA group), and 188 healthy friend of the patients with recent-onset RA (no RA group). Clinical status was measured using tender joint count, erythrocyte sedimentation rate, and overall physician assessment. Health status was measured using the physical, psychological, pain, and arthritis impact scores of the Arthritis Impact Measurement Scales. Scores on all clinical and health status measures indicated substantial disease effects in the group with recent-onset RA. For most of these measures, effect size analysis indicated that clinical and health status impacts in the recent-onset RA group were similar in magnitude to those found in the groups with more established disease, with scores in both groups being substantially different from those found in the no RA group. These results document the magnitude of the clinical and health status impacts in recent-onset RA. They lend support to recent arguments advocating aggressive therapy earlier in the course of this frequently disabling disease.
| 15 |
Gas embolism death after laparoscopy delayed by "trapping" in portal circulation. A young woman died suddenly about 1 hour after instillation of CO2 for diagnostic larparoscopy. Post-mortem x-rays revealed large volumes of gas in the portal system, the heart, and the brain. In addition, autopsy revealed gas bubbles in the coronary arteries, pulmonary hemorrhage and edema, and a probe-patent foramen ovale. We postulated the "trapping" of gas in the portal circulation and affirmed this by experiments in 6 dogs. We further postulate the delayed and intermittent release of this gas and of platelet aggregates into the systemic circulation would occur in volumes which would be insufficient to produce hemodynamic signs yet sufficient to produce serious pulmonary insult.
| 16 |
Comparative analysis of prosthetic heart valve replacement on the basis of 300 cases. 1. The 224 patients have been followed-up for postoperative intervals of 1 to 8 years after operation, and the average duration of the follow-up has been 4 years. 2. Six types of heart valve prostheses have been utilized and evaluated with the longest (9 years) period of follow-up (a Starr-Edwards prothesis) and the shortest a Björk-Shiley valve. The best clinical hemodynamic characteristics, no thromboembolic complications were observed with the Lillehei-Kaster valve. Evaluation of longterm wear and thrombosis require further follow-up studies. 3. All patients, but 21, improved in functional capacity and are NYHA class I and II. Most of the patients had heart failure at the time of operation. These patients would have had a life expectancy of about two years from the onset of symptoms. Seventy two patients with heart failure as a prime symptom have thus outlived their anticipated life expectancy. 4. Systemic embolization was the most common postoperative complication in spite of the anticoagulant therapy.
| 10 |
Some characteristics of cytosol binding protein for 1alpha,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol in rat intestinal mucosa. Cytosol binding protein for 1alpha,25-(OH)2D3 and 25-OHD3 was demonstrated in rat intestinal mucosa using sucrose density gradient ultracentrifugation analysis, Sephadex G-200 column chromatography and polyacrylamide disc gel electrophoresis. The binding protein has a sedimentation constant of 5-6S, a molecular weight of 100,000-120,000 daltons and a mobility in electrophoresis of Rf 0.42. Further analysis of binding behavior by DEAE-cellulose filter assays revealed that the bindig protein had a higher affinity for 25-OHD3 than for 1alpha,25-(OH)2D3, and that 1alpha,25-(OH)2D3 competed with 25-OHD3 for the same binding site on the protein. The apparent dissociation constant for 1alpha,25-(OH)2D3 and 25-OHD3 was 9.2 X 10(-9) M and 1.5 X 10(-9) M, respectively. The binding capacity was 3.1 pmoles/mg protein for both 1alpha,25-(OH)2D3 and 25-OHD3. The order of binding affinity was 25-OHD3 greater than 1alpha,25-(OH)2D3 greater than D3 = 1alpha-OHD3.
| 16 |
Sex differences in the relationship between strength, endurance and limb morphology. Studies were carried out to examine methods of measuring leg densities and to learn whether physical activity affects the composition of the leg. Sixty five female college students were tested to determine the center of mass of the leg and then the leg weight was determined using a single or double scale method. The center of mass was found to fall 43% of the distance distal from the trochanter. This was below the upper patella landmark used in the single scale method. It was indicated that the more dense the leg, the higher the center of mass. A second study measured the changes in leg densities and size following a five week training period. Seven males and seven females used a strength training apparatus. The results showed strength and girth changes occurred with females reducing the girth and both males and females increasing strength. The habituation to exercise may have played a part in the changes. Strength increases change much faster than size or weight. Females changed strength at a faster rate than males and subjects exercising very little had similar leg compositions when compared to heavy exercisers.
| 11 |
Fibrin coating of bladder tumor cells (T24) is not protective against LAK cell cytotoxicity. Certain evidence indicates that tumor cells in the circulation may be enshrouded with a coat of fibrin. It has been suggested that this fibrin coat protects tumor cells from attack by the immune system. This study compared the interaction of lymphokine activated killer (LAK) cells with tumor cells alone and with fibrin coating. LAK cell killing of cultured human bladder tumor cells (T24) was measured by a 4-hour chromium release assay. Tumor cells (3 x 10(6] were incubated with Na51CrO4 for 2 hours at 37 degrees C and 5% CO2 in serum-free medium. After washing, one half of the cells were coated with fibrin by exposure to recalcified platelet-poor plasma. Fibrin coating was confirmed by immunofluorescence with anti-human-fibrinogen-fluorescein-conjugated antibodies. LAK cells were prepared from peripheral blood lymphocytes by incubation with interleukin-2 at a concentration of 1000 units of interleukin-2/1 ml serum-free medium/1 million cells for 5 days at 37 degrees C, 5% CO2. Five thousand tumor cells with or without fibrin were incubated with varying concentrations of either LAK or peripheral blood lymphocytes (10,000 to 100,000 cells). After 4 hours the supernatants were harvested and counted in a gamma counter for 1 minute. Over a range of effector-to-target cell ratios of 10:1 to 100:1 (LAK to T24), no difference was seen in percentage of specific lysis for T24 alone versus fibrin-coated T24 cells. At a ratio of 100:1 (LAK to T24), percentage of specific lysis was 83.3% versus 87.7% for uncoated and coated T24 cells, respectively. This suggests that fibrin coating of tumor cells is insufficient to provide protection from LAK cell killing.
| 12 |
Binaural hearing spectacles with "no mould" by acoustic trauma. Patients with selective hearing loss in the trebles, as commonly seen in acoustic trauma, often have a considerable hearing handicap. They seldom benefit from the usual hearing aids with closed ear moulds. When Ewertsen (1970) and Cortois (1972) reported their experiences with binaural fitting of hearing spectacles, using a free plastic tube in the ear canal ("no mould"), we at the Hearing Centre in Namsos began to fit such hearing aids to 33 patients with acoustic traumas. All of them were followed-up in February--March 1978. The results have been evaluated on the basis of answers from the patients entered on questionnaires, and speech audiometry in open field, monosyllable, with 60 dB wide-band background noise. 27 patients (80%) stated that they were greatly satisfied, and 7 (20%) well satisfied. The average daily use was 4 1/2 hrs. All of the patients emphasized the great benefit obtained with the hearing aid at conferences, meetings, social occasions, etc. The average hearing gain was 13 dB. Among those who had discrimination loss there was an average gain of 30% .
| 11 |
Mechanism of opioid-induced atrial natriuretic peptide release in conscious rats. To examine the role of atrial stretch and vasopressin in opiate-induced atrial natriuretic peptide (ANP) release, we studied the effects of a mu receptor agonist fentanyl on plasma immunoreactive ANP (IR-ANP) and hemodynamics (mean arterial pressure, heart rate and right atrial pressure) in the conscious, chronically cannulated Wistar, Long-Evans (LE) and vasopressin-deficient Brattleboro (DI) rats. Infusion of fentanyl (3 and 10 micrograms/kg i.v.) produced an immediate decrease in heart rate in conscious Wistar rats, whereas mean arterial pressure did not change significantly. Heart rate returned to control levels within 2 min of the injection, except after the largest dose of fentanyl when heart rate remained decreased for 5 min. Administration of 10 micrograms/kg of fentanyl caused a marked increase in right atrial pressure (3.9 +/- 0.3 mm Hg, n = 9, P less than .001) associated with 3.5-fold increase in the plasma IR-ANP concentration (168 +/- 17 pg/ml vs. 567 +/- 116 pg/ml, n = 9, P less than .01). In contrast, right atrial pressure decreased by 0.8 +/- 0.3 mm Hg (P less than .05) in response to infusion of 3 micrograms/kg of fentanyl with a slight increase (34%) in plasma IR-ANP. One microgram per kilogram i.v. of fentanyl had no effect on hemodynamic variables and plasma IR-ANP levels. Infusion of V1 antagonist (5 micrograms/kg/min for 25 min) did not affect basal or fentanyl-stimulated changes in hemodynamics or plasma IR-ANP concentration in Wistar rats. Infusion of fentanyl (3 and 10 micrograms/kg) in the LE and DI rats produced similar short-lasting heart rate reductions as seen in Wistar rats. Furthermore, injection of 10 micrograms/kg of fentanyl decreased blood pressure and increased plasma IR-ANP and right atrial pressure in both strains. The analysis of changes in plasma IR-ANP and right atrial pressure in response to fentanyl showed that for a given increase in right atrial pressure, a smaller amount of IR-ANP was released in the DI than in the LE rats. These results demonstrate that at higher fentanyl doses, the increased ANP release is mediated primarily by elevation of right atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
| 15 |
A dominant selectable marker that is meiotically stable in Neurospora crassa: the amdS gene of Aspergillus nidulans. When Neurospora crassa is transformed using a Neurospora gene as the selectable marker, the vegetatively stable transformants obtained cannot be used successfully in a cross because the selectable marker will be inactivated by the process of RIP (repeat-induced point mutation). Introduction of the acetamidase-encoding gene amdS of Aspergillus nidulans into N. crassa by transformation yielded transformants that would grow in minimal medium containing acetamide as a sole nitrogen source. In mitotically stable transformants containing a single copy of the amdS gene, the capacity to utilize acetamide as a sole nitrogen source was maintained in the progeny of a sexual cross. Therefore, the A. nidulans amdS gene is an appropriate dominant selectable marker for use in transformation analyses with N. crassa in which sexual crosses will be subsequently performed.
| 21 |
Stereoselective determination of R(-)- and S(+)-MK-571, a leukotriene D4 antagonist, in human plasma by chiral high-performance liquid chromatography. A stereoselective high-performance liquid chromatographic method that utilizes fluorescence detection was developed for the selective and sensitive quantification of R(-)- and S(+)-enantiomers of MK-571 (1), a potent and specific leukotriene D4 antagonist, in human plasma. Racemic 1 was isolated from the acidified plasma using solid-phase extraction and the resulting residue was successfully reacted with isobutyl chloroformate and R(+)-1-(1-naphthyl)ethylamine in triethylamine-acetonitrile medium to form the diastereomer of each enantiomer. A structural analogue of 1 was used as internal standard. The derivatized sample was dissolved in 1,1,2-trichlorotrifluoroethane and an aliquot was chromatographed on a (R)-urea chiral column using a mobile phase containing 89% triethylamine-pentane (3:1000, v/v), 10% 2-propanol, and 1% acetonitrile at a flow-rate of 1.5 ml/min. The fluorescence response (excitation wavelength, 350 nm; emission wavelength, 410 nm) was linear (r2 greater than 0.999) for concentrations of enantiomers of 1 from 0.05 micrograms/ml, the lowest quantitation limit, up to 2.5 micrograms/ml. Intra-day coefficients of variation at 0.05 microgram/ml were 2.4% for the R(-)-isomer and 2.0% for S(+)-isomer. The corresponding inter-day coefficients of variation for R(-)- and S(+)-1 were 2.6 and 3.6%, respectively. The utility of the methodology was established by analysis of plasma samples from male volunteers receiving single intravenous and oral doses of racemic 1.
| 20 |
Comparison of the acylation of sn-glycerol 3-phosphate and membrane-bound lipid in the microsomal fraction from rabbit brain throughout maturation. 1. Age-related changes in the specific activity of palmitoyl-CoA synthetase, sn-glycerol 3-phosphate acyltransferase (EC 2.3.1.15) and the esterification of [3H]palmitate into endogenous lipid in the microsomal fraction from rabbit brain have been determined throughout development. 2. The increased specific activity of sn-glycerol 3-phosphate acyltransferase at the onset of myelination (rising in parallel with other lipogenic enzymes) is consistent with a direct role of the acyltransferase in promoting the accumulation of cerebral lipid. In adult brain microsomes, although the specific activity was low, the total activity was only 20% lower than during active myelination. 3. Palmitoyl-CoA, synthesized by the palmitoyl-CoA synthetase in the microsomal membrane, was the preferred substrate for the esterification of sn-glycerol 3-phosphate. There was no evidence for a pool of palmitoyl-CoA formed from palmitate. 4. The esterification of [3H]palmitate into membrane-bound lipid remained high throughout development and may be part of an acyl-exchange cycle via lysophospholipids. [3H]palmitate was incorporated into both neutral lipids and phospholipids, while phosphatidic acid was the major product of sn-[1(3)-3H]-glycerol-3-phosphate esterification. 5. The microsomal fraction contained a pool of unesterified fatty acid, which was activated and esterified into sn-glycerol 3-phosphate.
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Altitude and allergy to house-dust mites. A paradigm of the influence of environmental exposure on allergic sensitization. To further investigate the possibility of a cause and effect relationship between exposure to house-dust mite (HDM) allergens and respiratory disease associated with dust mite sensitivity, we compared schoolchildren living in the Alps, where exposure to HDM is low, with those living at sea level, where it is high. The study included 933 schoolchildren from the fourth and fifth grades. The protocol included the standardized 1978 American Thoracic Society (ATS) questionnaire for children, skin testing using common aero-allergens and controls, and antigenic measurements of dust samples from mattresses (Group I antigen). The prevalence of asthma with positive skin test to HDM and the overall prevalence of positive skin test to HDM were significantly lower in mountain schoolchildren. The mean geometric HDM antigenic level in mattresses was much lower in the Alps (0.36 micrograms/g dust) than at sea level (15.8 micrograms/g dust). In contrast, the prevalence of hay fever and positive skin test to grass pollens as well as the overall prevalence of positive skin tests to grass pollens were significantly higher in the Alps. These data illustrate a striking relationship between exposure to environmental allergens and atopic sensitization.
| 16 |
Molecules in mammalian brain that interact with the colchicine site on tubulin. Colchicine, a plant alkaloid, is a potent inhibitor of mitosis and other physiological processes that involve microtubules. These effects are mediated by the specific binding of colchicine to a high-affinity receptor site on tubulin, the major protein of microtubules. It seemed possible that the colchicine site on tubulin might also be the receptor for endogenous cellular molecules. We now report that mammalian brain does, in fact, contain a class of molecules that interact with the colchicine site on tubulin. Tubulin-agarose affinity chromatography has been used to isolate factors from soluble extracts of bovine brain that interact with tubulin. Certain of these factors inhibit the binding of [3H]colchicine to tubulin. Using the inhibition of colchicine binding as an assay, I have partially resolved at least two species. One is a protein and another may be a heat-stable peptide. In parallel to the action of colchicine, the smaller species inhibits the assembly of isolated microtubules. This class of molecules may include the endogenous ligands for which the colchicine site on tubulin is the receptor. They may have a significant role in the regulation of cellular microtubule function and assembly.
| 14 |
Iopanoic acid as an adjunct to carbimazole in the management of hyperthyroidism. The thiourea drugs take a few weeks to control the symptoms of hyperthyroidism whilst iodine containing radiographic contrast agents (iopanoic acid and sodium ipodate) have a more rapid effect. There is no report on the use of iopanoic acid administered in conjunction with carbimazole, so we evaluated the efficacy of this combination in the early medical management of patients with hyperthyroidism. Thirty hyperthyroid patients diagnosed by clinical and biochemical criteria were randomized into two treatment groups. Group A (n = 16) received iopanoic acid (500 mg orally twice a day for the first 3 weeks) and carbimazole (30 mg orally in three divided doses) while group B (n = 14) received carbimazole alone. Clinical examination and estimation of serum total T3, total T4 and TSH were done by radioimmunoassay at the start of therapy, weekly for 4 weeks and then at 6, 8 and 12 weeks. In the initial 3 weeks, iopanoic acid induced a significantly greater fall in mean serum total T3 levels (Z = 2.298, p < 0.02) and a slower fall in mean serum total T4 (Z = 2.396, p < 0.05) in group A patients compared to those in group B. This was accompanied by earlier clinical improvement in group A patients. The mean serum total T3 and T4 values rose to higher levels in group A at 4 weeks, one week after discontinuation of iopanoic acid. At the end of 12 weeks, however, there was no significant difference in the mean serum total T3 and T4 levels between the two groups (p > 0.05). Biochemical euthyroidism (i.e. total T3 < 3 nmol/L and total T4 < 170 nmol/L) was achieved later in group A patients than in group B (10.4 +/- 5.0 weeks v. 3.6 +/- 1.2 weeks, p < 0.0001). Iopanoic acid given together with carbimazole induces rapid clinical improvement in hyperthyroid patients than carbimazole alone. However, the delayed achievement of euthyroidism may preclude its routine use in the management of patients with hyperthyroidism except in those with thyrotoxic emergencies.
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Synergistic killing of Escherichia coli by near-UV radiation and hydrogen peroxide: distinction between recA-repairable and recA-nonrepairable damage. Wild-type cells and six DNA repair-deficient mutants (lexA, recA, recB, recA, recB, polA1, and uvrA) of Escherichia coli K-12 were treated with near-ultraviolet radiation plus hydrogen peroxide (H2O2). At low H2O2 concentrations (6 X 10(-6) to 6 X 10(-4) M), synergistic killing occurred in all strains except those containing a mutation in recA. This RecA-repairable damage was absent from stationary-phase cells but increased in logarithmic cells as a function of growth rate. At higher H2O2 concentrations (above 6 X 10(-4) M) plus near-ultraviolet radiation, all strains, including those with a mutation in recA, were synergistically killed; thus, at high H2O2 concentrations, the damage was not RecA repairable.
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A factor analytic study of daydreaming, imaginal process, and temperament: a replication on an adult male life-span sample. One hundred and seventy males aged 24 to 91 years were measured on daydreaming and related mental activity using the imaginal processes inventory and on temperament using the Guilford-Zimmerman Temperament Survey to determine if earlier results relating temperament to daydreaming in college populations were generalizable to the adult life-span. The earlier derived factor of "Neurotic-Anxious Absorption in Daydreaming" was found in this sample and had a negative correlation with chronological age, suggesting a decrease with increasing age. Other earlier derived factors on "Personal Acceptance-Utilization of Daydreaming," "Masculinity-Femininity," "Thinking Introversion," and "Social Extroversion" were also found in this sample, but were not related to age.
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Indications and guidelines for mammographic examinations. The value of mammography in evaluating the asymptomatic patient has been clearly demonstrated by the HIP program, as well as the National Cancer Institute's breast demonstration projects. A one-third reduction in mortality from breast cancer in mammographically screened women has been substantiated. Nonetheless, questions concerning the long-term effects of repeated radiation exposure associated with mammography have been raised, and for this reason judicious selection of women is urged. In general, women who are asymptomatic or at high risk for breast carcinoma should be evaluated with a planned regimen. Mammographic guidelines and recommendations for attaining the greatest benefit at the lowest possible risk are suggested.
| 16 |
Streptococcal pharyngitis in children. A comparison of four treatment schedules with intramuscular penicillin G benzathine. Four hundred children with streptococcal pharyngitis were treated randomly with single injections in groups of 100 each (1) with 600,000 units of penicillin G benzathine, (2) 1.2 million units of penicillin G benzathine, (3) 600,000 units of penicillin G benzathine and 600,000 units of penicillin G procaine, or (4) 900,000 units of penicillin G benzathine and 300,000 units of penicillin G procaine. Clinical response and severity of local reaction were judged in a double-blind manner at 24, 48, and 72 hours; throat cultures were taken then, and at 10, 21, and 42 days. Although the clinical response to 900,000 units of penicillin G benzathine and 300,000 units of penicillin G procaine was equal to 1.2 million units of penicillin G benzathine, the former cleared the streptococci more quickly, greatly reduced the incidence and severity of local reactions, and offered optimal therapy for streptococcal pharyngitis in the pediatric age group.
| 21 |
Implantable cardioverter defibrillator: data storage and retrieval with Patientlog. A pacemaker management system (Patientlog), implemented on a IBM personal computer (AT), was adapted for the control and the administrative management of patients with an implantable cardioverter defibrillator (ICD). Several parameters used for pacemakers were also suitable for ICDs, while some fields were defined within the available frame of the database, to cope with the specific technical information of ICDs. "Intervention-cards" display diagnostic (threshold) as well as complex surgical information (approach, lead systems, etc.). "Follow-up-cards" present charge time and the number of shocks in such a way that decision making is very easy. Fourteen patients were followed with a total of 21 interventions, six different types of devices, and more than 150 follow-ups. A correct control of ICD functions is easy. The system is adapted for programmable ICDs. Updated reports containing necessary information are generated immediately after each procedure or follow-up.
| 14 |
[Surgical treatment of left ventricular right atrial fistula (II-type): report of 12 cases]. 12 cases of left ventricular right atrial fistula (II-type) were identified and repaired by open heart surgery. Our date showed that defects of the septal leaflet of tricuspital valve can be divided into three groups: multiple-opening, single-opening and split defects. When there were VSD and fistula at the same position, the VSD was not repaired completely if the opening of tricuspital septal leaflet was mistaken as the VSD itself. It is important to expose the edge of the VSD completely by cutting tricuspital septal leaflet when repairing the VSD. The cutting septal leaflet can be sutured after closure of the VSD.
| 13 |
[Microbial contamination of twenty drugs of plant origin]. Twenty drugs of plant origin were analysed in order to determine the microbial contamination level. A light homogenizing method was used to avoid an increase in the antimicrobial capacity of certain drugs, which would falsify the analytical results. The total viable aerobic count (TVC) varied from 10(1) to 10(7) CFU/g and in 11 samples out of 21 was equal to or higher than 10(5) CFU/g. The number of fungi varied from one drug to another, but was generally lower than the aerobic TVC to the power of 10. No cases containing Aspergillus flavus were found. The total viable anaerobic count consisted mainly of facultative anaerobic germs. Aerobic spores and facultative anaerobic bacteria were abundant. They often represented more than 50% of the aerobic TVC and among them, Bacillus cereus was found. Concerning specified micro-organisms, Escherichia coli was found 3 times, Staphylococcus aureus 2 times and Pseudomonas (not aeruginosa) a few times. Salmonella was never found. The Enterobacteriaceae, on the other hand, were often found and in some cases their number can be greater than 10(4) CFU/g. The typed bacteria corresponded to Enterobacter spp. Some drug samples in bags were analysed. The level of contamination was identical to that found in the bulk drugs. The analysis in parallel of a black tea sample showed an aerobic TVC of 4.10(3) CFU/g. Specified micro-organisms were not found in the infusions. In comparison with non-boiled drugs, the survivors can represent up to 30% of the aerobic TVC.
| 10 |
Design of a novel system for the construction of vectors for Agrobacterium-mediated plant transformation. The loxP-Cre site-specific recombination system of phage P1 was used to develop a novel strategy to construct cointegrate vectors for Agrobacterium-mediated plant transformation. A pTi disarmed helper plasmid (pAL1166) was constructed by replacing the oncogenic T-DNA by a loxP sequence and a spectinomycin resistance marker in the octopine-type pTiB6 plasmid. The cre gene was cloned into an unstable incP plasmid. A third plasmid, which did not replicate in Agrobacterium and contained another loxP sequence together with a kanamycin resistance marker, was used to test the system. Electroporation of this third plasmid into an Agrobacterium strain harbouring both pAL1166 and the Cre-encoding plasmid resulted in kanamycin-resistant cells containing a cointegrate between pAL1166 and the incoming plasmid. Cointegration occurred by Cre-mediated recombination at the loxP sites, and the cointegrate was stabilized in the Agrobacterium cells by the loss of the Cre-encoding plasmid shortly after the recombination event had taken place.
| 16 |
Molecular determinants of channel function. The 40 years since the seminal papers of Hodgkin and Huxley appeared have been extraordinarily productive in terms of understanding the molecular basis for electrical activity. The Hodgkin-Huxley proposal that electrical excitability should be understood in terms of voltage-dependent changes in discrete sites has been resoundingly verified. Indeed, the Hodgkin-Huxley framework is remarkable in that its essential elements have remained largely intact as molecular understanding has advanced. This robustness is, at least in part, a result of the fact that Hodgkin and Huxley developed a mathematical model, based on simple physical arguments, that was sufficiently comprehensive to describe the kinetics of the voltage-clamped currents and yet simple enough to be predictive. The predictive features were demonstrated early by the reconstruction of both space-clamped and propagated action potentials on a desk-top calculator (293) and, later, when the sites of Hodgkin and Huxley developed into being well-characterized molecular structures. Voltage- and ligand-dependent ion-selective channels are now the established framework within which cellular electrophysiology is being pursued. Moreover, electrophysiological measurements of membrane and single-channel currents have become essential tools to examine molecular questions pertaining to channel structure and activity. The last 10 years have witnessed spectacular activity, which has resulted from two developments, the giga-seal patch clamp (249) and the elucidation of primary sequences of a number of channel-forming proteins (494), along with the first outlines of their low-resolution three-dimensional structures (651). The stage is now set for 1) applying a variety of convergent techniques to decipher molecular structural details at high resolution, and 2) seeking to understand the complex dynamic functions, gating, and ion selectivity at the molecular level. The early successes are likely to be in understanding the molecular determinants of ion conductance and selectivity, initially in terms of quantitative descriptions of how a sequence modification can alter a channel's permeability characteristics. Channel gating is a far more elusive target because it involves molecular rearrangements, which are poorly understood at any level of description and which may be modified by the channel's environment. The general mechanisms of ion permeation and gating will differ among different classes of ion channels, but a molecular understanding of either phenomenon must eventually be based on an understanding of intermolecular forces, which are invariant among all channel types.(ABSTRACT TRUNCATED AT 400 WORDS)
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Total axillary lymphadenectomy in the management of breast cancer. The optimal extent of axillary dissection in patients with breast cancer remains unclear. We report 278 total axillary lymphadenectomies (levels I, II, and III and Rotter's [interpectoral] nodes) that were performed in 264 closely followed up private patients. There have been no axillary recurrences to date (mean follow-up, 50 months). If only level I and II nodes had been removed, the false-negative staging error would have been only 2.6%. However, 29 (31.5%) of 92 pathological node-positive axillae contained apical and/or Rotter's metastases. The incidence of complications was comparable with that reported for partial lymphadenectomy. Arm lymphedema developed in 6% of nonirradiated patients; postoperative radiotherapy and gross nodal disease were significant risk factors for lymphedema. Total axillary lymphadenectomy largely prevents axillary, recurrence, eliminates the small staging error inherent in partial lymphadenectomy, and has acceptable morbidity, provided radiotherapy to the regional nodal areas is avoided.
| 16 |
Weight-related behaviors and concerns of fourth-grade children. Behaviors and concerns related to weight were measured among 457 fourth-grade children attending 10 rural schools in central Iowa. A questionnaire was used to gather data on the children's concerns about being overweight, concerns that certain types or amounts of food would contribute to their being overweight, alterations in food intake to avoid being overweight, and perceptions that peers and family members were concerned about being overweight. In addition, each child's height and weight were measured. Weight-related behaviors and concerns increased with increasing weight-for-age and body mass index (BMI) and were more prevalent among girls than boys. The frequency of drinking diet soft drinks was positively correlated with weight-for-age and BMI and tended to increase with an increase in weight-related behaviors and concerns. Girls were more likely than boys to report a desire to be thinner (60.3% vs 38.4%), whereas boys were more likely than girls to want to be taller (67.2% vs 49.1%). The desire for less body fat was significantly associated with an increase in the frequency of weight-related behaviors and concerns, the frequency of drinking diet soft drinks, weight-for-age, and BMI. These findings indicate a need for interventions that combat fear of obesity and restrictive eating among growing children.
| 14 |
[Immunoglobulins and nonspecific immunity factors in leukemias]. The authors report the data on immunoglobulins G, A, M content and their relationship with other factors of natural immunity in 55 patients with acute myeloblastic leukemia and in 43 patients with chronic lymphatic leukemia. The results have evidenced the impaired synthesis of immunoglobulins in acute in acute leukemia and the reduction of IgA and IgM already in the initial stage of chronic lymphatic leukemia. A correlation between mean values of immunoglobulins content and other factors of immunological resistance allowed a statement to be made that in the absence of impaired immunoglobulins synthesis there is a distinct coincidence of immunoglobulin content curves and titres of agglutinating and bacteriolytic antibodies.
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Arsenic and cancer: the still unanswered question. For some 2,500 years, arsenic was considered an important element of pharmacopeias and was praised for its medicinal qualities. However, an incidental link with cancer was suggested during the nineteenth century, and since that time a controversy has ensued with regard to the compound's tumorigenicity. Several epidemiological surveys, for example, have suggested that arsenic induces lung, liver, or skin cancer in humans. On the other hand, all experimental attempts to reproduce such neoplasms in laboratory animals have consistently failed, thereby denying support to the human data. Recently arsenic was reported to be mutagenic. However, because of the inconsistency of most mutagenesis findings at present, this also cannot be regarded as supporting evidence. Furthermore, a recent trend has been to consider arsenic as beneficial in cancer prevention and in maintaining the health of farm animals, and, perhaps, humans. A critical review of epidemiological and experimental data from the literature has been made in an attempt to present an objective picture of this controversial and sensitive question and to encourage further research, which may ultimately determine whether arsenic deserves its execrable reputation.
| 17 |
A personal computer network system for equitable allocation of cadaver organs. We developed a personal computer network system for the equitable allocation of cadaveric organs. This network consists of a host computer (IBM PS55 model 5570 T) and various kinds of personal computers manufactured by many different computer makers in Japan. The merits of our personal computer network include lower cost and an easy access to the host computer from all the centres participating in this network while using their own favourite personal computers. Among the programs made for allocating cadaveric organs, we present in this paper the program for livers. This program was developed with a modified version of the logic developed by Starzl et al. The grade modification for the United Network for Organ Sharing (UNOS) in the United States was used as the basis for classification of medical urgency. Our program weighed the factors of medical urgency, compatibility of blood group and waiting time. Distance factors were omitted because of the smaller area of the network compared to that of UNOS. This computer network would be linked to other computer networks in creating a national organ procurement and transplant network in Japan, in order to help them to catch up with other advanced transplant countries. Such an equal and objective computer system should allow organ transplantation to become more widely accepted.
| 14 |
Translocations of acrocentric chromosomes and their implications in the evolution of sheep (Ovis). Cytogenetic evidence suggests that the caprids (sheep and goats) evolved from a common ancestor with a 2n=60 karyotype. Although goats (Capra) retained the primitive 2n=60 karyotype, sheep (Ovis) underwent a sequential reduction in the number of chromosomes by means of acrocentric translocation. The formation of the first metacentric autosome (M1) occurred in the aoudad (Ammotragus) and urial (O. vignei), resulting in a 2n=58 karyotype. The G-bands are homologous, which implies both genotypes arose from a common ancestor, possibly a rupicaprid. Based on G-bands, acrocentric chromosomes 1 and 7 of the 2n=60 karyotype formed the M1. The X chromosome, which is the second longest acrocentric in the 2n=60 karyotype, became the longest acrocentric in Ammotragus and Ovis (2n=58). The second pair of metacentrics to evolve, which is ranked in the M3 position of the 2n=54 karotype, resulted from the translocations of acrocentric chromosomes 4 and 14 or 15 in the 2n=60 karyotype. The M2 was the third pair of metacentrics to be formed and resulted from the translocations of acrocentric chromosomes 3 and 12 or 13 in the 2n=60 karyotype. The G-bands of all 2n=54 karyotypes are homologous, which indicates origin from a common ancestor. Evidence is presented that suggests a prezygotic selection is bringing about a reduction in diploid chromosome numbers. The possible roles of fission and fusion in the karyotypic evolution of Ovis are discussed.
| 15 |
Increased luminal release of hyaluronan in uninvolved jejunum in active Crohn's disease but not in inactive disease or in relatives. Recently obtained data suggest that there is a subclinic inflammatory activity in the apparently uninvolved intestinal mucosa in Crohn's disease (CD). As CD is characterized by an activation of connective tissue and fibrosis, we investigated the extent to which hyaluronan (HA), an essential component of the connective tissue, was released into the lumen of an isolated jejunal segment in CD patients and in relatives. Patients with active CD of the terminal ileum (CD activity index, CDAI, > 150; n = 14), patients with CD in remission (CDAI < 150 n = 10), first-degree relatives of the CD patients (n = 21) and healthy controls (n = 43) were orally intubated with a catheter allowing occlusion and perfusion of a segment of the proximal jejunum. The jejunal fluid concentration of HA was 65 +/- 45 micrograms/l in patients with active CD in the terminal ileum, significantly higher than the value for 43 healthy controls (42 +/- 23 micrograms/l; p < 0.05), and the corresponding values for patients in remission (42 +/- 23 micrograms/l) and for first-degree relatives of the CD patients (53 +/- 52 micrograms/l), were not increased compared to the control group. To localize HA in the tissue, small bowel biopsies were taken during surgery from patients with CD and from controls and affinity stained for HA. There was an intense staining for HA in the lamina propria of the villi, both in biopsies from patients with CD and from controls, but no staining in the epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)
| 20 |
Effects of ryanodine on a myocardial membrane vesicular fraction. The effects of ryanodine on calcium transport were examined on a microsomal fraction isolated from guinea pig atrial muscle by sucrose density ultracentrifugation. The Ca+2 binding capacity of the fraction was sufficient to account for relaxation and was unaltered by the addition of 5x10(-5)M ryanodine. Exposure of the sarcoplasmic reticulum (SR) to concentrations of ryanodine which produce negative inotropy significantly reduced ATP-dependent calcium transport which was associated with a significant increase in the Ca+2 activated ATPase activity. The effect of ryanodine was to reduce the Ca/P ratio by 50%. These results suggest that the negative inotropic effect of ryanodine in guinea pig atrium is associated with the uncoupling of Ca+2 transport from ATP hydrolysis.
| 17 |
MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination. ME1a1, a 16-base-pair nuclear factor binding site residing between the c-MYC P1 and P2 transcription initiation sites, is required for P2 activity. A cDNA encoding a 477-amino acid zinc finger protein designated MAZ (MYC-associated zinc finger protein) was cloned from a HeLa lambda gt11 library by screening with a concatamerized ME1a1 binding site probe. In addition to six potential zinc fingers of the Cys2His2 type, MAZ contains an amino-terminal proline-rich domain and several polyalanine tracts. Its mRNA was present in all human tissues tested except for kidney, as a doublet of approximately 2.5 and 2.7 kilobases, along with differentially expressed minor species. MAZ bound specifically to the wild-type ME1a1 sequence but not to a ME1a1 mutant that also failed to yield P2 activity. When expressed as a fusion protein in a pMAL-c vector, MAZ binds with specificity to a GA box sequence (GGGAGGG) found in the c-MYC P2 promoter, to the P2 attenuator region within the gene's first exon, and to a related sequence involved in the transcriptional termination of the C2 gene. MAZ may encode a transcription factor with dual roles in transcription initiation and termination.
| 16 |
Characterization of the alpha and beta subunits of casein kinase 2 by far-UV CD spectroscopy. Although Chou-Fasman calculations of the secondary structure of recombinant casein kinase 2 subunits alpha and beta suggest they have a similar overall conformation, circular dichroism (CD) studies show that substantial differences in the conformation of the two subunits exist. In addition, comparison of the far-UV CD spectrum of reconstituted CK-2 with the spectra of the subunits indicates that conformational changes occur in the backbone region upon association. Such changes may explain the increased enzyme activity of the holoenzyme relative to that of the alpha subunit itself. In contrast, no changes in the far-UV CD spectrum of the alpha subunit are observed in the presence of casein or the synthetic decapeptide substrate RRRDDDSDDD. Furthermore, the alpha-helical structure of the alpha subunit (but not the beta subunit) can be increased in the presence of stoichiometric amounts of heparin, presumably by its binding to the polylysine stretch at amino acid positions 74-77. Heat denaturation experiments (25-90 degrees C) support the notion that heparin may provide a local protective function. A similar but much larger effect was also observed in the presence of the beta subunit only, which supports previous suggestions of a protective function for this subunit. These results indicate that the protection provided by the beta subunit and the increased enzyme activity of the holoenzyme may arise, in part, from a stabilization of the conformation of the enzyme complex and an increase in alpha-helical content.
| 19 |
Long-term treatment with anti-secretory drugs: could it affect morphology and cell kinetics of gastric mucosa? Drugs reducing gastric acid output are widely used and commonly considered free from relevant side effects. However, our knowledge on the consequences of long-term anti-secretory treatment is still lacking. Several observations both, in animal models and in man, indicate that a decreased gastric acid output may lead modifications of several features of epithelial gastric cells. These alterations can be determined by different mechanisms. The drugs can raise plasma levels of gastrin, which possibly cause a proliferative stimulus on fundic mucosa. Moreover, some drugs showed a direct effect on cell proliferation. Finally, hypochlorhydria reduces the antibacterial power of gastric juice. In this environment, bacterial flora can overgrow and synthesize also the N-nitrosocompounds. These observations suggest that prolonged treatments with powerful anti-secretory drugs should be carried out taking into account the hypothetical biological risk on gastric mucosa.
| 13 |
Anion/calcium ion ratios and proton production in some mitochondrial calcium ion uptakes. The uptake of Ca2+ by liver mitochondria, when phosphate movement is inhibited, occurs when Co2 is present and not in its absence. Uptake of Ca2+ to form CaCO3 yields 2H+/Ca2+. Heart mitochondria, when phosphate movement is inhibited, will take up Ca2+ with the exact equivalent of hydroxybutyrate, lactate or acetate. By providing a carrier for Cl- with tributyltin, a stoicheiometric uptake of Cl- with the Ca2+ takes place. The uptakes appear to occur without significant pH change; there appears to be no CO2-dependent uptake into heart mitochondria. Oxygenation of anaerobic heart mitochondria, in the presence of an inhibitor of phosphate movement and of generation of phosphate from internal ATP, does not yield significant change of external acidity in relation to the amount of O2 added. Use of Bromothymol Blue as an indicator of the distribution of a weak acid anion confirms that the transient nature of the response of the dye distribution to Ca2+ is connected with movement of endogenous phosphate. Bromothymol Blue accumulated in response to Ca2+ is discharged when entry of the Ca2+ (in the presence of mersalyl) is mediated with nigericin. It is concluded that Ca2+ uptakes will occur alternatively with the equivalent of anions or in exchange for endogenous K+ and that proton production is connected with the changes of ionization of phosphate (unless phosphate movement is inhibited) and in liver mitochondria with the hydration of CO2.
| 16 |
Uncertainty about the correlation among temporal envelopes in two comodulation tasks. The threshold of a 1250-Hz tonal signal was measured in the presence of five noise bands (each 50 Hz wide, centered at 850, 1050, 1250, 1450, and 1650 Hz) under five conditions of uncertainty about the waveform type ("correlated" or "uncorrelated"), and/or the specific waveform sample to be presented. The waveform type was correlated when the temporal envelopes of all of the noise bands were the same, and was uncorrelated when the temporal envelope of the band centered on the signal differed from the common envelope of the other bands. At the low-uncertainty end of the continuum of conditions, the same waveform type was presented throughout an entire block of trials, and, in addition, the same waveform sample was presented on the two observation intervals of a single trial (but changed across trials). At the high-uncertainty end of the continuum, both the waveform type and the waveform sample were chosen at random for every observation interval. Threshold estimates obtained from trials in which both observation intervals contained the same waveform type were not affected by uncertainty about the waveform sample within a trial, nor by uncertainty about the waveform type introduced across trials. Thus the comodulation masking release, or CMR (the difference in the thresholds obtained with the uncorrelated and correlated waveforms), calculated from these types of trials was robust across all of the uncertainty conditions. However, on those trials in which one correlated interval and one uncorrelated interval were paired, threshold estimates were influenced by a bias for listeners to choose the uncorrelated interval as the signal interval, whether or not it actually contained the signal. This bias reveals the importance of recognizing the contribution of the nonsignal interval in experiments involving masker uncertainty. Parallel results were obtained using the comodulation detection difference (CDD) task. In some conditions, marked individual differences were observed.
| 20 |
[Current status of reproduction control in France]. Fertility declined rapidly in France between 1965 and 1976, mainly because of a decrease in the number of births of parity 3 or more. This change was due to both a decline in the desire for children and to a large reduction in the number of unwanted births. The INED national survey of 1988 showed a rapid spread of medical contraceptive techniques (pill and IUD) since 1965. In the same survey, a significant proportion of women reported difficulties in conceiving: these difficulties resulted in a much longer time-interval before conception; in addition women tended to become more and more impatient in this regard.
| 14 |
A simple computer program for optimization of source loading in cervical intracavitary applicators. A computer program has been developed to aid in the brachytherapy of cancer of the cervix. Using a least-squares minimization algorithm, the program will optimize the source loading in intracavitary applicators so as to reproduce, as nearly as physical considerations allow, the dose distribution requested by the user. Applicator geometry and the relative positions of anatomical points of interest must be supplied to the program, as well as an inventory of available source strengths. Output from the computer includes the optimized source loading, time of application, and the resulting relative doses to the various user-selected points of interest.
| 17 |
Enzymes and long-term survival after first myocardial infarction. The study covers 342 patients still alive one month after the acute attack of their first myocardial infarction. Daily determinations of creatinine phosphokinase (CPK), lactic dehydrogenase (LDH) and glutamic oxaloacetic transaminase (SGOT) in serum were carried out during hospitalization, so that a maximum enzyme value could be obtained for each enzyme and patient. A follow-up examination was performed after an observation time ranging from 12 to 38 months. Having calculated the mean (x) of the maximum enzyme values, a parallel relationship was found between the maximum CPK, LDH and SGOT values and the long-term prognosis in myocardial infarction, inasmuch as patients with maximum enzyme values above or equal to the mean had a significantly higher 2-year mortality than patients with values below x. In order to detect any slight difference between the three enzymes with reference to the long-term prognosis, the material was divided into four groups: one with peak values less than x-x/2 (lowest), one with values from x-x/2 to x exclusive (next lowest), one with values from x to x+x/2 exclusive (next highest) and a group with peak elevations greater than or equal to x+x/2 (highest). A tendency to increasing mortality from the next lowest to the highest maximum enzyme values was found. On the other hand, patients with the lowest peak values had a tendency to higher mortality than patients in the next lowest group. This characteristic was observed with regard to both CPK and LDH and to some extent to SGOT.
| 17 |
Two members of the mouse mdr gene family confer multidrug resistance with overlapping but distinct drug specificities. We report the cloning and functional analysis of a complete clone for the third member of the mouse mdr gene family, mdr3. Nucleotide and predicted amino acid sequence analyses showed that the three mouse mdr genes encode highly homologous membrane glycoproteins, which share the same length (1,276 residues), the same predicted functional domains, and overall structural arrangement. Regions of divergence among the three proteins are concentrated in discrete segments of the predicted polypeptides. Sequence comparison indicated that the three mouse mdr genes were created from a common ancestor by two independent gene duplication events, the most recent one producing mdr1 and mdr3. When transfected and overexpressed in otherwise drug-sensitive cells, the mdr3 gene, like mdr1 and unlike mdr2, conferred multidrug resistance to these cells. In independently derived transfected cell clones expressing similar amounts of either MDR1 or MDR3 protein, the drug resistance profile conferred by mdr3 was distinct from that conferred by mdr1. Cells transfected with and expressing MDR1 showed a marked 7- to 10-fold preferential resistance to colchicine and Adriamycin compared with cells expressing equivalent amounts of MDR3. Conversely, cells transfected with and expressing MDR3 showed a two- to threefold preferential resistance to actinomycin D over their cellular counterpart expressing MDR1. These results suggest that MDR1 and MDR3 are membrane-associated efflux pumps which, in multidrug-resistant cells and perhaps normal tissues, have overlapping but distinct substrate specificities.
| 17 |
Sesamin is a potent and specific inhibitor of delta 5 desaturase in polyunsaturated fatty acid biosynthesis. Incubation with sesame oil increases the mycelial dihomo-gamma-linolenic acid content of an arachidonic acid-producing fungus, Mortierella alpina, but decreases its arachidonic acid content [Shimizu, S., K. Akimoto, H. Kawashima, Y. Shinmen and H. Yamada (1989) J. Am. Oil Chem. Soc. 66, 237-241]. The factor causing these effects was isolated and identified to be (+)-sesamin. The results obtained in experiments with both a cell-free extract of the fungus and with rat liver microsomes demonstrated that (+)-sesamin specifically inhibits delta 5 desaturase at low concentrations, but does not inhibit delta 6, delta 9 and delta 12 desaturases. Kinetic analysis showed that (+)-sesamin is a noncompetitive inhibitor (Ki for rat liver delta 5 desaturase, 155 microM). (+)-Sesamolin, (+)-sesaminol and (+)-episesamin also inhibited only delta 5 desaturases of the fungus and liver. These results demonstrate that (+)-sesamin and related lignan compounds present in sesame seeds or its oil are specific inhibitors of delta 5 desaturase in polyunsaturated fatty acid biosynthesis in both microorganisms and animals.
| 14 |
Specific binding of human fibrinogen fragment D to Aspergillus fumigatus conidia. The interaction of purified human fibrinogen with Aspergillus fumigatus conidia was investigated by immunofluorescence and electron microscopy and binding assays with radiolabeled proteins. We described the localization of the binding sites on the A. fumigatus conidia and on the fibrinogen molecule and determined the binding characteristics. Immunofluorescence revealed that the fixation of purified fibrinogen was selectively associated with conidia and suggested a role for the D domains of the fibrinogen molecule. Binding assays performed with 125I-radiolabeled proteins confirmed that binding sites were located specifically in the D domains. No reaction could be detected with fragment E. The binding of 125I-fragment D to conidia was time dependent, saturable, and specific. Scatchard analysis of the data revealed an average of 1,200 binding sites per conidium, and an apparent dissociation constant (Kd) of 2.2 x 10(-9) M was estimated. Pretreatment of the cells with proteolytic enzymes or heat abolished binding, demonstrating the protein nature of the binding sites. Ultrastructural localization of the fungal receptors was determined by transmission electron microscopy. Labeling appeared to be associated with the outer electron-dense layer of the conidial wall and progressively decreased during the germination process. Labeling of thin sections with fragment D and an antifibrinogen immune serum revealed that binding sites also lay in the inner part of the wall and in vacuoles. These results indicate the presence at the conidial surface of specific receptors for fibrinogen which could act as mediators of conidial adherence to host tissues.
| 17 |
Adults with congenital complete heart block: 25-year follow-up. Complete congenital heart block has been recognized since 1846, yet the prognosis of the disease has not been determined by comprehensive long-term studies. We reviewed 14 cases of complete congenital heart block at The Cleveland Clinic Foundation. The patients were followed for a mean of 25 years (range, 20 to 32 years). Ten patients had structurally normal hearts, and 4 had varying degrees of congenital heart disease. The patients were evaluated with regard to symptoms, and indications for permanent pacemaker implantation were studied. Seven patients received permanent pacemakers. Ages at the time of pacemaker implantation ranged from 15 to 38 years (mean, 25 years). Overall, the patients in our study tended to lead normal productive lives. The main indications for pacemaker implantation were symptoms alone. Guidelines for prophylactic pacemaker implantation have yet to be determined, and the development of these guidelines is difficult due to small numbers of patients at isolated centers. A large international study is needed to set these guidelines.
| 11 |
[Role of aminopeptidases in enkephalin catabolism: comparative study of the regional distribution of aminopeptidases and enkephalinase A in the rat brain]. In order to elucidate the role of aminopeptidases in enkephalin catabolism in rat brain, the local distribution of two types of cerebral cellular membrane aminopeptidases (puromycin-sensitive and puromycin-insensitive ones) and of the enkephalin system marker, enkephalinase A, was studied. It was found that the distribution patterns of the former enzymes differ essentially from that of enkephalinase A. Study of coupling between the enzymatic activities in different regions of rat brain revealed a strong correlation between the activities of puromycin-insensitive aminopeptidase and enkephalinase A in midbrain (including hypothalamus). It was supposed that in midbrain the role of aminopeptidase M in intrasynaptic inactivation of enkephalins is much more conspicuous than in other regions of rat brain. The puromycin-sensitive aminopeptidase activity does not seem to play a role in enkephalin catabolism.
| 20 |
An evaluation of clinical aspects of post-operative autotransfusion, either alone or in conjunction with pre-operative aspirin, in cardiac surgery. Two groups of 21 otherwise healthy patients undergoing coronary artery bypass grafting (CABG) for the first time were studied in order to evaluate the advantages and disadvantages of post-operative autotransfusion using a red cell 'salvage' method. Group 1 patients (control group) were transfused using donor blood only. Group 2 patients were transfused with their own (autologous) blood, salvaged post-operatively, although donor blood was also available to them if needed. The two groups were further subdivided according to whether the patients received aspirin pre-operatively or not. The four subgroups thus formed were comparable pre- as well as intra-operatively, with respect to all available clinical and laboratory criteria. The post-operative data, however, showed that the combination of pre-operative aspirin and autotransfusion leads to excessive post-operative bleeding, together with increased donor blood requirement. It was also shown that autotransfusion without aspirin does reduce the need for donor blood transfusion without any increase in post-operative bleeding. Although aspirin alone did not increase post-operative bleeding or donor blood requirement, its combination with autotransfusion should be avoided.
| 16 |
Smooth-muscle antibodies and antibodies to cytomegalovirus and Epstein-Barr virus in leukaemias and lymphomata. By means of the indirect immunofluorescent method, smooth-muscle antibodies (SMA) were detected significantly more often in patients with malignant diseases (11.7%) than in normal controls (3.3%) (0.02 greater than pgreater than 0.01). SMA occurred in 23.8% of patients with Hodgkin's disease, in 13.3% of patients with myeloproliferative diseases and in 4.7% of patients with lymphoproliferative diseases. Other tissue antibodies were rare and they were found to occur at the same frequency in patients and controls. The occurrence of cytomegalovirus (CMV) antibodies did not differ significantly in patients and controls and, in both groups, the frequency of these antibodies increased with increasing age. The frequency of Epstein-Barr-virus (EBV) antibodies increased also with increasing age both in patients and controls, but these antibodies were found more frequently in patients than in controls (p=0.03). No relationship between the occurrence of SMA and viral antibodies was demonstrated. Thus, the development of SMA in patients with malignancies could not be shown to be due to CMV or EBV infection.
| 15 |
Effect of linocmycin on the chlorophyll protein complex I content and photosystem I activity of greening leaves. 1. Greening barley and pea leaves treated with lincomycin have a reduced chlorophyll content. Lincomycin dose not alter the proportion of chlorophyll in chlorophyll-protein complex II (CPII) but greatly reduces that in chlorophyll-protein complex I (CPI). 2. Difference spectra show that chloroplasts from lincomycin-treated leaves are deficient in at least two long wavelength forms of chlorophyll ratio of chloroplasts is unaffected by lincomycin but the photochemical P-700/chlorophyll ratio is less than half of that of the control. It is less affected than the chlorophyll-protein complex I content. 4. Photosystem I activity expressed on a chlorophyll basis is unaffected by linocomycin but the light intensity for half saturation is increased 8-fold. 5. Chlorophyll-protein complex I apoprotein content is reduced by lincomycin. No evidence was found for an accumulation of its precursor(s). The relative abundance of major peptides of 18 000, 15 000 and 12 000 daltons in lincomycin-treated chloroplasts is attributed to a general inhibition of greening and associated membrane of formation.
| 12 |
Costs and acceptability of two special overlays for the prevention of pressure sores. In a randomized clinical trial, 187 adult patients with chronic neurologic conditions who were at a high risk of developing pressure sores were assigned for 3 months to either an alternating air (AA) mattress overlay or a silicore (S) mattress overlay. Costs associated with each overlay were calculated and compared by adding depreciation and yearly expenses related to maintenance, operation, and repair for 148 patients who completed the trial. Acceptability was measured by questionnaires and interviews involving 45 of the patients' primary nurses and a sample of 40 patients (20 from each overlay group). The annual cost of the AA overlay was 54% more than that of the S overlay. Although most nurses (more than 74%) believed that both overlays helped prevent pressure sores and deter their progression, many (more than 56%) would not recommend either type to other facilities or to patients at home due to specific negative features. Implications for manufacturers, investigators, clinicians, and administrators are identified.
| 17 |
Cardiac function in the treatment of arterial hypertension with propranolol. 1. Propranolol, when used for treating arterial hypertension, may influence determinants of both cardiac and vascular function; the consequent changes in cardiac performance may result from the interaction of different and possibly opposite effects. 2. Cardiac funtion was investigated in fifty-four primary hypertensive men in the pretreatment state and after 3 weeks of propranolol therapy at a daily dose of 320 mg. 3. beta-Receptor blockade caused depression of pre-injection left ventricular function, which was unrelated to the direction and the extent of changes in peripheral circulation. 4. The ejection left ventricular function could be either depressed or improved depending on the direction to which treatment shifted the vascular resistance, and consequently, the impedance to left ventricular ejection. 5. Withdrawal of the adrenergic support is probably the major factor responsible for the poor ventricular adaptation to an augmented impedance.
| 15 |
Management guidelines for health care workers exposed to blood and body fluids. The purpose of this article is to propose specific management guidelines for the immediate emergency department and subsequent occupational health treatment of health care workers (HCWs) following accidental exposures to blood or body fluids. These guidelines are based on a collective review of the literature and the recommendations of the Advisory Committee on Immunization Practices (ACIP) and authorities expert in this knowledge domain. Guidelines are needed to assure appropriate treatment and coordinated efforts by ED and occupational health providers. Although numerous infections can potentially be transmitted by exposure to blood and body fluids, these guidelines are intended only for evaluation and postexposure prophylaxis of hepatitis B, hepatitis C, and infection with HIV.
| 19 |
Neuropeptide Y stimulation of myosin light chain phosphorylation in cultured aortic smooth muscle cells. Neuropeptide Y (NPY) is released from an extensive network of postganglionic sympathetic perivascular neurons. NPY has been shown to affect vascular tone postsynaptically by 1) directly stimulating contraction; 2) inhibiting vasorelaxation; and 3) potentiating contraction elicited by exogenous vasoconstrictors. The molecular mechanisms mediating these effects of NPY are undefined. Therefore, we examined the possibility that NPY could stimulate smooth muscle contraction through myosin light chain phosphorylation in cultured porcine aortic smooth muscle cells. NPY (100 nM) caused a rapid, transient increase in myosin light chain (MLC) phosphorylation, an important regulatory event in the initiation of smooth muscle contraction. NPY-stimulated MLC phosphorylation was prevented by preincubation of cells with pertussis toxin and was independent of extracellular Ca2+. In parallel studies, NPY alone had no detectable effect on cellular cAMP or cGMP content; however, NPY potently inhibited forskolin-stimulated cAMP accumulation (IC50 = 0.03 nM) through a pertussis toxin-sensitive pathway. NPY had no detectable effect on basal phosphoinositide hydrolysis or protein kinase C activation but enhanced angiotensin II-stimulated production of inositol phosphates and activation of protein kinase C. These results indicate that NPY-stimulated MLC phosphorylation can occur in the absence of detectable changes in cAMP content, cGMP content, inositol phosphate production, or protein kinase C activation; however, the interactions between NPY and other vasoactive agents may be mediated by the indirect effects of NPY on adenylate cyclase activity and phosphoinositide hydrolysis.
| 21 |
Some effects of positive life events on community mental health. Measures of positive and negative events were derived from a life-event inventory to test the predictions of an equilibrium model and a positive mental health model of psychological well-being. These measures were related to indicators of individual and community well-being with data obtained through a household survey of 454 residents. Residents who reported more negative events also reported more psychological distress and less positive adjustment. Positive events were associated with reports of positive adjustment. An analysis of census tract scores on life events revealed that the relative absence of positive events in census tracts was associated with higher service utilization rates to the community mental health center serving those tracts. The number of negative events was unrelated to service rates for census tracts but was related to several demographic indicators of well-being.
| 16 |
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