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Biomedical subjects

J Weiss

Publications and source records attributed to J Weiss.

At least 361 records · Page 20Linked to original sources

Killing of gram-negative bacteria by neutrophils: role of O2-independent system in intracellular killing and evidence of O2-dependent extracellular killing.

For many strains of these two bacterial species, ingested bacteria are efficiently killed by O2-independent mechanisms. Intracellular killing depends not on 2de novo generation of toxic products of the respiratory burst but rather on intracellular delivery to pre-existing cytotoxic proteins. The principal O2- independent bactericidal system toward these bacteria appears to be BPI which rapidly binds to ingested bacteria and whose discrete action closely resembles the initial lesions produced by the intact neutrophil. In addition, at least for one strain of E. coli (S15), extracellular bacteria can be killed in an O2- dependent fashion.

Animals↗

Pseudotumor cerebri and nutritional rickets.

A bulging fontanelle due to benign increased intracranial pressure is not generally recognized as a manifestation of nutritional rickets but should be considered in the appropriate clinical setting. Two children who we saw presented with bulging anterior fontanelles were found to have pseudotumor cerebri in association with nutritional rickets.

Humans↗

Suprathreshold manipulations of testosterone and reproductive functioning in gonadally intact sexually experienced and inexperienced male rats.

Circulating titers of testicular and gonadotrophic hormones differ widely among conspecific mammalain males. The behavioral and physiological consequences of these differences were examined by injecting gonadally intact male rats with extra testosterone or an antiandrogen. Serum testosterone values increased and decreased, respectively, relative to control animals, although all values remained within normal physiological ranges. Results suggested that hormone-sensitive behavior and physiology were related to suprathreshold androgen differences in a dose-response fashion among virgin males. The relationship was more complex among sexually experienced males. Additional testosterone to the experienced males increased the frequency of both aggressive and sexual responding as well as the activity of sex accessory glands. Reductions of circulating testosterone, however, had minimal effects on behavior despite substantial atrophy of hormone-sensitive tissues. Indeed, fecundity was independent of hormone therapy as all experienced males successfully fathered pups. Suprathreshold hormone differences in natural populations of males may reflect sexual selection that is maintained by female choice of a mate.

Aggression↗

Oxygen-dependent and oxygen-independent mechanisms of microbicidal activity of neutrophils.

The essential role of the phagocyte in host defense against the enormous variety of microbial predators in our environment requires the availability of a "universal" weapon effective against most microbes, or an arsenal of different agents with specificity for different classes and species of microorganisms. Both polymorphonuclear leukocytes (PMN) and mononuclear phagocytes possess, or can produce, a wide range of antimicrobial agents providing these cells with an "overkill" capacity [1] that will usually bypass microbial defenses against a given antimicrobial device of the phagocyte. In this brief review we focus on the PMN because its antimicrobial systems have been analyzed most extensively. However, the killing mechanisms of mononuclear phagocytes and PMN are sufficiently similar to permit the insights gained from the study of the PMN to be applied to all phagocytes, including macrophages.

Animals↗

Uveal melanoma presenting after cataract extraction with intraocular lens implantation.

Four patients underwent cataract extraction with implantation of intraocular lenses. Preoperative ultrasonography did not include a comprehensive diagnostic B-scan analysis. Postoperative examination revealed uveal melanomas. The clinical presentations as well as the histopathologic findings of the two enucleated eyes are discussed. These cases emphasize the necessity for B-scan ultrasonography prior to cataract surgery when media opacity prevents adequate visualization of the fundus.

Aged↗

Torsades de pointes due to n-acetylprocainamide.

A 66-year-old female with chronic renal failure received five doses of procainamide and developed marked QT interval prolongation and recurrent episodes of torsades de pointes, which were temporally related to high serum n-acetylprocainamide (NAPA) levels and not to procainamide levels. Repeated hemodialysis was effective in lowering NAPA levels. Torsades de pointes is a potential hazard of NAPA accumulation during procainamide administration to patients with renal insufficiency.

Acecainide↗

Functional compartmentation of glycolytic versus oxidative metabolism in isolated rabbit heart.

To investigate whether energy derived from glycolytic and oxidative metabolism are preferentially used for different functions in heart, tension, intracellular potential, and extracellular [K+] and pH (using triple barrel K/pH electrodes, tip diameter 0.5 mm) were monitored in isolated arterially perfused rabbit interventricular septa during exposure to hypoxia and metabolic inhibitors. Myocardial content of high energy phosphates, lactate, and glycogen were determined under the same conditions. Inhibiting oxidative metabolism with hypoxia, dinitrophenol (10(-5)M), or Na-azide (10(-3)M) caused marked suppression of tension (by 73 +/- 5, 65 +/- 8, and 50 +/- 14%, respectively) and a small increase in [K+]0 (0.8 +/- 0.4, 0.5 +/- 0.25, and 0.4 +/- 0.2 mM, respectively) after 10 min. Inhibiting glycolysis with iodoacetate (IAA) (10(-3)M) had a much smaller suppressant effect on tension (28 +/- 24%) but markedly increased [K+]0 accumulation (by 1.8 +/- 1.1 mM) at 10 min. These differences, when IAA was compared individually to the other interventions, were highly significant. The shortening of action potential duration was not significantly different for the four interventions. pH0 increased slightly during IAA (+0.04-+0.06 U) and fell during the other interventions (-0.10--0.16 U), but this did not account for the differences in [K+]0 accumulation and tension between inhibition of glycolytic vs. oxidative metabolism. Except for hypoxia, total cellular content of high energy phosphates was not significantly depressed under the various conditions. This data suggests that energy from glycolysis is preferentially used to support sarcolemmal function (as manifested by K+ loss), whereas oxidatively derived energy preferentially supports contractile function. Indexing terms: cardiac metabolism, extracellular pH, metabolic inhibitors, hypoxia, extracellular K+ accumulation, and glycolysis.

Animals↗

Oxygen-independent intracellular and oxygen-dependent extracellular killing of Escherichia coli S15 by human polymorphonuclear leukocytes.

Effective killing of bacteria by polymorphonuclear leukocytes (PMN) is generally assumed to require intracellular sequestration and, depending on the bacterial species, can be both O2-dependent or O2-independent. Killing of several strains of Salmonella typhimurium and Escherichia coli by rabbit PMN does not require O2 and is apparently due to a granule-associated bactericidal/permeability-increasing protein (BPI) present in rabbit and human PMN. In this study we examined the O2 dependence of the killing of E. coli (S15) by human PMN. Ingested and noningested E. coli were separated by centrifugation after incubation with PMN in room air or under N2. In the presence of heat-treated serum approximately 50% of E. coli (10 bacteria/PMN) were taken up by PMN and rapidly (5-15 min) killed both in room air and under N2. The remaining extracellular bacteria (approximately 50%) were killed during 30-60 min of incubation in room air but not under N2. When uptake of E. coli by PMN was increased to approximately 80% by the use of C6-depleted serum (retaining heat-labile opsonins), bacterial survival under N2 was reduced from 54 +/- 7.6% to 13 +/- 5.5%. PMN from a patient with chronic granulomatous disease killed PMN-associated but not extracellular E. coli. BPI was detected, by indirect immunofluorescence, on the surface of PMN-associated E. coli within 5 min of incubation of E. coli with PMN both in room air and under N2. In contrast, at no time was BPI detected on the surface of extracellular E. coli, indicating that the non-PMN-associated E. coli had not been previously ingested. Thus, killing of ingested E. coli S15 by human as well as rabbit PMN does not require O2 and appears to be BPI-mediated. However, when ingestion is limited, extracellular bacteria can also be killed but principally by O2-dependent mechanisms.

Antimicrobial Cationic Peptides↗

Copulation induces an acute increase in epididymal sperm numbers in rats.

The temporal changes in epididymal sperm numbers during the month after sexual contact were examined in 80 adult albino rats. The comparably sexually experienced males in 6 experimental groups were allowed 3 ejaculations with ovariectomized females in which oestrus was induced by hormone injections. Epididymides were removed from the experimental males 1 h, 1 day, 2 days, 3 days, 7 days or 30 days later. Control males were sexually inexperienced or sexually experienced and living with females. Epididymal sperm counts revealed a pattern that resembled an inverted V-shaped function with a peak at 48 h after copulation. We suggest that sexual activity provokes an acute attenuation of sperm disposal within the epididymis with the result that more spermatozoa are available for ejaculation during sexually active times.

Animals↗

Recognition of HLA-A2 by cytotoxic T lymphocytes after DNA transfer into human and murine cells.

A gene coding for the major histocompatibility antigen HLA-A2 was transferred into human HLA-A2 negative M1 cells and murine L cells. Following transfection, these cells expressed molecules at the cell surface that are biochemically indistinguishable from HLA-A2 antigens on the human cell line JY from which the HLA-A2 gene was isolated. The M1A2 cells were recognized and lysed by a cytolytic T-cell clone specific for HLA-A2. The transfected L cells which express HLA-A2 in association with human beta 2-microglobulin were not lysed by this T-cell clone. The specific cytolysis of M1A2 cells could be inhibited by monoclonal antibodies to HLA-A2, and monoclonal antibodies to T3, T8, and LFA-1 on cytotoxic T lymphocytes. These results suggest that killing by allospecific T cells requires HLA-A2 antigens as well as other species-specific structures on the target cell surface.

Animals↗

Cardiac involvement in myotonic muscular dystrophy (Steinert's disease): a prospective study of 25 patients.

The presence, degree and frequency of disorders of cardiac conduction and rhythm and of regional or global myocardial dystrophy or myotonia have not previously been studied prospectively and systematically in the same population of patients with myotonic dystrophy. Accordingly, 25 adults with classic Steinert's disease underwent electrocardiography, 24-hour ambulatory electrocardiography, vectorcardiography, chest x-rays, echocardiography, electrophysiologic studies, and technetium-99m angiography. Clinically important cardiac manifestations of myotonic dystrophy reside in specialized tissues rather than in myocardium. Involvement is relatively specific, primarily assigned to the His-Purkinje system. The cardiac muscle disorder takes the form of dystrophy rather than myotonia, and is not selective, appearing with approximately equal distribution in all 4 chambers. Myocardial dystrophy seldom results in clinically overt ventricular failure, but may be responsible for atrial and ventricular arrhythmias. Since myotonic dystrophy is genetically transmitted, a primary biochemical defect has been proposed with complete expression of the gene toward striated muscle tissue, whether skeletal or cardiac. Specialized cardiac tissue and myocardium have close, if not identical, embryologic origins, so it is not surprising that the genetic marker affects both. Cardiac involvement is therefore an integral part of myotonic dystrophy, targeting particularly the infranodal conduction system, to a lesser extent the sinus node, and still less specifically, the myocardium.

Adult↗

Cimetidine, cigarette smoking, and recurrence of duodenal ulcer.

Three hundred seventy patients with recently healed duodenal ulcer entered into a one-year, double-blind, randomized multicenter trial comparing placebo with three different dose schedules of cimetidine (200 mg twice a day, 300 mg twice a day, and 400 mg at bedtime) for the prevention of recurrent duodenal ulcer. By the end of one year, the cumulative symptomatic recurrence rate as demonstrated by endoscopy was similar for the patients receiving the three dosages of cimetidine (19 per cent, 15 per cent, and 13 per cent, respectively; not significant), whereas the placebo-treated group had a 34.7 per cent symptomatic recurrence rate (P less than 0.01 as compared with each cimetidine group). Cigarette smoking was found to be an important variable; among the placebo recipients ulcer recurrence was significantly more likely in smokers (72 per cent) than in nonsmokers (21 per cent, P less than 0.001). The frequency of ulcer recurrence in smokers was significantly reduced by treatment with cimetidine (from 72 per cent to 34 per cent, P less than 0.). Smokers who received cimetidine were at least as likely to have a recurrence as were nonsmokers who received placebo (34 per cent vs. 21 per cent, not significant). Thus, smoking appears to be a major factor in recurrence of duodenal ulcer, and in smokers, giving up smoking may be more important in the prevention of ulcer recurrences than administration of cimetidine.

Cimetidine↗

The production of collagenase by adherent mononuclear cells cultured from human peripheral blood.

Mononuclear cells were isolated from human peripheral blood by Ficoll-Hypaque centrifugation, and the cells adherent to plastic substrata were cultured in serum-free media supplemented with lactalbumin hydrolysate. These cell cultures, which consisted predominantly of monocyte-macrophages as judged by nonspecific esterase staining, accumulated collagenase in the medium. This collagenase resembled other vertebrate collagenases in that it cleaved native triple-helical type I collagen at a locus 3/4-length away from the amino-terminal end of the molecule. The collagenase activity was inhibited by Na2EDTA, dithiothreitol, and fetal calf serum, while the addition of Ca++ or N-ethylmaleimide enhanced the enzyme activity. The accumulation of collagenase in the culture media was markedly enhanced by the incubation of cells with concanavalin A or phorbol myristic acetate. In the presence of cycloheximide, the levels of collagenase activity were markedly reduced, suggesting that active protein synthesis was required to express the enzyme activity. In additional experiments, monocytes were further purified by counterflow centrifugation-elutriation. The collagenase production was markedly increased in cultures enriched in monocyte-macrophages and devoid of polymorphonuclear leukocytes. The accumulation of collagenase in monocyte cultures incubated for 48 hours in the presence of concanavalin A or phorbol myristic acetate was of the same order of magnitude as in parallel cultures containing the same number of polymorphonuclear leukocytes purified by Ficoll-Hypaque centrifugation and Plasmagel sedimentation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion↗

Severe theophylline toxicity. Role of conservative measures, antiarrhythmic agents, and charcoal hemoperfusion.

The presenting symptoms, course, and treatment of 10 patients with severe theophylline toxicity (heart rate above 120, multifocal atrial tachycardia or premature ventricular contractions, hypotension, seizures) are described. Theophylline levels at presentation averaged 66 micrograms/ml (range 30 to 180 micrograms/ml). All patients had marked tachycardia; 80 percent had gastrointestinal symptoms, 50 percent were hypotensive, and 20 percent had seizures. A known history of poor compliance or other risk factors to overdosage was present in 60 percent. Of the five patients in whom drug clearances were determined, two had uniform first-order drug elimination. Three had biphasic elimination with an initial period of delayed elimination due to either zero-order kinetics or continued drug absorption. During the first-order elimination period, mean plasma theophylline clearance was 28.0 +/- 4.3 ml per minute with a half-life of 8.2 hours. In the patients with initially delayed elimination, the mean clearance during the slow phase was 9.6 +/- 3.3 ml per minute with an apparent half-life of 31 hours. One patient was treated with charcoal hemoperfusion but the others received conservative management alone; all recovered without permanent sequelae. Propranolol and verapamil were useful in controlling supraventricular tachycardia. It appears that most patients with severe theophylline toxicity can be managed without hemoperfusion, which should be considered only when drug clearance is reduced, and hypotension, tachycardia, ventricular ectopy, or seizures are refractory to conservative measures.

Aged↗