Protection of mouse islet isografts from early transplantation damage by nicotinamide treatment of recipients.
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Biomedical subjects
Publications and source records attributed to E Stein.
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Heterozygous familial hypercholesterolemia (hFH) is one of the most common monogenic disorders with serious health consequences, affecting approximately 1 in 500 persons in the United States. Persons with hFH generally manifest elevations of low density lipoprotein (LDL) cholesterol throughout their lives and have a markedly increased risk of death from coronary artery disease. The hypercholesterolemia of hFH is responsive to medication and diet, and, if detected early, aggressive LDL cholesterol control may prevent or substantially delay cardiovascular disease. However, evidence suggests that many persons with hFH are undetected and inadequately treated. On July 20-21, 1992, the National Heart, Lung, and Blood Institute sponsored a workshop to assess the current understanding of the diagnosis and management of hFH, to emphasize recommendations for identification and management that are known to be effective, and to identify opportunities and needs for intervention and research.
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BACKGROUND: Ocular and ocular adnexal injuries, both combat-related and accidental, are common during wartime. In a combat setting, the eye is particularly vulnerable to serious injury from tiny flying particles that might minimally affect other parts of the body. The purpose of this study is to examine the incidence of serious ocular and ocular adnexal injuries that occurred during Operations Desert Shield and Desert Storm. METHODS: The authors retrospectively reviewed serious ocular and ocular adnexal injuries treated by United States Army and Navy ophthalmologists that occurred during Operations Desert Shield and Desert Storm. Only those injuries that resulted in, or would have resulted in, hospital admission because of the ocular or ocular adnexal injury alone are presented. RESULTS: During Desert Shield, 20 patients (23 eyes) suffered serious ocular or ocular adnexal injuries compared with 160 patients (198 eyes) in Desert Storm. During Desert Storm, 78% of all serious injuries were caused by blast fragmentation from munitions. More than one third of the 98 globe lacerations reported in this article were 10 mm or less in size. Of 35 enucleations performed during Desert Storm, 94% were the result of munitions fragments. CONCLUSIONS: During Operation Desert Storm, fragmentation wounds from munitions were the most common cause of ocular and ocular adnexal morbidity. The authors' findings indicate that polycarbonate ballistic protective eyewear could have prevented many of the ocular injuries that they report.
Based on previous studies showing that allogeneic islets transplanted into the thymus can induce donor-specific unresponsiveness, we investigated in the nonobese diabetic (NOD) mouse the effect of intrathymic islet isografts on preventing autoimmunity directed against pancreatic islet antigens. Islets prepared from newborn NOD pancreata were injected into one lobe of the thymus of 10- to 11-day-old female NOD mice (experimental group) with no immunosuppression. PBS alone was used for injection into age- and sex-matched litter mates (control group). Thirty of 32 (94%) experimental mice remained normoglycemic for over 30 weeks. Well-formed islets with no indication of insulitis were found in the thymus of these 30 mice, whereas no grafted islets were found in the 2 mice that became diabetic at 17 and 19 weeks, respectively (technical failures). In the control group, 10 of 32 (31%) mice became diabetic between 20 and 29 weeks. This diabetic incidence was, however, lower than that in our colony female mice. In the pancreas of experimental mice, 90.9% of islets were free of infiltrates, whereas only 13.1% of islets were intact in control mice. The spleens of 30-week-old experimental mice contained a slightly higher percentage of CD8+ T cells (P < 0.05) than those of control mice. Cyclophosphamide injections at 30 weeks induced diabetes in 4 of 9 experimental mice. The 2 lines of evidence, (1) marked reduction in insulitis of intrathymic islet-grafted mice and (2) induction of diabetes after treatment with cyclophosphamide, suggest that both thymic clonal deletion and peripheral tolerance may play a role in preventing diabetes.
The purpose of this study is to determine if there is an anatomical correlate, namely adrenal hypertrophy, among people who have committed suicide. The adrenal weights and other relevant information were collected prospectively from 118 consecutive coroner's cases of sudden death in the province of Ontario. No statistically significant difference was found between the adrenal weights of those who had committed suicide, whether violent or non violent, and those dying suddenly of causes not self-inflicted. This was true irrespective of the age of the subjects, their sex or the centre at which the autopsy was performed. This finding does not support the findings of an earlier report of increased adrenal weight in successful suicides. The incidental finding of increased adrenal weight in all subjects is of some significance.
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Providing efficacious, compassionate, and efficient medical care to persons with HIV infection is one of the greatest challenges that will face US hospitals this decade. Unfortunately, there have been almost no studies of how organizational arrangements are related to the quality of care. We developed an interview protocol and conducted a pilot study to evaluate the instrument's ability to detect differences in selected interpersonal aspects of care provided to persons with AIDS. We evaluated the care received in two different treatment models in a major teaching hospital: a designated AIDS unit and general medical beds. We assessed several areas of patient care that are clinically important and that patients can evaluate: communication between patients and providers, patient education, respect for patient preferences, emotional support, involvement of family and friends, trust and confidence, physical care, pain management, AIDS knowledge, perceived segregation, confidentiality, and financial information. Patients generally were very satisfied with their hospital care, but many reported problems with certain aspects of their care. The instrument used detected differences between the care reported by patients treated in general hospital beds and in a designated AIDS unit in several specific aspects of care.
Male pseudohermaphrodites with 5 alpha-reductase deficiency have ambiguous genitalia and nonpalpable prostates on rectal examination, suggesting the dihydrotestosterone dependency of these structures. To clearly delineate the status of the prostate, male pseudohermaphrodites with 5 alpha-reductase deficiency had transrectal sonography of the prostate performed, and the results were compared to that of age-matched male controls. In six male pseudohermaphrodites, magnetic resonance imaging studies of the prostate were also performed. Heterozygote fathers also had transrectal sonography of the prostate performed and the results compared to age-matched controls. The prostates of the male pseudohermaphrodites appeared as platelike soft tissue structures posterior to the urethra on both prostatic ultrasound and magnetic resonance imaging. Prostatic volume, as determined on prostatic ultrasound by two different methods, was significantly smaller (approximately one-tenth) than the volume of age-matched controls. Transurethral ultrasound guided biopsy of the prostate in two affected subjects revealed stromal tissue. These results correlate with undetectable prostate-specific antigen in affected subjects, suggesting atrophic epithelium or lack of epithelial differentiation. This study demonstrates the dihydrotestosterone dependence of the prostate for normal differentiation and growth. The presence of some prostatic tissue in the male pseudohermaphrodites may be due to the fact that there is a decrease and not an absence of 5 alpha-reductase activity, and/or that the increased level of testosterone in subjects with this condition partially compensates for the decreased level of dihydrotestosterone. There was no difference, however, in prostate size between heterozygous fathers and age-matched control males. The heterozygote fathers had dihydrotestosterone production sufficient for normal prostate growth and development.
The pharmacological properties of two glutamate receptor subtypes, GluR-A/B and GluR-B/D, were examined in RNA-injected Xenopus oocytes using two-electrode voltage clamp. Concentration-response relations revealed that the potencies of L-glutamate, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) varied slightly between the two receptor subtypes, but the rank order of agonist potency did not. The EC50 values for GluR-A/B receptors were 3.31 microM for AMPA, 6.16 microM for glutamate, and 57.5 microM for kainate, whereas the EC50 values for GluR-B/D receptors were 5.01 microM, 32.3 microM, and 64.6 microM for AMPA, L-glutamate, and kainate, respectively. The potencies of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) were quantified by Schild analysis. The potency of NBQX at blocking currents mediated by GluR-A/B receptors changed depending on the agonist used to activate the receptors (pA2 values were as follows: for block of kainate, 7.23 +/- 0.01; L-glutamate, 6.78 +/- 0.02; AMPA, 6.95 +/- 0.02). Differences between agonists were less marked in cells expressing GluR-B/D receptors (pA2 values: kainate, 7.28 +/- 0.01; L-glutamate, 7.30 +/- 0.02; AMPA, 7.35 +/- 0.01). In each case, the slope of the Schild regression was not different from unity, consistent with competitive antagonism of these receptors by NBQX. CNQX also blocked GluR-A/B and GluR-B/D receptors competitively but was less potent than NBQX and did not differentiate between agonists or subunit combination. These data suggest that L-glutamate, kainate, and AMPA bind to different receptor substructures on recombinant AMPA receptors and that NBQX but not CNQX binds to these sites with different affinities. Moreover, because the properties of these binding sites vary between GluR-A/B and GluR-B/D receptors, our findings provide a basis for mutational analysis aimed at identifying receptor domains involved in agonist and antagonist binding.
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