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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 739 records · Page 41Linked to original sources
PubMed1994

Pathogenic natural anti-cardiolipin antibodies: the experience from monoclonal gammopathy.

Anti-cardiolipin antibodies (ACA) were detected in 19% of sera from patients with monoclonal gammopathies (MG). ACA were purified from the sera of patients with MG. One of the IgG-ACA was found to be monospecific with high affinity for cardiolipin, and to carry a pathogenic ACA Id (1.10). Active immunization of naive BALB/c mice with the purified IgG-ACA was followed by production in the mice of sustained high titres of ACA, associated with prolonged activated partial thromboplastin time (APTT) (61 +/- 14s versus 31 +/- 2s in control mice; P < 0.001) and thrombocytopenia (468,000 +/- 224,000/mm3 versus 994,000 +/- 92,000/mm3 in controls; P < 0.001). The titres of other autoantibodies (e.g. anti-DNA, anti-histones), although being high after immunization, decreased rapidly and were undetected after 1 month following the boost injection. The mice immunized with the IgG-ACA exhibited low fecundity (36% of mice became pregnant versus 62% observed in the group immunized with control IgG). The pregnant mice had increased resorption rate (the equivalent of fetal loss in the human) of 52 +/- 8% (versus 5 +/- 4% in the control group). The mean (+/- s.d.) embryo and placental weights in mice with anti-phospholipid syndrome (APLS) were significantly lower compared with the mice injected with control IgG (682 +/- 304 mg and 102 +/- 12 mg versus 1303 +/- 105 mg and 145 +/- 8 mg, respectively; P < 0.001). Serum monoclonal immunoglobulins having autoantibody activity may be regarded as an expansion of clones producing natural autoantibodies. Our results confirm the pathogenic role of natural ACA in the pathogenesis of the anti-phospholipid syndrome.

Adult↗
PubMed1994

Medical education change: a detailed study of six medical schools.

This article reports a comparative case study of six selected USA medical schools, undertaken to identify factors that facilitate or obstruct innovation in medical education. The findings suggest that the culture of each medical school results from a combination of intra-institutional and external factors. Together these forces influence substantially the fate of educational innovations. The institutional culture influences critical elements such as educational philosophy, leadership and resources provided in support of innovation. Equally important, the culture shapes the level and type of change a school considers and implements. The findings also suggest that the availability of resources and the creative impetus present in schools giving priority to research can benefit the educational goals and facilitate educational change.

Curriculum↗
PubMed1994

Rotavirus interaction with isolated membrane vesicles.

To gain information about the mechanism of epithelial cell infection by rotavirus, we studied the interaction of bovine rotavirus, RF strain, with isolated membrane vesicles from apical membrane of pig enterocytes. Vesicles were charged with high (quenching) concentrations of either carboxyfluorescein or calcein, and the rate of fluorophore release (dequenching) was monitored as a function of time after mixing with purified virus particles. Purified single-shelled particles and untrypsinized double-shelled ones had no effect. Trypsinized double-shelled virions induced carboxyfluorescein release according to sigmoid curves whose lag period and amplitude were a function of virus concentration and depended on both temperature and pH. The presence of 100 mM salts (Tris Cl, NaCl, or KCl) was required, since there was no reaction in isoosmotic salt-free sorbitol media. Other membrane vesicle preparations such as apical membranes of piglet enterocyte and rat placenta syncytiotrophoblasts, basolateral membranes of pig enterocytes, and the undifferentiated plasma membrane of cultured MA104 cells all gave qualitatively similar responses. Inhibition by a specific monoclonal antibody suggests that the active species causing carboxyfluorescein release is VP5*. Ca2+ (1 mM), but not Mg2+, inhibited the reaction. In situ solubilization of the outer capsid of trypsinized double-shelled particles changed release kinetics from sigmoidal to hyperbolic and was not inhibited by Ca2+. Our results indicate that membrane destabilization caused by trypsinized outer capsid proteins of rotavirus leads to fluorophore release. From the data presented here, a hypothetical model of the interaction of the various states of the viral particles with the membrane lipid phase is proposed. Membrane permeabilization induced by rotavirus may be related to the mechanism of entry of the virus into the host cell.

Animals↗
PubMed1994

Characterization of virus-like particles produced by the expression of rotavirus capsid proteins in insect cells.

Rotaviruses are triple-layered particles that contain four major capsid proteins, VP2, VP4, VP6, and VP7, and two minor proteins, VP1 and VP3. We have cloned each of the rotavirus genes coding for a major capsid protein into the baculovirus expression system and expressed each protein in insect cells. Coexpression of different combinations of the rotavirus major structural proteins resulted in the formation of stable virus-like particles (VLPs). The coexpression of VP2 and VP6 alone or with VP4 resulted in the production of VP2/6 or VP2/4/6 VLPs, which were similar to double-layered rotavirus particles. Coexpression of VP2, VP6, and VP7, with or without VP4, produced triple-layered VP2/6/7 or VP2/4/6/7 VLPs, which were similar to native infectious rotavirus particles. The VLPs maintained the structural and functional characteristics of native particles, as determined by electron microscopic examination of the particles, the presence of nonneutralizing and neutralizing epitopes on VP4 and VP7, and hemagglutination activity of the VP2/4/6/7 VLPs. The production of VP2/4/6 particles indicated that VP4 interacts with VP6. Cell binding assays performed with each of the VLPs indicated that VP4 is the viral attachment protein. Chimeric particles containing VP7 from two different G serotypes also were obtained. The ability to express individual proteins or to coexpress different subsets of proteins provides a system with which to examine the interactions of the rotavirus structural proteins, the role of individual proteins in virus morphogenesis, and the feasibility of a subunit vaccine.

Animals↗
PubMed1994

Preoperative parathyroid localization: prospective evaluation of technetium 99m sestamibi.

The utility of preoperative parathyroid localization remains controversial. The gold standard for identification of abnormal parathyroid glands is exploration of the neck by an experienced surgeon. However, both for the experienced and less experienced surgeon, it may be desirable to localize the abnormality before surgery. Such a study would not only direct the surgeon to the site of the lesion but also would help reduce unnecessary dissection, the number of negative explorations, and operative anesthesia time. Unfortunately, currently used noninvasive techniques including ultrasonography, thallium-technetium subtraction, computed tomography scan, and magnetic resonance imaging have had only limited success (35% to 78%) in demonstrating abnormal parathyroid glands. Thirty patients with proven hyperparathyroidism were enrolled to compare a new imaging agent, technetium 99m sestamibi, as an alternative to thallium 201 for subtraction scintigraphy with technetium 99m pertechnetate. Only 14 of 30 patients operated on at George Washington University underwent an identical surgical approach (exploration of all four glands) and had complete preoperative calcium and parathormone levels, postoperative calcium levels, and total time of surgical procedures to formulate the basis of this report. The remaining 16 had their surgeries at other institutions. A surgical approach different from that used at George Washington University and unavailability of postoperative calcium levels and times of surgical procedures from these institutions necessitated deletion of these 16 patients from this report. Technetium 99m sestamibi-technetium 99m subtraction scans accurately localized the abnormal parathyroid gland in 13 of 14 patients, as compared with only 9 of 14 thallium 201-technetium 99m pertechnetate subtraction scans. These results support technetium 99m sestamibi scanning as the superior modality for preoperative parathyroid localization.

Adult↗
PubMed1994

Immunochemical localization of inducible nitric oxide synthase in endotoxin-treated rats.

BACKGROUND: Administration of endotoxin to rodents produces widespread tissue induction of nitric oxide synthase (NOS). To understand the mechanisms of the resulting endotoxin shock, it is important to know the cellular distribution of the inducible NOS (iNOS). EXPERIMENTAL DESIGN: We have investigated the localization and time course of expression of iNOS in rats at time 0 (control) and 3, 6, 9, and 24 hours after administration of endotoxin and also in endotoxin- and cytokine-stimulated RAW 264 murine macrophage and A7r5 aortic smooth muscle cells. We have used a rabbit antiserum to a synthetic peptide selected from the deduced sequence of the cloned macrophage enzyme (residues 47-71) and immunochemical techniques. RESULTS: The antiserum reacted with an approximately 130-kilodalton protein (the molecular weight of iNOS) in Western blots of total cytoplasmic proteins from livers of endotoxin-treated rats, RAW 264 murine macrophages stimulated with endotoxin and combinations of cytokines, and purified liver iNOS, but not in control, untreated tissues. Strong cytoplasmic immunostaining was seen in RAW 264 murine macrophages and A7r5 rat aortic smooth muscle cells after stimulation, but not in nonstimulated cells. Three hours after endotoxin treatment in rats, iNOS immunoreactivity was detectable in many tissues and was at its strongest at 6 and 9 hours after stimulation. Staining was detected predominantly in macrophages distributed abundantly in heart, lung, liver, and kidney. It was also present in Kupffer cells and hepatocytes, biliary epithelium, mesangial cells, airway epithelium, and nerves supplying mesenteric blood vessels but was not detected in any vasculature. By 24 hours there was a reduction in the number of cells stained compared with that seen at 6 and 9 hours. In addition, at 24 hours after endotoxin treatment, granulomatous lesions showing iNOS staining were evident, particularly in the liver. CONCLUSIONS: Antiserum raised to macrophage NOS recognizes an inducible enzyme in a wide variety of cells. Macrophages are the major site of iNOS expression in endotoxin-treated rats and show greatest staining between 6 and 9 hours after treatment. Although staining was not seen in vascular cells in vivo, levels of the enzyme that are below the immunocytochemistry detection limit cannot be excluded.

Amino Acid Oxidoreductases↗
PubMed1994

Br/Rb ratio obtained by XRF analysis of kidneys of normal and tumor-bearing mice treated with cis-DDP.

The Br/Rb ratio in kidneys of normal and tumor-bearing mice was studied and a significant difference was found between the two groups. The mice were treated with cis-DDP with and without selenite, with selenite alone, and compared with controls. The animals were sacrificed 7d, 14d, and 21-28d after treatment. The kidneys were removed and subjected to Br and Rb determination by a novel X-ray fluorescence (XRF) method. The results are presented in terms of estimated net count rates under the BrK alpha and RbK alpha peaks. No significant differences were found in Br and Rb levels or in the Br/Rb ratio in kidneys of treated and untreated mice belonging to the same group-normals or lung carcinoma inoculated. However, there was a significant difference in the Br/Rb ratio between the two tested groups (normals and inoculated). Preliminary results on the Br/Rb ratio obtained from normal and malignant tissues of colorectal cancer (CRC) patients and from mice inoculated with melanoma, show the same trend as those from the group of mice with lung carcinoma. In all three groups tested the Br/Rb ratio was 2-4 times higher in normal than in malignant tissue.

Animals↗
PubMed1994

Chromosome abnormalities in human arrested preimplantation embryos: a multiple-probe FISH study.

Numerical chromosome abnormalities were studied in single blastomeres from arrested or otherwise morphologically abnormal human preimplantation embryos. A 6-h FISH procedure with fluorochrome-labeled DNA probes was developed to determine numerical abnormalities of chromosomes X, Y, and 18. The three chromosomes were stained and detected simultaneously in 571 blastomeres from 131 embryos. Successful analysis including biopsy, fixation, and FISH analysis was achieved in 86.5% of all blastomeres. The procedure described here offers a reliable alternative to sexing of embryos by PCR and allows simultaneous ploidy assessment. For the three chromosomes tested, numerical aberrations were found in 56.5% of the embryos. Most abnormal embryos were polyploid or mosaics, and 6.1% were aneuploid for gonosomes or chromosome 18. Extrapolation of these results to all human chromosomes suggests that the majority of abnormally developing and arrested human embryos carry numerical chromosome abnormalities.

Adult↗