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Biomedical subjects

S Jaffe

Publications and source records attributed to S Jaffe.

At least 19 recordsLinked to original sources

Nonclassical 3 beta-hydroxysteroid dehydrogenase deficiency: a review of our experience with 25 female patients.

OBJECTIVE: To report 15 new menarcheal women affected with nonclassical 3 beta-hydroxysteroid dehydrogenase deficiency (nonclassical 3 beta-HSD) and evaluation of glucocorticoid therapy in treated patients. DESIGN: Diagnosis of these new patients using a standard adrenocorticotropin test. Effects of glucocorticoid therapy on clinical hormonal and sonographic features of each patient are appreciated for periods varying between 4 months and 7 1/2 years. SETTING: All at The New York Hospital-Cornell Medical Center. The Pediatric Endocrinology Ambulatory Service; the Children's Clinical Research Center Core Laboratories; and the Department of Radiology. PATIENTS, PARTICIPANTS: Fifteen menarcheal women (14 to 30 years of age) newly diagnosed and 10 women previously diagnosed were evaluated for symptoms of hyperandrogenism and/or irregular menses. MAIN OUTCOME MEASURE(S): Positive effect of glucocorticoid therapy on signs and symptoms, hormonal levels, and ovarian imaging. RESULTS: Polycystic ovarian syndrome is noted in approximately half the cases. Glucocorticoid treatment greater than 3 months duration results in a reversal of symptoms in most cases.

3-Hydroxysteroid Dehydrogenases↗

Autocatalytic membrane conductance and memory.

A basic characteristic of biological memory is that it has a graded duration, which, even for so-called short-term memory, can vary from minutes to days (i.e. over about three orders of magnitude), depending on the training protocol, which one can think of as determining the "strength" of the memory. Furthermore, the molecular analysis of simple learning in invertebrates has revealed many examples where "learning" is produced by a decrease in an appropriate membrane conductance. This paper provides a quantitative analysis of a simple kinetic scheme whereby a conductance decrease can be produced by repetitive nerve impulses, with a duration that varies with stimulus frequency. The simplest model considered is based on the actual kinetics of the naturally-occurring ionophore Monazomycin. This model yields durations ranging only over a factor of about 10, for reasonable parameter values. However, a simple modification of the model yields memory durations ranging over three or more orders of magnitude. We also show that Monazomycin-like kinetics can appear as the result of a combination of simple uni- and bi-molecular reactions, thus making more plausible the possibility that the effects described here may operate in actual biological systems.

Animals↗

Alterations in organization of phospholipids in erythrocytes as factor in adherence to endothelial cells in diabetes mellitus.

Erythrocytes from patients with diabetes mellitus exhibit increased adherence to cultured human vascular endothelial cells. We investigated the alterations in erythrocyte surface characteristics that may contribute to their abnormal adherence. The organization of phospholipids in the lipid bilayer, as determined by phospholipase A2 treatment and chemical labeling with fluorescamine and trinitrobenzene sulfonic acid (TNBS), is altered in erythrocytes from diabetic patients. Specifically, 12-18% of phosphatidylserine in diabetic erythrocytes (n = 25) is accessible to phospholipase A2 hydrolysis and TNBS labeling, compared to none in normal subjects. These results suggest either a loss in lipid asymmetry or in vivo destabilization of erythrocyte membranes in diabetic patients, causing increased accessibility to phospholipase A2 degradation. The dye merocyanine 540 (MC-540), which is sensitive to the packing of lipids in the bilayer of the membrane, revealed more binding and fluorescence in erythrocytes from diabetic patients than in those from normal subjects. On flow cytometric analysis, 64.5 +/- 17.0% red blood cells (RBCs) in diabetic patients, compared to 35.1 +/- 25.9% RBCs in normal subjects, showed positive MC-540 binding, indicating significant (P less than .001) differences in the packing of lipids in the external leaflet of the bilayer. The results of our study suggest that a loss of lipid asymmetry and/or less ordered packing in the outer leaflet of the diabetic erythrocyte membrane may be responsible for the increased propensity of erythrocytes to adhere to vascular endothelium.

Adult↗

Separation of luminal and abluminal membrane enriched domains from cultured bovine aortic endothelial cells: monoclonal antibodies specific for endothelial cell plasma membranes.

Two kinds of membrane (luminal and abluminal membrane domains) fractions have been isolated from bovine aortic endothelial cells by fractionation of whole cell homogenate on discontinuous sucrose density gradients. The luminal membrane domain was enriched 12-16-fold for angiotensin-converting enzyme activity and 8-10-fold in alkaline phosphatase activity. The abluminal membrane domain displayed an enrichment of 8-fold in (Na+ + K+)-ATPase activity. Both of the membrane domains were minimally contaminated with mitochondria, microsomes and Golgi bodies, as assessed by their corresponding marker enzyme activities. 125I-labeling of endothelial cell monolayers by the Enzymo-Bead lactoperoxidase-catalyzed iodination procedure, followed by isolation of membranes, revealed that the radioactivity was predominantly associated with membranes enriched in angiotensin-converting enzyme activity, corresponding to the luminal membrane domain. However, when cells were radioiodinated in suspension culture, radioactivity was found equally associated in both the luminal and abluminal membrane fractions. Electron microscopy of freeze-fractured and sectioned material showed both luminal and abluminal membrane domains to be in the form of vesicles varying in size from 100 to 400 nm in diameter. To characterize the separation of endothelial cell membrane domains, we have attempted to prepare monoclonal antibodies specific for endothelial cells. Several clones were obtained, producing antibodies which bound to endothelial cells of arterial, venous and capillary origin. Two antibodies of these clones, XIVC6 and XVD2, were studied in more detail. In the ELISA assay, these antibodies reacted with bovine vascular endothelial cells, but not with human umbilical cord endothelial cells, nor with bovine corneal endothelial cells, smooth muscle cells or fibroblasts. Both of these antibodies are directed against an antigen of approximately 130 kDa, under reducing and non-reducing conditions, as assayed by the immunoprecipitation method. Western blot analysis of luminal and abluminal membrane fractions revealed that only MAb XVD2 reacted with an antigen, indicating that the antibody XIVC6 is directed against an epitope which is denatured by SDS. Moreover, MAb XVD2 preferentially reacted with the luminal membrane compared to the abluminal membrane domain of the endothelial cell. These monoclonal antibodies do not react with platelet membrane proteins, indicating that this 130 kDa membrane antigen is not common to both endothelial cells and platelets.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Increased adherence of oxidant-treated human and bovine erythrocytes to cultured endothelial cells.

Bovine erythrocytes, which normally lack phosphatidyl choline in their membranes, when treated with either H2O2 or diamide (1-3 mM), showed a partial appearance of phosphatidyl ethanolamine (PE 40%) and phosphatidyl serine (PS, 30-33%) in the external leaflet of the bilayer and a concomitant increased (four- to five-fold) propensity to adhere to cultured bovine aortic endothelial cells. Similar treatment of normal human erythrocytes caused an alteration in the organization of the phospholipid bilayer and also resulted in their increased adherence to endothelial cells derived either from human umbilical vein or bovine aorta. Treatment of RBCs with H2O2 at low concentration (0.5 mM) resulted in cross-linking of spectrin without significant changes in the orientation of aminophospholipids but the RBCs exhibited 15-20% increase in adherence to endothelial cells. Pretreatment of either human or bovine erythrocytes with antioxidants such as vitamin E (2 mM) prevented both oxidant-induced reorganization of phospholipids in the bilayer and enhancement of adherence to endothelial cells. Introduction of either phosphatidyl serine or phosphatidyl ethanolamine but not phosphatidyl choline into erythrocyte membranes increased their adherence to endothelial cells threefold. Oxidant-treated RBCs exhibited enhanced binding and fluorescence of Merocyanine 540 dye (MC-540), which is sensitive to the packing of lipids in the lipid bilayer. On flow cytometric analysis, 78% of H2O2 (0.5 mM)-treated erythrocytes compared to 30% of untreated RBCs exhibited MC-540 binding and fluorescence, indicating differences in the lipid packing in the outer leaflet of the bilayer. Oxidant-treated erythrocytes adhere preferentially to endothelial cells rather than to bovine aortic smooth muscle cells and skin fibroblasts. It is suggested that the alterations in the erythrocyte membrane surface due to spectrin cross-linking and the organization of the phospholipids concomitant with less ordered packing in the external leaflet of the bilayer, either induced by oxidative manipulation in normal RBC or in pathological erythrocytes, play a role in erythrocyte-endothelial cell interaction.

Animals↗

The capacity of chondrocytes to respond to serum is enhanced by organ culture in the absence of serum, stimulated by serum, and modified by ascorbate.

Cartilage slices maintained in organ culture have been shown to develop an enhanced capacity to respond to serum. The response was measured at the initiation of culture and after 3 and 7 days of culture in medium containing an inhibitor of DNA synthesis and 0, 1, or 16% serum. At these times, cartilage slices were washed to remove serum and inhibitor, and then exposed to various concentrations of serum for evaluation of DNA and proteoglycan synthesis. The range of the derived dose-response curves and the indicated sensitivity to low serum concentrations were the parameters used to evaluate the response capacity. Response capacity increased gradually, reaching a maximum after 8 days of culture. Considerable enhancement was obtained after maintenance in the absence of serum using both DNA and proteoglycan synthesis as markers. Additional, graded enhancement of response capacity was obtained when the cartilage slices were maintained in 1 or 16% serum. The effects of maintenance in serum were much greater when DNA synthesis rather than proteoglycan synthesis was used to measure the response. However, this serum-dependent enhancement was only prominent when ascorbate was present during the dose-response assay. Ascorbate caused a similar but less-marked increase in sensitivity to serum when proteoglycan synthesis was measured. The possibility that ascorbate may function as a cofactor during the progression phase of cell proliferation is discussed.

Animals↗

Changes in responsiveness to newborn pups in pregnant, nulliparous golden hamsters.

Virgin female hamsters were mated and tested once daily for maternal retrieving behavior beginning on days 0, 5, 9, 13, 15, of the 16 day gestation period to determine if responsiveness toward newborn pups changes as pregnancy proceeds. Upon initial exposure to 3 newborn pups, only a small percentage of early-to-mid-pregnant females exhibited maternal retrieving behavior spontaneously. In contrast, over half of the 15 day pregnant females displayed retrieving during the first test. Despite the high frequency of initial pup-directed aggression and cannibalism, maternal retrieval was induced in the majority of the females in all groups by repeated daily exposure to 3 newborn pups. However, no significant differences were observed in the number of pup exposure periods required to induce maternal retrieving in 0, 5, and 9 day pregnant females. It is concluded that the high level of maternal responsiveness observed in the parturient hamster develops somewhat abruptly during late pregnancy. In this respect, the pattern observed in the hamster differs from the more gradual increase in maternal responsiveness reported in mid-to-late-pregnant mice and rats.

Aggression↗

Tarsal tunnel syndrome: a manifestation of systemic disease.

In many respects, tarsal tunnel syndrome is analogous to carpal tunnel syndrome. Despite this fact, tarsal tunnel syndrome has lagged far behind its counterpart in recognition and understanding. Thought of as a local compression phenomenon, reports of systemic associations are now being seen with increased frequency. This article reviews both local and systemic considerations for tarsal tunnel syndrome. Analysis of our own group of patients revealed 49 with electrodiagnostically confirmed tarsal tunnel syndrome, 24 of whom had bilateral involvement. The incidence of systemic disease was found to be 34.7%.

Adolescent↗

Modified treatment of thumb ray dysplasia: a case report.

The abnormality of the carpometacarpal joint and lack of opposition are two of the more difficult components to treat in the thumb ray dysplasia syndrome. A trapezium arthroplasty and an extensor indicis proprius opponensplasty were used in a typical case. Active opposition was obtained.

Adult↗

Malignant hemangioendothelioma (angiosarcoma) of the salivary gland: an ultrastructural study.

A case of malignant hemangioendothelioma (angiosarcoma) of the submaxillary salivary gland is reported and its microscopic and ultrastructural features are described and compared to previous reports of angiosarcoma arising in other locations. These tumors may often contain areas of solid sheets of cells without vascular characteristics and may be confused with poorly differentiated carcinoma or other sarcomas. The ultrastructural features of angiosarcoma are compared to other poorly differentiated tumors. It is concluded that the ultrastructural features of angiosarcoma are distinctive and aid in the diagnosis of this neoplasm.

Aged↗