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Biomedical subjects

G Steiner

Publications and source records attributed to G Steiner.

At least 199 records · Page 11Linked to original sources
PubMed1989

Maturational steps of bone marrow-derived dendritic murine epidermal cells. Phenotypic and functional studies on Langerhans cells and Thy-1+ dendritic epidermal cells in the perinatal period.

The adult murine epidermis harbors two separate CD45+ bone marrow (BM)-derived dendritic cell systems, i.e., Ia+, ADPase+, Thy-1-, CD3- Langerhans cells (LC) and Ia-, ADPase-, Thy-1+, CD3+ dendritic epidermal T cells (DETC). To clarify whether the maturation of these cells from their ill-defined precursors is already accomplished before their entry into the epidermis or, alternatively, whether a specific epidermal milieu is required for the expression of their antigenic determinants, we studied the ontogeny of CD45+ epidermal cells (EC). In the fetal life, there exists a considerable number of CD45+, Ia-, ADPase+ dendritic epidermal cells. When cultured, these cells become Ia+ and, in parallel, acquire the potential of stimulating allogeneic T cell proliferation. These results imply that CD45+, Ia-, ADPase+ fetal dendritic epidermal cells are immature LC precursors and suggest that the epidermis plays a decisive role in LC maturation. The day 17 fetal epidermis also contains a small population of CD45+, Thy-1+, ADPase-, CD3- round cells. Over the course of 2 to 3 wk, they are slowly replaced by an ever increasing number of round and, finally, dendritic CD45+, Thy-1+, CD3+ EC. Thus, CD45+, Thy-1+, ADPase-, CD3- fetal EC may either be DETC precursors or, alternatively, may represent a distinctive cell system of unknown maturation potential. According to this latter theory, these cells would be eventually outnumbered by newly immigrating CD45+, Thy-1+, CD3+ T cells--the actual DETC.

Animals↗
PubMed1989

Demonstration of a new antinuclear antibody (anti-RA33) that is highly specific for rheumatoid arthritis.

Using immunoblot analysis with soluble nuclear extracts from HeLa cells, we identified autoantibodies to an antigen with a molecular weight of approximately 33,000 in 36% of 95 sera from rheumatoid arthritis patients, but in only 1 of 170 controls. The antigen, termed RA33, was resistant to DNase and RNase digestion but sensitive to proteinase K treatment. There was no discernible relation to other autoantibodies. Thus, this newly described autoantibody appears to be highly specific for rheumatoid arthritis.

Adult↗
PubMed1989

Dendritic epidermal T cells: activation requirements and phenotypic characterization of proliferating cells.

Dendritic epidermal T cells (DETC) are CD45+, Thy-1+, CD5-, CD8-, CD4- murine lymphocytes that express surface-bound CD3 antigens associated with T cell receptor gamma/delta heterodimers. Using epidermal cells greatly enriched for DETC and depleted of Langerhans cells, we found that DETC have growth requirements quite different from those of accessory cell-depleted lymph node and splenic T cells. Although the latter cells strongly proliferate in response to phorbol myristate acetate (PMA) + ionomycin, DETC, when exposed to interleukin-1 (IL-1), interleukin-3 (IL-3), concanavalin A (ConA), PMA, and ionomycin used either alone or in combination, do not exhibit significant mitotic activity. Recombinant interleukin 2 (rIL-2), albeit ineffective by itself, leads to vigorous proliferation of DETC when used with either ConA or PMA + ionomycin + IL-1. In contrast, the combination of PMA and recombinant interleukin-4 (rIL-4), which triggers growth of lymph node T cells, does not induce proliferation of DETC. Although a portion of proliferating DETC expressed CD8 antigens, essentially none bore detectable amounts of surface-bound CD4 or CD5 antigens, or both. Continuing stimulation of primary DETC cultures with lectin/lymphokine-rich media results in the propagation of cells with the essential phenotypic features of resident DETC.

Animals↗
PubMed1989

Impaired very low-density lipoprotein-triglyceride catabolism in acute and chronic fructose-fed rats.

Very low-density lipoprotein (VLDL)-triglyceride (TG) catabolism was compared in rats given chow and either a 10% fructose (F) or 10% glucose (G) drinking solution for both acute (A) (16 h) and chronic (C) (14 days) periods. VLDL-TG were labeled in F and G donor rats using different isotopic forms of glycerol. A mixture of the VLDLs was injected into F and G recipients and the decline in plasma TG radioactivities used as a measure of clearance. VLDL-TG from F donors was cleared more slowly than VLDL-TG from G donors. In F recipients, the half-life of VLDL-TG from either F or G donors was longer than that in G fed recipients. VLDL from the AF group, had a lower apoprotein E-to-C apoprotein ratio (E/C) than VLDL from the AG group. VLDL from both F groups had a lower E/C than did that from control rats. The E/C negatively correlated with plasma VLDL-TG. CF and CG VLDL had elevated CIII0 and lower CIII3 levels compared with their respective A groups and controls. The ratio of VLDL apoprotein B100, B95, and B48 did not differ between treatments. AF and AG VLDL were larger and enriched in TG compared with control or the CF and CG groups. The saturated fatty acid-to-unsaturated fatty acid ratio in VLDL-TG was higher in the G groups and AF group compared with controls. The present study suggests that the E/C may be lowered as a result of F consumption, thereby contributing to the impairment in VLDL-TG removal.

Animals↗
PubMed1989

Immunological host defense of the skin.

The experimental data presented and reviewed in this manuscript speak in favor of the existence of a skin-specific immune surveillance system for which Streilein [3] has coined the term SALT (skin-associated lymphoid tissues). SALT is comprised of (a) potent antigen presenting cells (LC); (b) distinctive populations of T lymphocytes some of which preferentially infiltrate the epidermis; (c) keratinocytes which produce several immunomodulatory cytokines, and (d) a set of draining peripheral lymph nodes that contain, along with the dermis, blood vessels with endothelial cells whose surface capture lymphocytes passing through the blood. An increasingly better understanding of the circuits and signals of SALT will hopefully result in the development of strategies to prevent a breakdown of this important host-defense mechanism.

Animals↗
PubMed1988

Photo-affinity labelling at the peptidyl transferase centre reveals two different positions for the A- and P-sites in domain V of 23S rRNA.

Photo-reactive 3-(4'-benzoylphenyl)propionyl-Phe-tRNA bound to the A- or the P-site was crosslinked to 23S RNA upon irradiation at 320 nm. The sites of reaction were identified as U-2584 and U-2585 at the A-site and A-2451 and C-2452 at the P-site. Minor crosslinks from both sites were observed at nucleotides A-2503 to U-2506. All sites identified lie in close proximity according to the secondary structure model and constitute part of the highly conserved loop region of domain V. Antibiotics known to inhibit peptidyl transferase activity had a pronounced effect on photo-crosslinking. In addition, tetracycline was also shown to photo-crosslink to this region. These experiments permit a dissection of the peptidyl transferase region on the 23S RNA into two distinct areas for the A- and P-site.

Acyltransferases↗
PubMed1988

Characterization of T cell receptors on resident murine dendritic epidermal T cells.

Cell lines derived from Thy-1+ dendritic epidermal cells (Thy-1+DEC) display a marked heterogeneity in T cell receptor (TcR) expression including CD3-associated alpha/beta, C gamma 1/delta or C gamma 2/delta and C gamma 4/delta TcR. In order to investigate whether this heterogeneity is primarily imposed by in vitro culture conditions or, alternatively, is already present within the epidermis, we studied TcR expression by Thy-1+DEC in situ and on freshly isolated epidermal cell suspensions greatly enriched for Thy-1+DEC. Immunolabeling experiments showed that resident Thy-1+DEC are CD45+, Thy-1+, CD3+, TcR V beta 8-, CD5-, CD4- CD8-, CD25- lymphocytes. Immunoprecipitation of lysates from 125I-surface-labeled Thy-1+DEC-enriched epidermal cells with anti-CD3 epsilon, anti-C gamma 1,2,3 and anti-C gamma 4 antibodies, respectively, and subsequent analysis of the precipitates by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed only CD3-associated 35 kDa/45 kDa gamma/delta heterodimers. The demonstration of TcR heterodimers on resident Thy-1+DEC strongly implies that these cells are functional T cells. The selective expression of C gamma 1/delta (C57BL/6) and C gamma 1/delta or C gamma 2/delta (C3H/He) TcR makes these cells useful for the study of gamma/delta TcR function.

Animals↗
PubMed1988

Triglyceride-rich lipoprotein metabolism during acute hyperinsulinemia in hypertriglyceridemic humans.

Chronic endogenous hyperinsulinemia is associated with increased rates of triglyceride production in humans. The effect of acute exogenous hyperinsulinemia on triglyceride production was studied in seven hypertriglyceridemic men before and during six hours of hyperinsulinemic-euglycemic clamping, and in two men before and during six hours of hyperinsulinemic-hyperglycemic clamping. Apparent triglyceride production rates were assessed qualitatively by examining the rate of decline of 3H-glycerol-labeled plasma triglyceride specific activity in the preclamp period, and again when a new steady state had occurred, during the final three hours of the clamp. During the euglycemic (91.2 +/- 3.0 mg glucose/dL plasma) clamps, plasma insulin levels were increased by 700% (0.76 +/- 0.12 to 5.3 +/- 0.29 ng/mL, P less than .001) and plasma glucagon levels decreased by 19%, compared with baseline. The apparent triglyceride production rate did not increase in five of six men during the euglycemic-hyperinsulinemic clamp, or in either man during the hyperglycemic-hyperinsulinemic clamp. During the clamp period the triglyceride declined in the plasma by 23.4 +/- 3.1%; and the apolipoprotein B by 10.5 +/- 1.5%. Hyperinsulinemia with euglycemia was also associated with a decline in the ratio of triglyceride to apolipoprotein B in the triglyceride-rich lipoproteins. This was more pronounced in very low density lipoprotein (VLDL) than in intermediate density lipoprotein (IDL). In this study, hyperinsulinemia led to a decrease in the plasma glucagon concentration. This decrease was positively correlated with the decrease in the slope of the triglyceride specific activity v time curve. Hence, the changes in triglyceride production were not due to an increase in plasma glucagon concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

An atherosclerosis risk factor assessment program for patients with peripheral arterial occlusive disease.

From a group of 251 high-risk patients less than 65 years of age, 84 with angiographic or vascular laboratory proven peripheral arterial occlusive disease were evaluated in detail. The following risk factors were identified: smoking in 91% with an average of 35 +/- 18 pack/years; treated or untreated hypertension in 40%; hyperlipidemia in 49%; obesity with a body weight greater than 120% of ideal in 18%; diabetes in 9%; family history of premature vascular disease in 70%; and hyperuricemia in 13%. Based on these results, we have introduced a practical approach for investigating and managing risk factors that can be administered by paramedical personnel, utilizing a questionnaire given to patients and standard blood tests to identify important risk factors. The results of the completed questionnaires and blood test are entered on a microcomputer. A program written using d-Base III stores the data, identifies the risk factors and grades their severity. We have designed an information booklet that highlights the individual patient's risk factors and suggests alternatives for management based on the sources of medical and community help available in our area.

Arterial Occlusive Diseases↗
PubMed1988

Very-low-density lipoprotein triglyceride kinetics in acute and chronic carbohydrate-fed rats.

Very-low-density lipoprotein (VLDL)-triglyceride (TG) kinetics were examined in rats maintained on either chow and water (control) or chow and a 10% carbohydrate drinking solution (fructose or glucose). The hexose solutions were available for an acute (16 h) or chronic (14 day) period. The acute fructose (AF), acute glucose (AG), and chronic fructose (CF) groups were hypertriglyceridemic (HTG) compared with control. Plasma TG concentration in chronic glucose (CG)-fed rats was similar to control. VLDL-TG was endogenously radiolabeled in donor rats with [2-3H]-glycerol. The fractional catabolic rate (FCR) was then determined by monitoring the clearance of plasma [3H]VLDL-TG in recipient animals. Donors and recipients were treated in an identical manner. AF and CF groups had an FCR significantly lower than rats given glucose for comparable periods. Both fructose groups and the AG group also had a lower FCR than control. In contrast, FCR in the CG group was significantly higher than controls. TG production rate (TGPR) in both AF and CF fed rats did not significantly differ from controls, suggesting that the HTG observed in these animals was solely from a catabolic defect. AG- and CG-treated glucose animals both had TGPR significantly higher than controls. Therefore, overproduction of VLDL-TG contributed to the HTG associated with this carbohydrate.

Animals↗
PubMed1988

Diabetes and atherosclerosis. Metabolic links.

Atherosclerosis is the most frequent complication of diabetes. Two of the many factors that may contribute to this are dyslipoproteinaemias and hyperinsulinaemia. The most frequent dyslipoproteinaemia in diabetics is hypertriglyceridaemia. This probably reflects an increase in intermediate density lipoprotein (IDL) concentration. Plasma levels of triglyceride and insulin are often correlated. This partly reflects a vicious circle in which hypertriglyceridaemia itself can cause insulin resistance and compensatory hyperinsulinaemia. The chronic hyperinsulinaemic state in vivo is, in turn, associated with an increase in the rate of production of very low density lipoprotein (VLDL) triglyceride. Such a vicious circle is of potential importance in atherogenesis in view of the association of both hypertriglyceridaemia and hyperinsulinaemia with early macrovascular disease.

Arteriosclerosis↗