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Biomedical subjects

G Steiner

Publications and source records attributed to G Steiner.

At least 19 recordsLinked to original sources
PubMed1992

Purification and partial sequencing of the nuclear autoantigen RA33 shows that it is indistinguishable from the A2 protein of the heterogeneous nuclear ribonucleoprotein complex.

RA33 is a nuclear autoantigen with an apparent molecular mass of 33 kD. Autoantibodies against RA33 are found in about 30% of sera from RA patients, but only occasionally in sera from patients with other connective tissue diseases. To characterize RA33, the antigen was purified from HeLa cell nuclear extracts to more than 90% homogeneity by affinity chromatography on heparin-Sepharose and by chromatofocusing. Sequence analysis of five tryptic peptides revealed that their sequences matched corresponding sequences of the A2 protein of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. Furthermore, RA33 was shown to be present in the 40S hnRNP complex and to behave indistinguishably from A2 in binding to single stranded DNA. In summary, these data strongly indicate that RA33 and A2 are the same protein, and thus identify on a molecular level a new autoantigen.

Amino Acid Sequence↗
PubMed1991

Detection of silent myocardial ischemia in diabetes mellitus.

The prevalence of silent myocardial ischemia and its relation to autonomic dysfunction and pain threshold was studied in 58 men with diabetes mellitus and without cardiac symptoms. All patients underwent 48-hour ambulatory electrocardiographic monitoring and exercise testing after assessment of their autonomic function and pain threshold. Silent myocardial ischemia, defined as greater than or equal to 1 mm of ST-segment depression on either exercise testing or ambulatory electrocardiographic monitoring, was corroborated by exercise-induced reversible defect(s) on tomographic thallium scintigraphy. Autonomic function was assessed by heart rate response to: (1) Valsalva maneuver, (2) deep breathing, and (3) upright posture, as well as by diastolic blood pressure response to sustained handgrip and systolic blood pressure response to upright posture. Autonomic dysfunction was defined as greater than or equal to 2 abnormal responses. Pain threshold measurements were performed using electrical cutaneous stimulation of both forearms. Of the 58 diabetic patients, 21 were found to have autonomic dysfunction (36%). Silent myocardial ischemia was detected in 10 patients (17%), and was significantly more frequent in patients with than without autonomic dysfunction (38 vs 5%, p = 0.003). There was no difference in the electrical pain threshold or tolerance in subjects with and without silent myocardial ischemia. It is concluded that silent myocardial ischemia in asymptomatic diabetic men occurs frequently and in association with autonomic dysfunction, suggesting that diabetic neuropathy may be implicated in the mechanism of silent myocardial ischemia.

Adult↗
PubMed1991

Differential expression of specific cytokeratin polypeptides in the basal and luminal epithelia of the human prostate.

The purpose of the present study was to identify cytokeratin polypeptides that are specifically associated with the basal and luminal epithelia of the human prostate. This aim was accomplished by immunohistochemical and immunoblot analysis of human prostate using cytokeratin-specific monoclonal antibodies. In immunohistochemical studies, monoclonal anticytokeratin 8.12 exhibited immunoreactivity with the basal, but not luminal, epithelial cells of fetal, juvenile, normal adult, and hyperplastic prostate. The 8.12 antibody did not stain prostate cancer tissues. Epithelia of 30 and 36 week fetal prostate contained only basal cells whereas both luminal and basal cells were noted in 7 month and 1 year old juvenile prostate. This finding suggests a stem cell function for the prostatic basal cells. Immunoblot analysis of proteins separated by two-dimensional electrophoresis showed that cytokeratins 5 and 15 were basal-cell-specific cytokeratins that were absent from prostatic carcinoma while cytokeratins 8 and 18 appear to be luminal-cell-specific. These results indicate that antibodies to specific cytokeratin polypeptides can be used not only to differentiate between prostatic basal and luminal cells but also to study the biological processes of prostatic organogenesis and carcinogenesis.

Adolescent↗
PubMed1991

Bone island (enostosis): clinical significance and radiologic and pathologic correlations.

This study was undertaken to explain the increased scintigraphic activity of some bone islands by correlating the clinical, radiographic, scintigraphic, and histopathologic findings. The material for the study consisted of six patients with bone islands who had undergone histopathologic examinations of the lesions. Based on histopathologic-radiologic correlations, we postulate that the osteoblastic activity of a bone island makes it appear "hot" on scintigraphy, although other factors such as the size of the lesion may play some role in this phenomenon. In addition, we tried to find a logical algorithm for the radiologic evaluation and management of sclerotic lesions that look like bone islands but exhibit increased uptake of radiopharmaceuticals on bone scan examination. We emphasize that the morphology of the lesion, as demonstrated on the radiologic examination, rather than its degree of activity on the bone scan is a guide to the correct diagnosis.

Adult↗
PubMed1991

Partial characterization of the fructose-induced defect in very-low-density lipoprotein triglyceride metabolism.

Very-low-density lipoprotein triglyceride (VLDL-TG) catabolism was studied in rats receiving either fructose or glucose as a 10% drinking solution. Consumption of either of the hexoses for 16 hours significantly elevated postheparin plasma (PHP) lipoprotein lipase (LPL) activity compared with normal control animals. Prolonged feeding of the carbohydrates for 14 days abolished the higher LPL activities, which were similar to control levels. PHP hepatic lipase (HL) activity was significantly reduced in carbohydrate-fed rats compared with control animals despite the duration of feeding. The kinetic parameters Km and Vmax cannot be obtained with lipoproteins and so the first-order rate constant (k1) of triglyceride hydrolysis was used to assess the effectiveness of VLDL-TG as substrates for endothelial lipases. VLDL-TG from fructose and VLDL-TG from glucose donors was lipolyzed with PHP LPL and HL from normal rats. The k1 (fraction of VLDL-TG lipolyzed) of VLDL-TG was found to be lower when donors had been fed fructose compared with VLDL that had come from glucose-fed donors. Rates of VLDL-TG removal from fructose and glucose donors were determined simultaneously in perfused livers of normal control, fructose-fed, and glucose-fed animals. Livers of fructose-fed animals cleared VLDL-TG at a slower rate than livers from glucose-fed or control rats. VLDL-TG from fructose-fed rats was cleared less effectively than VLDL-TG from glucose-fed rats in livers of both control and glucose-fed animals. We conclude that an impairment in the ability of fructose-fed rats to hydrolyze VLDL-TG, and of their livers to remove VLDL-TG, may in part explain fructose-induced hypertriglyceridemia.

Animals↗
PubMed1991

Insulin resistance and action in hypertriglyceridemia.

To define further the characteristics of insulin insensitivity associated with hypertriglyceridemia, the metabolic responses to the euglycemic insulin clamp were evaluated in 6 hypertriglyceridemic male patients and compared to 5 normal male controls. At baseline, the hypertriglyceridemic patients had elevated triglycerides (687 +/- 172 vs 78 +/- 7 mg/dl, P less than 0.005) and free fatty acids (702 +/- 36 vs 444 +/- 42 microM/l, P less than 0.005) concentrations. During the euglycemic insulin clamp, steady-state plasma glucose concentrations were similar in both groups (90.2 +/- 1.5 vs 88.8 +/- 2.3 mg/dl, ns) as were steady state insulin levels (142 +/- 10.1 vs 132.2 +/- 6.8 microU/ml**). The amount of glucose metabolized during the last hour of the clamp (M) was significantly reduced in the hypertriglyceridemic patient (2.9 +/- 0.4 vs 6.2 +/- 0.7 mg.min-1.kg-1, P less than 0.001). Changes in free fatty acid, glycerol, B-hydroxybutyrate, lactate and pyruvate during the euglycemic insulin clamp were similar indicating a preserved antilipolytic, antiketogenic and glycolytic intermediate (lactate + pyruvate) response to insulin and glucose infusion in the hypertriglyceridemic patients. In summary, hypertriglyceridemia is associated with insulin resistance as it relates to muscle glucose utilization. However, this is not universal, as a number of other insulin responsive pathways appear to be unaffected.

3-Hydroxybutyric Acid↗
PubMed1991

Solitary osseous sarcoidosis in a finger.

Sarcoidosis confined to a single bone in a patient with chronic systemic sarcoidosis and seen as a soft tissue mass is exceedingly rare. The combination of lytic and sclerotic changes within one bone has not been previously reported.

Adult↗
PubMed1991

Failure of chronic hyperinsulinemia to suppress pancreatic glucagon in vivo in the rat.

To determine the effects of chronic hyperinsulinemia on glucagon release, rats were made hyperinsulinemic for 14 days by supplementation of drinking water with sucrose (10%; sucrose-fed) to increase endogenous release or by implantation of osmotic minipumps (subcutaneous, s.c.; or intraperitoneal, i.p.) to deliver exogenous insulin (6 U/day). Both s.c. and i.p. rats also had sucrose in the drinking water to prevent hypoglycemia. Plasma insulin levels were significantly elevated in sucrose-fed, s.c., and i.p. rats. However, glucose levels were significantly elevated in sucrose-fed rats only. Surprisingly, plasma glucagon concentrations were elevated in i.p. and s.c. rats and were not suppressed in sucrose-fed rats. Inverse relationships were found between the plasma levels of insulin and glucose (n = 65; r = -0.42, p less than 0.0001) and between glucose and glucagon (n = 73; r = -0.46, p less than 0.0001). However, unexpectedly, a positive correlation between insulin and glucagon (n = 65; r = 0.47, p less than 0.0001) was established. As suppression of plasma glucagon levels below basal was not observed in any of the hyperinsulinemic or hyperglycemic rats, we wished to establish further whether pancreatic glucagon release could be suppressed below basal levels in the rat by another means. Thus, high doses of somatostatin (50-100 micrograms.kg-1.min-1) were infused for 45 min into normal rats without or with a concomitant hyperinsulinemic, hyperglycemic glucose clamp. Somatostatin fully suppressed insulin, but although plasma glucagon levels were decreased by somatostatin infusion relative to saline-infused animals, there was still no suppression below basal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Altering triglyceride concentrations changes insulin-glucose relationships in hypertriglyceridemic patients. Double-blind study with gemfibrozil with implications for atherosclerosis.

OBJECTIVE: To determine whether reducing triglyceride concentrations in humans reduces serum insulin levels and consider the implications of this for the insulin resistance of hypertriglyceridemia. RESEARCH DESIGN AND METHODS: Insulin and glucose levels were determined during an oral glucose tolerance test (OGTT) in 14 volunteers who had a range of basal triglyceride levels. A double-blind crossover design was used to study active and placebo gemfibrozil and relate triglyceride changes to insulin and glucose levels. Diet and weight were kept constant. RESULTS: Glucose concentrations during OGTT were the same in both treatment periods. Insulin concentrations were reduced in proportion to reductions in triglyceride. CONCLUSIONS: Triglyceride reduction in hypertriglyceridemic patients is associated with a decrease in serum insulin. This does not appear to be a direct effect of gemfibrozil, because it does not occur without a sufficient fall in triglyceride levels. Because glucose concentration remains the same despite the reduced insulin, the triglyceride reduction may result in greater sensitivity to insulin. Treatment of hypertriglyceridemia may break a vicious and potentially atherogenic cycle of hypertriglyceridemia and hyperinsulinemia.

Arteriosclerosis↗
PubMed1991

Recurrent hypoglycemia secondary to drug-dispensing error.

We present three patients who developed hypoglycemia due to inadvertent dispensing of sulfonylurea drugs. Each patient had a similar clinical course characterized by hypoglycemia that remitted during hospitalization and recurred after discharge. The cause of the hypoglycemia was determined only after close inspection of the patients' medications, not the label on the container. Our experience suggests that hypoglycemia due to drug-dispensing error may be more common than is generally recognized.

Aged↗
PubMed1991

Determination of cyclosporine by a competitive binding assay with cyclophilin.

A competitive protein-binding assay for cyclosporine based on use of the intracellular cyclosporine-binding protein cyclophilin (CYP) was used to measure cyclosporin A (CsA) and its bioactive metabolites in whole blood. CYP from cytoplasmic extracts or erythrocyte lysates was applied in the binding assay with use of [3H]CsA as tracer and charcoal adsorption for separating bound from free tracer. Binding affinities of various CsA analogs and metabolites correlated well with their reported in vitro immunosuppressive activities. The assay detected as little CsA as 50 micrograms/L (1 g = 0.832 mmol of CsA), analytical recovery was greater than 80%, and CVs were less than 8% for intra-assay and less than 11% for interassay precision in the range of 150-1000 micrograms/L. We used this assay to measure CsA concentrations in blood and compared the results with those measured by HPLC or by CsA-specific (monoclonal) and CsA-nonspecific (polyclonal) radioimmunoassays. Binding assay results were, in nearly all cases, less than those measured by the nonspecific RIA and frequently greater than 20% above the values determined by the CsA-specific assays. Individual patients had pronounced differences in the relative proportions of CsA, CYP-binding (bioactive) metabolites, and cross-reacting CsA metabolites. Because the presence of bioactive metabolites may considerably contribute to the immunosuppressive activity of CsA, we consider the binding assay clinically useful for measuring CsA in biological fluids.

Administration, Oral↗
PubMed1990

Glycation of very low density lipoprotein from rat plasma impairs its catabolism.

Rat VLDL were glycated in vitro in the presence or absence of a reducing agent. Prior to glycation, the VLDL triglyceride was endogenously radiolabelled with [3H]-oleic acid. Post glycation the VLDL B-apoprotein was exogenously radiolabelled with [131]I. The double labelled VLDL was then injected into normal rats and the decline in plasma radioactivity of the two isotopes was used as a measure of triglyceride and particle clearance. VLDL glycated in either the presence or absence of reducing agent exhibited a significantly slower removal of triglyceride and apoprotein B compared to normal VLDL. The ability of glycated VLDL triglyceride to act as substrate for lipoprotein lipase and hepatic lipase was examined. Increasing concentrations of normal and glycated VLDL triglyceride were incubated with post-heparin plasma. The kinetics of triglyceride hydrolysis were determined in a manner analogous to Michaelis-Menten analysis. Glycated VLDL was found to be poorer than normal VLDL as a substrate for lipoprotein lipase. Glycation of VLDL appears to interfere with the lipolysis of its triglyceride. This may explain the delayed clearance of glycated VLDL triglyceride in vivo. Glycation also extended the mean plasma residence time of the VLDL particle. These factors may, in part, contribute to the hypertriglyceridaemia observed in subjects with diabetes mellitus.

Animals↗
PubMed1990

Thymus-independent generation of Thy-1+ epidermal cells from a pool of Thy-1- bone marrow precursors.

Thy-1+ dendritic epidermal cells (Thy-1+ DEC) and immature thymocytes share several phenotypic features: CD45+, Thy-1+, asialo-GM1+, CD3+, CD4-, and CD8-. In view of this similarity, it has been suggested that the epidermis may be a site of either post-thymic or extra-thymic T-cell development. In order to address this issue, we used C3H/He/Han (Thy-1.2)----AKR/Ola (Thy-1.1) radiation bone marrow chimeras. Animals were first either thymectomized or sham-thymectomized, then lethally irradiated (750R) and, finally, reconstituted with allogeneic bone marrow cells previously depleted of Thy-1-bearing cells. Six weeks after bone marrow transplantation, spleens and lymph nodes of sham-treated animals, but not of thymectomized animals, contained large numbers of CD3+ donor-type Thy-1+ cells. The epidermis of both thymectomized and sham-treated animals contained not only many recipient-type CD3+, Thy-1+ DEC, but also small numbers of CD3-, donor-type Thy-1+ cells. After 4 months, the frequency of donor cells had greatly increased, but they still lacked CD3 antigens. Most of the donor cells had a rounded shape, but some exhibited a dendritic configuration. These results demonstrate that Thy-1- bone marrow-derived precursors of Thy-1+ DEC can migrate to the epidermis without thymic influence and yet acquire Thy-1 antigens during their journey. Although donor-type Thy-1+ epidermal cells failed to mature into CD3+ dendritic epidermal cells, the experimental model used in this study may be a versatile tool for studying the influence of thymic and extrathymic epithelia on T-cell maturation.

Animals↗
PubMed1990

Treatment of psoriatic arthritis by extracorporeal photochemotherapy.

Five patients with long-standing seronegative arthritis resistant to conventional therapy and who also had psoriasis of the skin were treated with photopheresis. This mode of treatment combines a lymphocyte-enrichment procedure with 8-methoxypsoralen-photochemotherapy. There was a marked in vitro effect on treated lymphocytes, with a reduction of viability, proliferation and mitogen response. There was a slight to moderate clinical improvement in four of the five patients with regard to the strength of grip, swelling, pain, morning stiffness, the dosage of non-steroidal anti-rheumatic drugs and the radiographical changes. The skin lesions did not respond to photopheresis. Short-term side-effects were minimal and consisted of a temporary sensitivity of the eyes to light and signs of circulatory dysregulation immediately after treatment. This experimental therapy has some measurable but not dramatic effect in improving psoriatic arthropathy.

Adult↗