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Biomedical subjects

J Ginsberg

Publications and source records attributed to J Ginsberg.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effects of protein kinase C activators on the in-vitro action of thyrotrophin in pigs.

The ability of the non-phorbol protein kinase C (PKC) activator 12-hydroxy-daphnetoxin (mezerein) to modulate differentiated thyroid function was examined in vitro. A dose-dependent inhibition of TSH-stimulated iodide organification was observed in porcine thyroid cells exposed to mezerein. Under identical conditions mezerein caused the translocation of PKC from its inactive cytosolic form to an active membrane-bound form in thyroid cell extracts. The relative biological potencies of mezerein and the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), to inhibit thyroid function in vitro corresponded to their abilities to activate PKC. This effect was also observed when dibutyryl cyclic AMP was used, implying a post-receptor site of action. To provide further evidence for this concept, the effects of mezerein and TPA on receptor-related events were studied. Neither mezerein nor TPA had any effect on the binding of radiolabelled TSH to solubilized porcine thyroid membranes. However, both mezerein and TPA were capable of stimulating cyclic AMP (cAMP) production in porcine thyroid cells in the basal state but could not augment TSH or forskolin-activated cAMP release. These data provide evidence that activation of PKC plays a role in the regulation of differentiated thyroid function in vitro and suggest that the effects of PKC are complex, with independent actions on cAMP accumulation and post-receptor events.

Animals↗
PubMed1987

Effect of fenofibrate treatment on plasma lipoprotein lipids, high-density lipoprotein cholesterol subfractions, and apolipoproteins B, AI, AII, and E.

In this segment of a multicenter study, 36 hypercholesterolemic patients were randomly assigned to fenofibrate or placebo treatment to assess effects on plasma concentrations of lipoprotein cholesterol and triglyceride, high-density lipoprotein-cholesterol subfractions, and apolipoproteins E, B, Al, and All. All of these factors are of known or potential value in determining the patient's risk of arteriosclerosis. Observations were made during initial screening and placebo phases, a 24-week, double-blind treatment phase, and a subsequent 24-week, open-label fenofibrate phase. There were three possible expressions of fenofibrate efficacy. Changes in lipoprotein cholesterol and total triglyceride concentrations observed in these patients were very similar to those seen with the larger multicenter cohort: total triglyceride levels decreased 38 to 46 percent, low-density lipoprotein cholesterol levels decreased 13 to 20 percent, and high-density lipoprotein cholesterol levels increased 4 to 13 percent. Triglyceride concentrations were significantly reduced (p less than 0.01) in very low-density lipoprotein (50 to 56 percent, similar to those of total triglyceride and very low-density lipoprotein cholesterol), and in low-density lipoprotein cholesterol levels (17 to 21 percent). A slight but statistically insignificant decrease in high-density lipoprotein triglyceride was observed (9 to 15 percent). High-density lipoprotein2 cholesterol levels did not change significantly, whereas high-density lipoprotein3 cholesterol levels increased 8 to 16 percent, accounting for all of the increase in high-density lipoprotein cholesterol. Apoprotein All levels increased significantly (13 to 20 percent) whereas those of apolipoprotein Al did not, consistent with an increase in high-density lipoprotein3 levels, where apolipoprotein All is more abundant relative to apolipoprotein Al than in high-density lipoprotein2. Apolipoprotein B levels decreased 20 to 26 percent and those of apolipoprotein E went from 29 to 34 percent, relative to the 16 to 20 percent decreases in very low-density lipoprotein and low-density lipoprotein triglyceride and cholesterol levels. Five patients with combined elevations of triglyceride and low-density lipoprotein cholesterol treated with fenofibrate, had reductions primarily in triglyceride, total apolipoprotein E (50 percent reduction), and apolipoprotein B (18 percent) levels. High-density lipoprotein3 cholesterol levels increased 19 percent and high-density lipoprotein2 cholesterol levels were unchanged. Low-density lipoprotein cholesterol levels declined slightly in four patients and a slight rise was observed in a fifth patient.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Cervical cord compression due to extension of a papillary thyroid carcinoma.

A 76-year-old man with a long-standing neck mass presented with the acute onset of paraplegia. Computed tomographic scanning of the neck revealed direct involvement of the mass with several cervical vertebral bodies and extension into the spinal canal. Biopsy of the mass demonstrated well-differentiated papillary thyroid carcinoma. He received external radiation to the lesion but died shortly thereafter. This is the first report of cervical cord compression due to extension of a papillary thyroid carcinoma.

Aged↗
PubMed1987

The effects of dithiothreitol on thyroid stimulation in vitro.

There is evidence that the porcine TSH receptor contains essential disulphide bridge(s) which can be disrupted by dithiothreitol (DTT). The aim of the present study was to determine whether exposure of intact thyroid cells to DTT leads to altered thyroid stimulation. TSH-stimulated iodine organification in cultured porcine thyroid cells was studied following short-term DTT exposure; a dose-dependent inhibition was observed with DTT but not oxidized DTT. Cell viability, follicle formation, and total protein synthesis were preserved. A minimum of 30 min incubation with DTT was required for inhibition. However, under identical conditions, DTT had no effect on TSH or forskolin-stimulated cyclic AMP (cAMP) production. These results suggest that DTT inhibition of organification is mediated by post-receptor mechanisms likely involving thyroid peroxidase. The effects of DTT on thyroid stimulation in vitro does not appear to involve disruption of the disulphide bridge(s) in the TSH receptor.

Animals↗
PubMed1987

Nucleotide sequence and promoter mapping of the Escherichia coli Shiga-like toxin operon of bacteriophage H-19B.

We determined the nucleotide sequence of the Shiga-like toxin-1 (SLT-1) genes carried by the toxin-converting bacteriophage H-19B. Two open reading frames were identified; these were separated by 12 base pairs and encoded proteins of 315 (A subunit) and 89 (B subunit) amino acids. The predicted protein subunits had N-terminal hydrophobic signal sequences of 22 and 20 amino acids, respectively. The predicted amino acid sequence of the B subunit was identical to that of the B subunit of Shiga toxin. The A chain of ricin was found to be significantly related to the predicted A1 fragment of the SLT-1 A subunit. S1 nuclease protection experiments showed that the two cistrons formed a single transcriptional unit, with the A subunit being proximal to the promoter. A probable promoter was identified by primer extension, and transcription was found to increase dramatically under conditions of iron starvation. A 21-base-pair sequence with dyad symmetry was found in the region of the SLT-1 -10 sequence, which was found to be 68% homologous to a region of dyad symmetry found in the -35 region of the promoter of the iucA gene on plasmid ColV-K30, which specifies the 74,000-dalton ferric-aerobactin receptor protein. Betley et al. (M. Betley, V. Miller, and J. Mekalanos, Annu. Rev. Microbiol. 40:577-605, 1986) have recently summarized evidence suggesting that the slt operon is under the control of the fur regulatory system. The area of dyad symmetry found in both promoters may represent a regulatory site. A rho-independent terminator sequence was found 230 base pairs downstream from the B cistron stop codon.

Amino Acid Sequence↗
PubMed1986

Protein kinase C activators modulate differentiated thyroid function in vitro.

Exposure of porcine thyroid cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) leads to inhibition of differentiated thyroid function. We investigated whether this effect is mediated via protein kinase C activation. TPA, phorbol 12,13-didecanoate and phorbol 12,13-dibutyrate inhibited TSH-stimulated iodine organification in porcine thyroid cells by 98, 96 and 45%, respectively. Non-tumour promoting phorbol esters had no effect. The diacylglycerol analogue, sn-1,2-dioctanoylglycerol had similar but quantitatively less activity than TPA. Dibutyryl cAMP could not reverse any inhibition noted. Under conditions that caused significant inhibition of differentiated function, TPA caused translocation of thyroidal protein kinase C from the cytosol to its membrane-bound form. These data provide evidence that the mechanism of phorbol action on thyroid function in vitro includes activation of protein kinase C.

Animals↗
PubMed1986

Clinical applications of assays for thyrotropin-receptor antibodies in Graves' disease.

Graves' disease is characterized by hyperthyroidism, diffuse goitre, infiltrative ophthalmopathy and, rarely, pretibial myxedema. In 1956 a substance capable of prolonged thyroid stimulation was discovered in the serum of some patients with Graves' disease and termed long-acting thyroid stimulator (LATS). It was shown to be an antibody that could interact with the receptor for thyroid-stimulating hormone (TSH). The term LATS is usually reserved for the activity measured in a laborious in-vivo bioassay in mice. Today the activity of TSH-receptor antibodies (TSH-R Ab) can be measured by in-vitro bioassays or by radioreceptor assays. These assays are now becoming commercially available. TSH-R Ab assays may be useful in predicting the response to therapy for Graves' disease, investigating euthyroid ophthalmopathy and predicting the likelihood of neonatal hyperthyroidism.

Animals↗
PubMed1986

Thyrotrophin blocking antibodies in the sera of mothers with congenitally hypothyroid infants.

We examined IgG from 15 mothers of infants with congenital hypothyroidism for their ability to block TSH-stimulated iodine organification in vitro. Only one out of 15 of these IgGs exhibited TSH-blocking activity. This IgG could inhibit TSH action by 30-50%. It could not block radiolabelled TSH from binding to its receptor but did inhibit dibutyryl cyclic AMP stimulation of iodine organification implying a unique effect on post-receptor processes via a membrane binding site distant from the TSH binding site. Interestingly there was no evidence of autoimmune thyroid disease in the mother. These results suggest that the transplacental passage of TSH-blocking antibodies plays little, if any, role in the development of congenital hypothyroidism.

Antibodies↗
PubMed1985

Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin.

To minimize the cutaneous flushing symptoms associated with niacin use, a time-release capsule form of niacin has been formulated. Thus study compares the effects of time-release niacin with those of unmodified niacin on lipoprotein lipids, including HDL2 and HDL3, apoproteins A-I and A-II, clinical chemistries, symptomatic side effects, and adherence to the medication regimen. Seventy-one primarily hypercholesterolemic subjects were randomized to either unmodified niacin or time-release niacin ad took medication for a six-month period. The two groups were closely matched on anthropomorphic and lipid variables. Adherence to the therapeutic regimen at a dose of 1.5 g/d in the first month of treatment was similar in the two groups. Thereafter, at a dose of 3.0 g/d, adherence was in excess of 90% among subjects taking unmodified niacin but only 64% among those taking time-release niacin, chiefly because of aggravated gastrointestinal symptoms; cutaneous flushing side effects, however, were slightly less common with time-release niacin. At these levels of adherence, LDL cholesterol (C) was reduced 21% by unmodified niacin and 13% by the time release form. Plasma total triglyceride was reduced more with unmodified niacin (27%) than with time-release niacin (8% maximum), and HDL-C and HDL2-C were increased significantly with unmodified niacin (26% and 36%) and were not significantly changed by time-release niacin. Increased to a similar degree on both regimens were HDL3-C (approximately 35%) and apoA-I (approximately 12%). ApoA-II was not affected by either drug regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Thyroid stimulation by (Fab)2 and Fab fragments of TSH receptor antibody.

The TSH receptor binding and thyroid stimulating properties of (Fab)2 and Fab fragments of Graves' IgG have been investigated. (Fab)2 fragments were prepared by pepsin digestion of IgG and Fab fragments by reduction of (Fab)2 or papain digestion of IgG. (Fab)2 and Fab were effective in inhibiting TSH binding to its receptor with all five patients' sera studied and both preparations stimulated cyclic AMP release from isolated thyroid cells. However Fab fragments were less active thyroid stimulators than their parent (Fab)2 in all five cases. These studies indicate that antibody divalency is not essential for thyroid stimulation by TSH receptor antibodies.

Antibodies↗
PubMed1984

Decreased cognitive function in aging non-insulin-dependent diabetic patients.

A cross-sectional study was conducted to determine whether normal, age-related declines in cognitive function are accelerated in non-insulin-dependent (type II) diabetes mellitus. Study participants ranged in age from 55 to 74 years. Results indicate that cognitive function is inferior in the patients with type II diabetes compared with a comparably aged, nondiabetic control group. On the basis of a series of cognitive tests, it appears that the cognitive impairment is due to a deficiency in memory retrieval rather than to an attentional or encoding deficit. Cognitive performance is poorer in diabetic patients with peripheral neuropathy or elevated hemoglobin A1c levels. The apparent cognitive impairment in aging patients with type II diabetes may complicate adherence to medical regimens.

Aged↗
PubMed1983

Transient neonatal hyperthyrotrophinaemia: a serum abnormality due to transplacentally acquired antibody to thyroid stimulating hormone.

In a screening programme for neonatal hypothyroidism an otherwise healthy female infant was found to have a high concentration of thyroid stimulating hormone in a filter paper blood spot and in serum. A high concentration was also found in the maternal serum. Mother and baby were both biochemically euthyroid with normal serum thyroxine concentrations. The apparently high concentration of thyroid stimulating hormone in the mother was due to the presence of an IgG antibody that bound to human but not bovine thyroid stimulating hormone. Maternal serum inhibited the action of human thyroid stimulating hormone in an in vitro bioassay for the hormone. It is suggested that the baby acquired the antibody transplacentally, especially as the concentration of thyroid stimulating hormone subsequently fell. It is concluded that maternal serum should be assayed for thyroid stimulating hormone when a neonate is found to have a high concentration of the hormone and a normal concentration of thyroxine to establish the incidence of this finding and to avoid inappropriate replacement treatment.

Female↗
PubMed1983

TSH receptor binding and thyroid stimulation by sera from patients with Graves' disease.

An investigation of the ability of TSH receptor antibodies to bind to the TSH receptor and stimulate thyroid function is described. Binding studies were carried out using 125I-labelled TSH and detergent solubilised porcine TSH receptors, and the parameter of thyroid stimulation employed was 125I-organification in isolated porcine thyroid cells. Different Graves' sera were found to show different dose-response relationships and three types of antibody activity were evident in the six samples studied. In two samples receptor binding and thyroid stimulating activities were approximately parallel. In two receptor binding was detectable at lower doses than stimulation while in the last two stimulation was detectable at lower doses than binding. It is proposed that these characteristics are due to different populations of receptor antibodies which exhibit different degrees of TSH agonism. Furthermore one of the reasons for the relatively poor correlation between TSH receptor binding and thyroid stimulation observed in series of individual Graves' sera may be the presence of different populations of antibodies showing different dose-response relationships with regard to binding and stimulation.

Autoantibodies↗
PubMed1982

Evidence that the porcine thyrotropin (TSH) receptor contains an essential disulphide bridge.

The effects of reducing agents on membrane bound and detergent solubilised porcine TSH receptors have been investigated. Both 2-mercaptoethanol and dithiothreitol appeared to inhibit the TSH-binding activity by a direct effect on the TSH receptor itself and Scatchard analysis suggested that this was primarily due to an alteration in TSH-binding capacity. In addition, some binding activity could be recovered by reoxidation of reduced receptor preparations. These results suggest therefore that the porcine TSH receptor contains an essential disulphide bridge.

Animals↗
PubMed1981

Ocular abnormality associated with partial duplication of chromosome 13.

We studied a one-year-old child with multiple malformations and a tandem duplication of the distal two-thirds of 13q. The overall findings were similar to those usually found with partial duplication of chromosome 13. The ocular pathologic findings, including monocular spherophakia, were not suggestive of any known chromosomal syndrome, and their cytogenetic significance is not known. A review of 42 other cases of partial duplication 13 revealed a high (85%) incidence of ocular anomalies, most of which were comparatively minor or involved the ocular adnexa. Although ocular anomalies in this syndrome are associated with changes in different regions of chromosome 13, the major ones are usually associated with duplication of the proximal third of 13q and minor ones with the distal two-thirds of 13q.

Abnormalities, Multiple↗
PubMed1980

Aplasia of the optic nerve with aniridia.

Aplasia of the optic nerve is a rare anomaly whose pathogenesis and relationship to other congenital disorders is poorly understood. We recently examined a 4-day-old infant who exhibited unilateral aplasia of the optic nerve and aniridia, as well as other ocular and extraocular anomalies. This report is prompted by our interest in the early morphogenesis of the eye and by a possible linkage between optic nerve aplasia, aniridia and associated anomalies in our patients.

Abnormalities, Multiple↗