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Biomedical subjects

B Wolf

Publications and source records attributed to B Wolf.

At least 289 records · Page 16Linked to original sources
PubMed1984

Hypothyroidism increases pancreatic thyrotropin-releasing hormone concentrations in adult rats.

The effect of hypothyroidism on pancreatic TRH (P-TRH) and P-TRH-degrading activity (P-TRH-DA) was studied in adult rats. Hypothyroidism was induced in three groups during 4, 6, or 9 weeks by propylthiouracil (PTU) in drinking water and a low iodine diet (LID). Another group received PTU-LID for 6 weeks, followed by 5 weeks on a normal diet to restore euthyroidism. A possible toxic effect of PTU per se was eliminated by treating one control group with PTU and T3. P-TRH and TRH-DA were measured by specific RIA. In the hypothyroid groups, P-TRH concentrations (mean +/- SEM) were increased 10-fold (6.95 +/- 2.09; 5.51 +/- 1.3; 9.79 +/- 3.3 pg/(mg X 100 g BW), respectively, with a control value of 0.55 +/- 0.39, P less than 0.01). This increase was reversible, as shown by the group on PTU-LID followed by a normal diet (0.58 +/- 0.39, NS). P-TRH-DA present in the control group was decreased after 4 weeks of PTU-LID treatment and totally abolished after 6 and 9 weeks of PTU-LID treatment. In conclusion, these results suggest that thyroid status modulates P-TRH concentrations. This effect may be due to the disappearance of the TRH-DA in response to hypothyroidism. P-TRH stores may be regulated by the enzyme(s) involved in P-TRH-DA.

Animals↗
PubMed1984

Streptozotocin treatment at birth induces a parallel depletion of thyrotropin-releasing hormone and insulin in the rat pancreas during development.

Elevated concentrations of TRH have been detected in the rat pancreas during the early days of life. The purpose of this study was to investigate further the cellular location of this peptide in the pancreas using streptozotocin (STZ) injected at birth. Pancreatic TRH and insulin contents were measured at different ages from birth until 35 days in rats injected with STZ and results compared with controls injected with the vehicle. A transitory hyperglycemic state was observed from day 1 to day 5 (maximum value 2.9 +/- 0.31 g/liter). After this period, although slightly hyperglycemic, STZ rats were not glucosuric . TRH and insulin contents followed two distinct patterns from days 1 to 5 and days 5 to 35. During the first period, an acute depletion of both substances was observed, the lower value observed reaching 2.7% and 9% of control values, respectively, for TRH and insulin. The TRH surge at day 2 was blunted. During the second period, insulin content increased to reach 42% of controls. On the contrary, recovery of TRH was not observed; TRH content was 9% of control at day 35. These results indicate that TRH is located in STZ-sensitive cells, in agreement with recent immunohistochemical data. The impaired capacity for TRH recovery remained unexplained and seems to indicate a difference in the biogenesis of insulin and TRH.

Aging↗
PubMed1984

Developmental pattern of TRH-degrading activity and TRH content in rat pancreas.

Thyrotrophin-releasing hormone (TRH), like several other neuropeptides, has been detected in the gastro-intestinal tract of adult rats. More recently, elevated concentrations of TRH have been found in the neonatal rat pancreas. This study was undertaken to evaluate pancreatic TRH degrading activity (TRH-DA) in infant rats from birth until adult life. Pancreatic TRH of age-matched rats was also measured by radioimmunoassay. TRH-DA was present in normal adult rat pancreas; though absent at birth and in the early postnatal period up to day 7, this activity was detected during the remainder of the developmental period. TRH content (pg +/- SEM per pancreas) was 1139 +/- 88 on day 1, reached a peak value of 7360 +/- 758 at day 2 and then decreased steadily to adult level. TRH-DA has been found to be present at birth in hypothalamus and liver but not in plasma. The developmental patterns of TRH-DA in plasma and in pancreas were parallel and seem to be thyroid hormone dependent. The absence of TRH-DA in the neonatal pancreas may also be related to the high TRH concentrations detected in this organ during the neonatal period.

Aging↗
PubMed1984

Effects of hypo- and hyperthyroidism on pancreatic TRH-degrading activity and TRH concentrations in developing rat pancreas.

High concentrations of thyrotrophin-releasing hormone (TRH) in the rat pancreas were detected during the first few days of life decreasing thereafter while pancreatic TRH-degrading activity (TRH-DA) absent at birth appeared on day 14 and increased to reach adult values by day 21. This period of life is also remarkable by the low level of circulating thyroid hormones. Since TRH-degrading activity may be thyroid hormone dependent it was of interest to study the effects of thyroid status fluctuations both on TRH-DA and TRH content during the neonatal period. In this study, hypo- and hyperthyroidism were induced by 6-n-propyl-2-thiouracil (PTU) and triiodothyronine (T3) respectively. Pancreatic TRH-DA and TRH concentrations were measured at different ages from birth until day 29, in treated animals and results compared to control age-matched rats. In hypothyroid rats, pancreatic TRH concentrations remained significantly higher after day 16 while TRH-DA was lower during the whole period studied. Following T3 treatment, pancreatic TRH concentrations decreased significantly from day 3 onwards. However, no significant changes were found for TRH-DA except a two-fold increase on day 28. These results suggest that two different mechanisms may account for thyroid hormones action: 1) a direct effect on pancreatic TRH 2) an inductive saturable effect on TRH-DA. Furthermore a fine tuner modulatory role of TRH-DA on TRH concentrations cannot be excluded.

Age Factors↗
PubMed1984

Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies.

Monoclonal antibodies (MoAbs) were raised against epidermal growth factor (EGF) receptors on a human epidermoid carcinoma cell line, A431. Administration of anti-EGF receptor MoAbs inhibited tumor formation in athymic mice by A431 cells and by another epidermal carcinoma cell line, T222. When one of the same MoAbs was used in therapy against Li-7 (a human hepatoma) and HeLa cells (a cervical carcinoma), tumor growth was not affected. The number of EGF receptors on A431 cells was about 100-fold higher than on T222, Li-7, and HeLa cells, suggesting that the number of EGF receptors may not be an important determinant in suppressing tumor growth. Three anti-EGF receptor MoAbs were used in the present studies. MoAbs 528 (immunoglobulin G2a) and 225 (immunoglobulin G1) are capable of competing with EGF for receptor binding and inhibit proliferation of A431 cells in culture. The other MoAb, 455 (immunoglobulin G1), is incapable of blocking the binding of EGF to its receptors and has no effect on the proliferation of cultured A431 cells. All three MoAbs inhibited A431 tumor growth in athymic mice, indicating that the antibody isotype and the site of binding on the EGF receptor are not the determinants of antiproliferative activity in vivo. The observation that MoAb against the receptor for EGF is cytostatic rather than cytocidal in vitro against A431 cells, yet completely prevents tumor growth in vivo, suggests that some host animal responses also may be involved in the antitumor effect. MoAbs against growth factor receptors could provide useful immunotherapeutic agents.

Animals↗
PubMed1984

Differences in the ultrastructural localization of carcinoembryonic antigen in human breast and in colon tumour cells.

The ultrastructural localization of carcinoembryonic antigen (CEA) has been compared in human breast and in human colon tumour cells, utilising immunohistological methods at the electron microscope level. Colon tumours (cell line LS 174 T, and xenografted human colon tumours in nude mice) are characterized by a strong CEA-positivity attached to the outer cell membrane. In contrast, mammary carcinomas (bioptically prepared solid tumours) showed to extracellular membrane - bound labelling. In these tumours, extracellular CEA-localization was mainly found on electron dense bodies.

Animals↗
PubMed1984

Thymic hormone containing cells. IV. Fluctuations in the thyroid hormone levels in vivo can modulate the secretion of thymulin by the epithelial cells of young mouse thymus.

The influence of thyroid status on serum level and thymic content of thymulin, a thymic hormone, has been studied in young rats and mice treated by tri-iodothyronine (T3) or 6N-propyl-2-thiouracil (PTU). We showed that in vivo T3 administration induces in young animals an increase of their thymulin serum levels and of the number of thymulin containing cells in their thymuses. Conversely, a treatment with PTU decreases the thymulin serum levels and the number of cells containing the hormone. These findings suggest that thyroid hormones stimulate the synthesis and secretion of thymulin and represent further evidence for the hormonal influence on the regulation of thymic endocrine secretion.

Animals↗
PubMed1984

A screening method for biotinidase deficiency in newborns.

We describe a method for neonatal screening for biotinidase (EC 3.5.1.12) deficiency. Biotinidase activity is assessed colorimetrically from dried samples of whole blood spotted on the same filter papers as used in the neonatal screening for phenylketonuria. After the reaction, samples from normal infants are characteristically purple, whereas those from affected individuals are straw-colored. To confirm the deficiency, the enzyme is quantitatively assayed in additional blood spots or serum. A pilot study has been initiated with samples obtained by the Commonwealth of Virginia for phenylketonuria testing.

Amidohydrolases↗
PubMed1983

A sensitive radioassay for biotinidase activity: deficient activity in tissues of serum biotinidase-deficient individuals.

A new, sensitive radioassay for the determination of biotinidase activity was developed which measures the release of [14C-carboxyl]-p-aminobenzoate from N-biotinyl-[14C-carboxyl]-p-aminobenzoate. Biotinidase activity in serum from normal individuals is comparable to that determined by the colorimetric assay, but the radioassay is approximately 100 times more sensitive. Biotinidase deficiency was confirmed in the serum of patients who were previously shown to have reduced activities by the colorimetric assay. Although biotinidase activity was not detectable in extracts of normal peripheral blood leukocytes and fibroblasts using the colorimetric assay, activities could be measured by the radioassay. Using this method we demonstrated deficient biotinidase activity in extracts of leukocytes and fibroblasts from affected patients.

Carbon Radioisotopes↗
PubMed1983

Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency.

Late-onset multiple carboxylase deficiency is characterized clinically by skin rash, alopecia, seizures and ataxia and occasionally by candidiasis and developmental delay. Biochemically, these individuals exhibit findings consistent with a combined deficiency of the biotin-dependent carboxylases. We have found that the activity of the enzyme biotinidase is also deficient in the sera of five affected children (0 to 3% of mean control activity, 5.80 +/- 0.89 nmol X min-1 X ml-1 serum), and believe that it represents the primary biochemical defect in this disease. Biotinidase catalyzes the removal of biotin from the epsilon-amino group of lysine, through which biotin is covalently bound to the four known human carboxylases, thereby regenerating biotin for reutilization. The deficient activity in our patients was not due to an inhibitor, particularly biotin. It is also not a consequence of feedback control in affected individuals under treatment with pharmacologic doses of biotin. The biotinidase activities of the parents of those children who were available for study were intermediate between deficient and normal values (46% to 65% of mean normal activity). Children lacking biotinidase activity are unable to recycle biotin, and are thus entirely dependent upon exogenous biotin to prevent deficiency. Our findings indicate that the primary biochemical defect in late-onset multiple carboxylase deficiency is in biotinidase activity which is inherited as an autosomal recessive trait.

Amidohydrolases↗
PubMed1983

The measurement of propionyl-CoA carboxylase and pyruvate carboxylase activity in hair roots: its use in the diagnosis of inherited biotin-dependent enzyme deficiencies.

Two mitochondrial biotin-dependent enzymes, propionyl-CoA carboxylase and pyruvate carboxylase, are measurable in hair roots. A third biotin-dependent enzyme, beta-methylcrotonyl-CoA carboxylase, was barely detectable in hair roots. The diagnosis of isolated propionyl-CoA carboxylase deficiency was confirmed in hair roots of a known affected patient. This method should be a rapid and accurate method for the diagnoses of the various carboxylase deficiencies, particularly isolated pyruvate carboxylase deficiency in individuals with lactic acidosis, as well as for the assessment of biotin responsiveness in these patients.

Acidosis↗