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Biomedical subjects

M Szabo

Publications and source records attributed to M Szabo.

At least 73 records · Page 4Linked to original sources
PubMed1980

Somatostatin-like immunoreactivity in transplantable medullary carcinoma of rat thyroid: partial chromatographic and biological characterization.

Somatostatin-like immunoreactivity (SRIF-LI) has previously been demonstrated immunohistochemically in rat thyroid parafollicular cells. Studies were therefore performed to determine whether SRIF-LI was present in a transplantable medullary carcinoma of the thyroid (MCT) in the WAG/Rij strain of rat. SRIF-LI was found in MCT in significantly higher concentrations than in normal thyroid tissue. Thyroid and MCT SRIF-LI showed parallelism with the synthetic SRIF and RIA displacement curves and coeluted with synthetic SRIF on immunoaffinity chromatography. On gel filtration, thyroid SRIF-LI and the major peak of MCT SRIF-LI coeluted with synthetic SRIF. SRIF-LI of a larger molecular size was also present in the MCT. MCT and thyroid SRIF-LI coeluted with synthetic SRIF on high pressure liquid chromatography. MCT SRIF-LI purified by affinity chromatography was equipotent to synthetic SRIF in inhibiting dibutyryl cAMP-stimulated GH release by rat pituitary cells in monolayer culture. Serum SRIF-LI was elevated in tumor-bearing rats and showed characteristics similar to those of MCT SRIF-LI and synthetic SRIF on affinity and high pressure liquid chromatography (HPLC). Tumor-bearing rats showed diminished secretion of insulin after orally administered glucose and impaired secretion of GH in response to pentobarbital compared to normal control rats. The results indicate that SRIF-LI is produced in excessive quantities by a transplantable rat MCT and impairs the secretion of GH and insulin. The immunological, chromatographic, and biological properties of MCT SRIF-LI suggest that it is indistinguishable from synthetic SRIF.

Animals↗
PubMed1980

Ectopic production of somatostatin-like immuno- and bioactivity by cultured human pulmonary small cell carcinoma.

Eleven continuous cultures of human pulmonary small cell carcinoma cells were examined, and eight were shown to secrete quantities of somatostatin-like immunoreactivity (SRIF-LI) ranging from 0.07-27 ng/ml culture medium/4 days, SRIF-LI was also found in a 2-N acetic acid extract of one of three human pulmonary small cell carcinomas obtained at autopsy as well as in the extract of a solid tumor resulting from inoculation of nude, athymic mice with SRIF-LI-producing, cultured small cell carcinoma cells. The SRIF-LI produced by one continuous cell line, DMS 53, was characterized in terms of its immunological, chromatographic, and biological properties. SRIF-LI from DMS 53 culture media and lysed cells was heat stable and exhibited parallel displacement to synthetic SRIF standard in a double antibody RIA. DMS 53 SRIF-LI was quantitatively retained on an immunoaffinity column of sheep anti-SRIF-Sepharose 4B under neutral conditions and could be eluted with 2 N acetic acid. Gel filtration chromatography of immunoaffinity-purified SRIF-LI revealed multiple molecular weight forms, the largest of which had an apparent molecular weight of 10,000-12,000 daltons and may represent a precursor form. This high molecular weight SRIF-LI form was resistant to exposure to denaturing conditions (8 M urea or 4 M urea plus 0.5% mercaptoethanol), suggesting the absence of noncovalent and/or disulfide linkages. A low molecular weight form coeluted with synthetic SRIF. Additional evidence for the identity of this form with the tetradecapeptide was provided by highly specific reverse phase high performance liquid chromatography. The rate of degradation of high molecular weight SRIF-LI by the cultures was markedly reduced in comparison to that of the SRIF monomer, resulting in a preferential accumulation of high molecular weight SRIF-LI in 4-day culture medium. Bioactivity of DMS 53 SRIF-LI was assessed in 4-day primary monolayer cultures of rat adenohypophyseal cells where 10(-10)-10(-9) M synthetic SRIF elicited a linear log-dose suppression of 5 X 10(-4) M synthetic SRIF elicited a linear log-dose suppression of 5 X 10(-4) M dibutyryl cAMP-stimulated rat GH release. Immunoaffinity-purified SRIF-LI from DMS 53 lysed cells and 1-h serum-free incubation medium, which consisted predominantly of monomeric SRIF, was equipotent to synthetic SRIF, SRIF-LI from 4-day culture medium consisted mostly of the high molecular weight form and exhibited a reduced bioassay potency ratio relative to synthetic SRIF of 0.73 (95% confidence limits, 0.99-0.53). Chromatographically purified high molecular weight SRIF-LI had significant bioactivity with a bioassay to immunoassay ratio of 0.19 (95% confidence limits, 0.33-0.09). The demonstration of ectopic SRIF, production by human pulmonary small cell carcinoma is consistent with the proposed derivation of this tumor from a cell type in the amine precursor uptake and decarboxylation cell series.

Animals↗
PubMed1979

Acromegaly associated with a bronchial carcinoid tumor: evidence for ectopic production of growth hormone-releasing activity.

A patient with acromegaly, pituitary enlargement, and elevated plasma GH levels also had a bronchial carcinoid tumor. Signs and symptoms of active acromegaly along with elevated GH levels persisted for 11 yr after hypophysectomy and pituitary stalk section. Resection of the bronchial carcinoid reduced plasma GH to barely detectable levels. Extracts of the frozen carcinoid tumor were devoid of significant GH, but when added to isolated pituitary cells of estrogen-primed male rats in 4-day primary culture exhibited specific GH-releasing activity in vitro. These findings strongly suggest that the patient's acromegaly resulted from continual stimulation of pituitary somatotrophs by a GH-releasing factor secreted by the bronchial carcinoid.

Acromegaly↗
PubMed1976

Dissociation of prolactin-releasing activity from thyrotropin-releasing hormone in porcine stalk median eminence.

The prolactin (PRL)-releasing activity of porcine stalk median eminence (pSME) was characterized by an in vivo bioassay and concomitant radioi-munoassay of plasma PRL and thyrotropin (TSH) levels. Methanol extracts of pSME stimulated PRL release in 3-day estrogen-primed rats when administered by the intracarotid route in doses ranging from 0.1 to 2.0 pSME equivalents. Synthetic thyrotropin-releasing hormone (TRH) stimulated the release of PRL and TSH in the dose range of 10 to 300 ng. PRL release was greater in response to a maximally effective dose of pSME than the release elicited by a maximal dose of TRH, and pSME administered together with a greater than mazimally effective dose of TRH caused additional PRL but not TSH secretion. Lysine vasopressin and prostaglandin E1 and E2 stimulated PRL release only at doses several orders of magnitude greater than the dose present in pSME. Somatostatin inhibited the release of TSH but not that of PRL whether the stimulus employed was pSME or TRH. The effective inhibitory dose of somatostatin was also significantly greater than the reported hypothalamic content. When pSME was subjected to incubation with plasma, a treatment reported to inactivate TRH, TSH-releasing activity was destroyed to a greater extent than was PRL-releasing activity. When pSME was adsorbed onto charcoal, the supernatant solution was devoid of TRH, as determined by complete removal of a [3H]TRH marker, yet substantial PRL-releasing activity was retained. TSH-releasing activity eluted from the charcoal with methanol was considerably greater than that expected on the basis of the recovery of [3H]TRH, suggesting the presence in the crude extract of a TSH-release inhibitor or of a TSH-releasing factor other than TRH. Based on the above evidence, we conclude that crude pSME contains PRL-releasing substance(s) distinct from the tripeptide TRH.

Animals↗
PubMed1975

Effects of porcine stalk median eminence and prostaglandin E2 on rat growth hormone secretion in vivo and their inhibition by somatostatin.

The studies described were performed to develop a technically simple, yet sensitive in vivo model for growth hormone (GH) releasing activity in porcine stalk median eminence (pSME) extracts, to compare the GH releasing effects of pSME with those of prostaglandin E2 (PGE2), and to study the effect of somatostatin (SRIF) on the above stimuli. The use of the one day estrogen-primed male rat in conjunction with intracarotid injection of test materials provided a model sensitive to the injection of one pSME. Neither increasing the duration of estrogen pre-treatment nor reserpine resulted in a greater response. The GH releasing effects of pSME were directly related to the preinjection GH level. Two successive injections of pSME at 30 minute intervals evoked similar responses. In contrast, PGE2 effects were not potentiated by estrogen pre-treatment and were independent of the preinjection GH level. The GH releasing effect of pSME was not related to its content of TRH or K+. Extracts of porcine cerebral cortex also contained GH releasing activity, although at a lower concentration than in pSME. Somatostatin inhibited the GH releasing effects of pSME, PGE2, and cerebral cortex extract. These results provide evidence for the direct inhibitory effect of SRIF on GH secretion in vivo and suggest that SRIF is capable of blocking a variety of different stimuli to GH release.

Animals↗
PubMed1975

Big growth hormone (GH): conversion to small GH without peptide bond cleavage.

Mercaptoethanol treatment of big growth hormone (GH) obtained from human pituitary resulted in a 60% conversion to small GH. Further dissociation was obtained by combined treatment with the reducing agent plus urea. The results indicate that the existence of big GH is dependent upon the formation of inter-polypeptide chain disulfide bonds.

Binding Sites↗
PubMed1973

Thyrotropin and cyclic nucleotide effects on prostaglandin levels in isolated thyroid cells.

Thyrotropin increases prostaglandin levels in isolated thyroid cells. Since comparable results were obtained with butyrated cyclic adenosine monophosphate derivatives as well as with the phosphodiesterase inhibitors quazodine and theophylline, it appears that cyclic adenosine monophosphate mediates this effect of thyrotropin. These observations suggest that intracellular prostaglandins play a role in modulating thyrotropin action on thyroid.

Animals↗