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S Reichlin

Publications and source records attributed to S Reichlin.

At least 127 records · Page 7Linked to original sources
PubMed1983

Organ-specific binding of a thyrotropin-releasing hormone-diphtheria toxin complex after intravenous administration to rats.

We have previously demonstrated that a hybrid protein consisting of TRH linked to CRM45, a fragment of diphtheria toxin which lacks its native cell-binding moiety, specifically binds to TRH receptors in vitro. In this study we have examined its in vivo binding and shown that after iv injection, this complex labeled with 125I is selectively concentrated in the normal anterior pituitary and that concomitant administration of cold TRH reduces its uptake. Displaceable uptake was also demonstrated in the hypothalamus and testis, whereas nondisplaceable binding exceeding that of CRM45 alone was shown in the ovary and the breast parenchyma of lactating rats. Similar experiments with tritiated TRH were performed. We found that although there was uptake of the material by many tissues, almost all of the radioactivity was in the form of TRH degradation products. Therefore, we conclude that TRH linked to a large carrier like CRM45 may be a more revealing indicator of in vivo binding affinities than native TRH.

Animals↗
PubMed1983

Partial purification and characterization of thyrotropin binding inhibitory immunoglobulins from normal human plasma.

Whole human plasma contains a factor that inhibits the binding of bovine TSH to human thyroid membranes. To determine whether this activity is attributable to the presence of small amounts of immunoglobulin G (IgG) molecules that bind specifically to the thyroid, we have extracted from normal human plasma by a process of selective membrane adsorption a subfraction of IgG that is much more potent in TSH binding inhibition that the starting IgG. The enriched fraction was shown to be IgG by multiple criteria: precipitation in ammonium sulfate, elution by the anion exchange resin DEAE-cellulose, and electrophoresis in sodium dodecyl sulfate-urea polyacrylamide gel. Pretreatment with staphylococcal protein A, with specifically binds IgG, completely removed its activity. Significant TSH binding inhibition was retained under salt conditions, which have been shown to optimize the sensitivity and specificity of the TSH receptor. The enriched fraction was not an antimicrosomal or antithyroglobulin antibody, and did not bind to the TSH label. A similar enriched subfraction of bovine TSH binding inhibitory IgG could be prepared using membranes obtained from kidney and liver, suggesting that the membrane antigen with which it bound was not thyroid specific. These data indicate that in the plasma of individuals presumed to be free of thyroid disease there circulates low concentrations of an IgG which reacts with a thyroid membrane antigen(s). It may be an autoantibody or a normal constituent of plasma with specific binding properties.

Animals↗
PubMed1983

Sympathetic postganglionic unmyelinated axons in the rat peripheral nervous system.

We determined the contribution made to the unmyelinated axon population of the rat peripheral nervous system by sympathetic paravertebral ganglion cells. Sympathectomy, achieved by administration of guanethidine to neonatal rats, led to atrophy of the sympathetic paravertebral ganglion chain, a 95% decrease in peripheral nerve norepinephrine, and loss of 20 to 26% of the unmyelinated axons in a cutaneous nerve (sural), a muscular nerve (nerve to soleus), and a mixed nerve (sciatic). These data indicate that up to a quarter of the total population of peripheral nerve unmyelinated axons are sympathetic ganglia-derived.

Animals↗
PubMed1983

Unmyelinated axon subpopulations in the rat peripheral nervous system.

Using the neurotoxin capsaicin, we examined subpopulations of unmyelinated axons in mixed (sciatic), cutaneous (sural), and muscular (nerve to soleus) nerves. Administration of capsaicin to neonatal rats caused reduction of the sciatic nerve immunoreactive (IR)-substance P (by 45%) and IR-somatostatin (by 84%) contents. This correlated with a substantial reduction in unmyelinated axons in the sciatic and sural nerves (45% and 65%, respectively), although there was no significant decrease in unmyelinated axons in the nerve to soleus. In a parallel study, we have shown that sympathetic ganglia-derived unmyelinated axons account for about 20 to 25% of the total unmyelinated axon population in both the sural nerve and the nerve to soleus. Thus, in the sural nerve, the majority of unmyelinated axons are dorsal root ganglia-derived, contain either substance P or somatostatin, and are capsaicin-sensitive; whereas in the nerve to soleus, the majority of unmyelinated axons are dorsal root ganglia-derived but are insensitive to capsaicin and do not contain substance P or somatostatin. These latter unmyelinated axons presumably contain a yet to be defined neurotransmitter and may be the axons connecting with muscular ergoreceptors, a subpopulation of unmyelinated axons that are biochemically and functionally distinct from the unmyelinated axons of cutaneous nerves.

Animals↗
PubMed1982

Effects of neurotransmitters and cyclic AMP on somatostatin release from cultured cerebral cortical cells.

The influence of cortical neurotransmitters and cyclic AMP on the release of immunoreactive somatostatin (IRS)from cultured cortical cells was examined. Cells were obtained by mechanoenzymatic dispersal of telencephalons of 17-day-old rat embryos and were maintained as monolayers in minimum essential medium with 10% heat-inactivated horse serum. After the cultures had stabilized morphologically and in cellular IRS content they were subjected to rapid sequential changes of a buffered salt solution with or without test substances added. The amount of somatostatin released was measured by a specific radioimmunoassay. Acetylcholine and the GABA antagonist, picrotoxin, both stimulated IRS release. The cholinergic stimulation was predominantly muscarinic. GABA and histamine, to a lesser extent, were inhibitory and norepinephrine and serotonin produced no net change in IRS release. Both cAMP and theophylline (DMX) stimulated IRS release. These results confirm the potential of intrinsic cortical somatostatinergic neurons to respond to endogenous neurotransmitters and further establishes somatostatin as a cortical neuromodulator.

Acetylcholine↗
PubMed1982

Age-related probability of development of hereditary medullary thyroid carcinoma.

Hereditary medullary thyroid carcinoma is inherited as an autosomal dominant trait; at birth each child of an affected parent has a 50% chance of developing the disease. Measurement of plasma calcitonin concentrations after provocative calcium or pentagastrin stimulation has proved useful in the early diagnosis of this disease. To determine the age-related risk of conversion from a negative to a positive provocative test, 445 members of 11 kindreds were studied with sequential tests. Of 159 family members with a 50% risk at birth of developing medullary thyroid carcinoma 38 converted from a negative to a positive test result (mean age of conversion was 15 years). By means of methods previously described for determining the age-related probability for developing Huntington chorea, we present a method for determining the probability of development of medullary thyroid carcinoma. An individual at risk whose test result was negative had the following probability of converting to a positive test result at a later date: age (years)/probability, 0/0.5; 5/0.49; 10/0.41; 15/0.25; 20/0.16; 25/0.10, 30/0.05; and 35/0. We conclude that hereditary medullary thyroid carcinoma is regularly detectable in the pediatric age group and that screening should begin by age 5 years and be continued at regular intervals until age 35.

Adolescent↗
PubMed1982

Sodium- and calcium-dependent somatostatin release from dissociated cerebral cortical cells in culture.

The influence of membrane depolarization on somatostatin release from cerebral cortical neurons was examined. Fetal rat telencephalic cells, obtained by mechanoenzymatic dispersal, were maintained as organotypic monolayer cultures for 12 days before experimental studies. The immunoreactive somatostatin (IRS) released into the medium during a treatment epoch was compared to the amount released from the same cells during an immediately preceding control period. Potassium (60 mM) induced an increase in IRS secretion which was dependent on extracellular calcium concentration and could be prevented by the addition of the calcium channel blockers, cobalt or verapamil. Depolarization by veratridine, a sodium ionophore, also stimulated IRS release. The effect of veratridine was reversed by simultaneous exposure of the cells to either tetrodotoxin, a sodium channel blocker, or verapamil, a calcium channel blocker. These findings indicate that IRS release by cerebral cortical cells is stimulated by membrane depolarization and is dependent on both Na+ and Ca++ entry into the cells.

Animals↗
PubMed1982

Surgical cure of prolactinoma reverses abnormal prolactin repsonse to carbidopa/L-dopa.

To determine whether the abnormalities in dopaminergic regulation of PRL secretion in patients with prolactinomas persist after resection of the adenoma, we evaluated PRL inhibitory responses to L-dopa alone and L-dopa given after pretreatment with the dopa decarboxylase inhibitor carbidopa before and after transsphenoidal selective resection of prolactinomas in 23 women. Eighteen women were cured by surgery (normal PRL, menses, no galactorrhea), while 5 women were not cured. Preoperatively, the PRL inhibitory responses to L-dopa cured, 4 .3 +/- 3.8%; uncured, 50.1 +/- 5.5% of baseline) was blunted by pretreatment with the decarboxylase inhibitor carbidopa (cured, 79.1 +/- 4.1%; uncured, 76.8 +/- 9.2%). Postoperatively, this blunting disappeared in the cured patients (L-dopa, 49.1 +/- 3.5%; carbidopa/L-dopa, 56.3 +/- 5.1%), but the blunting persisted in the uncured patients (L-dopa, 49.3 +/- 7.9%; carbidopa/L-dopa, 69.3 +/- 4.2%). The return to normal of the carbidopa/L-dopa test in cured prolactinoma patients after surgery is evidence that in these individuals, preoperative abnormalities of secretion are due to either intrinsic abnormalities of the tumor or alteration of hypothalamic function secondary to tumor secretion. In those patients not cured by surgery, dynamic tests of function remain abnormal, findings attributable to either incomplete tumor resection or the presence, in some patients, of underlying hypothalamic dysregulation.

Adenoma↗
PubMed1981

Effects of thyroid hormones and thyrotropin-releasing hormone on thyrotropin biosynthesis by mouse pituitary tumor cells in vitro.

Mouse thyrotropic tumor cells grown in primary culture were shown to synthesize TSH and proteins, as determined by the incorporation of radioactive proline into immunoprecipitable TSH and trichloroacetic acid-precipitable proteins. The net TSH content of the cells and medium determined by RIA is also increased during 24 h of incubation, and newly formed hormone is detected in the medium within 1 h after the addition of proline tracer. To study the effect of T4 and T3 on TSH synthesis, cultures were pulse-labeled with [3H]proline after they had been exposed to either T3 or T4. After 48 but not 24 h, exposure to either T3 or T4 was followed by inhibition. When studied after 48 h of incubation, T4, (10(-13) M) or T3 (10(-11) M) at the lowest concentration tested, was inhibitory to TSH synthesis. At concentrations of T4 and T3 greater than 10(-9) M, the inhibitory effects on TSH synthesis were partially reversed, suggesting a biphasic response. Incubation in TRH (10(-7) M) for 24 h led to a significant increase in TSH synthesis, total protein, acid-precipitable protein, and total DNA. The effect of TRH on TSH biosynthesis was a function of the logarithm of its concentration over the range of 10(-11)-10(-7) M. The inhibitory action of 10(-6) M T3 on TSH synthesis was reversed by exposure to 10(-10) or 10(-7) M TRH.

Animals↗
PubMed1981

Immunoreactive adrenocorticotropin in the gastrointestinal tract and pancreatic islets of the rat.

Radioimmunoassayable ACTH is detectable in the gastrointestinal tract and pancreatic islets of the rat by using a midportion ACTH antiserum. Portions of the gastrointestinal tract and isolated pancreatic islets were extracted with 0.1 N HCl. Serial dilutions of the extracts resulted in inhibition curves parallel with human alpha ACTH-(1-39). The highest concentrations were in the isolated pancreatic islets (20 pg/ml protein) and the gastric antrum-pylorus (17.9 +/- 1.2 pg/ml protein). Chromatographic characterization of the stomach extract showed a main peak, with an elution constant identical to that of [125I]iodo-ACTH-(1-39) and an elution pattern identical to that of rat pituitary extracts and medium from incubated rat pituitaries.

Adrenocorticotropic Hormone↗
PubMed1981

Somatostatin in rat tissues is depleted by cysteamine administration.

Administration of cysteamine (mercaptoethylamine) induces in rats severe perforating duodenal ulcers. Because the ulcerogenic properties of cysteamine are markedly reduced by treatment with somatostatin, we considered the possibility that cysteamine-induced duodenal ulcer might be mediated by depletion of tissue somatostatin, and thereby of its paracrine influences on gastrin and gastric acid secretion. To test this hypothesis, we measured the concentration of immunoreactive somatostatin (IR-somatostatin) in stomach and duodenal mucosa at intervals after administration of a single ulcerogenic dose (30 mg/kg by stomach tube). IR-somatostatin in these tissues fell rapidly to reach a minimum at 4 h (stomach 31%, duodenum 60% of control respectively). IR-somatostatin in hypothalamus and pancreas decreased gradually to a minimum at 7 h. Another duodenal ulcerogen, propionitrile (10 mg/100 g bw, s.c.) which is more toxic than cysteamine, and several stressful procedures including ether anesthesia, restraint and s.c. formalin did not lower stomach or duodenal IR-somatostatin. Gut, pancreas and hypothalamic VIP levels were not influenced by cysteamine. These findings suggest that cysteamine is a relatively specific depletor of tissue somatostatin. Because blood levels of somatostatin fell, and only trivial amounts of the peptide were found in the stomach lumen after cysteamine administration, it appears likely that this agent acts at the cellular level to cause breakdown of preformed somatostatin and/or to acutely reduce its synthesis.

Animals↗
PubMed1981

Growth hormone secretory status is a determinant of the thyrotropin response to thyrotropin-releasing hormone in euthyroid patients with hypothalamic-pituitary disease.

To assess the influence of endogenous GH secretion on the TSH and T3 responses to TRH administration in patients with hypothalamic-pituitary disease, we analyzed tests in a selected group of 26 euthyroid patients with hypothalamic-pituitary disease and in 15 normal controls. Basal TSH levels and the TSH response to TRH were significantly greater in GH-deficient patients (group 1) than in patients with normal anterior pituitary function and unimpaired GH reserve (group II). However, the T3 response to TRH was significantly less in group 1 than in group II patients. In acromegaly (group III), the TSH response to TRH was blunted, while basal and stimulated T3 levels were no different compared to control levels. These findings suggest that endogenous GH depresses the TSH response to TRH while enhancing the thyroid secretion of T3 in response to the evoked TSH released.

Adolescent↗
PubMed1981

Bromocriptine therapy in acromegaly: use in patients resistant to conventional therapy and effect on serum levels of somatomedin C.

Seven patients with clinically active acromegaly who had not responded completely to previous surgical or radiation therapy were treated with bromocriptine. Bromocriptine was well tolerated; only one of the seven patients discontinued treatment secondary to side effects. Six of the seven patients improved during bromocriptine therapy, although GH levels were normalized in only two patients. All patients had elevated levels of somatomedin C (Sm-C) before therapy even when basal levels of GH were less than 10 ng/ml. One patient normalized both GH and Sm-C during bromocriptine therapy and had an excellent clinical response. Five patients had moderately good clinical responses; four of these patients had substantial falls in GH levels, but Sm-C levels fell minimally if at all in four and actually increased in one patient. In one patient, there was no change in clinical status, GH levels, or Sm-C levels. Thus, the clinical response did not correlate well with changes in Sm-C in most patients. The patterns of response to provocative stimuli of GH secretion in acromegaly were maintained during bromocriptine therapy, as has been previously been reported. Based on our experience, bromocriptine appears to be a useful adjunct in the therapy of acromegaly, even in patients who have had prior ablative therapy.

Acromegaly↗