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Biomedical subjects

A Grossman

Publications and source records attributed to A Grossman.

At least 235 records · Page 13Linked to original sources
PubMed1985

N-myc amplification in multiple homogeneously staining regions in two human neuroblastomas.

Molecular characterization of two human neuroblastoma cell lines has revealed that both contain multiple homogeneously staining regions (HSRs), each representing a chromosome site of N-myc amplification. The newly established cell line CHP-382/JK had two cytogenetically distinct populations with several identical chromosomal abnormalities, indicating a common progenitor cell. Each population had one HSR, one on chromosome 5 at q31-34 and the other on chromosome 2 at q31-32. Chromosomal in situ hybridization with the N-myc probe pNb-1 demonstrated that both HSRs contained amplified copies of N-myc. Southern blot analysis confirmed amplification of N-myc sequences in genomic DNA of CHP-382/JK. Chromosomal features of CHP-382/JK shared with other neuroblastoma cell lines were the deletion of 1p and the presence of extra 17q material. In addition, the cells were highly reactive to monoclonal antibody PI 153/3 used to identify human neuroblastoma. CHP-382/JK cells were further characterized as neuronal cells by the expression of neurotoxin-responsive Na+ channels. Another neuroblastoma cell line, CHP-134, contained a single cell population with three HSRs, one in the short arm of each chromosome 7 and one in the long arm of a chromosome 6. All three HSRs contained amplified copies of N-myc as shown by in situ hybridization with the N-myc probe pNb-1. One of the 7p HSRs was acquired during culture of CHP-134 cells, whereas the 2q HSR of CHP-382/JK was lost. Such findings highlight the continued process of N-myc amplification and transposition in vitro. To our knowledge, amplification of N-myc in multiple HSRs has not been documented previously in neuroblastoma cell lines.

Antibodies, Monoclonal↗
PubMed1985

The relationship between serum prolactin and immunocytochemical staining for prolactin in patients with pituitary macroadenomas.

We have studied the relationship between mean pretreatment levels of serum prolactin and the presence of positive immunohistochemical staining for prolactin in the pituitary tumours of 55 patients. Pretreatment serum prolactin was significantly higher in patients with tumours showing many prolactin immunostaining cells than in those with none (P less than 0.001). When the pretreatment serum prolactin exceeded 6000 mU/l, the tumours contained over 90% of prolactin positive cells; one patient was an exception who had received long-term high dose bromocriptine therapy, and her tumour showed only occasional cells with positive staining. When the pretreatment serum prolactin level was under 2500 mU/l, a tumour was found which showed either no cells or fewer than 1% of cells which stained for prolactin. There was no significant difference in pretreatment serum prolactin levels between 11 patients with craniopharyngiomas and 34 patients with pituitary macroadenomas showing no prolactin immunostaining. Seventy-one percent (32) of the 45 patients with craniopharyngiomas or tumours with negative immunostaining for prolactin, had raised pretreatment serum prolactin levels (above 360 mU/l) although this was usually only slightly elevated; the levels exceeded 2500 mU/l in six (13%) of them (two craniopharyngiomas, four pituitary tumours) but in none did the levels exceed 6000 mU/l. Four of the 55 pituitary tumours showed occasional cells (less than 1%) that stained positively for growth hormone. In none of the patients with these tumours was there evidence of acromegaly or pathologically elevated circulating growth hormone levels.

Adenoma↗
PubMed1985

Evidence for the participation of endogenous opioids in the sympathoadrenal response to hypoglycaemia in man.

The effects of the long acting met-enkephalin analogue D-Ala2-MePhe4-met-enkephalin-O-ol (DAMME) and the opiate antagonist naloxone on the plasma catecholamine responses to insulin-induced hypoglycaemia have been investigated in two separate studies. DAMME depressed basal noradrenaline and adrenaline at 15 min, and blunted both the noradrenaline and adrenaline responses to hypoglycaemia. Naloxone did not alter basal plasma catecholamines, but caused a significant enhancement of the adrenaline response to hypoglycaemia. Neither DAMME nor naloxone altered the blood glucose response to insulin-induced hypoglycaemia. These data are consistent with an inhibitory modulation of endogenous opioids in the sympathoadrenal response to insulin-induced hypoglycaemia in man.

Adrenal Medulla↗
PubMed1985

Comparison of the clinical activity of mesulergine and pergolide in the treatment of hyperprolactinaemia.

The clinical activity of the new ergoline, mesulergine, was compared to pergolide in the treatment of hyperprolactinaemia. Mesulergine was given to 22 women and five men with hyperprolactinaemia. Serum prolactin was substantially lowered in 10 women; two subsequently conceived and completed normal pregnancies. Twelve women stopped treatment due to side-effects, usually nausea and vomiting, or inadequate responses. The side-effects were generally similar to those on bromocriptine; in one patient they were better and in four worse than on bromocriptine. The male patients were more tolerant of mesulergine, and substantial falls in serum prolactin were seen with evidence of tumour shrinkage. Twenty-seven women with hyperprolactinaemia received pergolide; serum prolactin was lowered or normalized in 16. Side-effects necessitating cessation of treatment were similar to those seen with bromocriptine. Nevertheless, four women tolerated pergolide better than bromocriptine and two women adequately treated with mesulergine had previously been intolerant of pergolide. We conclude that both pergolide and mesulergine may be useful and effective drugs in the treatment of hyperprolactinaemia as alternatives to bromocriptine.

Adenoma↗
PubMed1985

The effect of dopamine agonist therapy on large functionless pituitary tumours.

Fifteen patients (12 male) with large pituitary tumours and serum prolactin levels below 1000 mU/l were given dopamine agonist therapy (bromocriptine, mesulergine or pergolide) for a mean of 9 months (range 3-36 months). Serum prolactin became undetectable in all. Despite this, significant suprasellar extensions and any associated neurological defect remained in 14 patients, who therefore were referred for surgery. In one patient there was evidence of spontaneous pituitary infarction unrelated to dopamine agonist therapy. At operation 12 patients had apparently functionless pituitary adenomas which failed to immunostain for prolactin, one had an epidermoid cyst and one a Rathke's pouch cyst. We conclude that patients with large pituitary tumours and only a mildly elevated serum prolactin are unlikely to have prolactinomas, and that such tumours are not likely to show significant tumour shrinkage with medical treatment with dopamine agonists.

Adenoma, Chromophobe↗
PubMed1985

The use of growth hormone-releasing hormone in the diagnosis and treatment of short stature.

We have assessed the role of growth hormone-releasing hormone (GHRH) as a diagnostic test in 40 children and young adults with growth hormone deficiency (GHD), principally using the GHRH(1-29)NH2 analogue. Following 200 micrograms GHRH as an acute intravenous bolus, serum GH rose to normal or just subnormal levels in 13 out of 17 children with structural lesions, and in 8 of 14 patients with idiopathic GHD or panhypopituitarism. Of 9 children (mean age 12 years) with GHD following treatment with cranial irradiation for nonendocrine tumours, all responded acutely to GHRH. 12- and 24-hour infusions with GHRH(1-29)NH2, and 1- and 2-week treatments with twice-daily subcutaneous GHRH(1-29)NH2, showed persistent stimulation of GH release. It is concluded that many children with GHD of diverse aetiology will respond both acutely and chronically to treatment with GHRH.

Adolescent↗
PubMed1985

Evidence that the [3H]estradiol-binding protein in pancreas is localized in exocrine cells.

Extracts of rat pancreas contain significant amounts of an [3H]estradiol-binding protein. The amount of steroid-binding activity that could be measured varied considerably depending on the tonicity of the homogenizing medium. High speed supernatants of homogenates initially prepared in isotonic buffer contained about 10% of the binding activity as homogenates prepared in hypotonic buffer. Extraction with hypotonic buffer of pellets obtained by the isotonic procedure yielded most of the remaining [3H]estradiol-binding activity. In an attempt to avoid errors resulting from incomplete homogenization and to detect possible changes in intracellular distribution of [3H]estradiol-binding activity, pancreata were initially homogenized in isotonic buffer and centrifuged at high speed (100,000 X g; 1 hr). The pellet was then extracted with hypotonic buffer and centrifuged again at high speed, and both supernatants were analyzed for [3H]estradiol-binding and amylase activities. Two or 14 days after treatment of male rats with streptozotocin, no apparent decline or redistribution of [3H]estradiol-binding activity to the cytosol was noted despite extensive alteration of beta-islet cells, as determined by electron microscopic examination of sections of these pancreata and significant loss of insulin, as measured by RIA. Amylase activity was unaffected 2 days after streptozotocin treatment, but was depressed to about 1% of control levels at 14 days. Administration of insulin to the latter group of animals resulted in return of amylase to normal levels and a modest increase (approximately 50%) in [3H]estradiol-binding activity. Since amylase levels remained unchanged 2 days after streptozotocin treatment, during which time beta-islet cells were irreversibly altered, and amylase activity was restored to normal levels by insulin treatment after its depletion in chronically treated animals, it follows that neither amylase nor the [3H]estradiol-binding protein could have been associated with beta-islet cells. This was consistent with the observation that M cells (a tumor line of beta-cells only) and 14B cells (a cloned variant of this insulinoma) had neither detectable amounts of amylase nor [3H]estradiol-binding activity. To determine whether estrogen-binding activity was associated with any other type of islet cell, islets of Langerhans were isolated by the sedimentation procedure of Lacy and Kostianovsky. In this procedure, several washing steps are employed to separate the suspended acinar cells from the denser islets that sediment rapidly. During this isolation procedure, the cells from each wash were analyzed for protein, [3H]estradiol-binding protein, and amylase a

Amylases↗
PubMed1985

Effects of dopamine and morphine on immunoreactive somatostatin and LH-releasing hormone secretion from hypothalamic fragments in vitro.

Dopamine and morphine modulate GH and LH release, probably at a hypothalamic locus. To investigate this in more detail, we studied the influence of these substances on somatostatin and LH-releasing hormone (LHRH) release from rat hypothalamic fragments in vitro. Hypothalamic fragments were incubated in Earle's medium. After 60 min of preincubation, medium from two 20-min incubations was collected and somatostatin and LHRH levels measured by radioimmunoassay. Dopamine (10 nmol/1-0.1 mmol/l) induced a progressive increase (r = 0.41; P less than 0.01) in basal somatostatin levels. K+ (30 mmol/l)-induced somatostatin release was also increased (r = 0.54; P less than 0.01) by increasing doses of dopamine. Metoclopramide (10 mumol/l) blocked the dopamine (1 mumol/l)-induced increase in somatostatin release. No significant relationship between dopamine and LHRH was found either basally or after K+ (30 mmol/l) stimulation. Basal somatostatin was negatively correlated (r = -0.63; P less than 0.01) with morphine concentrations. No significant correlation was found after K+ (30 mmol/l) depolarization. Basal LHRH release was not influenced by morphine, while K+ (30 mmol/l)-induced release was significantly lower than controls only at a concentration of 10 nmol/l. These results suggest that dopamine and morphine act at a hypothalamic level to modulate GH release through alterations in somatostatin secretion. Dopamine and morphine have no consistent effect on hypothalamic LHRH release.

Animals↗
PubMed1985

Endorphins: what are they? How are they measured? What is their role in exercise?

A generalized knowledge of opiates has been available for centuries, but it was not until 1975, following the isolation of the first endogenous opioids, that it was appreciated that their analgesic properties were mediated via specific receptors. Three general classes of opioids are now recognized: the endorphins, the enkephalins, and the dynorphins. Assaying of the endogenous opioid peptides has never been simple, and now radioimmunoassay has replaced the earlier bioassays. When coupled with immunohistochemical techniques, radioimmunoassay allows precise localization of opioids in various tissue sections. There is evidence that plasma concentration of endorphins, and possibly also met-enkephalin, increases with exercise. In addition, the opioid peptides have important implications for the effects of other hormonal functions, including the pituitary hormones and catecholamines. Few studies during exercise are available, and naloxone has been used widely as the agent to determine the role of endogenous opioids on hormonal secretions. Slightly conflicting results have been obtained, depending on the dosage of naloxone used. With high-dose naloxone, there appears to be overall endorphin inhibition of cortisol, prolactin, and growth hormone secretion. Endorphins do not appear to exert a major influence on the cardiovascular response to exercise, but in high-intensity exercise, they appear to partially inhibit the ventilatory response to exercise.

Adrenocorticotropic Hormone↗
PubMed1985

Endorphins: "opiates for the masses".

Endogenous opioid peptides rose to prominence with the discovery of the enkephalins in 1975. Since then, a vast amount of research has been directed toward understanding their role in normal and pathophysiological situations. Although the place of endogenous opioids in psychiatry remains uncertain, there is good evidence that a variety of tumors may secrete endorphins or enkephalins, and these may contribute to the non-metastatic complications of malignant disease. In addition, changes in cerebrospinal fluid met-enkephalin and beta-endorphin after acupuncture may be involved in the effectiveness of this therapy in the treatment of heroin withdrawal and severe pain. The hormonal effects of opiate agonists and antagonists are now well characterized; exercise-induced changes in circulating catecholamines are markedly enhanced by the opiate antagonist naloxone. It is possible that the opiate inhibition of catecholamine release during exercise is a reflection of endogenous opioid modulation of effort perception.

Acupuncture Therapy↗
PubMed1985

Vestibular evaluation of infants and preschool children.

This article presents an updated summary of vestibular test modifications employed at the Boys Town National Institute for Communication Disorders in Children. In addition, we report the results of vestibular evaluations of 104 full-term and premature children (47 male and 57 female) ranging in age from 3 months to 6 years, including a group of postmeningitic patients. The evaluations utilized harmonic acceleration (HA). No age-related maturational differences in HA gain, phase, or symmetry for an 0.08 Hz screening frequency were found when full-term and premature infants were compared. Infrared video technology was adapted to provide continuous visual monitoring of head and eye position in the totally darkened test enclosure.

Caloric Tests↗
PubMed1984

The synthetic protease substrate N-benzoyl-L-argininyl-p-nitroanilide activates specific binding of [3H]estradiol to a protein in rat pancreas: relationship of structure to activity.

N-benzoyl-L-arginyl-p-nitroanilide (BAN), a synthetic substrate for trypsin-like proteolytic enzymes, is a potent activator of [3H]estradiol-binding to a protein present in rat pancreas. When partially purified, this protein is almost devoid of [3H]estradiol-binding activity in the absence of an endogenous accessory factor. BAN can mimic the natural coligand in this steroid binding reaction. The effect of BAN is specific since a number of derivatives of this substance are inactive or may even inhibit steroid binding. It is unlikely that BAN exerts this stimulatory action indirectly, possibly by preventing proteolytic inactivation of the [3H]estradiol-binding protein, since preincubation of the protein in the absence of BAN resulted neither in reduced rate, nor extent, of steroid binding following BAN addition. Also, a number of protease inhibitors had no effect on the binding reaction. Of those inhibitors tested, only antipain significantly enhanced binding of [3H]estradiol, but only about 20 percent as effectively as BAN.

Anilides↗
PubMed1984

Glucose-induced changes in somatostatin-14 and somatostatin-28 released from rat hypothalamic fragments 'in vitro'.

Previous data suggest that somatostatin is present and released from the hypothalamus in several molecular forms, basally and after K+ or electrical stimulation. In order to evaluate the proportions of somatostatin-14 (S14) and somatostatin-28 (S28) released during a stimulus which may be more closely related to the control of growth hormone secretion 'in vivo', we studied the molecular forms of somatostatin released from hypothalamic fragments ' in vitro', during incubations with different glucose concentrations (1.35 and 22mM), which we have previously shown to be inversely related to somatostatin release. Sephadex G-50 chromatography demonstrated that both forms are released in the same proportions (S14: 70%; S28: 30%) during incubation with different glucose concentrations; there is a parallel increase in both forms when low glucose is used. Although on a molar basis less S28 is released than S14, the higher potency, longer duration of action and higher affinity for pituitary receptors of S28 suggests that it may be of major physiological importance.

Animals↗
PubMed1984

Growth hormone releasing factor: comparison of two analogues and demonstration of hypothalamic defect in growth hormone release after radiotherapy.

Human pancreatic growth hormone releasing factor (hpGHRF(1-40] stimulates the release of growth hormone in normal subjects and some patients with growth hormone deficiency. A study comparing the shorter chain amidated analogue hpGHRF(1-29) with an equivalent dose of hpGHRF(1-40) in seven normal subjects showed no significant difference in growth hormone response between the two preparations. Six patients with prolactinomas were also tested; these patients had received megavoltage radiotherapy previously but had developed growth hormone deficiency as shown by insulin induced hypoglycaemia. In all six patients 200 micrograms hpGHRF(1-40) or hpGHRF(1-29)NH2 produced an increase in the serum growth hormone concentration. These data suggest that hpGHRF(1-29)NH2 may be useful for testing the readily releasable pool of growth hormone in the pituitary and that cases of hypothalamo-pituitary irradiation resulting in growth hormone deficiency may be due to failure of synthesis or delivery of endogenous GHRF from the hypothalamus to pituitary cells.

Adult↗
PubMed1984

Treatment of prolactinomas with megavoltage radiotherapy.

The outcome of treatment of 36 women with prolactinomas using megavoltage radiotherapy combined with interim dopamine agonists (bromocriptine, lysuride, pergolide) was reviewed; 16 of the women showed radiological evidence of a macroadenoma. The most common presenting symptom was secondary amenorrhoea; 26 of the patients had galactorrhoea. In 29 patients who wished to conceive the ovulation rate (as indicated by circulating progesterone concentrations) was 97% and the successful fertility rate 86%. No patient had enlargement of the tumour during pregnancy and there were no complications of radiotherapy. No further tumour enlargement was detected in serial skull radiographs, and an improvement in size of the fossa was noted in 45% of those assessed. When medical treatment was withdrawn a mean of 4.2 years (range 1-11) after radiotherapy in the 27 patients who had completed their families the serum prolactin concentration had fallen appreciably in 26 of them and later became normal in eight. The incidence of growth hormone deficiency rose from 24% of the whole group before radiotherapy to 79% afterwards. Only one patient required thyroxine, and one was receiving gonadotrophin. No patient became deficient in adrenocorticotrophic hormone. A regimen of megavoltage radiotherapy and interim bromocriptine allows women with prolactinomas safely to undergo pregnancy and results in the long term prospect of tumour shrinkage and control of hyperprolactinaemia.

Adenoma↗
PubMed1984

Evidence that somatostatin (SRIF14) is the primary coligand in pancreas required for specific binding of [3H]estradiol in pancreatic tissue: demonstration that [3H]estradiol and [125I]SRIF14 form complexes of varying size with a specific binding protein.

There is present in rat pancreas a protein that requires an accessory factor in order to bind [3H]estradiol. To identify this accessory factor 874g of dog pancreas were acid extracted, and following selective filtration and dialysis, the low molecular weight constituents (less than 10,000) were concentrated by lyophilization. Samples of this lyophilizate were fractionated by high performance liquid chromatography (HPLC) and eluate fractions analyzed for their capacity to enhance binding of [3H]estradiol to a protein fraction from rat pancreas that had been purified relatively free of endogenous accessory factor. Such enhancement of [3H]estradiol-binding activity eluted predominantly in one peak that coincided with the elution profile of pure somatostatin (SRIF14). Analysis of eluate fractions for somatostatin-like immunoreactive material (SLIM) indicated coincidence of SLIM with the factor that enhanced binding of [3H]estradiol. It appears likely that accessory factor in pancreas is primarily somatostatin (SRIF14). Following incubation of [125I]SRIF14 and [3H]estradiol with a partially purified binding-protein fraction from rat pancreas, a complex containing labeled [125I] and [3H] was separated by Sephadex G-200 column chromatography. In the presence of 25 microM SRIF14, which activates [3H]estradiol-binding maximally in the presence of 10 nM steroid, a protein peak containing both radiolabeled ligands eluted in the void volume indicating an apparent molecular size in excess of 200,000 Daltons. At a concentration of 1 microM SRIF14, a complex eluted at a position corresponding to an apparent Mr of 120,000. Evidently, the steroid and polypeptide mutually enhance binding to this pancreatic protein, and depending on their concentrations form structures of widely varying sizes.

Animals↗