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Biomedical subjects

M Berelowitz

Publications and source records attributed to M Berelowitz.

At least 55 records · Page 3Linked to original sources

Self-incineration: a controlled comparison of in-patient suicide attempts. Clinical features and history of self-harm.

A systematic survey of in-patient accidents and injuries in an inner London hospital over 9 years established that, after incisions and overdoses, self-incineration was one of the commoner methods of violent self-harm. A case-controlled study of in-patient suicide attempts compared a series of 12 self-incinerators with 12 patients using other methods. Irrespective of method, the suicide attempt was predominantly a psychotic act of young single people with chronic, severe disorders and considerable past parasuicide, in a setting of escalating self-harm. Younger age, greater psychiatric morbidity, absence of alcoholism, a history of childhood arson, past and current self-burning were the features specific to self-incineration, which had a 25% mortality rate.

Adjustment Disorders↗

Evidence for multiple molecular weight forms of somatostatin-like material in Escherichia coli.

Extracts of Escherichia coli grown in defined medium contain somatostatin-related material (1-10 pg/g wet weight of cells). Preconditioned medium had no immunoactive somatostatin whereas, conditioned medium had 110-150 pg/l. Following purification of the extracted material on Sep-pak C18, Bio-Gel P-6 and HPLC, multiple molecular weight forms of somatostatin- (SRIF-) related material were identified. The material in one peak reacted in both the N-terminal and C-terminal SRIF immunoassay and coeluted on HPLC with SRIF-28, whereas that in a second peak eluted near SRIF-14 and was reactive only in the C-terminal SRIF assay. The two peaks are thus similar to SRIF-28 and SRIF-14 of vertebrates. These findings add support to the suggestion that vertebrate-type peptide hormones and neuropeptides have early evolutionary origins.

Chromatography, Gel↗

Two distinct insulin-related molecules in the guinea pig: immunological and biochemical characterization of insulin-like immunoactivity from extrapancreatic tissues of the guinea pig.

In this study we extracted guinea pig brain and testis with; the extract was adsorbed to and eluted from cartridges (the Sep-Pak C18 procedure). We found this procedure superior for recovering crystalline insulin added to buffers or tissues, and for recovering endogenous insulin from plasma, but inferior for recovery of insulin from tissues. However, we did find 'rat/pork' type-insulin in guinea pig brain and testis (5-50 pg/g wet weight tissue). Our results with the Sep-Pak C18 procedures were reproduced by four other laboratories (who found 4-60 pg/g wet weight of tissue) and similar findings were also obtained by an independent investigator. Thus, we conclude that extrapancreatic tissues of guinea pigs have a second type of insulin-related material that is more typical of other mammalian insulins, but that the amount recovered is dependent upon the extraction procedure utilized.

Animals↗

Modulation of somatostatin binding to rat pituitary membranes by exogenously administered growth hormone.

The effect of exogenously administered GH on somatostatin (SRIF) receptor regulation was studied in rat anterior pituitary membranes. A single class, high affinity specific receptor for SRIF was identified by binding studies with [125I-Tyr11]SRIF [binding capacity (mean +/- SD), 129.4 +/- 23.3 fmol/mg protein; binding affinity, 2.8 +/- 0.6 X 10(10) M-1]. A single injection of rat GH (150 micrograms) caused a significant reduction in capacity, but not in affinity, of SRIF receptors 2 and 6 h after injection (mean decrease, 23% and 24%, respectively) from that in controls. In contrast, mean SRIF binding capacity 24 h after a single injection of rat GH was increased 48% above control values, but affinity was unaffected. Measurement of membrane SRIF content indicated that these changes could not be explained by alterations in receptor occupancy. When rat GH was injected repeatedly for 3 days (150 micrograms/rat X day), the mean binding capacity, though not the affinity, of SRIF receptors was decreased 23% from that in controls 24 h after the last injection. The results can be explained by stimulation of SRIF release from the hypothalamus by GH and somatomedins, with subsequent internalization of the pituitary plasma membrane SRIF receptor. They suggest yet another level of neuroendocrine regulation of GH secretion.

Animals↗

Somatostatin-like material is present in flowering plants.

Extracts of spinach contain somatostatin (SRIF)-related material (6-80 pg/g wet wt). The SRIF-related material, when purified on HPLC, was recovered as two major mol wt forms; one that eluted with a retention time similar to that of synthetic SRIF-28 and reacted in both N- and C-terminal-specific immunoassays, and a second peak that eluted with a retention time similar to that of SRIF-14 and reacted only in the C-terminal immunoassays. The purified material was active in a sensitive bioassay, and the bioactivity was neutralized in the presence of anti-SRIF antiserum. Since we have previously described the presence of similar material in bacteria, we also tested extracts of the flowering plant Lemna gibba G3, which was grown under sterile conditions. The Lemna extracts also had SRIF-related material (3.0 pg/g wet wt). Since plants are probably derived evolutionarily from unicellular organisms, the presence of SRIF-like material in higher plants gives support for the hypothesis that vertebrate-type peptide hormones have early evolutionary origins.

Animals↗

Impaired growth hormone responses to growth hormone-releasing factor in obesity. A pituitary defect reversed with weight reduction.

To investigate whether the impaired growth hormone secretion associated with obesity is a result of a hypothalamic or a pituitary disorder and whether it is a cause or a consequence of obesity, we studied plasma growth hormone responses to growth hormone-releasing factor in morbidly obese patients before gastrointestinal surgical therapy, in formerly obese subjects who had lost considerable weight postoperatively, and in non-obese controls. Growth hormone secretion was also assessed in response to insulin-induced hypoglycemia (in seven patients preoperatively and four postoperatively). In patients studied preoperatively, growth hormone responses to growth hormone-releasing factor were markedly impaired (P less than 0.001 as compared with controls), whereas in patients studied postoperatively they were partially restored to normal (P less than 0.05 as compared with those studied preoperatively). Growth hormone responses to insulin-induced hypoglycemia were similarly diminished in obese patients studied before operation (P less than 0.02). The growth hormone response to growth hormone-releasing factor was inversely correlated with the percentage of ideal body weight (P less than 0.01) and directly correlated with the growth hormone response to insulin (P less than 0.01). The impaired responsiveness to growth hormone-releasing factor suggests that the diminished response to insulin hypoglycemia is mediated by an impaired pituitary response to endogenous growth hormone-releasing factor. The reversibility of the defect after weight reduction suggests that it is a consequence rather than a cause of obesity.

Adolescent↗

Somatostatin 28(1-14) immunoreactivity in primary afferent neurons of the rat spinal cord.

Somatostatin 28(1-14) immunoreactivity is present in dorsal root ganglion cells and in the superficial laminae of the spinal cord in the rat. The distribution of somatostatin 28(1-14) immunoreactive varicosities in the dorsal horn corresponds well to the distribution of somatostatin 14 immunoreactive elements. Some dorsal root ganglion cells exhibit both somatostatin 14 and somatostatin 28(1-14) immunoreactivities.

Animals↗

'Borderline personality': diagnostic attitudes at the Maudsley Hospital.

About a quarter of the psychiatrists at the Maudsley Hospital use the diagnosis of 'borderline' personality. The description of the borderline patient obtained in this study does not overlap with any existing ICD personality disorder but has characteristics of the schizoid, paranoid, hysteric, explosive, anankastic and antisocial personalities. The item that discriminated best between borderlines and controls was 'brief, unsystematized , psychotic episodes', which is not included in the DSM-III definitions of borderline diagnoses. Items of the DSM-III 'schizotypal' set--e.g. 'suspiciousness' and 'ideas of reference'--discriminated better between borderline cases and controls, whereas items of the DSM-III 'borderline personality' set--e.g. 'impulsivity' or 'unpredictability'--scored more frequently in both groups. These are similar to American findings.

Attitude of Health Personnel↗

Biofeedback improvement of lower esophageal sphincter pressures and reflux symptoms.

During a course of 10 biofeedback sessions in a single subject, the lower esophageal sphincter pressure measured with an open-tipped perfused catheter assembly showed significant and progressive increase with each session, until it reached normal levels. There was also a decrease in symptomatic reflux episodes, from three times daily to once every 2 weeks. Macroscopic esophagitis was detected by endoscopy before the first session, but was no longer evident in the endoscopic examination after biofeedback training. After the biofeedback training program, the subject was able to control his lower esophageal sphincter without biofeedback.

Adult↗

Somatostatin-like immunoactivity and biological activity is present in a human pheochromocytoma.

Somatostatin (SRIF)-like immunoreactivity (SRIF-LI) has previously been demonstrated immunohistochemically in sympathetic nerves and ganglia and in adrenal medullary cells. Studies were therefore performed to determine whether SRIF-LI was present in an adrenal pheochromocytoma. Acetic cid extracts of pheochromocytoma tissue contained high SRIF-LI concentrations (5.52 micrograms/g wet wt). On Sephadex G-75 gel filtration, the major peak of pheochromocytoma SRIF-LI coeluted with synthetic SRIF. SRIF-LI of a larger molecular size was also present in the tumor. Pheochromocytoma SRIF-LI coeluted with synthetic SRIF on reverse phase high pressure liquid chromatography. Pheochromocytoma SRIF-LI purified by high pressure liquid chromatography was equipotent to synthetic SRIF in inhibiting (Bu)2cAMP-stimulated GH release by rat pituitary cells in monolayer culture. Serum SRIF-LI was elevated in the patient before surgery and was restored toward normal after removal of the tumor. Serum levels of GH, TSH, and insulin were not obviously different before and after tumor removal. The results indicate that SRIF-LI is produced in excessive quantities by a pheochromocytoma. The immunological, chromatographic, and biological properties of the pheochromocytoma SRIF-LI suggest that it is indistinguishable from synthetic SRIF. This finding extends the list of peptides produced by pheochromocytoma and may provide an additional serum marker for the tumor in man.U

Adrenal Gland Neoplasms↗

Evidence for lactotroph dopamine resistance in idiopathic hyperprolactinemia.

Previous studies in patients with idiopathic hyperprolactinemia (IH) that have suggested the presence of decreased central dopaminergic tone have assumed normal responsiveness of lactotrophs to dopamine (DA). We have examined DA sensitivity in 17 women with IH and 19 female controls by evaluating the plasma PRL responses to successive infusions of increasing concentrations of DA (4, 40, and 400 ng/kg . min) as well as to a dopaminergic agonist, bromocriptine (2.5 mg, orally), and to a dopaminergic agonist, bromocriptine (2.5 mg, orally), and to a dopaminergic receptor blocker, domperidone (2 mg, iv). PRL levels in controls were unchanged during a saline infusion, but decreased by 34 +/- 7% (mean +/- SE) at the end of the lowest DA infusion (P less than 0.05 vs. saline). Progressive PRL suppression was produced with each increasing dose. In contrast, in patients with IH, the lowest dose produced no significant suppression from basal PRL levels (P less than 0.001 vs. controls); at 40 ng/kg . min DA, fractional suppression was evident but was less than that in controls (P less than 0.01); at 400 ng/kg . min, fractional PRL suppression in IH patients was indistinguishable from that in controls (70 +/- 6% vs. 73 +/- 4%). Patients with IH also exhibited markedly reduced and delayed PRL response to domperidone (P less than 0.02 vs. controls). Significant impairment of the PRL-lowering effect of bromocriptine was observed in the IH patients between 1 and 2 h (P less than 0.02 vs. controls), and their responses to bromocriptine were again delayed. The results indicate the presence of a relative resistance to DA in patients with IH. This resistance is compatible with a decrease in the number or affinity of lactotroph DA receptors.

Adult↗

Somatostatinoma syndrome: does a clinical entity exist?

We report here 2 patients with somatostatin-secreting tumours and hypersomatostatinaemia. One subject, a 36 year old woman with diabetes, flushing, labile blood pressure and diarrhea, had elevated basal plasma levels of somatostatin-like immunoreactivity (SLIR) and calcitonin. Plasma SLIR increased further following tolbutamide administration. Plasma levels of prostaglandin E2 (PGE2) and pancreatic polypeptide (PP), normal in the basal state, showed exaggerated responses to pentagastrin and secretin, respectively. Immunocytochemistry of the tumour tissue revealed cells containing somatostatin-, calcitonin-, PGE2- and PP-like immunoreactivity. The other patient, a 52 year old male, had an SLIR-secreting tumour of the proximal duodenum and elevated basal and post-tolbutamide SLIR levels but no signs or symptoms suggestive of increased SLIR production. Tumour tissue revealed cells containing somatostatin- and calcitonin-like immunoreactivity. We conclude that patients with somatostatinomas do not always exhibit a predictable syndrome. Patients with these tumours may exhibit a range of clinical, biochemical and immunocytochemical features typical of endocrine tumours of mixed-cell origin, such that the dominant signs and symptoms associated with these neoplasms cannot readily be ascribed to overproduction of any single hormone.

Adenoma, Islet Cell↗

Immunoreactive neurotensin in the pancreas of genetically obese and diabetic mice. A longitudinal study.

Immunoreactive neurotensin (IR-NT) content in 2 N acetic acid extracts of pancreas was measured in genetically diabetic (C57BL/KsJ db/db and ob/ob) and obese (C57BL/6J ob/ob and db/db) mice and normal littermate controls from 5 to 24 wk of age to determine the relationship of any changes to the development of metabolic abnormalities. Pancreatic IR-NT in obese mice showed no consistent change compared with lean littermate controls. In contrast, diabetic mice demonstrated an increase in pancreatic IR-NT that occurred at 6-8 wk of age, and maximal about the time of islet B-cell failure (8-10 wk), and persisted over the study period. Pancreatic IR-NT eluted in two peaks on reverse phase high-pressure liquid chromatography, one of which exhibited a retention time similar to that of synthetic NT. These findings suggest that pancreatic IR-NT concentration is regulated by insulin, with elevated levels occurring in association with insulin deficiency and its metabolic consequences but not with insulin resistance. Taken together with the previous demonstration that NT influences pancreatic islet hormone secretion, the present findings support a possible role of endogenous NT in islet hormone regulation.

Aging↗

Are messenger molecules in microbes the ancestors of the vertebrate hormones and tissue factors?

Peptides very similar to hormones and other messenger molecules of vertebrates have been detected in extracts of unicellular eukaryotes (and prokaryotes). We present arguments to suggest the possibility that these molecules 1) originated evolutionarily in unicellular microbes, 2) serve as intercellular messenger molecules in these organisms, and 3) represent the phylogenetic ancestors of the hormones and neurotransmitters as well as paracrine and other tissue factors of the vertebrates. We suggest that the biochemical elements of intercellular communication arose very early in evolution and are highly conserved; evolution largely changed the anatomy, i.e., the nature of the secretory cell, the target cell, and the fluid compartment that carries the messenger molecule from one to the other. Such an approach suggests a more rational relationship between different modes of intercellular chemical signaling in vertebrates.

Animals↗

The effect of intravenous growth hormone infusion on cerebrospinal fluid somatostatin levels in the rhesus monkey.

CSF was continuously withdrawn over 13 days from the cervical subarachnoid space of two rhesus monkeys during the intravenous infusion of saline or human growth hormone (GH) and samples collected during sequential 2 h periods were assayed for somatostatin (SRIF). SRIF-like immunoreactivity (SRIF-LI) concentrations were decreased during GH infusion as compared to saline infusion (P less than 0.005) and the maximal effect occurred during the hours of darkness (18.00-06.00 h). Since in vivo GH administration stimulates hypothalamic SRIF-LI release, CSF SRIF-LI does not appear to be derived primarily from the hypothalamus but rather from extrahypothalamic brain by a mechanism inhibited by GH.

Animals↗