Release of proinsulin from the human fetal beta cell.

beta cells in the human fetal pancreas are immature in that they release little or no insulin in response to nutrients, such as glucose. The aim of this study was to examine further the immaturity of these cells, specifically regarding the storage and release of the precursor of insulin, proinsulin. Explants of human fetal pancreas were cultured in vitro for 3 weeks. Levels of proinsulin remained relatively constant throughout at 0.04 +/- 0.002 (S.E.M.) pmol/mg per day with a molar ratio of proinsulin to insulin of 2.2 +/- 0.11%. This low ratio was slightly greater than that observed in culture medium conditioned by adult human islets (0.3 +/- 0.1%), but similar to that found in acid-ethanol extracts of cultured explants (1.4 +/- 0.3%). Passaging of human fetal pancreas for 3 months in diabetic nude mice, which should have caused some maturation of the fetal beta cell, did not change the proportion of proinsulin present. Culture of explants in the presence of 12-O-tetra-decanoylphorbol-13-acetate resulted in some inhibition of proinsulin release, but much less than that for insulin, so that the molar ratio increased to 15.4 +/- 1.6% from the control 3.5 +/- 0.3%. Static stimulation of cultured explants with 10 mmol Ca2+/l, 10 mmol theophylline/l, and these two agents together caused 15-, 4- and 10-fold enhancement respectively of proinsulin release; glucose, leucine, arginine and KCl had no effect. In contrast, all these agents caused significant insulin release, the last four to a much smaller extent (less than or equal to three fold) than the first three (10-, 19- and 65-fold respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical problem-solving using video simulation: an investigation

This paper examines the use of videotape simulation as a research method for the exploration of clinical problem-solving, the challenges posed and the strategies employed to overcome the difficulties encountered are discussed. The simulation forms part of a larger comparative study of outcomes of pre-registration nurse education programmes, commissioned by the English National Board for Nursing, Midwifery and Health Visiting.     

Further experience with radiation therapy and concomitant intravenous chemotherapy in advanced carcinoma of the lower female genital tract

Sixty-seven patients with advanced carcinoma of the lower female genital tract (cervix, vagina, and vulva) were treated with radiation and concomitant intravenous cisplatin and/or 5-fluorouracil. Fifty-seven patients (85%) responded completely clinically. Thirty-five (61%) complete responders recurred with a median time to recurrence of 6 months. Twenty-six of the thirty-five patients who recurred had some component of local failure. The 22 complete responders who have not recurred have been followed a median of 13 months. Acute toxicity was minimal, with only 6 patients requiring interruption of therapy. Nine (13%) patients developed severe late complications and eight required surgery. The actuarial 5-year survival is 22%. This treatment regimen is disappointing in terms of both survival and local control.     

Breaking points on a progressive ratio schedule reinforced by intravenous apomorphine increase daily following 6-hydroxydopamine lesions of the nucleus accumbens

It has been shown previously that 6-hydroxydopamine (6-OHDA)-induced lesions of the nucleus accumbens cause extinction of cocaine self-administration behavior, yet fail to affect the rate of apomorphine self-administration on a Fixed Ratio 1 schedule of reinforcement. Since the dopamine (DA) receptors in this nucleus should become supersensitive, and since these receptors are thought to mediate the reinforcing effects of apomorphine, then some change in apomorphine self-administration would be expected. We have therefore reinvestigated the effect of 6-OHDA lesions on apomorphine self-administration using a progressive ratio schedule of reinforcement. Rats were trained to self-administer apomorphine (0.033 mg/inj, IV) on a schedule in which the response requirements increased after each reinforcement. The breaking point was defined as the final ratio completed during each daily session. Sham lesions had no effect on the breaking points, and a steady increase in the breaking point was observed in the 6-OHDA-lesioned animals which may parallel the development of DA receptor supersensitivity.     

Collateral vessel regression in a child with primary congenital glaucoma.

The presence of collateral vessels in a young child with glaucoma is rare. The authors describe a case of collateral vessel regression with intraocular pressure reduction in a child with primary congenital glaucoma. Six months following 180 degrees goniotomies in each eye, the intraocular pressure was reduced, dilation of the retinal arteries and veins resolved, and collateral vessels in both eyes regressed. Intraocular pressure reduction may lead to the regression of collateral vessels in children with primary congenital glaucoma.     

Early life precursors of psychiatric outcomes in adulthood in subjects at risk for schizophrenia or affective disorders.

In the New York High-Risk Project (NYHRP), 186 offspring of schizophrenic, affectively ill, and psychiatrically normal parents have been followed prospectively from 1971-72 to the average age of 27 years in 1990 with the goal of identifying early precursors of later psychopathology. In this report, we use path analyses to examine the relationship of several life-history variables to three pathological outcomes in the offspring: namely, psychosis, psychiatric hospitalization, and psychological dysfunction. The chief direct relationship with these outcomes is the effect of having a schizophrenic parent. The latter effect is also mediated indirectly by IQ.     

G proteins (Gi,Go) in the medial temporal lobe in schizophrenia: preliminary report of a neurochemical correlate of structural change

Summary We have measured the amount of Gi (the inhibitory G-protein) or Go (a similar G-protein of unknown function) in 5 areas of the medial temporal lobe of control and schizophrenic brains utilizing pertussis toxin-catalyzed ADP ribosylation. The material used has previously been shown to have asymmetrical structural abnormalities of the ventricular system. The amount of Gi or Go was reduced on the left side in the hippocampus, amygdala and parahippocampal gyrus, the difference reaching significance in the hippocampus. This data is the first report of a neurochemical correlate of the structural change in the brains of patients with schizophrenia. Decreased Gi or Go in hippocampus may relate to other reported neurochemical deficits or other transmembrane signalling abnormalities. Further investigations of these indices of secondary messenger function in relation to structural changes are indicated.