Growth hormone (GH) binding protein and GH interactions in vivo in the guinea pig.

GH binding proteins (GHBPs) are present in the blood of several species and by complexing with circulating GH may alter its clearance and distribution. The actions of human GHBP (hGHBP) have hitherto been studied indirectly via their effects on the clearance of hGH. In the present experiments, recombinant preparations of hGHBP and a shorter variant lacking exon 3 (delta 3hGHBP) were tested in vivo, either alone or after preincubation with recombinant hGH, recombinant 20K methionyl-hGH, or rat GH.

Longitudinal Gompertzian analysis of ALS mortality in England and Wales, 1963-1989: estimates of susceptibility in the general population.

Mortality statistics in amyotrophic lateral sclerosis (ALS), which is more commonly and generally termed motoneurone disease (MND) in the United Kingdom, have been shown to reflect the incidence of previously diagnosed cases of the disease in a more complete way than in other conditions [1,2]. An analysis of changing patterns of mortality may therefore be a particularly appropriate way of tracing the underlying trends in the disease and is in principle a useful way of investigating the relationship between environmental and genetically controlled factors in the genesis of the condition. The majority of analyses so far have concentrated on the crude rise in reported mortality rates evident in recent decades in a number of countries [2-5], on the uneven geographical distribution [6,7] and on the complex range of plausible causes for these reported rises.

Colo-rectal carcinoma 1975 and 1990: no improvement in the stage of disease at resection.

There is no overall consensus as to what screening patterns should be adopted for individuals of average risk for colo-rectal carcinoma. The single most important prognostic factor in survival is the stage of the colo-rectal neoplasm at the time of resection. Consequently significant resources have been directed to early detection while the disease is at a curative stage.

Reserpine-induced processing of chromogranin A in cultured bovine adrenal chromaffin cells.

The effect of reserpine on the processing of the secretory granule protein chromogranin A (CgA) in isolated bovine adrenal chromaffin cells was investigated using two radioimmunoassays employing site-specific antisera. The two antisera were directed against closely associated regions of the CgA molecule which would be exposed by specific processing: antiserum L331 was raised against the C-terminus of the regulatory peptide pancreastatin, and the second antiserum, L300, was raised against the synthetic peptide [Tyr0]CgA306-313 (YLSKEWEDA), a sequence that lies immediately C-terminal to pancreastatin and adjacent to a dibasic amino acid cleavage site. Chronic reserpine treatment of chromaffin cells produced a time- and dose-dependent increase in processing, as demonstrated by an increase in pancreastatin- and YLSKEWEDA-immunoreactivity (ir).

Imaging of medullary carcinoma of the thyroid using 111In-labelled anti-CEA monoclonal antibody fragments.

The distribution of 111In-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody fragments [F(Ab')2] was studied in five patients either with known inoperable medullary carcinoma of the thyroid (MCT) or evidence of recurrence/metastases based on elevated calcitonin (hCT) levels. All five cases had elevated serum CEA levels and positive immunohistochemical stains for both hCT and CEA prior to scintigraphy. In two patients with identified inoperable disease both planar and SPECT scans were positive.

Hepatic steroid hydroxylating enzymes are controlled by the sexually dimorphic pattern of growth hormone secretion in normal and dwarf rats.

In rats, the onset of the sexually dimorphic pattern of growth hormone (GH) secretion and increased hepatic GH-binding capacity at puberty are temporally correlated with the sex-dependent expression of some hepatic cytochrome P450 enzymes involved in steroid metabolism. There are indications that the expression of the GH receptor gene itself is dependent on the sexually differentiated pattern of GH secretion. However, the molecular mechanisms by which a given pattern of GH secretion turns on a specific set of genes in the hepatocyte are not yet understood.

Release of oxytocin into blood and into cerebrospinal fluid induced by naloxone in anaesthetized morphine-dependent rats: the role of the paraventricular nucleus.

Abstract Opioid actions on oxytocin secretion into blood and cerebrospinal fluid (CSF) were investigated in urethane-anaesthetized female rats after intracerebroventricular (icv) infusion of morphine sulphate or vehicle for 5 days. Serial femoral arterial blood samples and cisterna magna CSF samples were collected for radioimmunoassay. Naloxone was given to assess endogenous opioid tone in icv vehicle-infused rats and to precipitate withdrawal in morphine-dependent animals.

The interaction of growth hormone releasing hormone and somatostatin in the generation of a GH pulse in man.

Objective: To study the regulation of the growth hormone (GH) response to growth hormone releasing hormone (GHRH) in the presence or absence of somatostatin pretreatment.

Design: Seven healthy adult male volunteers of normal height and weight and aged between 19 and 29 years underwent four separate studies (each containing three cycles in one day) in random order. The studies were separated from each other by at least a week.

A distinct 2,5-di-(tert-butyl)-1,4-benzohydroquinone-sensitive calcium store in bovine adrenal chromaffin cells.

The fluorescent Ca2+ indicator Fura 2 was used to monitor Ca2+ release induced by the Ins(1,4,5)P3-mobilizing agonist angiotensin II (Ag II), caffeine and 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tuBHQ), in intact bovine adrenal chromaffin cells. Under low external Ca2+ conditions, tuBHQ, Ag II and caffeine elicited Ca2+ rises, indicating Ca2+ release from internal stores. Prior addition of Ag II had no noticeable effect on the extent of release of Ca2+ induced by tuBHQ.

Characterisation of distinct inositol 1,4,5-trisphosphate-sensitive and caffeine-sensitive calcium stores in digitonin-permeabilised adrenal chromaffin cells.

The effect of inositol 1,4,5-trisphosphate [Ins-(1,4,5)P3] and caffeine on Ca2+ release from digitonin-permeabilised bovine adrenal chromaffin cells was examined by using the Ca2+ indicator fura-2 to monitor [Ca2+]. Permeabilised cells accumulated Ca2+ in the presence of ATP and addition of either Ins(1,4,5)P3 or caffeine released 17% or 40-50%, respectively, of the accumulated Ca2+, indicated by sustained rises in [Ca2+] in the cell suspension. Prior addition of Ins(1,4,5)P3 had no effect on the magnitude of the response to a subsequent addition of caffeine.

Corticotrophin-releasing factor-41, vasopressin and oxytocin release into hypophysial portal blood in the rat: effects of electrical stimulation of the hypothalamus, amygdala and hippocampus.

The role of the paraventricular nuclei (PVN), amygdala and hippocampus in the control of the hypothalamic-pituitary-adrenal axis has been studied by determining the effect of electrical stimulation of the PVN, amygdala and hippocampus on the release of corticotrophin-releasing hormone (CRF-41) and arginine vasopressin (AVP) into hypophysial portal blood and ACTH and corticosterone into peripheral blood. Adult female Wistar rats were anaesthetized with sodium pentobarbitone and stimulation was carried out through previously implanted bipolar, glass-insulated platinum electrodes. Hypophysial portal blood was collected 30 min before and 30 min during the application of the stimulus which consisted of trains (30 s on and 30 s off) of biphasic rectangular pulses with a frequency of 50 Hz, pulse width 1 ms and amplitude 1 mA.

A review of the aetiology of multiple sclerosis: an ecological approach.

Multiple sclerosis (MS) is a disease of unknown aetiology characterized by myelin destruction. Approaches to the aetiology of the condition have noted its differential geographic and demographic distribution; a tentative and inconsistent link with infectious agents; a genetic susceptibility; and a tendency to track with dietary lipids. This review proposes a multidisciplinary approach to the aetiology of MS, emphasizing the interlocking and interdependent nature of current aetiological arguments.

Confidentiality for whom?

Confidentiality has been argued to be a cornerstone both of medical and social research encounters, particularly because of the protection it offers for patients and informants. In practice the idea of confidentiality is fractured. Professional interests in the organisation of medical work, and concerns for the collective interest amongst social researchers may lead to individual confidentiality being undermined.

Changes in a proposed new neuroendocrine marker of oestrogen receptor function in postpartum women.

We describe a novel neuroendocrine test which reflects a central response to activation of oestrogen receptors. This is achieved by measurement of plasma levels of oestrogen-stimulated neurophysin (ESN) following an oestrogen challenge. In normal women the ESN response to ethinyl oestradiol is dose-dependent.

Cortisol in pregnancy toxaemia of sheep.

Of 31 pregnant ewes with clinical signs of pregnancy toxaemia, 24 had hypoglycaemia and hyperketonaemia at the time that a single blood sample was obtained. Twenty-five of these had a plasma cortisol concentration in excess of 10 ng/ml and six had a value below this. All the seven animals which did not show both hypoglycaemia and hyperketonaemia had a plasma cortisol concentration in excess of 10 ng/ml.