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Showing papers by "St Bartholomew's Hospital published in 1981"


Journal ArticleDOI
TL;DR: Results indicate that Iodogen can be used for a wide range of proteins and peptides, can permit theoretical iodine incorporation with minimal oxidation damage, and can produce tracer stable for up to 3 months.

1,096 citations


Journal ArticleDOI
TL;DR: The observations suggest that the initiation of pathogenesis may precede the abrupt clinical onset of diabetes by several years, even in children, which has important implications, both for research and for possible future prophylaxis.

490 citations


Journal ArticleDOI
TL;DR: A structure closely resembling synovium is formed as early as 6 days, providing a convenient method for studying large quantities of facsimile synovial tissue under a wide variety of easily administered stimuli.
Abstract: We have attempted to verify the suggestion that synovial membrane is the result of mechanical disruption of connective tissue, and may occur at any site. Mechanical disruption of the subcutaneous connective tissue was achieved in rats and mice by the repeated injection of air. The resulting cavities developed a lining structure with many of the features of synovial membrane as judged by electron microscopy, and light microscopy using haematoxylin and eosin and van Gieson stains, esterase activity and immunofluorescent staining for Ia antigen. A structure closely resembling synovium is formed as early as 6 days, providing a convenient method for studying large quantities of facsimile synovial tissue under a wide variety of easily administered stimuli.

478 citations


Journal ArticleDOI
TL;DR: Two new, rapid and sensitive radioimmunoassays for human C-reactive protein (CRP) have been established using antiserum coupled to magnetizable cellulose particles, which facilitate phase separation.

316 citations



Journal ArticleDOI
TL;DR: Effects of Drugs and Systemic Hormones on Liver Blood Flow Adrenergics a-Adrenoceptor Stimulant Stimulants and Blocking Drugs,B-Admiral Stimulantes and Blocked Drugs Epinephrine Sympathomimetics Dopamine Drugs Which Interfere with Adrenergic Function.

219 citations


Journal ArticleDOI
TL;DR: The catabolic enzyme in cholinergic metabolism, acetylcholinesterase, selected as an example of a non‐energy‐metabolising enzyme, showed significant decreases in all regions of the brain in aging, although its highest activity remained in the striatum.
Abstract: The regional enzyme activities of glucose metabolism in the rat brain were investigated. Hexokinase (EC 2.7.1.1) and pyruvate dehydrogenase (EC 1.2.4.1), key enzymes for glucose metabolism, showed no changes in activity in all the regions studied of the aging brain as compared with the adult brain. However, the activity of d-3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) is low throughout the adult brain and, in contrast with hexokinase and pyruvate dehydrogenase, its activity decreases significantly during aging. Other enzymes that showed significant decreases during aging are aldolase (EC 4.1.2.13), lactate dehydrogenase (EC 1.1.1.27), citrate synthase (EC 4.1.3.7), and NAD+-linked isocitrate dehydrogenase (EC 1.1.1.41). The catabolic enzyme in cholinergic metabolism, acetylcholinesterase (EC 3.1.1.7), selected as an example of a non-energy-metabolising enzyme, also showed significant decreases in all regions of the brain in aging, although its highest activity remained in the striatum. These results are discussed with respect to the energy metabolism in various brain regions and their status with aging.

214 citations


Journal ArticleDOI
TL;DR: In this article, Caeruloplasmin: Physiological and Pathological Perspectives are discussed. But they focus on the Caeruloplasmin and do not discuss Caerula's properties.
Abstract: (1981). Caeruloplasmin: Physiological and Pathological Perspectives. CRC Critical Reviews in Clinical Laboratory Sciences: Vol. 14, No. 4, pp. 257-329.

211 citations


Journal ArticleDOI
01 Oct 1981-Blood
TL;DR: Normal menses were established in the five women who discontinued oral contraceptives at the end of MVPP therapy, and one of them is now pregnant.

171 citations


Journal ArticleDOI
01 Jan 1981
TL;DR: The results suggest that met‐enkephalin‐like opioid peptides exert a tonic inhibitory control of LH release in both menopausal and young subjects of both sexes, and involves modulation of pulsatile LHRH release.
Abstract: SUMMARY The effect of a long-acting analogue of met-enkephalin (DAMME) and naloxone on gonadotrophin secretion has been investigated in man. In menopausal women DAMME induced a progressive fall in LH to approximately 60% of basal levels at 3 h, which was blocked by naloxone; there was a smaller fall in FSH that did not attain statistical significance. However, the LHRH-induced rise in LH and FSH in young male volunteers was unaffected by pretreatment with a high-dose DAMME infusion. Naloxone infusion in young male and female normal subjects produced a significant rise in both LH and FSH. Long-term infusion of naloxone appeared to increase the rate, and possibly the amplitude, of LH pulsatility. These results suggest that met-enkephalin-like opioid peptides exert a tonic inhibitory control of LH release in both menopausal and young subjects of both sexes. This control is most likely to be at the level of the hypothalamus, and involves modulation of pulsatile LHRH release.

164 citations


Journal ArticleDOI
14 May 1981-Nature
TL;DR: The potentiating properties of a naturally occurring human pro-γ-MSH glycopeptide are reported on the ACTH-induced steroidogenic response of isolated perfused rat and human adrenocortical cells.
Abstract: The amino-terminal region of the common corticotropin/β-lipotropin (β-LPH) precursor has been identified in the AtT-20 mouse tumour cell as a glycopeptide with an apparent molecular weight of 16,000 (the ‘16K fragment’)1,2 A third melanotropin core sequence or γ-MSH similar to that found in ACTH and β-LPH was predicted to occur in this glycopeptide from the complementary DNA sequence of mRNA isolated from bovine pituitary intermediate tissue3. Recently, the mouse 16K fragment has been found to have a small but significant potentiation on the corticosteroidogenesis elicited by ACTH in a static cell system, an effect that could be enhanced when the glycopeptide was pretreated with trypsin4. This synergism could also be mimicked by synthetic γ-MSH peptides in vitro and in vivo5. We report here the potentiating properties of a naturally occurring human pro-γ-MSH glycopeptide6 on the ACTH-induced steroidogenic response of isolated perfused rat and human adrenocortical cells.

Journal ArticleDOI
01 Dec 1981-BJUI
TL;DR: Vascular invasion and spindle cells indicated a poor prognosis; the position of the tumour, oncocytic elements, calcification, lymphocytic infiltration or the predominance of clear cell or granular cells did not influence survival.
Abstract: Summary— Seventy-two patients with renal carcinoma (RC) in a solitary kidney or bilateral synchronous tumours underwent parenchyma-sparing excision of their neoplasms. This was performed in situin 51 and extracorporeally in 21 kidneys, with a complication rate respectively of 1 7 and 43%. The 5-year survival rates were 78% for unilateral disease, 48% for bilateral synchronous and 38% for bilateral asynchronous disease. Survival correlated with Pcategory, grade and diameter of the tumour. Vascular invasion and spindle cells indicated a poor prognosis; the position of the tumour, oncocytic elements, calcification, lymphocytic infiltration or the predominance of clear cell or granular cells did not influence survival.

Journal ArticleDOI
TL;DR: The hypothesis that migraine is caused by a primary abnormality of platelet behaviour was investigated, and platelets taken from patients with classical migraine during a headache-free period demonstrated significantly higher spontaneous platelet aggregation and platelet adhesion than platelets from controls.

Journal ArticleDOI
TL;DR: Ten patients with renal failure and nine adrenalectomized patients with Cushing's disease and four patients with Addison's disease had elevated plasma ACTH, β‐LPH and β‐endorphin but normal plasma met‐enkephalin levels.
Abstract: SUMMARY Studies were performed to define the responses of plasma met-enkephalin to various endocrine and pathological stimuli and to determine the relationship between plasma β-endorphin and met-enkephalin. During insulin-induced hypoglycaemia ACTH, β-LPH and β-endorphin immunoreactivity rose in parallel, but plasma met-enkephalin did not change significantly. Sephadex G75 chromatography of samples taken at the time of the peak response (45 min) confirmed the rise in both β-LPH and β-endorphin. During administration of dexamethasone, 0·5mg 6 hourly for 48 h, plasma cortisol and ACTH became undetectable at 24 h, and β-LPH and β-endorphin fell significantly by 24 h and were undetectable by 48 h; plasma met-enkephalin, however, showed no significant change. Nine adrenalectomized patients with Cushing's disease and four patients with Addison's disease had elevated plasma ACTH, β-LPH and β-endorphin but normal plasma met-enkephalin levels. Each of ten patients with renal failure had markedly elevated plasma met-enkephalin immunoreactivity which co-eluted with synthetic met-enkephalin on BioGel P4 chromatography. Trypsin and carboxypeptidase-B digestion of the P4 chromatography fractions generated met-enkephalin immunoreactivity in earlier fractions, indicating the presence of a potential high molecular weight met-enkephalin precursor. The results imply that different control mechanisms govern β-endorphin and met-enkephalin plasma levels and that the adrenal is not the only source of plasma met-enkephalin. The elevated levels of met-enkephalin in renal failure may be due to impaired clearance of met-enkephalin or of its precursor or to increased met-enkephalin production.

Journal ArticleDOI
TL;DR: It is concluded that in normal subjects fat and protein are potent stimuli for somatostatin release and that both 1600 and 3500 mol wt forms of somatstatin immunoreactivity are stimulated by feeding.

Journal ArticleDOI
TL;DR: CyA is mildly and reversibly hepatotoxic and there is slight nephrotoxicity in the rat on the basis of histology and small elevations in creatinine, and that CyA at the doses used causes increased protein catabolism is indicated.

Journal ArticleDOI
TL;DR: Systemic administration of carrageenan may, however, induce disseminated intravascular coagulation and inflict damage on both the liver and kidney, which precludes its use as a clinical immune suppressant.
Abstract: Carrageenans (kappa, lambda and iota) are sulphated polysaccharides isolated from marine algae that can markedly suppress immune responses both in vivo and in vitro. Impairment of complement activity and humoral responses to T-dependent antigens, depression of cell-mediated immunity, prolongation of graft survival and potentiation of tumour growth by carrageenans have been reported. The mechanism responsible for carrageenan-induced immune suppression is believed to be its selective cytopathic effect on macrophages. This property of carrageenan has led to its adoption as a tool for analysing the role of these cells in the induction and expression of immune reactivity. Systemic administration of carrageenan may, however, induce disseminated intravascular coagulation and inflict damage on both the liver and kidney. This is an important consideration in the interpretation of the effects of carrageenan in vivo and precludes its use as a clinical immune suppressant.

Journal ArticleDOI
TL;DR: The data are interpreted as suggesting that rat corticotrophs contain angiotensin II receptors, and that these may be involved in ACTH release in response to hypovolaemic stress.
Abstract: In a rat anterior pituitary dispersed cell system, angiotensin II was found to stimulate the release of ACTH at concentrations ranging from 100 pmol/l to 1 mumol/l, with a maximal response being given by 10 nmol/l. The angiotensin II antagonist, saralasin, was able to block completely at a concentration of 1 mumol/l the stimulation of ACTH induced by 10 nmol/l angiotensin II, but had no effect on the basal release. The log dose-response curve for ACTH release by angiotensin II was shifted to the right in a parallel fashion by saralasin 10 nmol/l, suggesting competitive antagonism. The stimulation of ACTH release by a rat stalk-median eminence extract or by arginine vasopressin was unaffected by saralasin. The data are interpreted as suggesting that rat corticotrophs contain angiotensin II receptors, and that these may be involved in ACTH release in response to hypovolaemic stress.

Journal ArticleDOI
TL;DR: There is evidence to suggest that this cheese effect, a facilitated tyramine-induced hypertensive response, is pharmacologically distinct from MAO inhibition proper, and it is conceivable that its central counterpart, an enhanced noradrenaline release due to the access of traces of tyramines to the CNS, is a prerequisite for any therapeutic benifit obtainable with the MAO-inhibitory drugs in general.
Abstract: The selective monoamine oxidase (MAO) B inhibitor (-)deprenyl failed to produce any greater benefit than placebo in a limited double-blind trial conducted in depressive patients. Its relative freedom from the so-called cheese effect was confirmed, however, in drug-treated patients challenged IV with tyramine. There is evidence to suggest that this cheese effect, a facilitated tyramine-induced hypertensive response, is pharmacologically distinct from MAO inhibition proper. Thus, it is conceivable that its central counterpart, an enhanced noradrenaline release due to the access of traces of tyramine to the CNS, is a prerequisite for any therapeutic benifit obtainable with the MAO-inhibitory drugs in general.

Journal ArticleDOI
TL;DR: Despite their extensive and rapidly increasing use, non-labelled techniques are limited to the assay of proteins and other large molecules present at relatively high concentrations, since only in such circumstances are the resultant antigen complexes sufficiently large to form a precipitin line or scatter light.
Abstract: NON-LABELLED IMMUNOASSAYS Several immunoassay techniques do not require the use of a labelled reactant.f Some depend on the precipitation line which forms in a gel support when a protein antigen comes into contact with its specific antibody while other manual and automated procedures depend, for end-point detection, on the increase in light scattering produced. Despite their extensive and rapidly increasing use, non-labelled techniques are limited to the assay of proteins and other large molecules present at relatively high concentrations, since only in such circumstances are the resultant antigen : antibody complexes sufficiently large to form a precipitin line or scatter light. Additional disadvantages include the need for relatively large amounts of monospecific antisera; problems with very turbid or haemolysed samples; and the possibility of erroneous results in the presence of antigen excess-due to the prozone phenomenon.

Journal ArticleDOI
TL;DR: The results suggest that opiate peptides are unlikely to play a major role in the tonic or hypoglycaemia‐stimulated release of prolactin and GH, although they may be of importance in the control of TSH.
Abstract: Opiate peptides are known to influence the secretion of several anterior pituitary hormones under basal conditions. Further studies on prolactin, GH and TSH have therefore been performed in normal subjects, under basal and stimulated conditions, using an opiate agonist and antagonist. Sixteen mg naloxone had no effect on the basal release of prolactin or GH, but lowered TSH. An infusion of the met-enkephalin analogue DAMME (1 mg) increased GH, and produced an exaggerated response of both prolactin and TSH to 200 micrograms TRH i.v. The peak responses of both prolactin and GH to hypoglycaemia were unaffected by pretreatment with either low-dose (0.4 mg) or high-dose (25 mg) naloxone, or DAMME (0.25 mg). These results suggest that opiate peptides are unlikely to play a major role in the tonic or hypoglycaemia-stimulated release of prolactin and GH, although they may be of importance in the control of TSH.

Journal ArticleDOI
01 Dec 1981-BJUI
TL;DR: In a selected series of 14 patients, upper tract urothelial tumours were excised with preservation of the ipsilateral kidney with a 5-year survival rate of 83%.
Abstract: Summary— In a selected series of 14 patients, upper tract urothelial tumours were excised with preservation of the ipsilateral kidney. The 5-year survival rate was 83%. The ipsilateral local recurrence rate was 5/14 (36%) but in 4 cases salvage surgery was effective and in 2 cases a functioning kidney was still preserved. The results of conservative surgery and its indications are discussed.

Journal ArticleDOI
01 Feb 1981-Steroids
TL;DR: The direct assay has been validated and employed for in vitro adrenal superfusion studies using either rat or human adrenal cells and has exceeded the capacity of earlier radioimmunoassays requiring initial extraction and chromatography.

Journal ArticleDOI
TL;DR: The method has advantages of speed, small sample requirement and complete resolution of the three major metabolites of verapamil, and the limit of accurate measurement of the assay is 2 micrograms/l.

Journal ArticleDOI
TL;DR: Diabetics with retinopathy and those diabetics without clinical evidence of vascular disease had levels of ß‐thromboglobulin and platelet factor 4 significantly higher than controls.
Abstract: Mean levels of beta-thromboglobulin and platelet factor 4 were highly significantly elevated in diabetes compared to controls (72.6 v. 36.3 ng/ml, P less than 0.0005; 48.5 v. 16.5 ng/ml, P less than 0.0005; respectively) as was malondialdehyde formation (12.4 v. 8.1 nmol/10(9) platelets, P less than 0.0005). Diabetes with retinopathy had significantly higher levels of beta-thromboglobulin than those without retinopathy (79 v. 70 ng/ml; P less than 0.042). However, those diabetics without clinical evidence of vascular disease had levels of beta-thromboglobulin and platelet factor 4 significantly higher than controls. beta-Thromboglobulin did not correlate with glycosylated haemoglobin but did correlate significantly with individual lipid and lipoprotein levels (beta-thromboglobulin v. total triglyceride, P less than 0.029; v. VLDL triglyceride, P less than 0.041; v. LDL cholesterol, P less than 0.042; v. HDL/total cholesterol ratio, P less than 0.02). Abnormal platelet function may contribute to the vascular complications of diabetes mellitus.

Journal ArticleDOI
TL;DR: A monoclonal antibody, MI/N1, is described that reacts predominantly with fresh neuroblastoma tissue, human Neuroblastoma cell lines, and cells of the myeloid lineage, suggesting a heterogeneity in antigenic expression on fresh tumour cells.
Abstract: Summary: A monoclonal antibody, MI/N1, is described that reacts predominantly with fresh neuroblastoma tissue, human neuroblastoma cell lines, and cells of the myeloid lineage. Investigation of the binding of this antibody to four different neuroblastoma cell lines showed CHP 100 bound approximately 4 times more antibody than CHP 126. Only 30% of the cells in the line CHP 100 bound MI/N1 as determined by indirect immunofluorescence. Thus, both quantitative and qualitative differences in the expression of antigen recognised by MI/N1 are detected on human neuroblastoma cell lines. Inasmuch as only five of eight marrow aspirates heavily infiltrated with neuroblasts bound the monoclonal, this also suggests a heterogeneity in antigenic expression on fresh tumour cells. Absorption studies indicate that the antigen recognised by MI/N1 is present on human foetal brain and adult human cerebellum. At a dilution of 1/750, equal volumes of foetal brain and adult cerebellum absorbed out 30 and 60% of the reactivity to the human neuroblastoma cell line CHP 100. No reactivity was found towards murine neuroblastoma cells or rat brain. Expression of antigen on cells in the myeloid lineage appears dependent upon their stage of maturation, increasing as cells mature to neutrophils and eosinophils. It is suggested that the quantitative and qualitative differences seen in the expression of antigen on neuroblastoma cells may relate to their being blocked at different stages of differentiation.

Journal ArticleDOI
TL;DR: The results are interpreted as suggesting that there are inhibitory opiate receptors controlling the release of ACTH, β‐LPH, and β‐endorphin.
Abstract: Thirteen patients with either Addison's disease, or Cushing's disease treated by bilateral adrenalectomy, were infused with the long-acting met-enkephalin analogue DAMME In patients with Addison's disease significant and pronounced falls in ACTH and N- and C-terminal beta-LPH were seen; chromatography suggested that beta-endorphin fell concomitantly Three out of four patients with Cushing's disease who had not received pituitary irradiation, also showed a decrease in plasma ACTH and N- and C-terminal beta-LPH; however, no change was seen in any of the irradiated patients The changes were naloxone reversible The levels of plasma met-enkephalin were normal and did not change after DAMME in any group of patients These results are interpreted as suggesting that there are inhibitory opiate receptors controlling the release of ACTH, beta-LPH, and beta-endorphin

Journal ArticleDOI
TL;DR: The data suggest that the pulsatile release of LH is under inhibitory opiate control, and the frequency of LH secretory episodes and the mean LH levels increased in both sexes.
Abstract: SUMMARY The gonadotrophin response to naloxone infusion has been investigated in three adult males, and three adult females in the early follicular phase. The frequency of LH secretory episodes and the mean LH levels increased in both sexes. The data suggest that the pulsatile release of LH is under inhibitory opiate control.

Journal ArticleDOI
TL;DR: In this paper, the authors treated men with repeated 7-day courses of methylprednisolone (MP) 32 mg three times a day from days 21 to 28 (in a few cases days 1 to 7) of their wives' menstrual cycles.

Journal ArticleDOI
TL;DR: Pollution in the dental outpatient surgery was assessed by measuring atmospheric nitrous oxide levels and comparing these with the venous blood concentrations in the operator‐anaesthetist and his assistant.
Abstract: Summary Pollution in the dental outpatient surgery was assessed by measuring atmospheric nitrous oxide levels and comparing these with the venous blood concentrations in the operator-anaesthetist and his assistant. The effects of scavenging on both measurements have also been determined. Without scavenging the nitrous oxide level in the blood of the dentist was over four times that of the average anaesthetist working in an operating theatre. Some of the factors contributing to these high levels, and the effectiveness of scavenging are discussed.