Biomedical subjects
Publications and source records attributed to V Chan.
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Receptor sites for lactogenic hormones such as prolactin (PRL), human growth hormone (HGH), and placental lactogens, are widely distributed in mammalian tissues, including mammary glands, steroid-secreting cells of the adrenal, testis, and ovary, and target cells of steroid hormone action such as liver, prostrate, and kidney. Although the biological functions of lactogen binding sites remain uncertain, a relationship between prolactin and lipoprotein metabolism is implied by the occurrence of prolactin receptors in steroidogenic cells of the gonads and adrenal, and by the ability of prolactin to increase esterified cholesterol in the testis. Recently, loss of testicular prolactin receptors has been observed following elevation of circulating luteinising hormone (LH) concentrations by the gonadotropin releasing hormone (GnRH) and its agonist analogues. The hormone dependence of lactogen receptor sites in steroid-secreting cells was further analysed in rat testis, ovary, and adrenal glands after treatment with the respective trophic hormones, gonadotropin and ACTH. In each of these tissues, rapid and transient loss of lactogen receptors was observed after trophic hormone stimulation. These findings indicate that increased turnover of lactogen receptors is an important component of the target-cell response, and suggest that prolactin receptors might be involved in the transport of lipoprotein precursors for steroid biosynthesis.
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Agonist analogs of gonadotropin-releasing hormone (GnRH) have been shown to exert antigonadal effects in male and female animals. In hypophysectomized male rats treated with follicle-stimulating hormone, administration of a potent GnRH agonist caused depletion of luteinizing hormone and prolactin receptors and marked suppression of serum testosterone levels. The possibility that such direct effects of GnRH agonists on testicular function could be expressed through specific receptors located in the interstitial cells of the testis was supported by the selective concentration of a 125I-labeled GnRH agonist by the testis in vivo. Specific receptors for the releasing hormone were demonstrated in testis particles and dispersed interstitial cells by direct binding analysis with the 125I-labeled GnRH agonist. The binding affinity (Ka = G X 10(9) M-1) and peptide specificity of the testicular GnRH binding sites were similar to those of anterior pituitary and ovarian GnRH receptors. The presence of GnRH receptors in the testis indicates that these sites mediate the direct inhibitory actions of GnRH agonists upon testicular endocrine function.
The presence of Hb New York was confirmed in a Chinese family in which affected members have occasional red cells with Hb-H-like inclusions and a relative decrease in alpha chain synthesis, suggestive of a coexisting alpha thalassaemia trait. However, globin gene mapping and DNA hybridization revealed no deletion of the alpha genome. Timed-incubation experiments showed that the rate of synthesis of beta NY chain was greater than that of normal beta chain in the early periods. Chromatographic separation of Hb NY and Hb A before chain analysis revealed preferential binding of newly synthesized alpha chains to beta NY, with a four-fold increase in specific activity of the alpha Hb NY chains. It is concluded that beta NY chain is being synthesized more rapidly and its increased turnover may account for this presentation of apparent alpha chain deficiency.
Of 154 Chinese patients who underwent gynaecological operations, four showed a positive 125I fibrinogen leg scan for venous thrombosis, and overall incidence of 2 . 6%. In those who were on oral contraceptives and had major pelvic surgery for benign conditions, the incidence was 10 . 5%; in those who had Wertheim hysterectomy for carcinoma of cervix, it was 6 . 7%. This confirms the rarity of post-operative thromboembolism in the Chinese. Fragment E showed a biphasic rise after major operation due to tissue injury and venous thrombosis. In patients with malignancy, the postoperative 'fibrinolytic shutdown', represented by decreased plasminogen activator together with increased alpha 1 antitrypsin and C1- inhibitor levels, was more marked. In addition, alpha 2 macroglobulin level was lower and fell significantly after operation. In patients on oral contraceptives, fragment E levels were higher after surgery and there was no decrease in plasminogen activator levels. Antithrombin III levels did not fall except in three of the four patients with venous thrombosis. A marked increase in fragment E level and a decrease in antithrombin III level might be useful diagnostic markers for postoperative venous thrombosis.
The alpha-thalassemia-2 (alpha-thal-2) genotype or mild alpha-thalassemia gene consists of a single structural alpha-globin gene on the chromosome that normally bears two alpha-globin genes. We used blot hybridization to investigate variation in the molecular organization of this genotype and to determine the distributions of these variations in the world population. Two different patterns of gene organization responsible for the alpha-thal-2 genotype were found: the first was the result of a 4.2-kilobase pair deletion involving the normal 5' alpha-globin gene (leftward deletion alpha-thal-2 genotype), and the second probably the result of a crossover deletion of a DNA fragment bridging the two normal alpha-globin genes (rightward deletion alpha-thal-2- genotype). The rightward deletion was found in all 9 Black subjects, all 8 Mediterranean subjects, and 4 of 13 Chinese subjects. The leftward deletion was found in four and the nondeletion alpha-thalassemia lesion was found in five of the nine remaining Chinese subjects. It is likely that these deletions are related to specific DNA sequences that determine DNA recombinational events.
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A radioimmunoassay (RIA) had been developed for the determination of antithrombin III (AT III) in man. The detection limit was 25 microgram/dl. AT III-RIA level and biological activity (anti-Xa) was significantly correlated (r = 0.737, P less than 0.001). Plasma levels in 36 healthy males (mean +/- SD, 19.9 +/- 2.5 mg/dl) and 21 healthy females (19.1 +/- 2.4 mg/dl) were similar. Serial AT III measurements in normal menstruating females showed lower levels during midcycle and higher concentrations during menstruation. In carcinomas, the AT III levels were lower than normal, particularly in hepatocellular carcinoma. In cirrhosis of liver, the levels were markedly decreased and in some patients were below that found in congenital AT III deficiency. Patients with deep vein thrombosis and patients with heart valve replacement had lower levels than normal, while patients with cerebral vascular occlusion had normal levels. The possible use of AT III as a diagnostic tool of post-operative deep vein thrombosis was demonstrated in one patient after hysterectomy. The increased sensitivity, specificity and precision of this type of assay offer distinct advantages over existing methods of AT III estimation.
Pituitary-thyroid function in male heroin addicts and addicts after abstinence (ex-addicts) was studied and compared with that of healthy euthyroid men. In heroin addicts the increases in circulating total thyroxine and triiodothyronine levels were accompanied by an increase in the thyroid hormone uptake test. These changes may reflect a quantitative increase in thyroxine binding globulin. Reverse triiodothyronine concentrations in heroin addicts were normal. The thyrotrophin-releasing hormone elicited a diminished thyrotrophin response in heroin addicts which was significantly different from that in control subjects and ex-addicts. An elevation of serum prolactin was noted in heroin addicts, while ex-addicts had normal levels. Gradual recovery of pituitary-thyroid function occurred after heroin withdrawal.
The thyroid function of patients with three different types of organification defect was studied. All patients were characterized by a high thyroidal 131I uptake and a positive perchlorate discharge. Patients with Pendred's syndrome who had goitre and congenital nerve deafness were mostly euthyroid with normal circulating thyroid hormone levels. Only two of them had compensated euthyroidism with elevated total T3, high basal TSH and delayed return to basal value with TRH. The patients who were euthyroid with large goitres and normal hearing had elevated total T3 and an exaggerated TSH response to TRH. The thyroid function of these two groups of patients contrasted with that of goitrous cretins, who were clinically hypothyroid with low circulating total T4, increased T3 and decreased rT3 levels. The data suggest that in patients with intrathyroidal iodine deficiency secondary to organification defect, there is preferential T3 production in an effort to maintain euthyroid state, and this is further substantiated in the case of gross thyroid insufficiency either by enhanced peripheral conversion of T4 to T3, or reduced metabolic clearance of T3 and increased clearance of rT3, resulting in elevated T3 and decreased rT3 levels.
Five men and three women with active acromegaly were treated with bromocriptine. After three months' therapy (30 mg/day) mean GH during the day decreased by 50% in six out of eight subjects. In the remaining two subjects (non-responders) GH was persistently over 100 micrograms/l. Mean GH during glucose tolerance test were not significantly decreased in three out of the eight subjects, of whom two were the nonresponders. The minimum dose of bromocriptine required to achieve maximum GH suppression ranged from 7.5 to 20 mg/day. In contrast, serum prolactin (PRL) throughout the day suppressed significantly in all subjects after 5 mg/day bromocriptine. Decreases in clinical symptoms, hand volume, urinary hydroxyproline and calcium excretion were seen in about half of the subjects. Three of the four subjects with diabetes mellitus showed improvement in glucose tolerance. Although minor side effects were uncommon, one patient died because of massive gastrointestinal haemorrhage from a duodenal ulcer.
Heparin antithrombin III binding was studied by crossed immunoelectrophoresis. In plasma and purified antithrombin III standard, multicomponent patterns were obtained with low concentrations of mucosal heparin. There is evidence that antithrombin III may bind more than one heparin molecule. At high heparin concentration (greater than 16 U/ml), single symmetrical peaks were obtained. Serum samples showed two antithrombin III peaks due to a decreased heparin binding of the slower peak (2.1-3.9 times), which was probably antithrombin III-activated procoagulant complexes. Heparin analogue (A 73025) also bound antithrombin III in vitro but the mobility of the peak was slower than with mucosal heparin and only a single peak was obtained in serum samples. Radioimmunoassay showed a decreased binding of antithrombin III antibody to heparin-antithrombin III complex. Venous occlusion to the forearm resulted in a slow second peak in the plasma. Heparin therapy gave rise to a double peak in the plasma antithrombin III profile and with continuous infusion, quantitative decreases were noted in all subjects studied, two of whom rethrombosed at the end of 7 days therapy.
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The effect of acute myocardial infarction on the secretions of LH, FSH and testosterone was studied in thirteen male patients. Plasma testosterone fell transiently on the fourth day after acute myocardial infarction. This was accompanied by a rise in LH on the same day which persisted for a week after infarction. Serum FSH showed no significant change. The data suggest that following the medical stress of myocardial infarction, testosterone concentration was suppressed resulting in a compensatory rise in LH.
The effect of surgical stress on the secretions of LH, FSH, testosterone (T) and oestradiol (E2) were studied in twelve male patients. During surgery LH rose significantly; post-operatively, LH fell but remained persistently elevated a week after operation. However, T and E2 fell progressively to a nadir on the second and fifth post-operative day respectively and remained suppressed. Serum FSH showed no significant change. Despite a post-operative decrease in sex hormone binding globulin (SHBG) binding capacity, non-SHBG bound T showed a decrease parallel to T. Multiple sampling studies showed that the secretions of LH were increased and that of T were decreased post-operatively. Following surgery, LH responses to LHRH were magnified, FSH and T responses showed no significant change when compared with the pre-operative responses. These data suggest that secretions of LH were increased during surgery. Following surgical stress, T and E2 concentrations were suppressed resulting in a compensatory elevation of LH concentrations.