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Biomedical subjects

R Silman

Publications and source records attributed to R Silman.

At least 19 recordsLinked to original sources
PubMed1999

The pineal and extra-pineal origins of 5-sulphatoxy N-acetyl-serotonin in humans.

In humans 6-sulphatoxy melatonin (SaMT) is the principal metabolite of endogenous and exogenous melatonin. 5-sulphatoxy N-acetyl-serotonin (SNAS) is a minor metabolite of exogenous melatonin, but it has not been established whether the levels of endogenous SNAS in plasma derives principally from endogenous melatonin. We have developed the first radioimmunoassay (RIA) for SNAS and used it (together with RIAs for melatonin and SaMT) to determine whether endogenous SNAS derives from endogenous melatonin or from platelet serotonin. Our results show a) the values of endogenous SNAS, unlike endogenous SaMT, increased with blood collection procedures that increased the values of serotonin, b) the values of endogenous SNAS in urine or in platelet-poor plasma were approximately the same as those of endogenous SaMT, but, unlike SaMT, did not show a diurnal rhythm, and c) we confirmed that SNAS was a minor metabolite of orally ingested melatonin. Thus, our conclusion is that SNAS is a minor metabolite of exogenous melatonin, but is not a significant metabolite of endogenous melatonin. In all probability, endogenous SNAS is principally the metabolite of platelet serotonin.

Administration, Oral↗
PubMed1998

First trimester maternal serum concentrations of fetal antigen 2 in normal pregnancies and those affected by trisomy 21.

Serum concentrations of fetal antigen 2 (FA-2), the amino-propeptide of the alpha1 chain of collagen type I, were measured in peripheral blood from women with normal (n = 234) and trisomy 21 affected (n = 14) pregnancies between 9 and 11 weeks gestation. Serum FA-2 concentrations were seen to be stable throughout this period, and though raised FA-2 concentrations were seen at the 10th week of gestation, a statistically significant difference between normal and trisomy 21 affected pregnancies was not found overall. Therefore it seems unlikely that FA-2 has a role in first trimester screening for trisomy 21, despite the fact that significantly higher FA-2 concentrations in trisomy 21 and significantly lower concentrations in trisomy 18 had been previously demonstrated in amniotic fluid in the second trimester.

Biological Assay↗
PubMed1998

Elevated nocturnal melatonin is a consequence of gonadotropin-releasing hormone deficiency in women with hypothalamic amenorrhea.

Elevated nocturnal melatonin is found in women with idiopathic hypogonadotropic hypogonadism (IHH), but it is not known whether this is implicated in the etiology of their GnRH deficiency. It is unlikely that nocturnal melatonin can be implicated in the etiology of the GnRH deficiency of Kallmann's syndrome (KS), because this condition is caused by defective neuronal migration in embryonic life. We therefore measured nocturnal melatonin in women with IHH and KS to determine whether it was elevated in one or both conditions and thereby to determine whether it was implicated as cause or consequence of GnRH deficiency. Four women with IHH, 3 women with KS, and 7 individually matched (age and body size) controls were recruited. Frequent day- and nighttime samples were taken for LH pulsatility studies. All patients showed absent or diminished LH pulsatility, compared with their respective controls. Samples were also taken over 24 h for melatonin and 6-sulphatoxymelatonin (the principle metabolite of melatonin and an independent marker of its secretion). Melatonin and 6-sulphatoxymelatonin levels were elevated in 6 of 7 patients (compared with their matched controls) and were significantly elevated in the KS group (compared with their controls). The finding of elevated nocturnal melatonin (and its metabolite) in GnRH-deficient women with KS (as well as IHH) suggests that nocturnal melatonin is elevated as a consequence of GnRH deficiency, irrespective of its etiology.

Adult↗
PubMed1998

Radioimmunoassay of bound and free melatonin in plasma.

We describe a nonextraction procedure, and two extraction procedures, for RIA of melatonin in human plasma. All procedures showed a diurnal rhythm of melatonin in human subjects, with interindividual differences greater than interprocedure differences. However, further investigations demonstrated considerable variability of recovery in the nonextraction procedure, suggesting a variability of binding proteins between samples. Combining recovery and dialysis experiments in the extraction procedures, we demonstrated that chloroform was unable to extract albumin-bound melatonin from a human serum albumin solution but, paradoxically, was able to extract bound and free melatonin from a plasma sample. The methanol extraction procedure extracted free and bound melatonin from all sources. These results indicate that albumin binding can substantially affect the RIA procedures. We conclude that assays should be validated against free and bound melatonin and that the two forms should be independently investigated when assessing bioactivity.

Circadian Rhythm↗
PubMed1996

Evidence for the Bauman variant in Kallmann's syndrome.

BACKGROUND AND OBJECTIVE: Idiopathic hypogonadotrophic hypogonadism (IHH) is a condition of gonadotrophin releasing hormone (GnRH) deficiency. IHH associated with anosmia is Kallmann's syndrome. A variant has been described by Bauman where a patient with Kallmann's syndrome apparently regained normal hypothalamo-pituitary function 2 years after the initial diagnosis. GnRH secretory activity can be assessed by measuring LH pulsatility. Our objective was to define the pattern of LH pulsatility in men with IHH and Kallmann's syndrome compared with those of normal controls, and to determine whether there is evidence for a Bauman variant of Kallmann's syndrome. DESIGN: Patients with IHH and Kallmann's syndrome were recruited from the endocrine clinic. Long-term hormone replacement therapy was discontinued. LH pulsatility was determined. PATIENTS: Three men with IHH, 3 men with classical Kallmann's syndrome and 5 normal male volunteers. MEASUREMENTS: Baseline serum FSH, LH and testosterone. Intensive blood sampling every 10 minutes for serum LH from 1000 to 1600 h during the day and 2200 to 0400 h during the night to measure LH pulsatility. RESULTS: The volunteer group showed normal LH pulsatility. In the patient group, LH secretion was apulsatile in one, showed significantly diminished amplitude in four, and there was normal pulsatility in one patient which remained normal 5 months later. CONCLUSION: Three patients with idiopathic hypogonadotrophic hypogonadism and 2 with Kallmann's syndrome had variable degrees of GnRH deficiency. One patient with Kallmann's syndrome had apparently normal GnRH activity, which remained normal 5 months later. This patient appears to have the Bauman variant of Kallmann's syndrome.

Adult↗
PubMed1995

The typing of fetal antigen 2 in human amniotic fluid.

Fetal antigen 2 (FA-2) has been identified in amniotic fluid and shown to be of fetal origin. In this study we have extended previous observations on FA-2 heterogeneity with respect to both size and charge using gel filtration, ion-exchange chromatography, non-dissociating polyacrylamide gel electrophoresis and sodium dodecyl sulphate polyacrylamide gel electrophoresis. From the diversity of forms we have been able to define two principal FA-2 types, type A and type B. Type A has a high molecular mass (140 kDa), has subunits of 33 kDa and 29 kDa, and elutes at approximately 0.27 mol/l sodium chloride from diethylaminoethyl (DEAE)-Sephacel. Type B has the same mass and subunits as type A, but elutes at approximately 0.24 mol/l sodium chloride from DEAE-Sephacel. Other low molecular mass forms of FA-2 have also been identified. All FA-2 forms described were shown to be common to all amniotic fluid samples studied and were not attributable to artefacts of collection or storage. It was also demonstrated that the recently described FA-2 RIA is specific for FA-2 types A and B and the conversion of arbitrary units FA-2 into micrograms applies to type A. The typing is discussed with respect to (i) the aminopropeptide of the alpha 1 chain of human procollagen type I, (ii) the 24 kDa phosphoprotein in developing bone and (iii) fetal calf ligament protein 1 (FCL-1), suggesting that they are the same protein.

Amniotic Fluid↗
PubMed1995

Abnormal amniotic fetal antigen 2 concentrations in trisomy 18 and trisomy 21.

Fetal antigen 2 (FA-2) is a human protein, first identified in amniotic fluid, and shown to be identical to the aminopropeptide of the alpha 1 chain of collagen type I. It exists in several different size and charge forms. In the present study, FA-2 was measured in amniotic fluid using two different assays: a rocket line immunoelectrophoretic assay which measured total FA-2, and a radioimmunoassay which was specific for the high molecular mass forms of FA-2. Both assays gave similar results. FA-2 concentrations were measured in amniotic fluid samples collected from normal pregnancies at 10-23 weeks gestation; they were shown to rise steeply from 10-14 weeks, peak at 17 weeks and then fall slightly by 23 weeks. Comparison between amniotic fluid from normal pregnancies and pregnancies affected by trisomy, showed significantly higher FA-2 concentrations in trisomy 21 and significantly lower concentrations in trisomy 18.

Amniotic Fluid↗
PubMed1988

Is there a central nervous withdrawal syndrome associated with discontinuing long-term treatment with propranolol?

Thirty healthy volunteers were treated with beta-adrenoceptor blocking doses of long-acting propranolol for at least 28 days before being randomized to continue propranolol treatment, receive identical placebo under double-blind conditions, or discontinue all treatment. No evidence of a central nervous withdrawal syndrome occurred during the next 28 days as assessed by changes in psychomotor tests, rating scales, visual analogue scales, tremor recordings and melatonin excretion. Three subjects in the placebo withdrawal group but none in the propranolol group complained of insomnia for up to 14 days of the withdrawal period.

Adult↗
PubMed1987

Automation in clinical microbiology: a new approach to identifying micro-organisms by automated pattern matching of proteins labelled with 35S-methionine.

A new rapid automated method for the identification and classification of microorganisms is described. It is based on the incorporation of 35S-methionine into cellular proteins and subsequent separation of the radiolabelled proteins by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The protein patterns produced were species specific and reproducible, permitting discrimination between the species. A large number of Gram negative and Gram positive aerobic and anaerobic organisms were successfully tested. Furthermore, there were sufficient differences within species between the protein profiles to permit subdivision of the species. New typing schemes for Clostridium difficile, coagulase negative staphylococci, and Staphylococcus aureus, including the methicillin resistant strains, could thus be introduced; this has provided the basis for useful epidemiological studies. To standardise and automate the procedure an automated electrophoresis system and a two dimensional scanner were developed to scan the dried gels directly. The scanner is operated by a computer which also stores and analyses the scan data. Specific histograms are produced for each bacterial species. Pattern recognition software is used to construct databases and to compare data obtained from different gels: in this way duplicate "unknowns" can be identified. Specific small areas showing differences between various histograms can also be isolated and expanded to maximise the differences, thus providing differentiation between closely related bacterial species and the identification of differences within the species to provide new typing schemes. This system should be widely applied in clinical microbiology laboratories in the near future.

Automation↗
PubMed1986

Method for the typing of Clostridium difficile based on polyacrylamide gel electrophoresis of [35S]methionine-labeled proteins.

A typing method for Clostridium difficile based on the incorporation of [35S]methionine into cellular proteins, their separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and their visualization by autoradiography is described. On analysis of the radiolabeled-protein profiles, nine distinct groups were observed (A to E and W to Z). The method, which is simple, reproducible, and readily expandable, has been applied in epidemiological studies to demonstrate cross-infection and hospital acquisition of C. difficile.

Adult↗
PubMed1985

Dramatic increase of placental protein 5 levels following injection of small doses of heparin.

In the course of an investigation on the effects of thyroid releasing hormone in pregnant women we noted a dramatic increase in the levels of placental protein 5 (PP5) in maternal blood. This increase ranged from 10 times to over 40 times the basal levels. Further study showed that the rise was associated with the use of heparin to maintain the patency of the cannula through which the samples were collected. Furthermore, the phenomenon appeared to be systemic rather than local, and may well be due to a direct effect of heparin on PP5 secretion by the placenta.

Female↗