bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between growth hormone (GH) status, serum leptin and body composition in healthy and GH deficient elderly subjects
Authors: Gill Matthew S. , Toogood Andrew A. , O'Neill Paul A. , Adams Judith E. , Thorner Michael O. , Shalet Stephen M. , Clayton Peter E. 
Published: November 2003

OBJECTIVEGrowth hormone (GH) secretion declines with age and is affected by body composition. The signal that mediates the latter relationship remains ill‐defined. Leptin, the protein product of the adipocyte specific ob gene, is thought to accurately reflect fat mass and could therefore be a candidate to influence GH secretion. We have therefore investigated the relationship between GH status, leptin and body composition in normal and GH‐deficient elderly subjects.DESIGNGH secretion was assessed by 20‐minute sampling over 24 hours and serum leptin concentrations were measured in a single morning, fasted sample.PATIENTSTwenty‐one GH deficient elderly patients (61–83 years) and 22 gender‐ and BMI‐matched controls (61–88 years).MEASUREMENTSBody composition was assessed by dual‐energy X‐ray absorptiometry (DEXA). GH was measured in an ultrasensitive chemiluminescent assay and serum leptin was determined by radioimmunoassay.RESULTSLeptin was correlated with percentage body fat in both sexes (male r = 0.75, female r = 0.89, both P < 0.001). Male patients had increased fat mass (FM) (P < 0.01) and leptin concentrations (P < 0.05) but similar lean mass (LM) compared with controls. However, leptin concentration per unit FM was identical in both groups (P = 0.3). In contrast, female patients had lower LM (P < 0.05) but similar FM to controls, yet their leptin concentration per unit FM was twice that of the controls (P < 0.05). In multiple linear regression (MLR) leptin was determined positively by FM and negatively by LM (controls r 2 = 76%; patients r 2 = 73%, both P < 0.0001). When controlled for gender, GH secretion in the controls was correlated negatively with leptin (r = −0.68, P < 0.01) and negatively with percentage body fat (r = −0.73, P < 0.01). In MLR, using leptin as a marker of body composition, 66% of the variability in GH secretion in the controls could be explained by gender (38%) and by leptin (28%).CONCLUSIONSBoth decreased lean mass and increased fat mass raise serum leptin concentrations in normal and growth hormone‐deficient elderly subjects. Leptin is therefore a marker of body composition rather than fat mass alone. The influence of body composition on growth hormone secretion in the elderly may be mediated through leptin, acting as a peripheral signal from adipose tissue to decrease GH secretion.
Inferior petrosal sinus AVP in patients with Cushing's syndrome
Authors: Yanovski Jack A. , Friedman Theodore C. , Nieman Lynnette K. , Chrousos George P. , Cutler Gordon B. , Doppman John L. , Kalogeras Konstantine T. 
Published: November 2003

OBJECTIVEIn both normal volunteers and patients with Cushing's disease, one dominant inferior petrosal sinus (IPS) contains higher concentrations of AVP and ACTH than the contralateral (non‐dominant) IPS, but ovine corticotrophin‐releasing hormone (oCRH)‐stimulated AVP in the petrosal sinuses is greater in Cushing's disease than in normal volunteers. To distinguish whether greater oCRH‐releasable AVP might be specifically related to the presence of a pituitary corticotrophinoma, or be due to hypercortisolism per se, we compared IPS AVP in patients with Cushing's disease with those of patients with other causes of Cushing's syndrome.PATIENTSTwenty‐three patients with Cushing's disease, 16 patients with the syndrome of ectopic ACTH and seven patients with Cushing's syndrome of adrenal origin.MEASUREMENTSAVP and ACTH, measured both before and 3, 5 and 10 minutes after oCRH in the petrosal sinuses, and in a peripheral vein.RESULTSIn all three groups, AVP concentrations were lateralized such that most of the AVP was found in one, dominant IPS. oCRH significantly increased IPS ACTH only in patients with Cushing's disease (P  <  0.001), whereas it significantly increased dominant IPS AVP levels in all three patient groups (P  <  0.01). However, neither dominant nor non‐dominant IPS AVP (basal or oCRH‐stimulated) were significantly different among patients with Cushing's disease, ectopic ACTH or Cushing's syndrome of adrenal origin. Basal and oCRH‐stimulated IPS AVP were negatively correlated with urine free cortisol.CONCLUSIONSInferior petrosal sinus AVP levels are similar in all forms of Cushing's syndrome, and thus the higher inferior petrosal sinus AVP levels in patients with Cushing's disease compared with normal volunteers are unlikely to be related specifically to the presence of the pituitary corticotrophinoma. While AVP may play a role in pituitary corticotroph tumourigenesis or may be secreted by some pituitary corticotroph tumours, the observation that CRH‐stimulated inferior petrosal sinus AVP levels are higher in Cushing's disease than in normal volunteers appears most likely to be related to the low endogenous CRH levels induced by hypercortisolism, rather than a consequence of Cushing's disease itself. We hypothesize that low endogenous CRH leads to increased sensitivity of central nervous system CRH receptors to exogenous CRH, and thus to greater ovine CRH‐stimulated AVP.
Antithyroid therapy improves bony manifestations and bone metabolic markers in patients with Graves' thyrotoxicosis
Authors: Nagasaka Shoichiro , Sugimoto Hideharu , Nakamura Tomoatsu , Kusaka Ikuyo , Fujisawa Genro , Sakuma Nobuko , Tsuboi Yasushi , Fukuda Shuichi , Honda Kazufumi , Okada Koji , Ishikawa San‐e , Saito Toshikazu 
Published: November 2003

OBJECTIVEAbnormal bone metabolism in patients with Graves' thyrotoxicosis is well documented, but the precise time‐course of its recovery remains poorly understood. The present study was undertaken to clarify longitudinal improvement in bony manifestations, especially in cortical bone, and bone metabolic markers in thyrotoxicosis.DESIGNTwo year prospective follow‐up study in patients with Graves' disease.PATIENTSTen consecutive patients with Graves' disease (seven males and three females, of mean (±SEM) age 39.3  ±  3.9 years) were enrolled in the study and treated with antithyroid drugs. Thirteen sex‐ and age‐matched patients with the disease in remission served as controls.MEASUREMENTSBony manifestations were evaluated both by fine cortical bone striations in the metacarpals on magnified roentgenograms and lumbar bone mineral density (BMD) measurement. Urinary deoxypyridinoline (dPYR) and serum pyridinoline cross‐linked telopeptide domain of type I collagen (ICTP) were monitored as markers of bone resorption, as well as serum osteocalcin (OC), carboxy‐terminal propeptide of type I procollagen (PICP) and alkaline‐phosphatase (ALP) as markers of bone formation.RESULTSInitial elevated free thyroid hormone levels were normalized within a month of starting therapy. Striation indices of the metacarpals were 1.89  ±  0.16 before therapy, higher than those of 0.49  ±  0.12 in the controls (P  <  0.0001); the indices gradually decreased to 1.00  ±  0.20 (12 months) and 0.48  ±  0.12 (24 months). Lumbar BMD Z‐scores increased from −0.22  ±  0.46 to 0.21  ±  0.47 (12 months) and 0.68  ± 0.48 (24 months) (P  =  0.0029). Before therapy, urinary dPYR and serum ICTP concentrations were much higher than the control values (dPYR, +553%; ICTP, +396%, P  <  0.0001), which declined promptly in the 2nd month. Serum OC, PICP and ALP were also significantly higher than in controls at first (OC, +287%; PICP, +225%; ALP, +196%), and remained elevated until 4 or 8 months.CONCLUSIONSBone resorption and cortical bone striations occur in untreated patients with Graves' thyrotoxicosis. The bone resorption rapidly ameliorates after normalization of thyroid hormone levels. In contrast, the accelerated bone formation persists for at least 4–8 months, suggesting positive uncoupling of bone remodelling. This dominant bone formation could result in the improvement in cortical bone striations and the increase in bone mineral density of trabecular bone.
Effect of resistance exercise and growth hormone on bone density in older men
Authors: Yarasheski Kevin E. , Campbell Jill A. , Kohrt Wendy M. 
Published: November 2003

OBJECTIVEThe purpose of this study was to evaluate whether 16 weeks of heavy resistance exercise training combined with daily growth hormone administration (GH) increases bone mineral density in 64–75‐year‐old men greater than resistance exercise training without GH supplementation.DESIGNEighteen healthy, elderly men (67 ± 1 year) followed a 16‐week progressive resistance training programme (75–90% maximum strength, 5–10 repetitions/set, 4 sets/day, 4 days/week) after double‐blind, random assignment to either a GH (12.5 or 18 μg/kg/day, equivalent to 25 or 36 mU/kg/day, n = 7) or placebo (n = 11) group.MEASUREMENTSBefore and at the end of 16 weeks of resistance exercise with or without GH administration, body composition, whole body and regional bone mineral density (BMD) were determined by dual‐energy X‐ray absorptiometry. Serum osteocalcin and IGF‐I were determined by radioimmunoassay before, during and at the end of treatment.RESULTSIncrements in fat‐free mass and training‐specific maximum voluntary muscle strength were similar in both groups after training. Serum insulin‐like growth factor‐I (IGF‐I) and osteocalcin levels were increased (P < 0.05) after exercise training plus GH. In comparison to initial measures, bone mineral density (g/cm2) of the proximal femur (Ward's triangle) was increased (P < 0.05) after 16 weeks of exercise training plus placebo treatment. Sixteen weeks of exercise training plus GH treatment did not increase whole body, spine or hip (femoral neck, trochanter, Ward's triangle) bone mineral density more than exercise plus placebo treatment.CONCLUSIONSThese findings suggest that in these older men with normal bone mineral density, short‐term resistance exercise training increased regional bone mineral density, but the addition of daily GH administration did not enhance whole body or regional bone mineral density despite GH‐induced increments in serum IGF‐I and osteocalcin. This implies that GH administration during a 16‐week resistance exercise training programme may increase bone turnover without increasing bone mineral accumulation.
Additional value of measurement of urinary cortisone and unconjugated cortisol metabolites in assessing the activity of 11β‐hydroxysteroid dehydrogenase in vivo
Authors: Best Ruth , Walker Brian R. 
Published: November 2003

OBJECTIVEIt has been shown recently that 11β‐hydroxysteroid dehydrogenase (11β‐HSD) is expressed as at least 2 isozymes. In the liver, 11β‐HSD1 converts cortisone to cortisol; in the kidney, 11β‐HSD2 converts cortisol to cortisone. Conventional assessment of 11β‐HSD activity in vivo has relied on gas chromatographic measurement of the ratios of conjugated cortisol and cortisone metabolites. However, these do not permit distinction between the tissue‐specific activities of the enzymes and do not reflect all forms of 11β‐HSD deficiency. In this report, we have assessed the usefulness of measuring unconjugated cortisol metabolites and free cortisol and cortisone in urine as indices of renal 11β‐HSD activity in man.DESIGNSix healthy male subjects established in sodium balance were given either glycyrrhetinic acid (170 mg t.d.s., to inhibit 11β‐HSD2), carbenoxolone (100 mg t.d.s., to inhibit both 11β‐HSD1 and 11β‐HSD2) or both inhibitors in combination.MEASUREMENTSUrinary electrolytes were measured and the concentrations of total and unconjugated urinary cortisol and its metabolites were determined by gas chromatography mass spectrometry.RESULTSGlycyrrhetinic acid and carbenoxolone inhibited renal 11β‐HSD2 to a similar degree, as judged by similar sodium retention. As previously reported, conventional measurement of ratios of total cortisol to cortisone metabolites were influenced to a greater extent by glycyrrhetinic acid (100–200% increase in ratio from baseline) than by carbenoxolone (< 30% increase). However, the effect of carbenoxolone was readily detected by measurement of urinary unconjugated cortisol/cortisone (130–480% increase of ratio from baseline) and also by measurement of ratios of unconjugated cortisol metabolites (60–130% increase).CONCLUSIONSMeasurement of free cortisol and cortisone in urine provides the most sensitive index of renal 11β‐HSD activity. Measurement of total and conjugated urinary steroids is insensitive in circumstances where 11β‐HSD activity in liver or elsewhere may be abnormal.
Strong association between serum levels of leptin and testosterone in men
Authors: Behre Hermann M. , Simoni Manuela , Nieschlag Eberhard 
Published: November 2003

OBJECTIVELeptin serves as a hormonal signal linking food intake and energy expenditure to fat mass. As significant effects of testosterone administration on body composition and adipose tissue have been described recently, we examined a possible association between serum levels of leptin and testosterone which has not been reported so far.SUBJECTSThree groups comprising a total of 58 adult age‐matched males were included in this cross‐sectional analysis by computer‐assisted clinical database selection. Group 1 (n=22) consisted of untreated hypogonadal patients with testosterone serum levels lower than 7 nmol/l. The inclusion criterion for Groups II (n=20) and III (n=16) was a serum testosterone level higher than 30 nmol/l. Group II involved hypogonadal patients under effective androgen substitution therapy; Group III comprised males without any endocrine disorder attending our clinic.MEASUREMENTSMorning blood samples were taken for determination of serum levels of leptin, testosterone, oestradiol and sex‐hormone binding globulin (SHBG). Serum levels of leptin were measured by homologous radioimmunoassay, the other hormones by standard immunoassays.RESULTSNo significant differences in serum leptin, serum testosterone, and body mass index (BMI) were detected between Group II (3.7 ± 1.5 μg/l, 40.3 ± 7.6 nmol/l, 24.4 ± 4.9 kg/m2, respectively (mean ± SD)), and Group III (4.0 ± 2.0 μg/l, 35.9 ± 6.5 nmol/l, 24.8 ± 2.6 kg/m2, respectively). However, hypogonadal patients of Group I who were selected for low testosterone serum levels (4.3 ± 1.7 nmol/l) had significantly higher leptin serum levels of 18.8 ± 9.7 μg/l (P < 0.001) and significantly higher BMI of 30.0 ± 6.6 kg/m2 (P < 0.001). Multiple linear regression analysis revealed a significant independent association of leptin with testosterone serum levels (partial correlation coefficient = − 0.84; P < 0.001) and with BMI (partial correlation coefficient = 0.44; P= 0.001), whereas serum levels of oestradiol and SHBG had no additional influence.CONCLUSIONSThis study demonstrates a close association between serum levels of testosterone and leptin in males which has not been described previously.Serum testosterone levels could be an important contributor to the known gender difference in serum leptin levels which can be found even after correction for body composition. These findings might be of clinical relevance for testosterone substitution therapy of hypogonadal as well as ageing men.
Genomic sequence analysis of a key residue (Arg183) in human Gαq in invasive non‐functional pituitary adenomas
Authors: Farrell W. E. , Talbot J. A. , Bicknell E. J. , Simpson D. , Clayton R. N. 
Published: November 2003

OBJECTIVEWith isolated exceptions the only oncogene significantly associated with pituitary tumours is a constitutively active Gs protein (Gαs). The recent cloning of the cDNA of human Gαq has facilitated the study of this activator of the phospholipase Cβ/Ca2+/protein kinase C pathway. Since, with isolated exceptions, non‐functional tumours are responsive in vitro to TRH and GnRH which activate Gq, we have investigated the genomic sequence of Gαq, in non‐functional (NF) invasive pituitary adenomas, at a residue corresponding to the one most frequently mutated in Gαs.PATIENTS AND MEASUREMENTSWe studied 27 invasive NF pituitary tumours by direct sequencing of DNA derived from archival slide extracted tumour cells. Primers were designed to encompass Arg183 (corresponding to Arg201 of Gαs) which when mutated has been shown to have oncogenic potential when transfected into cultural rat fibroblasts. In a previous study we have described allelic loss at tumour suppressor gene loci (TSG) in 7 of these 27 tumours.RESULTSWe successfully amplified genomic DNA with primers designed from the cDNA sequence of Gαq with specific exclusion of a processed pseudogene. No mutations were found at Arg183, in either the tumours showing allelic losses at specific TSG loci, or in the 20 remaining tumours in which we found no losses at the TSG loci investigated.CONCLUSIONSMutations at this key residue in Gαq occur infrequently, if at all, in invasive non‐functional pituitary tumours. However we cannot exclude the possibility of mutation(s) at the other key residue of Gαq, Gln209, implicated in GTP hydrolysis, or in other components of this pathway.
Cascading predation effects of Daphnia and copepods on microbial food web components
Authors: Zöllner Eckart , Santer Barbara , Boersma Maarten , Hoppe Hans‐Georg , Jürgens Klaus 
Published: November 2003

Summary1. We performed a mesocosm experiment to investigate the structuring and cascading effects of two predominant crustacean mesozooplankton groups on microbial food web components. The natural summer plankton community of a mesotrophic lake was exposed to density gradients of Daphnia and copepods. Regression analysis was used to reveal top–down impacts of mesozooplankton on protists and bacteria after days 9 and 15.2. Selective grazing by copepods caused a clear trophic cascade via ciliates to nanoplankton. Medium‐sized (20–40 μm) ciliates (mainly Oligotrichida) were particularly negatively affected by copepods whereas nanociliates (mainly Prostomatida) became more abundant. Phototrophic and heterotrophic nanoflagellates increased significantly with increasing copepod biomass, which we interpret as an indirect response to reduced grazing pressure from the medium‐sized ciliates.3. In Daphnia‐treatments, ciliates of all size classes as well as nanoflagellates were reduced directly but the overall predation effect became most strongly visible after 15 days at higher Daphnia biomass.4. The response of bacterioplankton involved only modest changes in bacterial biomass and cell‐size distribution along the zooplankton gradients. Increasing zooplankton biomass resulted either in a reduction (with Daphnia) or in an increase (with copepods) of bacterial biovolume, activity and production. Patterns of bacterial diversity, as measured by polymerase chain reaction–denaturing gradient gel electrophoresis (PCR–DGGE), showed no distinct grouping after 9 days, whereas a clear treatment‐coupled similarity clustering occurred after 15 days.5. The experiment demonstrated that zooplankton‐mediated predatory interactions cascade down to the bacterial level, but also revealed that changes occurred rather slowly in this summer plankton community and were most pronounced with respect to bacterial activity and composition.
The distribution and location of the symbiontLagenophrys asellion the freshwater isopodAsellus aquaticus
Authors: Roberts G. N. , Chubb J. C. 
Published: November 2003

Summary1. The distribution and location of the ciliated protozoan Lagenophrys aselli on the freshwater isopod Asellus aquaticus were studied in relation to water flow over the third pleopod surface.2. At low densities L. aselli had a significant preference for the anterior centre of the pleopod; however, at the highest densities this preference was no longer significant. The distribution ranged from closer than random at low densities to further than random at the highest densities, and may have been a product of feeding and reproduction of L. aselli as well as the short intermoult period of the host.3. An individual L. aselli has an effective area of both the lorica and the ciliated feeding disc. The ciliated feeding disc, when extended, may contribute to the presence of a small anterior–posterior gap being left between individuals.
Genetic structure in a montane mayfly Baetis bicaudatus (Ephemeroptera: Baetidae), from the Rocky Mountains, Colorado
Authors: Hughes Jane M. , Mather Peter B. , Hillyer Mia J. , Cleary Cath , Peckarsky Barbara 
Published: November 2003

Summary1. Populations of a number of sub‐tropical stream insect species have been found to show unexpected patterns of genetic variation, with more differences between samples from the same stream than between whole streams or between subcatchments. Many samples also showed deviations from Hardy–Weinberg proportions. It has been proposed that these patterns result from limited numbers of matings contributing to a given stream reach, because adults emerge throughout the year, and low levels of larval drift between reaches. These patterns may be less likely in a northern hemisphere montane species with synchronous emergence of adults and high levels of drift. We tested the hypothesis that patterns of genetic variation in a montane mayfly from the Rocky Mountains, Colorado, would reflect a pattern of ‘isolation by distance’ with samples from the same creek being more similar than samples from different creeks and that deviations from Hardy–Weinberg proportions would be minimal.2. Based on allozyme variation, the hypothesis of minimal deviations from Hardy–Weinberg proportions was not supported and there was no evidence of isolation by distance. Nevertheless the levels of differentiation among samples from within the same stream were less than those reported for most subtropical species.3. Results from analysis of a fragment of the cytochrome oxidase gene (subunit 1) revealed contrasting patterns. The levels of genetic differentiation were an order of magnitude higher between streams than among samples within streams. In addition, although there was no significant isolation by distance effect overall, a nested clade analysis provided evidence for restricted gene flow with isolation by distance for some clades.4. We suggest that these contrasting results may reflect the differences in male and female dispersal patterns. While differentiation at nuclear gene markers (allozymes) give information about both male and female dispersal, mitochondrial DNA markers reflect only female dispersal. We suggest that in this species, female dispersal may be more restricted, perhaps mostly along stream channels, whereas male dispersal is more widespread. An alternative explanation for the different results is the different evolutionary rates of the mitochondrial and nuclear markers.
Timing of spawning and glochidial release in Scottish freshwater pearl mussel (Margaritifera margaritifera) populations
Authors: Hastie Lee C. , Young Mark R. 
Published: November 2003

Summary1. The timing of reproduction was investigated in six Scottish freshwater pearl mussel populations from 1993 to 2002. Gravid females were examined and the release of mussel larvae (glochidia) was monitored.2. Annual spawning (oviposition) and spat (glochidial release) events occurred during June to July and June to September, respectively.3. Between‐river differences in timing seem to be related to water temperature. Mussels in the warmest rivers tend to spawn and spat first, and vice‐versa.4. Thermal variations also seem to influence the timing of reproduction within rivers, which can be delayed by several weeks during cold years. At least 3000°‐days occur between annual episodes of glochidial release.5. The timing of spawning is determined gradually, probably by a thermal summation effect.6. The release stage occurs as a sudden, synchronised event, with most of the glochidia spat over 1–2 days, indicating that it is triggered by an environmental cue. Sudden changes in water temperature and/or river level often result in spats, and the underlying mechanism may be respiratory.