bluuebunny/crossref_metadata_2025_split huggingface dataset:
IGF‐I and testosterone levels as predictors of bone mineral density in healthy, community‐dwelling men
Authors: Rucker Diana , Ezzat Shereen , Diamandi Anastasia , Khosravi Javad , Hanley David A. 
Published: December 2004

Summaryobjective  Age‐related decline in IGF‐I and gonadal hormones have been postulated to play an important role in the pathogenesis of age‐related bone loss in men. In this cross‐sectional study, the relation between serum IGF‐I and gonadal hormones with bone mineral density (BMD) was examined in community‐dwelling men.design and subjects  Serum IGF‐I, testosterone and BMD were examined in 61 community‐dwelling men over the age of 27, who were randomly selected from the Calgary cohort of 1000 subjects in the Canadian Multicentre Osteoporosis Study. In the present study, IGF‐I, serum testosterone, SHBG, free androgen index (FAI), parathyroid hormone (PTH), 25‐hydroxy‐vitamin D [25(OH)D] and other markers of bone turnover were measured. BMD was measured at the spine and hip (HOLOGIC 4500). Simple linear regression was used to assess the linear relation between IGF‐I, testosterone, BMD and other biochemical markers of bone metabolism and potential confounding variables and subsequent multivariate regression models were constructed separately for each BMD measurement to assess the importance of IGF‐I and testosterone in the presence of potential confounding variables.results  Serum IGF‐I, FAI and SHBG significantly decreased as a function of age, whereas serum levels of PTH increased. Only 25(OH)D, total testosterone and FAI were positively associated with serum IGF‐I after adjusting for age and BMI. Multiple linear regression models revealed that IGF‐I was a significant predictor of BMD at the total hip, femoral neck and femoral trochanter neck (P ≤ 0·001). In contrast, the FAI was a significant predictor of BMD at the lumbar spine and wards area (P ≤ 0·011), and SHBG was a significant predictor at the total hip and femoral trochanter (P ≤ 0·045).conclusion  These data support the hypothesis that the age‐related decline in bone mass in men is associated with declining levels of IGF‐I and testosterone.
Gender variation in PTH sensitivity and rhythmicity following growth hormone replacement in adult growth hormone‐deficient patients
Authors: White H. D. , Ahmad A. M. , Syed A. A. , Clewes A. , Peter R. , Vora J. P. , Fraser W. D. 
Published: December 2004

Summarybackground  Adult GH deficiency (AGHD) is associated with osteoporosis and reduced bone turnover; factors improved by GH replacement (GHR), with men gaining greater benefit than women. Reduction in sensitivity of bone and kidney to the effects of PTH may underlie AGHD changes in bone turnover. We determined the gender difference in PTH target‐organ sensitivity following GHR in AGHD patients.design, patients and measurements  Twenty AGHD patients (10 men) were admitted to hospital before and after GHR initiation. Half‐hourly blood samples were collected for PTH, calcium, nephrogenous cyclic AMP (NcAMP, marker of PTH activity), type‐I collagen C‐telopeptide (CTX, bone resorption marker) and procollagen type‐I amino‐terminal propeptide (PINP, bone formation marker).results  The 24‐h mean PTH concentration decreased in both genders (P < 0·001), with maximal changes seen 6 and 12 months following GHR in men and women, respectively. Increases in 24‐h mean NcAMP (P < 0·05), calcium (P < 0·001) and bone turnover markers (P < 0·001) occurred in both genders following GHR, with maximal changes at 1 month in men, but at 3 months for NcAMP, calcium and CTX and 12 months for PINP in women. Maximal NcAMP increase was higher in men (P = 0·009).conclusions  Following GHR, PTH target‐organ sensitivity increased in both genders, demonstrated by simultaneous reduction in PTH concentration and increase in NcAMP, calcium and bone turnover. In women, improvement in renal PTH sensitivity was delayed and reduced, and changes in bone turnover were delayed, with increase in bone resorption preceding bone formation. Both factors may contribute to the reduced bone mineral density (BMD) response to GHR observed in women.
Earlier initiation of GH therapy does not influence adult height but enables earlier start of pubertal induction in children with multiple pituitary hormone deficiency
Authors: Kawai Masahiko , Momoi Toru , Mamada Mitsukazu , Yorifuji Tohru , Nakahata Tatsutoshi 
Published: December 2004

Summaryobjective  For patients with GH and gonadotrophin deficiency, adult height and sexual maturation are important not only for their physical but also psychological status. GH therapy is usually initiated soon after diagnosis but the differences in the age for initiation of therapy have not been previously examined. In this study, we assessed the influence of timing of initiation of GH therapy on adult height and the time of initiation of pubertal induction.design, patients and measurements  Height‐related data from 16 short children (13 boys and three girls) with GH and gonadotrophin deficiency who reached adult height after 10·9 ± 2·3 years of GH therapy were analysed retrospectively.results  Adult height (0·00 ± 0·69 SD) improved remarkably compared to height SDS at the start of GH therapy (−3·75 ± 0·94 SD). The age at which GH therapy was started ranged from 3·2 to 12·0 years, but we found that such a difference in age did not affect adult height. However, an earlier start of GH therapy allowed earlier pubertal induction without loss of height potential.conclusions  Earlier initiation of GH therapy is not required for normalization of adult height in patients with GH and gonadotrophin deficiency but it makes earlier pubertal induction possible, which is important for quality of life.
Lack of association of the vitamin D receptor gene with Graves’ disease in UK Caucasians
Authors: Collins J. E. , Heward J. M. , Nithiyananthan R. , Nejentsev S. , Todd J. A. , Franklyn J. A. , Gough S. C. L. 
Published: December 2004

Summaryobjective  Vitamin D modulates the immune system by suppressing the proliferation of activated T cells, with its actions being directed through the vitamin D receptor (VDR). A number of single nucleotide polymorphisms (SNPs) have been identified in the VDR gene, of which several have been associated with autoimmune diseases, including type 1 diabetes and Graves’ disease (GD) in Japanese females. The aim of this study was to test for association of polymorphisms of the VDR gene in the genetic susceptibility to GD in UK Caucasians.design  Target DNA for five previously published SNPs, four novel SNPs and one microsatellite marker was amplified by the polymerase chain reaction (PCR). Subsequent genotyping was performed using restriction fragment length polymorphism (RFLP) or microsatellite genotyping analysis, according to the type of VDR polymorphism.patients  We obtained DNA from a case–control dataset consisting of 768 patients with GD and 864 control subjects. All patients and control subjects were Caucasians born in the UK, and all gave informed, written consent.measurements  Frequencies of the alleles and genotypes of the ten VDR gene polymorphisms were compared between patients and control subjects using the χ2 test. Odds ratios were calculated using Woolf's method with Haldane's modification for small numbers and D prime (D′) was calculated to assess the level of linkage disequilibrium (LD) between the ten polymorphisms.results  No differences in allele or genotype frequencies were observed between GD cases and control subjects for any of the nine SNPs studied. The S allele of the PolyA microsatellite marker was slightly more frequent in GD cases when compared with control subjects (χ2= 4·364, P = 0·04). Strongest LD between markers was observed towards the 3′ end of the VDR gene but there was no evidence of association with disease.conclusion  This is the largest and most comprehensive study of the VDR gene in GD to date and these data suggest that these polymorphisms of the VDR gene do not contribute to GD susceptibility in the UK.
Plasma homocysteine in polycystic ovary syndrome: does it correlate with insulin resistance and ethnicity?
Authors: Wijeyaratne Chandrika N. , Nirantharakumar K , Balen Adam H. , Barth Julian H. , Sheriff Rezvi , Belchetz Paul E. 
Published: December 2004

Summarybackground  Polycystic ovary syndrome (PCOS) is associated with insulin resistance and premature coronary artery disease (CAD). Hyperhomocysteinaemia is a recognized risk factor for atherosclerosis, particularly among migrant South Asians, and has recently been shown to be correlated positively with the degree of insulin resistance/hyperinsulinaemia.objectives  To compare total plasma homocysteine (Hcy) in PCOS with controls from ethnic groups at high and low risk of insulin resistance.methods  Case control study of three ethnic groups, Sri Lankans (SL), British Asians (BA) and white Europeans (C), with and without PCOS at specialist centres in Sri Lanka and Yorkshire, UK. Fasting total plasma Hcy concentration was analysed by fluorescence polarization immunoassay and examined for any correlation with age, body mass index (BMI), central obesity, fasting insulin and insulin sensitivity [calculated by the Quantitative Insulin Sensitivity Check Index (QUICKI) method], lipids and testosterone in each ethnic group.results  Eighty SL with PCOS and 45 controls, 47 BA with PCOS and 11 controls, and 40 C with PCOS and 22 controls were studied. Both Asian groups with PCOS were younger than affected Europeans (P = 0·008). Sri Lankans with PCOS had significantly lower BMI values than other affected groups: mean ± SEM (SL) 26·3 ± 0·95; (BA) 30·59 ± 7·54; (C) 32·1 ± 5·95 kg/m2 (P = 0·006). However, waist : hip ratios (WHR) of Sri Lankans with PCOS were similar to others: mean ± SEM (SL) 0·97 ± 0·01 (BA) 1·04 ± 0·02 (C) 0·92 ± 0·01, P = 0·33. Mean plasma Hcy was significantly higher in all PCOS groups than in their ethnically matched controls (Student's t‐test): (SL) 10·2 ± 1·9 vs 9·0 ± 3·8, P = 0·01; (BA) 7·9 ± 1·9 vs 6·8 ± 2·5, P < 0·0001; (C) 8·3 ± 2·3 vs 6·8 ± 1·5, P = 0·0007 µmol/l. Sri Lankans with PCOS had significantly greater Hcy concentrations than British Asians and Europeans with PCOS [P = 0·001; single‐factor analysis of variance (anova)] and also significantly greater fasting insulin concentrations [(SL) 242·9 ± 38·9; (BA) 89·4 ± 8·9; (C) 48·6 ± 4·8 pmol/l (P = 0·0003)] and significantly lower QUICKI [(SL) 0·308 ± 0·004; (BA) 0·335 ± 0·005; (C) 0·375 ± 0·002 (P = 0·0007)]. Fasting plasma Hcy correlated best with fasting insulin (r = 0·56, P = 0·0001) and QUICKI (r =−0·53, P < 0·0001) in Sri Lankans with PCOS. Hcy in PCOS subjects from all three ethnic groups correlated significantly with fasting insulin following adjustment for age, BMI and WHR (r = 0·45, P = 0·0001), but this was not evident in the controls (r =−0·32, P = 0·1).conclusions  Elevation of fasting plasma homocysteine in PCOS varies with ethnicity and correlates significantly with fasting insulin. High homocysteine in young Sri Lankans with PCOS has major implications for their long‐term risk for atherosclerosis.
Long‐term skeletal effects of recombinant human growth hormone (rhGH) alone and rhGH combined with alendronate in GH‐deficient adults: a seven‐year follow‐up study
Authors: Biermasz Nienke R. , Hamdy Neveen A. T. , Pereira Alberto M. , Romijn Johannes A. , Roelfsema Ferdinand 
Published: December 2004

Summarybackground  GH‐deficient patients respond to recombinant human GH (rhGH) replacement therapy by increasing bone mineral density (BMD) at a rate of about 1% a year for at least 4 years. Predictive factors for a beneficial effect on bone are a low bone mass at baseline and gender. Whether the beneficial skeletal effects of GH are sustained in the long term remains to be established. It is also not known whether osteoporotic GH‐deficient patients may require additional antiresorptive drugs and whether this treatment would be effective concomitantly with GH replacement.design  We performed a long‐term, controlled study in 30 GH‐deficient adults: 15 with osteoporosis and 15 control subjects with low bone mass. All patients were treated with rhGH for at least 4 years; thereafter, 3 years of additional alendronate treatment was given to patients with osteoporosis, while controls continued on GH therapy alone. The GH dose was individualized to maintain an IGF‐I within the normal reference range for the duration of the study, and was equal between genders.results  At the end of 4 years of rhGH replacement therapy, a significant increase in mean lumbar spine BMD was observed in both the osteoporosis group (3·6%) and the control group (7·0%), with no significant difference between groups. Males had a larger increase in BMD than females (P = 0·032). After 4 or 5 years of GH treatment patients with persisting osteoporosis received additional alendronate (10 mg/day) for 3 years. Lumbar spine BMD increased by 8·7% after 3 years (P = 0·001) vs 1·5% (P = NS) in the control group continuing on rhGH replacement alone. The alendronate effect was gender independent (P = 0·59). Mean bone area of the lumbar spine did not change in both groups for the duration of the study. Femoral neck BMD increased significantly in the osteoporosis group (3·5%) and was unchanged in the control group. Five osteoporotic GH‐deficient patients had a total of 12 vertebral fractures before start of alendronate. Only one of these patients developed two new vertebral fractures within the first year of treatment with alendronate.conclusion  We observed a significant increase in lumbar spine BMD in the first 4 years of rhGH replacement. The effect of GH on bone was gender dependent, but not BMD dependent. After more than 4 years of GH replacement, BMD seemed to reach a plateau, at least as measured in the 3–4 years thereafter, as no significant increase was present in patients treated with GH alone. By contrast, alendronate rapidly augmented BMD and this effect was maintained for at least 3 years. These increases in BMD were associated with a low incidence of (vertebral) fractures. The long‐term use of GH does not preclude a beneficial effect of an additional antiresorptive agent in GH‐deficient patients with osteoporosis.
Distribution pattern of somatostatin and cortistatin mRNA in human central and peripheral tissues
Authors: Dalm Virgil A. S. H. , Van Hagen P. Martin , De Krijger Ronald R. , Kros Johan M. , Van Koetsveld Peter M. , Van Der Lely Aart‐Jan , Lamberts Steven W. J. , Hofland Leo J. 
Published: December 2004

Summarybackground  Somatostatin receptors (sst) and their endogenous ligand, somatostatin (SS), are widely expressed throughout the human body. Recently, the cDNA of a novel SS‐like peptide, named cortistatin (CST), has been cloned. This CST was found to be expressed in more restricted areas, like brain cortex, testes, kidney, stomach and leucocytes. Further studies demonstrated a selective expression of CST in tissues and cells of the human immune system, while SS was not expressed.objective  In the present study we investigated the expression pattern of both SS mRNA and CST mRNA in various human central and peripheral tissues by quantitative RT–PCR (Q–PCR), in order to evaluate whether CST is more widely expressed in man than described to date and to investigate the relationship between SS and CST expression levels in various tissues. Previously, two different CST mRNA isoforms have been described. Therefore, we investigated the expression of both isoforms by RT–PCR in the different tissues as well.results  We demonstrate for the first time that CST mRNA is widely expressed in the human body. Interestingly, a selective expression of CST mRNA and not SS mRNA was only found in isolated cells of the human immune system, whereas different tissues expressed both SS and CST mRNA.conclusion  CST may have a broader functional role than previously assumed.
Effects of recombinant LH (rLH) supplementation during controlled ovarian hyperstimulation (COH) in normogonadotrophic women with an initial inadequate response to recombinant FSH (rFSH) after pituitary downregulation
Authors: De Placido G. , Alviggi C. , Mollo A. , Strina I. , Ranieri A. , Alviggi E. , Wilding M. , Varricchio M. T. , Borrelli A. L. , Conforti S. 
Published: December 2004

Summarybackground  This study was aimed to evaluate the effect of different recombinant LH (rLH) doses on the ovarian outcome of normogonadotrophic women with an initial inadequate response to recombinant FSH (rFSH) after pituitary downregulation.methods  Only women undergoing a ‘long protocol’ with a GnRH‐agonist followed by rFSH administration were enrolled. On the eighth day of stimulation, 46 patients with serum E2 levels < 180 pg/ml and with no follicle > 10 mm were randomized in two groups to receive a supplementation with a daily rLH dose of 75 (group A) or 150 IU (group B), respectively. Forty‐six normal responders continuing their monotherapy with rFSH formed the control group (C).results  The mean number of oocytes retrieved and the percentage of mature oocytes in the group B (9·65 ± 2·16, 79·0%) were comparable with those observed in the group C (10·65 ± 2·8, 82·5%) and significantly higher when compared with the group A (6·39 ± 1·53, 65·7%). The mean number of ampoules of rLH was significantly higher in the group B (14·4 ± 2·0 vs. 9·65 ± 1·1), whereas these patients received a significantly lower mean number of rFSH ampoules (44·6 ± 7·4 vs. 36·1 ± 3·8). Seven (30·4%), 9 (39·1%) and 22 (47·8%) pregnancies were achieved in the groups A, B and C, respectively.conclusions  These results suggest that patients with initial inadequate responses to rFSH after pituitary downregulation benefit from the addition of a daily dose of 150 IU of rLH, starting from the eighth day of stimulation.
The three S‐layer‐like homology motifs of the S‐layer protein SbpA of Bacillus sphaericus CCM 2177 are not sufficient for binding to the pyruvylated secondary cell wall polymer
Authors: Huber Carina , Ilk Nicola , Rünzler Dominik , Egelseer Eva M. , Weigert Stefan , Sleytr Uwe B. , Sára Margit 
Published: December 2004

SummaryThe S‐layer protein SbpA of Bacillus sphaericus CCM 2177 recognizes a pyruvylated secondary cell wall polymer (SCWP) as anchoring structure to the peptidoglycan‐containing layer. Data analysis from surface plasmon resonance (SPR) spectroscopy revealed the existence of three different binding sites with high, medium and low affinity for rSbpA on SCWP immobilized to the sensor chip. The shortest C‐terminal truncation with specific affinity to SCWP was rSbpA31‐318. Surprisingly, rSbpA31‐202 comprising the three S‐layer‐like homology (SLH) motifs did not bind at all. Analysis of the SbpA sequence revealed a 58‐amino‐acid‐long SLH‐like motif starting 11 amino acids after the third SLH motif. The importance of this motif for reconstituting the functional SCWP‐binding domain was further demonstrated by construction of a chimaeric protein consisting of the SLH domain of SbsB, the S‐layer protein of Geobacillus stearothermophilus PV72/p2 and the C‐terminal part of SbpA. In contrast to SbsB or its SLH domain which did not recognize SCWP of B. sphaericus CCM 2177 as binding site, the chimaeric protein showed specific affinity. Deletion of 213 C‐terminal amino acids of SbpA had no impact on the square (p4) lattice structure, whereas deletion of 350 amino acids was linked to a change in lattice type from square to oblique (p1).
The morphogenetic MreBCD proteins of Escherichia coli form an essential membrane‐bound complex
Authors: Kruse Thomas , Bork‐Jensen Jette , Gerdes Kenn 
Published: December 2004

SummaryMreB proteins of Escherichia coli, Bacillus subtilis and Caulobacter crescentus form actin‐like cables lying beneath the cell surface. The cables are required to guide longitudinal cell wall synthesis and their absence leads to merodiploid spherical and inflated cells prone to cell lysis. In B. subtilis and C. crescentus, the mreB gene is essential. However, in E. coli, mreB was inferred not to be essential. Using a tight, conditional gene depletion system, we systematically investigated whether the E. coli mreBCD‐encoded components were essential. We found that cells depleted of mreBCD became spherical, enlarged and finally lysed. Depletion of each mre gene separately conferred similar gross changes in cell morphology and viability. Thus, the three proteins encoded by mreBCD are all essential and function in the same morphogenetic pathway. Interestingly, the presence of a multicopy plasmid carrying the ftsQAZ genes suppressed the lethality of deletions in the mre operon. Using GFP and cell fractionation methods, we showed that the MreC and MreD proteins were associated with the cell membrane. Using a bacterial two‐hybrid system, we found that MreC interacted with both MreB and MreD. In contrast, MreB and MreD did not interact in this assay. Thus, we conclude that the E. coli MreBCD form an essential membrane‐bound complex. Curiously, MreB did not form cables in cell depleted for MreC, MreD or RodA, indicating a mutual interdependency between MreB filament morphology and cell shape. Based on these and other observations we propose a model in which the membrane‐associated MreBCD complex directs longitudinal cell wall synthesis in a process essential to maintain cell morphology.
Analysis of Campylobacter jejuni capsular loci reveals multiple mechanisms for the generation of structural diversity and the ability to form complex heptoses
Authors: Karlyshev Andrey V. , Champion Olivia L. , Churcher Carol , Brisson Jean‐Robert , Jarrell Harold C. , Gilbert Michel , Brochu Denis , St Michael Frank , Li Jianjun , Wakarchuk Warren W. , Goodhead Ian , Sanders Mandy , Stevens Kim , White Brian , Parkhill Julian , Wren Brendan W. , Szymanski Christine M. 
Published: December 2004

SummaryWe recently demonstrated that Campylobacter jejuni produces a capsular polysaccharide (CPS) that is the major antigenic component of the classical Penner serotyping system distinguishing Campylobacter into >60 groups. Although the wide variety of C. jejuni serotypes are suggestive of structural differences in CPS, the genetic mechanisms of such differences are unknown. In this study we sequenced biosynthetic cps regions, ranging in size from 15 to 34 kb, from selected C. jejuni strains of HS:1, HS:19, HS:23, HS:36, HS:23/36 and HS:41 serotypes. Comparison of the determined cps sequences of the HS:1, HS:19 and HS:41 strains with the sequenced strain, NCTC11168 (HS:2), provides evidence for multiple mechanisms of structural variation including exchange of capsular genes and entire clusters by horizontal transfer, gene duplication, deletion, fusion and contingency gene variation. In contrast, the HS:23, HS:36 and HS:23/36 cps sequences were highly conserved. We report the first detailed structural analysis of 81‐176 (HS:23/36) and G1 (HS:1) and refine the previous structural interpretations of the HS:19, HS:23, HS:36 and HS:41 serostrains. For the first time, we demonstrate the commonality and function of a second heptose biosynthetic pathway for Campylobacter CPS independent of the pathway for lipooligosaccharide (LOS) biosynthesis and identify a novel heptosyltransferase utilized by this alternate pathway. Furthermore, we show the retention of two functional heptose isomerases in Campylobacter and the sharing of a phosphatase for both LOS and CPS heptose biosynthesis.