bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of independent relationship between plasma adiponectin, leptin levels and bone density in nondiabetic female adolescents
Authors: Huang Kuo‐Chin , Cheng Wern‐Cherng , Yen Ruoh‐Fang , Tsai Keh‐Sung , Tai Tong‐Yuan , Yang Wei‐Shiung 
Published: July 2004

Summaryobjectives  Adiponectin has been implicated in the pathophysiology of metabolic syndrome and coronary artery disease in humans. Whether adiponectin is related to bone mineralization remains unclear in adults as well as in adolescents. In this study, we aimed to determine the relationship between plasma adiponectin, leptin concentrations and bone density, including total‐body bone mineral density (BMD) and bone mineral content (BMC) in adolescence.patients and measurements  We studied 105 nondiabetic female adolescents [mean age 15·4 ± 1·9 years, and mean body mass index (BMI), 23·1 ± 4·0 kg/m2]. A venous blood sample was taken after 12 h of fasting to measure fasting plasma adiponectin and leptin levels. BMD and BMC of the whole body were measured by dual‐energy X‐ray absorptiometry.results  In simple correlation analysis, plasma adiponectin and leptin levels correlated significantly with total‐body BMD (r =−0·523 and r = 0·443, P < 0·001, respectively) and BMC (r =−0·471 and r = 0·396, P < 0·001, respectively). However, plasma adiponectin and leptin were related to both BMD and BMC in opposite directions. In multivariate linear regression analyses, only BMI or fat mass (FM) and Tanner stage, but not plasma adiponectin and leptin, were significantly related to BMD and BMC following adjustment for other variables.conclusions  The results suggest that plasma adiponectin and leptin concentrations are not related to the total‐body BMD and BMC independent of the chronological age, BMI or FM, and Tanner stage in nondiabetic female adolescents, although they were highly correlated in simple correlation analyses. The biologic roles of adiponectin in bone still need further clarification.
Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients: efficacy and lack of predictive value of prolactin status
Authors: Cozzi Renato , Attanasio Roberto , Lodrini Sandro , Lasio Giovanni 
Published: July 2004

Summarybackground  Somatostatin analogues (SA) are currently the mainstay in the medical treatment of acromegaly. However, even high doses of depot SA for prolonged periods do not achieve GH–IGF‐I normalization in some patients. Even though some data were reported about the addition of cabergoline, a long‐acting dopamine agonist (DA), to SA in resistant patients, definite data are still lacking.design  Prospective open trial.patients  In 19 acromegalic patients with active disease (34–82 years old, seven males, 12 females) resistant to chronic (9–12 months) depot SA (octreotide‐LAR, 30 mg/28 days in 13 patients, lanreotide, 60 mg/28 days intramuscularly in six patients) cabergoline was added (combined treatment). In these patients, SA treatment had partially relieved GH and IGF‐I hypersecretion but no patient had achieved ‘safe’ GH and normal IGF‐I‐values. Eight patients had PRL levels greater than 15 µg/l (range 16–60 µg/l; 1 µg = 21·2 mIU). Immunohistochemistry (IHC) was positive for PRL in four out of eight operated patients.results  The addition of cabergoline, using the minimal effective and the maximal tolerated dose (range 1–3·5 mg/week), decreased GH from 6·6 ± 0·9 to 4·6 ± 0·6 µg/l (P = 0·018), and IGF‐I from 552 ± 44 to 428 ± 54 µg/l (P = 0·019) after 6 months (median, range 3–18 Months). Combined treatment decreased GH to < 2·5 µg/l in four patients (21%) and normalized IGF‐I for age in eight patients (42%). It obtained a decline of both GH and IGF‐I (−49 ± 7%, and −47 ± 5%, respectively) in nine patients (47%), and a partial improvement in six (32%) patients (GH decreased by 43 ± 8% in four, and IGF‐I by 35–38% in two patients). No change was observed in two patients, and worsening in two other patients. Results were not dependent on PRL status (serum levels or IHC). Combined treatment was well tolerated.conclusions  The addition of cabergoline to depot SA‐resistant acromegalic patients is effective, not dependent on PRL values and normalizes IGF‐I levels in 42% of patients. The association of long‐acting DA and SA deserves a more relevant role in the therapeutical algorithm of acromegaly.
Polymorphisms in oestrogen and progesterone receptor genes: possible influence on prolactin levels in women
Authors: Westberg Lars , Ho Hoi‐Por , Baghaei Fariba , Nilsson Staffan , Melke Jonas , Rosmond Roland , Holm Göran , Björntorp Per , Eriksson Elias 
Published: July 2004

Summaryobjective  Oestrogen and progesterone are known to influence the release of human prolactin. The present study was undertaken in order to investigate the possible influence of polymorphisms of the genes encoding the oestrogen receptor (ER)α, ERβ and the progesterone receptor (PGR), on prolactin levels in premenopausal women.design and measurements  Serum levels of prolactin were measured in the follicular phase of the menstrual cycle. Subjects were genotyped with respect to a TA repeat polymorphism of the ERα gene, a CA repeat polymorphism of the ERβ gene, and two polymorphisms of the PGR gene: one insertion polymorphism (PROGINS) and one single nucleotide polymorphism (G331A).subjects  A population‐based cohort of 270 42‐year‐old women.results  The CA repeat polymorphism of the ERβ gene and the G331A polymorphism of the PGR gene appeared to be associated with prolactin levels. In contrast, we found no evidence for an influence of the PROGINS polymorphism of the PGR gene or the TA repeat polymorphism of the ERα gene on the levels of this hormone.conclusions  These data suggest that genetic variants of both the ERβ and the PGR may influence prolactin release.
Systematic dose‐extension of octreotide LAR: the importance of individual tailoring of treatment in patients with acromegaly
Authors: Turner Helen E. , Thornton‐Jones Viv A. , Wass John A. H. 
Published: July 2004

Summaryobjective  The depot long‐acting somatostatin analogue octreotide LAR (LAR) provides effective and well‐tolerated treatment for acromegaly. Despite a 4‐weekly recommended injection frequency, prolonged duration of GH suppression has been observed in some patients following treatment with long‐acting somatostatin analogues. The aim of our study was to perform a prospective systematic study to determine whether extending the interval between doses of LAR allows maintenance of ‘safe’ GH in selected patients with acromegaly.patients and methods  Twenty‐two patients (15 men, seven women), mean age 58·9 years (35–81 years) with active acromegaly (mGH > 5 mU/l), requiring treatment were selected to receive treatment with LAR. Eleven patients had received previous treatment with both transsphenoidal surgery and radiotherapy, while six had received surgery alone. All patients were commenced on treatment with 20 mg LAR intramuscularly (i.m.) every 4 weeks. Mean GH (mGH) was measured after three consecutive injections immediately prior to the fourth injection. The dose frequency was systematically reduced after every four injections if mGH < 5 mU/l. Once mGH > 5 mU/l, the dose frequency was increased and mGH reassessed.results  The dosing interval was successfully increased to greater than 4 weeks in 20/22 patients (90·9%). Six of 22 (27·3%) were receiving injections every 8 weeks and 3/22 (13·6%) every 12 weeks. GH and IGF‐I were lower on treatment compared with baseline (P < 0·01). There was no difference in individual mGH and IGF‐I between the values on 4‐weekly dosing and those at final dose frequency. There was no relationship between final dose frequency and either mean GH or IGF‐I prior to LAR, patient age, or previous treatment. The percentage suppression following 100 µg octreotide subcutaneously did not predict subsequent dose frequency of LAR. The drug cost if patients had continued at 4‐weekly intervals would be UK£187 850, compared with UK£101 065 for the individually titrated dose frequency (P < 0·01). This represents a final cost of 53·8% of the 4‐weekly injection price.conclusion  Individual tailoring of LAR administration maintains control of acromegaly, with reduced injection frequency and improved cost‐effectiveness.
Abnormal regulation of thirst and vasopressin secretion following surgery for craniopharyngioma
Authors: Smith D. , Finucane F. , Phillips J. , Baylis P. H. , Finucane J. , Tormey W. , Thompson C. J. 
Published: July 2004

Summaryobjective  In this study we aimed to establish the frequency of postoperative diabetes insipidus and the incidence and characteristics of abnormalities of thirst in a cohort of patients with craniopharyngioma, in whom neurosurgery had been performed.design  Diabetes insipidus was determined by either standard criteria for diagnosis in the immediate postoperative period, or by water deprivation test, in all craniopharyngioma and pituitary tumour patients who underwent surgery in Beaumont Hospital between the years 1986 and 1998. Osmoregulated thirst and vasopressin release were studied during a 2‐h infusion of hypertonic (5%) saline followed by a 30‐min period of free access to water.patients  Data on the incidence of postoperative diabetes insipidus was collected in 26 patients with craniopharyngioma and 154 patients with pituitary adenomata. We recruited 16 healthy control patients, 16 patients with cranial diabetes insipidus following pituitary tumour surgery and 16 patients with cranial diabetes insipidus following craniopharyngioma resection for the hypertonic saline infusion study.results  Twenty‐five patients out of 26 (96%) patients developed diabetes insipidus after surgery for craniopharyngioma, a much higher incidence than after surgery for suprasellar (26/88, 30%, P < 0·001) or intrasellar pituitary tumours (9/66, 14%, P < 0·001). Hypertonic saline infusion identified abnormal thirst responses in five of the 16 craniopharygioma patients studied; all of the pituitary tumour patients had a normal thirst response. Three of the craniopharyngioma patients had adipsic diabetes insipidus whilst two had polydipsic diabetes insipidus.conclusion  This study demonstrates following surgery for craniopharyngioma there is a high incidence of cranial diabetes insipidus and a significant incidence of abnormal thirst responses to osmotic stimuli.
Subclinical hypothyroidism is associated with a low‐grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years
Authors: Kvetny J. , Heldgaard P. E. , Bladbjerg E. M. , Gram J. 
Published: July 2004

Summaryobjective  Mild thyroid failure is associated with an increased risk for development of atherosclerosis, but whether subclinical hypothyroidism is related to risk for cardiovascular disease is controversial. The purpose of the present study was to examine a possible association between subclinical hypothyroidism and cardiovascular disease.design  Cross‐sectional study of a general population.patients  Twelve hundred and twelve subjects, men and women, between 20 and 69 years old without thyroid disease not treated with drugs interfering with thyroid function or analysis of TSH were included.measurements  Clinical signs of cardiovascular disease based on a questionnaire and medical records and laboratory analysis of lipids, atherothrombotic risk markers, C‐reactive protein and TSH.results  The main findings were a high incidence of subclinical hypothyroidism (19·7%) in a general population. Subclinical hypothyroidism was associated with higher concentrations of triglycerides and C‐reactive protein. Below 50 years of age cardiovascular disease was more frequent in males with subclinical hypothyroidism compared to euthyroid males. Subclinical hypothyroidism was a predictor of cardiovascular disease in males below 50 years with an odds ratio of 3·4 (95% confidence interval 1·6–6·8) for developing cardiovascular disease compared to euthyroid age‐matched males.conclusion  Our study demonstrates that patients with subclinical hypothyroidism have increased levels of triglycerides and signs of low‐grade inflammation (raised C‐reactive protein levels) and that subclinical hypothyroidism might be a risk factor for development of cardiovascular disease in younger males.
BRAF mutations in an Italian cohort of thyroid cancers
Authors: Fugazzola Laura , Mannavola Deborah , Cirello Valentina , Vannucchi Guia , Muzza Marina , Vicentini Leonardo , Beck‐Peccoz Paolo 
Published: July 2004

Summaryobjective  Recently, a somatic point mutation of the BRAF gene (V599E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC) with a variable frequency (about 25–70%) in different series from USA, Japan, Portugal and Ukraine.design  In the present study, the genetic analysis of BRAF in an Italian cohort of 65 thyroid tumours with corresponding normal tissues and 21 thyroid benign disorders is reported.methods  For BRAF analysis, the somatic DNA was PCR amplified by means of specific intronic primers and PCR products were directly sequenced. Statistical analyses were obtained by means of Fisher's exact test.results  All mutations detected involved a T > A transversion at 1796 (V599E) and were heterozygous. Overall, BRAFV599E mutation was found in 18/56 (32·1%) PTCs. According to the histological type of the tumour, the mutation was present in 38·3% of cases of conventional PTC (18/47), in 0/6 follicular variant of PTC, in 0/3 oncocytic variant of PTC. No BRAF mutations were detected either in five follicular carcinomas, or in four poorly differentiated or undifferentiated cancers or in benign thyroid disorders. No statistically significant correlation of BRAF mutation with patient age and gender, with multicentricity of the tumour, with the lymphocytic infiltration of the tissue, with the stage and with the recurrence rate, was found. BRAFV599E tended to be associated, although not significantly, with a greater volume and extension of the tumour and with lymph‐nodal metastases at surgery.conclusions  In conclusion, the present study on the first Italian series of thyroid cancers shows a frequency of 38·3% of BRAFV599E in the classical variant of PTC, confirming the key role of this mutation in promoting tumourigenesis.
The relationship between circulating osteoprotegerin levels and bone mineral metabolism in healthy women
Authors: Oh Ki Won , Rhee Eun Jung , Lee Won Young , Kim San Woo , Oh Eun Sook , Baek Ki Hyun , Kang Moo Il , Choi Moon Gi , Yoo Hyung Joon , Park Sung Woo 
Published: July 2004

Summaryobjective  Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the RANK ligand. Moreover, OPG has been shown to be an important inhibitor of osteoclastogenesis in animal models. However, the relationship between circulating OPG levels and female bone status in human populations is unclear. In this study we undertook to investigate the relationship between circulating OPG levels and bone mineral metabolism in healthy women.patients and measurements  Our subjects were 287 women aged 37–73 years (mean age 51·5 years). The serum concentrations of OPG were determined by enzyme‐linked immunosorbent assay (ELISA). The biochemical markers of bone turnover and FSH were measured using standard methods. Bone mineral densities at the lumbar spine and femoral neck were measured by dual‐energy X‐ray absorptiometry.results  Postmenopausal women had a significantly higher mean value of serum OPG than premenopausal women (1358·5 ± 32·5 pg/ml vs. 1228·8 ± 33·3 pg/ml, P < 0·01). Serum OPG levels were positively correlated with age (r = 0·169, P < 0·01), as were urine deoxypyridinoline levels (r = 0·133, P < 0·05) and serum FSH levels (r = 0·187, P < 0·01) in a bivariate correlation analyses. In a multiple regression analysis, only urine calcium excretion was identified as a significant predictor for serum OPG levels.conclusions  Circulating OPG levels were found to be associated with urine calcium excretion and menopause in healthy women. Our observations suggest that circulating OPG levels reflect an antiresorptive activity in bone, and they are related to endogenous oestrogen levels.
Effects of clomiphene and raloxifene on gonadotrophin secretion in postmenopausal women: evidence of nongenomic action
Authors: Garas A. , Trypsianis G. , Kallitsaris A. , Milingos S. , Messinis I. E. 
Published: July 2004

Summaryobjective  To evaluate the effect of raloxifene (R) and clomiphene (Cl) on FSH and LH secretion in postmenopausal women.design  Postmenopausal volunteer women participated in two experimental (Exp) procedures. In Group 1, the women received R (180 mg/day orally) for 30 days plus oestradiol (E2) through skin patches (100 g/24 h) from days 21 to 30 (R‐Exp). After a month's break the same women received Cl (150 mg/day orally) for 30 days plus E2 as above (Cl‐Exp). In Group 2, the women received E2 for 30 days plus R from days 21 to 30 (R‐Exp) and after a month's break they received E2 for 30 days plus Cl from days 21 to 30 (Cl‐Exp). Daily doses were as in Group 1. A GnRH test (100 g intravenously) was performed in all women on days 0, 10, 20 and 30 of each experiment.patients  Sixteen healthy postmenopausal women were divided into two groups (eight women in each group).measurements  The area under the curve (AUC) of ΔFSH and ΔLH response to GnRH (net increase above the basal value) was calculated.results  In Group 1, basal levels of FSH and LH did not change significantly during the R‐Exp, while they decreased significantly in the Cl‐Exp (P < 0·001). The addition of E2 did not have any effect. The AUC of LH response to GnRH increased significantly in the R‐Exp (P < 0·05) and that of FSH in the Cl‐Exp (P < 0·05). In Group 2, basal levels of FSH and LH declined significantly during treatment with E2 in both the R‐Exp (P < 0·01) and the Cl‐Exp (P < 0·001). However, the addition of Cl (for 10 days) interrupted this decrease, while the addition of R stimulated FSH levels significantly (P < 0·05). E2 suppressed significantly the AUC of LH in both experiments (P < 0·05). The addition of Cl did not affect the AUC in response to GnRH, while the addition of R increased the AUC of both LH and FSH (P < 0·05).conclusions  These results demonstrate for the first time that in contrast to Cl, R does not exert oestrogenic effects on basal gonadotrophin secretion. Although the antioestrogenic action of these drugs was evident only after pretreatment with E2, both R and Cl stimulated GnRH‐induced gonadotrophin secretion in oestrogen‐deprived women. It is hypothesized that these two compounds sensitize the pituitary to GnRH through mechanisms not involving the oestrogen receptor complex (nongenomic).
Association of a thyroglobulin gene polymorphism with Hashimoto's thyroiditis in the Japanese population
Authors: Ban Yoshiyuki , Tozaki Teruaki , Taniyama Matsuo , Tomita Motowo , Ban Yoshio 
Published: July 2004

Summaryobjective  The aetiology of the autoimmune thyroid diseases (AITDs), Graves’ disease (GD) and Hashimoto's thyroiditis is largely unknown. However, genetic susceptibility is believed to play a major role. Two whole genome scans from Japan and from the USA identified a locus on chromosome 8q24 which showed evidence for linkage with AITD and HT. Recent studies have demonstrated an association between a Tg polymorphisms and AITD, suggesting that Tg is the susceptibility gene on 8q24.patients  We studied 308 Japanese AITD patients (194 GD and 114 HT patients) and 417 Japanese control subjects in association studies.design  Case–control association studies were performed using D8S284 and D8S272, microsatellite markers located in the 8q24 region, Tgms1 and Tgms2, microsatellite markers in introns 10 and 27, respectively, of Tg, and a SNP in exon 33 of Tg.results  No differences in allele frequencies were observed between AITD patients and controls for D8S284, D8S272 and Tgms1. Similarly, for Tgms2 and the exon 33 SNP no significant differences in allele frequency distribution were observed for all AITD patients. However, when analysing the HT patients alone we found a significant association between the 330 bp/352 bp genotype of Tgms2 and HT (HT = 16·7%, controls = 7·1%; corrected P‐value = 0·01, OR = 2·6).conclusion  Our results confirm the previous reports of an association between the Tg gene and AITD and suggest that Tg is an AITD susceptibility gene.
A single nucleotide polymorphism in the CD40 gene on chromosome 20q (GD‐2) provides no evidence for susceptibility to Graves’ disease in UK Caucasians
Authors: Heward Joanne M. , Simmonds Matthew J. , Carr‐Smith Jackie , Foxall Helen , Franklyn Jayne A. , Gough Stephen C. L. 
Published: July 2004

Summaryobjective  A genome‐wide screen in Graves’ disease (GD) has shown linkage to chromosome 20q, designated GD‐2. The gene encoding CD40, which stimulates lymphocyte proliferation and differentiation, maps to this region, and a single nucleotide polymorphism (SNP) at position −1 of the Kozak sequence within the gene has been reported to be associated with GD. The aim of this study was to determine whether this SNP of the CD40 gene confers susceptibility to GD in UK Caucasians.design  A large case–control cohort consisting of 800 patients with GD, and 785 control subjects with no history of autoimmune disease, was used to genotype this SNP by polymerase chain reaction restriction fragment length polymorphism.results  Despite adequate power (> 99%) to detect an effect, if present (odds ratio of 1·5), no significant difference in allele or genotype frequency of the CD40 SNP was observed between patients with GD and control subjects (P = 0·087 and P = 0·145, respectively).conclusions  These data suggest that this polymorphism of the CD40 gene is not associated with GD in the UK and is therefore not contributing to disease susceptibility in the chromosomal region designated GD‐2.
MotPS is the stator‐force generator for motility of alkaliphilic Bacillus, and its homologue is a second functional Mot in Bacillus subtilis
Authors: Ito Masahiro , Hicks David B. , Henkin Tina M. , Guffanti Arthur A. , Powers Benjamin D. , Zvi Lior , Uematsu Katsuyuki , Krulwich Terry A. 
Published: August 2004

SummaryThe stator‐force generator that drives Na+‐dependent motility in alkaliphilic Bacillus pseudofirmus OF4 is identified here as MotPS, MotAB‐like proteins with genes that are downstream of the ccpA gene, which encodes a major regulator of carbon metabolism. B. pseudofirmus OF4 was only motile at pH values above 8. Disruption of motPS resulted in a non‐motile phenotype, and motility was restored by transformation with a multicopy plasmid containing the motPS genes. Purified and reconstituted MotPS from B. pseudofirmus OF4 catalysed amiloride analogue‐sensitive Na+ translocation. In contrast to B. pseudofirmus, Bacillus subtilis contains both MotAB and MotPS systems. The role of the motPS genes from B. subtilis in several motility‐based behaviours was tested in isogenic strains with intact motAB and motPS loci, only one of the two mot systems or neither mot system. B. subtilis MotPS (BsMotPS) supported Na+‐stimulated motility, chemotaxis on soft agar surfaces and biofilm formation, especially after selection of an up‐motile variant. BsMotPS also supported motility in agar soft plugs immersed in liquid; motility was completely inhibited by an amiloride analogue. BsMotPS did not support surfactin‐dependent swarming on higher concentration agar surfaces. These results indicate that BsMotPS contributes to biofilm formation and motility on soft agar, but not to swarming, in laboratory strains of B. subtilis in which MotAB is the dominant stator‐force generator. BsMotPS could potentially be dominant for motility in B. subtilis variants that arise in particular niches.