bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Polymorphic CYP19 TTTA Repeat Influences Aromatase Activity and Estrogen Levels in Elderly Men: Effects on Bone Metabolism
Authors: Gennari Luigi , Masi Laura , Merlotti Daniela , Picariello Lucia , Falchetti Alberto , Tanini Annalisa , Mavilia Carmelo , Del Monte Francesca , Gonnelli Stefano , Lucani Barbara , Gennari Carlo , Brandi Maria Luisa 
Published: June 2004

Abstract
Current evidence suggests that estrogen plays a dominant role in determining bone mineral density (BMD) in men, and inactivating mutations in the aromatase CYP19 gene have been associated with low bone mass in young males. We previously reported an association between a TTTA repeat polymorphism in intron 4 of the CYP19 gene and osteoporotic risk in postmenopausal females. Here we explore the role of this polymorphism as a genetic determinant of BMD in a sample of elderly males who were recruited by direct mailing and followed longitudinally for 2 (n = 300) and 4 (n = 200) yr. Six different allelic variants, containing seven, eight, nine, 10, 11, and 12 TTTA repeats, were detected. There was a bimodal distribution of alleles, with two major peaks at seven and 11 repeats and a very low distribution of the nine-repeat allele. Men with a high-repeat genotype (&gt;nine repeats) showed higher lumbar BMD values, lower bone turnover markers, higher estradiol levels, and a lower rate of BMD change than men with a low-repeat genotype (&lt;nine repeats). The association with BMD was not significant in the subgroup of patients with high body mass index (&gt;25), suggesting that the effect of CYP19 genotypes on bone may be masked by the increase in fat mass. Moreover, the high-repeat genotype was less represented, although not significantly, in the vertebral fracture group with respect to the nonvertebral fracture group. Functional in vitro analysis after incubation with [3H]-androstenedione showed a higher aromatase activity in fibroblasts from subjects with a high-repeat genotype than in fibroblasts from subjects with a low-repeat genotype. In conclusion, differences in estrogen levels due to polymorphism at the aromatase CYP19 gene may predispose men to increased age-related bone loss and fracture risk.
Effects of Testosterone on Mood, Aggression, and Sexual Behavior in Young Men: A Double-Blind, Placebo-Controlled, Cross-Over Study
Authors: O’Connor Daryl B. , Archer John , Wu Frederick C. W. 
Published: June 2004

Abstract
The prospects of wider application of testosterone (T) in novel indications such as male contraception have prompted renewed interest in the investigation of nonreproductive actions and safety of androgens. This study investigated potential changes in mood and behavior in response to elevations in circulating T concentrations produced by the new long-acting preparation, T undecanoate (TU).
Twenty-eight eugonadal men were randomized into one of two treatment groups: A1) active, receiving 1000 mg TU im followed by A2) washout, followed by A3) placebo, receiving 4 ml castor oil im; B1) placebo, 4 ml castor oil im; B2) washout followed by B3) active, receiving 1000 mg TU im. Mood, self- and partner-reported physical and verbal aggression, anger, hostility, irritability, assertiveness, self-esteem, and sexual function were assessed.
A single injection of 1000 mg TU im increased plasma T concentrations from 20.7 ± 1.5 to 37.5 ± 2.2 nmol/liter at wk 1 and 31.6 ± 1.5 nmol/liter at wk 2, and estradiol from 74.0 ± 4.9 to 120.4 ± 10.7 pmol/liter at wk 1, and 100.0 ± 6.3 pmol/liter at wk 2.
The T increment was associated with detectable but minor mood changes. Increased circulating T was associated with significant increases in anger-hostility from baseline (mean score = 7.48) to wk 2 (mean score = 10.71) accompanied by an overall reduction in fatigue-inertia (treatment = 6.21 vs. placebo = 7.84). TU treatment did not increase aggressive behavior or induce any changes in nonaggressive or sexual behavior. Changes in estradiol were not associated with any behavioral alterations.
Our results suggest that exogenous TU-induced elevation of circulating T, to the range likely to be used in hormonal male contraception, has limited psychological effects. Future research should investigate the implications of these minor mood changes.
Myocardial Blood Flow and Flow Reserve in Response to Hormone Therapy in Postmenopausal Women with Risk Factors for Coronary Disease
Authors: Duvernoy C. , Martin J. , Briesmiester K. , Bargardi A. , Muzik O. , Mosca L. 
Published: June 2004

Abstract
Estrogen has beneficial effects on markers of coronary heart disease (CHD) risk, but may increase overall CHD events. The effects of hormone therapy on vascular endothelial function have been mixed, and require further assessment. We studied the myocardial blood flow (MBF) response to postmenopausal combination hormone therapy (CHT) in postmenopausal women with risk factors for CHD.
We performed dynamic [13N]ammonia positron emission tomography in 15 postmenopausal women in a 7-month placebo-controlled crossover trial of continuous conjugated equine estrogen/cyclical micronized progesterone. MBF was measured at rest, after sympathetic stimulation with the cold pressor test (CPT), and after iv adenosine infusion, to determine baseline, endothelium-dependent, and maximal flows, respectively.
Response to CPT was neutral in all women at baseline (−0.51 ± 27%). Adenosine induced a marked increase in MBF (161 ± 111%). Treatment with 3 months of combined estrogen/progestin CHT did not change CPT or adenosine MBF responses. Myocardial flow reserve was unchanged as well.
In this group of postmenopausal women at higher cardiovascular risk, no association was found between CHT assignment and change in MBF. Further study is needed to clarify the effects of CHT on the endothelium of women with presumably diseased vasculature.
Testosterone Metabolic Clearance and Production Rates Determined by Stable Isotope Dilution/Tandem Mass Spectrometry in Normal Men: Influence of Ethnicity and Age
Authors: Wang Christina , Catlin Don H. , Starcevic Borislav , Leung Andrew , DiStefano Emma , Lucas Geraldine , Hull Laura , Swerdloff Ronald S. 
Published: June 2004

Abstract
The metabolic clearance rate (MCRT) and production rate (PRT) of testosterone (T) were measured using constant infusion of trideuterated (d3) T and quantitating serum d3T by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Serum unlabeled T (d0T) was measured by LC-MS-MS, and serum total T (d3T + d0T) was measured by RIA. Mean MCRT (measured by LC-MS-MS) in young white men (1272 ± 168 liters/d) was not significantly different from young Asian men (1070 ± 166 liters/d). Mean PRT was also not significantly different between the two ethnic groups (whites, 9.11 ± 1.11 mg/d; Asians, 7.22 ± 1.15 mg/d; P = 0.19 using d0T data). Both the mean MCRT (812 ± 64 liters/d; P &lt; 0.01) and the PRT (3.88 ± 0.27 mg/d; P &lt; 0.001) were significantly lower in middle-aged white men when compared with their younger counterparts. The mean MCRT and PRT calculated using serum total T or d0T data showed a diurnal variation, with levels at midday significantly higher than those measured in the evening in the young (MCRT, P &lt; 0.01; PRT, P &lt; 0.001) and to a lesser extent in the older men (MCRT, P &lt; 0.05; PRT, P &lt; 0.05 using total T and P &lt; 0.001 using d0T data). We conclude that using LC-MS-MS to detect d3T in serum after constant infusion of stable isotope-labeled T allows the measurements of MCRT and PRT, which can be used to study androgen metabolism repeatedly after physiological or pharmacological interventions.
Diet-Induced Weight Loss Is Associated with an Improvement in β-Cell Function in Older Men
Authors: Utzschneider Kristina M. , Carr Darcy B. , Barsness Suzanne M. , Kahn Steven E. , Schwartz Robert S. 
Published: June 2004

Abstract
Although weight loss in older subjects has been shown to improve insulin sensitivity, it is unclear what effect this lifestyle intervention has on β-cell function. To determine whether diet-induced weight loss can improve β-cell function in older subjects, we studied 19 healthy male subjects (age, 65.4 ± 0.9 yr; body mass index, 30.9 ± 0.6 kg/m2; mean ± sem) before and after a 3-month 1200-kcal/d diet. The insulin sensitivity index (SI) was quantified using Bergman’s minimal model. The acute insulin response to glucose (AIRg) and the maximal glucose-potentiated insulin response (AIRmax) were determined and then adjusted for SI (SI × AIRg and SI × AIRmax), thus providing measures of β-cell function. Subjects demonstrated significant weight loss (95.6 ± 2.4 to 86.1 ± 2.5 kg; P &lt; 0.001). Both fasting plasma glucose [97.3 ± 1.6 to 95.1 ± 1.3 mg/dl (5.4 ± 0.09 to 5.3 ± 0.07 mm); P = 0.05] and insulin [18.5 ± 1.3 to 12.2 ± 1.0 μU/ml (110.9 ± 7.7 to 73.5 ± 5.9 pm); P &lt; 0.001] levels decreased. With weight loss, SI increased [1.59 ± 0.24 to 2.49 ± 0.32 × 10−4 min−1/(μU/ml) (2.65 ± 0.4 to 4.15 ± 0.5 × 10−5 min−1/pm); P &lt; 0.001], whereas both AIRg [63.4 ± 13.4 to 51.0 ± 10.7 μU/ml (380 ± 80 to 306 ± 64 pm); P &lt; 0.05] and AIRmax [314 ± 31.4 to 259.9 ± 33.4 μU/ml (1886 ± 188 to 1560 ± 200 pm); P &lt; 0.05] decreased. Overall β-cell function improved (SI × AIRg, 9.63 ± 2.28 to 12.78 ± 2.58 × 10−3 min−1, P &lt; 0.05; and SI × AIRmax, 51.01 ± 9.2 to 72.69 ± 13.4 × 10−3 min−1, P &lt; 0.05). Thus, the weight loss-associated improvements in both insulin sensitivity and β-cell function may explain the beneficial effects of a lifestyle intervention on delaying the development of diabetes in older subjects.
Recombinant Human Chorionic Gonadotropin But Not Dihydrotestosterone Alone Stimulates Osteoblastic Collagen Synthesis in Older Men with Partial Age-Related Androgen Deficiency
Authors: Meier Christian , Liu Peter Y. , Ly Lam P. , de Winter-Modzelewski James , Jimenez Mark , Handelsman David J. , Seibel Markus J. 
Published: June 2004

Abstract
Several randomized trials of androgen supplementation in older men have been undertaken. However, the relative contributions of testosterone (T) and estrogens on bone metabolism in aging men are controversial. Within the setting of two double-blind, placebo-controlled studies, we evaluated the effect of dihydrotestosterone (DHT) and recombinant human chorionic gonadotropin (rhCG) on bone turnover in healthy, community-dwelling older men with partial androgen deficiency (total T ≤ 15 nmol/liter). In the first study, 35 men (age 68.3 ± 6.8 yr; baseline T, 13.9 ± 3.3 nmol/liter) were randomized to receive either daily transdermal DHT (n = 17) or placebo for 3 months. In the second study, 40 men (age 67.4 ± 5.4 yr; baseline T, 11.4 ± 2.2 nmol/liter) were randomized to receive either rhCG sc (n = 20), two injections weekly, or placebo for 3 months. The following parameters were measured before, monthly during, and 1 month after treatment: serum T, estradiol (E2), and LH; markers of bone formation, serum amino-terminal propeptide of type I procollagen (S-PINP) and osteocalcin; markers of bone resorption, serum carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline. Compared with placebo, treatment with DHT significantly increased serum DHT and suppressed LH and T levels, whereas E2 concentrations and markers of bone turnover did not change. In contrast, rhCG therapy significantly increased both T and E2, with the increases in E2 being supraphysiological. At the same time, rhCG significantly increased S-PINP concentrations with peak levels after 1 month (Δ40%; P = 0.02 compared with placebo). In contrast, serum osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline levels did not change. The change in S-PINP levels correlated with the change in E2 levels (r = 0.59; P = 0.02) but not with a change in T.
We conclude that in older men with partial age-related androgen deficiency, rhCG treatment stimulates osteoblastic collagen formation proportionally to increased E2 concentrations but does not alter markers of mature osteoblastic function or bone resorption. In contrast, treatment with a pure, nonaromatizable androgen (DHT) has no effect on bone turnover despite a 20-fold increase in serum levels. Bone resorption was not accelerated during unchanged (DHT) or increased (rhCG) E2 levels, suggesting that minimal E2 levels are needed to maintain stable resorption, although direct androgen receptor-mediated effects cannot be excluded. If androgen supplementation is required for aging men, aromatizable androgens with sufficient endogenous estrogenic activity may have the most beneficial effects on bone.
Pharmacological Treatment of Insulin Resistance at Two Different Stages in the Evolution of Type 2 Diabetes: Impact on Glucose Tolerance and β-Cell Function
Authors: Xiang Anny H. , Peters Ruth K. , Kjos Siri L. , Goico Jose , Ochoa Cesar , Marroquin Aura , Tan Sylvia , Hodis Howard N. , Azen Stanley P. , Buchanan Thomas A. 
Published: June 2004

Abstract
The purpose of this study was to compare the impact of treating insulin resistance with a thiazolidinedione drug before vs. at the onset of diabetes on glucose levels and β-cell function.
Nondiabetic Hispanic women of Mexican or Central American descent with prior gestational diabetes mellitus (GDM) were randomized to troglitazone (early intervention), 400 mg/d, or placebo (later intervention). Women who developed diabetes were placed on open-label troglitazone. Glucose tolerance, insulin resistance, and β-cell function were measured at randomization, at the diagnosis of diabetes, and 8 months post trial to determine the long-term impact of the two treatment strategies on glucose levels and β-cell function.
During a mean follow-up of 4.3 yr between baseline and posttrial tests, glucose tolerance (oral glucose tolerance test glucose area, P = 0.04) and insulin resistance (MINMOD SI, P = 0.02) worsened more in women randomized to late intervention (n = 69) than to early intervention (n = 57). Insulin secretion (acute insulin response in the iv glucose tolerance test, P = 0.09) and β-cell compensation for insulin resistance (disposition index, P = 0.07) also tended to worsen more in the late intervention group. Among women in the late intervention group who developed diabetes, oral glucose tolerance test glucose area (P = 0.0001) and β-cell function (P ≤ 0.04) deteriorated significantly during development of diabetes on placebo and then did not change significantly (P &gt; 0.50) during treatment with troglitazone and posttreatment washout.
In high-risk Hispanic women, amelioration of insulin resistance can stabilize glycemia at the time diabetes develops. These findings highlight the role of insulin resistance in the genesis of progressive β-cell dysfunction during the evolution of type 2 diabetes.
Changes in Muscle Myostatin Expression in Obese Subjects after Weight Loss
Authors: Milan G. , Dalla Nora E. , Pilon C. , Pagano C. , Granzotto M. , Manco M. , Mingrone G. , Vettor R. 
Published: June 2004

Abstract
Myostatin is a member of transforming growth factor-β superfamily that plays an important inhibitory role during muscle development; in fact mutations of myostatin gene result in a hypermuscular phenotype. Moreover myostatin-deficient mice have a significant reduction in fat depots and a depression of adipogenesis. Little is known about myostatin function in muscle growth regulation in humans and in particular during caloric restriction. In the present work we quantified by real-time RT-PCR myostatin expression in muscle biopsies of a group of morbidly obese patients before and after weight loss obtained by biliopancreatic diversion (BPD). The patients reduced body weight by 38.9%, mostly due to fat-mass loss, showing also a significant reduction in the 24-hour EE as assessed by the respiratory chamber. Myostatin mRNA levels result clearly decreased after weight loss, suggesting a role in counteracting the progressive decline of muscle mass after BPD. Myostatin may provide therefore another mechanistic explanation for the control of energy partitioning between protein and fat, working against muscle wasting. Our data suggest that myostatin might represent an important regulator of skeletal muscle size also in conditions of food restriction in obese subjects.
Detection of BRAF Mutation on Fine Needle Aspiration Biopsy Specimens: A New Diagnostic Tool for Papillary Thyroid Cancer
Authors: Xing Mingzhao , Tufano Ralph P. , Tufaro Anthony P. , Basaria Shehzad , Ewertz Marge , Rosenbaum Eli , Byrne Patrick J. , Wang James , Sidransky David , Ladenson Paul W. 
Published: June 2004

Abstract
Numerous biomolecular markers have been studied to improve the accuracy of fine needle aspiration biopsy (FNAB) in the diagnostic and prognostic evaluation of thyroid tumors, but none of them has yet become clinically useful. The recently discovered BRAF mutation, which occurs specifically in papillary thyroid cancers (PTC) with a high prevalence and is associated with poor clinicopathological outcomes, has the potential to be a useful diagnostic and prognostic marker for PTC. In the present study, we investigated whether detection of BRAF mutation on FNAB specimens was technically possible and could be used as an adjunct diagnostic tool with routine FNAB. Evaluation of a new colorimetric mutation detection method demonstrated 100% sensitivity and 100% specificity in comparison with conventional DNA sequencing as the “gold standard” in a large pool of DNA samples from various primary thyroid tumor specimens and cell lines. We found this novel technique even more sensitive in detecting BRAF mutation on FNAB specimens than conventional sequencing. In a series of 48 patients undergoing thyroidectomy, mostly for thyroid cancer or for suspicion of cancer, we performed preoperative FNAB and, using the colorimetric mutation detection method, identified BRAF mutation on the cytological specimens. Prospective analysis showed that 50% of the nodules that proved to be PTC on surgical histopathology were correctly diagnosed by BRAF mutation analysis on FNAB specimens; there were no false positive findings. Thus, we have demonstrated the usefulness of BRAF mutation detection on FNAB specimens that can help diagnose and identify those PTC patients who may need more aggressive surgical treatment and vigilant clinical monitoring.
Serum Inhibin B and Follicle-Stimulating Hormone Levels as Tools in the Evaluation of Infertile Men: Significance of Adequate Reference Values from Proven Fertile Men
Authors: Andersson Anna-Maria , Petersen Jørgen H. , Jørgensen Niels , Jensen Tina K. , Skakkebæk Niels E. 
Published: June 2004

Abstract
Inhibin B and FSH levels in 289 idiopathic infertile men were compared with reference materials consisting of 303 proven fertile men (reference group 1) and 307 healthy men from the general population with unknown fertility status (reference group 2). The diagnostic power of these two serum markers of spermatogenesis was evaluated by the use of receiver operating characteristic plot analysis, and an example of how both markers can be used simultaneously in a bivariate reference chart is presented.
Inhibin B levels were significantly lower and FSH levels were significantly higher in the infertile men, compared with either reference group, but with significant overlap, especially with reference group 2. Nevertheless, approximately 50% of the infertile men had an inhibin B or FSH, respectively, below the 2.5 percentile or above the 97.5 percentile of reference group 1, whereas only approximately 25% of the infertile men had an inhibin B or FSH, respectively, below the 2.5 percentile or above the 97.5 percentile of reference group 2. Fourteen and 11% of reference group 2 had an inhibin B or FSH, respectively, below the 2.5 percentile or above the 97.5 percentile of reference group 1, suggesting that a significant number of individuals from the general population with unknown fertility but otherwise healthy may actually be subfertile.
In conclusion, 1) proven fertile men constitute the most appropriate reference group in the evaluation of the FSH-inhibin B axis; the sensitivity of these markers to identify infertility increased by approximately 20% when fertile men rather than men from the general population were used as control group; 2) FSH alone had a slightly higher positive predictive value than inhibin B alone, but the positive predictive value were highest when both markers of spermatogenesis were used in an inhibin B/FSH ratio; and 3) a bivariate reference chart is a valuable objective tool in the simultaneous evaluation of FSH and inhibin B as two interrelated markers.
Metabolic and Body Composition Factors in Subgroups of Obesity: What Do We Know?
Authors: Karelis Antony D. , St-Pierre David H. , Conus Florence , Rabasa-Lhoret Remi , Poehlman Eric T. 
Published: June 2004

Abstract
Obesity is thought to be a heterogeneous disorder with several possible etiologies; therefore, by examining subtypes of obesity we attempt to understand obesity’s heterogeneous nature. The purpose of this review was to investigate the roles of metabolic, body composition, and cardiovascular disease risk in subtypes of obesity. We briefly consider two subtypes of obesity that have been identified in the literature. One subset of individuals, termed the metabolically healthy, but obese (MHO), despite having large amounts of fat mass compared with at risk obese individuals shows a normal metabolic profile, but remarkably normal to high levels of insulin sensitivity. Preliminary evidence suggests that this could be due at least in part to lower visceral fat levels and earlier onset of obesity. A second subset, termed the metabolically obese, but normal weight (MONW), present with normal body mass index, but have significant risk factors for diabetes, metabolic syndrome, and cardiovascular disease, which could be due to higher fat mass and plasma triglycerides as well as higher visceral fat and liver content. We also briefly consider the potential role of adipose and gastrointestinal hormonal profiles in MHO and MONW individuals, which could lead to a better understanding of potential factors that may regulate their body composition. This information will eventually be invaluable in helping us understand factors that predispose to or protect obese individuals from metabolic and cardiovascular disease. Collectively, a greater understanding of the MHO and MONW individual has important implications for therapeutic decision making, the characterization of subjects in research protocols, and medical education.