bluuebunny/crossref_metadata_2025_split huggingface dataset:
Programmed Cell Death in Human Ovary Is a Function of Follicle and Corpus Luteum Status*
Authors: Yuan Wei , Giudice Linda C. 
Published: January 2014

Abstract
Although extensive investigation on follicular apoptosis (programmed cell death) has been conducted in the infraprimate ovary, there is little information regarding apoptosis and its relationship to follicular status in the human. In this study, apoptosis was investigated in 116 human ovarian follicles (primordial to dominant) and 5 corpora lutea from a total of 27 premenopausal women. Follicles and corpora lutea were evaluated for the presence of DNA fragmentation, characteristic of apoptosis, by two methods: in situ hybridization using 3′ end-labeling of DNA with digoxigenin-labeled nucleotides and subsequent digoxigenin antibody and peroxidase staining, and/or biochemical analysis of low molecular weight DNA laddering. Follicle functional status was evaluated by determining follicle sizes and follicular fluid androgen/estrogen (A/E) ratios. No apoptosis was observed in 67 primordial, primary, or secondary follicles. Positive staining for DNA fragmentation was found in a few granulosa cells in 0.1- to 2-mm follicles, whereas abundant staining in granulosa was detected in 2.1- to 9.9-mm follicles. In contrast, no DNA fragmentation was detected in dominant follicles (10–16 mm). The frequency of apoptosis in follicles was calculated to be 37% in 0.1- to 2-mm follicles, 50% in 2.1- to 5-mm follicles, and 27% in 5.1- to 9.9-mm follicles. Abundant low molecular weight DNA laddering was only found in androgen-dominant follicles and not in estrogen-dominant follicles. Positive staining for DNA fragmentation and low molecular weight DNA laddering were observed in degenerating but not healthy-appearing corpora lutea. In the former, DNA fragmentation was found primarily in large luteal cells. These data suggest that follicular atresia in human ovary results from normal programmed cell death and primarily occurs in the granulosa cell layers of the early antral and &lt;10-mm antral follicles primarily. Furthermore, because apoptosis occurs as early as the 200-mm stage, follicle selection may begin as early as the initial formation of the antrum. The results also suggest that degeneration of the corpus luteum occurs by apoptotic mechanisms.
How Is Whole Body Protein Turnover Perturbed in Growth Hormone-Deficient Adults?1
Authors: Hoffman David M. , Pallasser Robert , Duncan Mark , Nguyen Tuan V. , Ho Ken K. Y. 
Published: January 2014

Adult patients with GH deficiency have reduced lean body mass (LBM), muscle mass, and muscle strength, suggesting an underlying abnormality of protein metabolism. As acute GH administration has previously been reported to decrease protein oxidation and increase protein synthesis in GH-deficient (GHD) adults, we investigated whether the converse might occur in untreated GH deficiency by undertaking studies of whole body protein turnover in 10 GHD and 13 normal subjects using a 3-h primed constant infusion of 1-[13C]leucine. Dual energy x-ray absorptiometry was used to quantify LBM and fat mass (FM).
In normal subjects, LBM was the major, independent determinant of leucine appearance (Ra; r = 0.80; P = 0.0009), leucine oxidation (r = 0.81; P = 0.0008), and leucine incorporation into protein (r = 0.75; P = 0.003). However, in an analysis of covariance, FM was also a significant independent determinant of leucine Ra (P = 0.002) and leucine incorporation into protein (P = 0.003). After correcting for LBM and FM, GHD patients had significantly reduced rates of leucine Ra (109.9 ± 4.4 vs. 125.5 ± 3.7 μmol/min, respectively; P = 0.02) and leucine incorporation into protein (87.0 ± 3.9 vs. 100.3 ± 3.3 mmol/min; P = 0.02) compared to normal subjects. There was no significant difference in the corrected rates of leucine oxidation between the two groups (22.9 ± 1.3 vs. 25.2± 1.0, GHD vs. normal; P = 0.20).
In summary, GHD adults have reduced rates of protein synthesis and protein breakdown, but normal rates of irreversible oxidative loss; these findings are discordant with what was predicted from the acute changes in protein metabolism observed with GH administration. We conclude that normalization of protein oxidation may be a homeostatic mechanism that operates to constrain protein loss in GHD adults.
Development of a Health-Related Quality-of-Life Questionnaire (PCOSQ) for Women with Polycystic Ovary Syndrome (PCOS)1
Authors: Cronin L. , Guyatt G. , Griffith L. , Wong E. , Azziz R. , Futterweit W. , Cook D. , Dunaif A. 
Published: January 2014

Objective: To develop a self-administered questionnaire for measuring health-related quality of life (HRQL) in women with polycystic ovary syndrome (PCOS).
Methods: We identified a pool of 182 items potentially relevant to women with PCOS through semistructured interviews with PCOS patients, a survey of health professionals who worked closely with PCOS women, and a literature review. One hundred women with PCOS completed a questionnaire in which they told us whether the 182 items were relevant to them and, if so, how important the issue was in their daily lives. We included items endorsed by at least 50% of women in the analysis plus additional items considered crucial by clinicians and an important subgroup of patients in a factor analysis. We chose items for the final questionnaire taking into account both item impact (the frequency and importance of the items) and the results of the factor analysis.
Results: Over 50% of the women with PCOS labelled 47 items as important to them. Clinicians chose 5 additional items from the infertility domain, 4 of which were identified as important by women who were younger, less educated, married, and African-American. The Cattell’s Scree plot from a factor analysis of these 51 items suggested 5 factors that made intuitive sense: emotions, body hair, weight, infertility, and menstrual problems. We chose the highest impact items from these 5 domains to construct a final questionnaire, the Polycystic Ovary Syndrome Questionnaire (PCOSQ), which includes a total of 26 items and takes 10–15 minutes to complete.
Conclusions: We have used established principles to construct a questionnaire that promises to be useful in measuring health-related quality of life. The questionnaire should be tested prior to, or concurrent with, its use in randomized trials of new treatment approaches.
Tumor Necrosis Factor-α in Sera of Obese Patients: Fall with Weight Loss
Authors: Dandona Paresh , Weinstock Ruth , Thusu Kuldip , Abdel-Rahman Ehad , Aljada Ahmad , Wadden Thomas 
Published: January 2014

abstract
In view of the recent demonstration that obesity in animals and humans is associated with an increase in tumor necrosis factor-α (TNFα) expression, that this expression falls with weight loss, and that TNFα may specifically inhibit insulin action, the possibility that TNFα may be a mediator of insulin resistance has been raised. We have undertaken this study to investigate whether serum TNFα concentrations are elevated in obese subjects, whether they fall after weight loss, and whether this fall parallels the fall in insulin release after glucose challenge. Obese patients (age range: 25–54, weight mean ± sd: 96.4 ± 13.8 kg, body mass index: 35.7 ± 5.6 kg/m2) were started on a diet program. The mean weight fell to 84.5 ± 11.3 (P &lt; 0.0001) and body mass index to 31.3 ± 4.9 (P &lt; 0.0001). Plasma TNFα concentrations were markedly elevated in the obese (3.45 ± 0.16 pg/mL), when compared with controls (0.72 ± 0.28 pg/mL), and fell significantly (2.63 ± 1.40 pg/mL) after weight loss (P &lt; 0.02). The magnitude of insulin release after glucose (75 g) challenge (area under the curve) also fell significantly (P &lt; 0.01) after weight loss. The magnitude of weight loss and fall in TNFα were related to basal body weight (r = 0.57, P &lt; 0.001) and basal TNFα (r = 0.55, P &lt; 0.001) concentrations, respectively, but not to each other or to the glucose-induced insulin release (area under the curve). We conclude that obesity is associated with increased plasma TNFα concentrations, which fall with weight loss. Because circulating TNFα may mediate insulin resistance in the obese, a fall in TNFα concentrations may contribute to the restoration of insulin resistance after weight loss, Thus, TNFα may be an important circulating cytokine, which may provide a potentially reversible mechanism for mediating insulin resistance.
Albumin Synthesis and Bone Collagen Formation in Human Immunodeficiency Virus-Positive Subjects: Differential Effects of Growth Hormone Administration1
Authors: McNurlan Margaret A. , Garlick Peter J. , Frost Robert A. , DeCristofaro Kim A. , Lang Charles H. , Steigbigel Roy T. , Fuhrer Jack , Gelato Marie 
Published: January 2014

Loss of lean tissue often accompanies human immunodeficiency virus (HIV) infection. Exogenous human recombinant GH (hrGH) has been shown to be beneficial in reversing this wasting. However, catabolic effects of hrGH on muscle protein metabolism have also been reported. Therefore, the responsiveness of other GH-sensitive tissues, including bone formation and albumin synthesis, has been examined.
Anabolic activity in bone, from serum levels of carboxy-terminal propeptide of type I collagen, was stimulated by 2 weeks of hrGH in controls (56 ± 15%, P = 0.002), patients with asymptomatic HIV (24 ± 10%, not significant), patients with AIDS (47 ± 7%, P &lt; 0.001), and patients with AIDS and &gt;10% weight loss (21 ± 12%, P = 0.02). Albumin synthesis, determined from the incorporation of L-[2H5]phenylalanine, was increased in response to hrGH in controls (23 ± 7%, P &lt; 0.05), HIV+ subjects (39 ± 16%, P &lt; 0.05), and patients with AIDS (25 ± 7%, P &lt; 0.01). Patients with AIDS and weight loss, however, did not increase albumin synthesis (−0.6 ± 12%) in response to hrGH.
The results indicate variable anabolic responses to hrGH. Bone collagen synthesis remained sensitive to hrGH, whereas, the anabolic action of hrGH on the synthesis of albumin diminished with severity of disease. However unlike muscle protein synthesis, albumin synthesis was not depressed below basal levels by hrGH.
Diurnal Rhythms of Luteinizing Hormone, Follicle-Stimulating Hormone, and Testosterone Secretion before the Onset of Male Puberty1
Authors: Mitamura Ryo , Yano Koichi , Suzuki Naoki , Ito Yoshiya , Makita Yoshio , Okuno Akimasa 
Published: January 2014

To investigate hormonal change before the onset of male puberty, we measured LH and FSH in serum samples drawn every 20 min for 24 h and measured testosterone hourly for 24 h. Forty-six boys (32 prepubertal and 14 pubertal) of short stature, between 4.4–19.3 yr of age, participated in this study. LH and FSH were measured using a time-resolved immunofluorometric assay, and testosterone was measured using high sensitivity RIA capable of detecting a testosterone concentration of 0.01 ng/mL.
Diurnal rhythms of LH, FSH, and testosterone were apparent in all subjects, including those aged 4–5 yr. Serum LH and FSH concentrations showed night-day variation in a pulsatile fashion. The serum testosterone concentration was elevated at early morning in all subjects. Mean 24-h LH, FSH, and testosterone concentrations of prepubertal subjects who did not attain puberty for at least 3 yr were 0.10 U/L, 0.63 U/L, and 0.06 ng/mL, respectively, whereas those of prepubertal subjects who attained puberty within 1 yr (0.54 U/L, 1.68 U/L, and 0.10 ng/mL, respectively) were significantly higher. Furthermore, mean 24-h LH, FSH, and testosterone concentrations increased with developing puberty. All of the 46 subjects showed positive cross-correlation between the LH and testosterone time series. The mean lag time from the LH to the testosterone time series in the prepubertal subjects who attained puberty within 1 yr (4.7 ± 2.4 h, mean ± sd) was shorter than that in the prepubertal subjects who attained puberty after at least 3 yr (7.3± 2.2 h). This lag time decreased with developing puberty, plateauing at 1.4 ± 0.9 h at midpuberty.
Thus, the diurnal rhythms of LH, FSH, and testosterone already exist at 4–5 yr of age; serum LH, FSH, and testosterone levels increase before the onset of puberty; and a time delay is observed between the LH and testosterone time series that decreases before the onset of puberty.
Low Dose Estrogen and Calcium Have an Additive Effect on Bone Resorption in Older Women1
Authors: Prestwood K. M. , Thompson D. L. , Kenny A. M. , Seibel M. J. , Pilbeam C. C. , Raisz L. G. 
Published: January 2014

Previous studies have shown that treatment with estrogen or calcium decreases bone turnover in older women. The mechanisms by which estrogen and calcium exert their effects are probably different. We therefore examined the possibility of an additive or synergistic effect of combined treatment with calcium and low dose estrogen on bone turnover in older women, using biochemical markers.
Thirty-one healthy women over 70 yr of age were randomized to 12 weeks of treatment with either micronized 17β-estradiol [0.5 mg/day Estrace (E2)] or 1500 mg/day elemental calcium, given as carbonate plus vitamin D (800 IU/day; Ca+D). At the end of the initial 12-week treatment period, both groups received both Ca+D and E2 for an additional 12 weeks. Eleven older women were followed for 36 weeks without any treatment and served as a control group.
Serum and urine were collected at baseline, at 12 and 24 weeks on treatment, and at 12 weeks after treatment was terminated for measurement of biochemical markers of bone turnover. Markers of bone formation were bone alkaline phosphatase, osteocalcin, and type I procollagen peptide; markers of bone resorption were urinary cross-linked C-telopeptides and N-telopeptides of type I collagen, serum cross-linked N-telopeptides of type I collagen, urinary free deoxypyridinoline cross-links, and serum bone sialoprotein. Repeated measures ANOVA was used to determine changes in bone turnover measures over time by group.
All markers of bone resorption decreased with initial treatment and decreased further with combination therapy (P &lt; 0.001). Markers of bone formation decreased with Ca+D treatment, but not with E2 alone; there was no additional effect of combination therapy on formation markers compared to Ca+D alone. Neither markers of formation nor resorption changed in the control group.
These results suggest that there is an additive effect of low dose estrogen and calcium on bone resorption, but not on bone formation, in older women. Thus, the combination of low dose estrogen plus calcium is likely to be more effective in older women than either treatment alone.
Joint Basal and Pulsatile Hypersecretory Mechanisms Drive the Monotropic Follicle-Stimulating Hormone (FSH) Elevation in Healthy Older Men: Concurrent Preservation of the Orderliness of the FSH Release Process: A General Clinical Research Center Study*
Authors: Veldhuis J. D. , Iranmanesh A. , Demers L. M. , Mulligan T. 
Published: January 2014

Abstract
To appraise the neuroendocrine mechanisms that underlie a selective (monotropic) elevation of serum FSH concentrations in healthy older men, we sampled blood in 11 young (ages 21–34) and 8 older men (ages 62–72) men every 2.5 min overnight. Serum FSH concentrations were quantitated in an automated, high-sensitivity, chemiluminescence-based assay. Rates of basal and pulsatile FSH secretion were estimated by deconvolution analysis, and the orderliness of the FSH release process via quantitated the approximate entropy statistic. Statistical analysis revealed that healthy older men manifest dual neuroendocrine hypersecretory mechanisims; specifically, a 2-fold increase in the basel (nonpulsatile) FSH secretion rate, and a concurrent 50% amplification of FSH secretory burst mass (and amplitude). The regularity or orderliness of ad seriatim FSH release is preserved in older individuals. We postulate that higher basel FSH secretion in older men is a consequence of reduced testosterone negative feedback, whereas amplified FSH secretory burst mass reflects net enhanced stimulation of gonadotrope cells by endogenous FSH secretagogues (e.g. GnRH and/or activin). The foregoing specific mechanisms driving heightened FSH secretion in older men contrast with the lower-amplitude pulsatility and more disorderly patterns of LH release in the same individuals. Thus, the present data illuminate an age-dependent disparity in the disruption of FSH neuroregulation in the aging male.
Leptin and Androgens in Male Obesity: Evidence for Leptin Contribution to Reduced Androgen Levels*
Authors: Isidori Andrea M. , Caprio Massimiliano , Strollo Felice , Moretti Costanzo , Frajese Gaetano , Isidori Aldo , Fabbri Andrea 
Published: January 2014

AbstractLeptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8–55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = −0.51 and r = −0.38, P &lt; 0.01 and P &lt; 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU im) was 30–40% lower than in controls and inversely correlated with leptin levels (r = −0.45 and r = −0.40, P &lt; 0.01 and P &lt; 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P &lt; 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.
The Effect of Deydroepiandrosterone Supplementation to Symptomatic Perimenopausal Women on Serum Endocrine Profiles, Lipid Parameters, and Health-Related Quality of Life1
Authors: Barnhart Kurt T. , Freeman Ellen , Grisso Jeanne Anne , Rader Daniel J. , Sammel Mary , Kapoor Shiv , Nestler John E. 
Published: January 2014

Dehydroepiandrosterone (DHEA), an androgenic steroid hormone, exhibits an age-related decline. Perimenopausal women have only approximately 50% of peak DHEA levels. Despite limited scientific data, DHEA has gained recognition as a dietary supplement to reduce the symptoms of aging and improve well-being. This randomized, double-blind placebo-controlled trial examined the effects of 50 mg/day of oral DHEA supplementation, for 3 months, on 60 perimenopausal women with complaints of altered mood and well-being.
Changes in the serum endocrine profile of women in the DHEA group were significantly greater than the placebo group, including a 242% [95% confidence interval (CI) +60.1, +423.9] increase in DHEAS, a 94.8% (95% CI +34.2, +155.4) increase in testosterone, and a 13.2% (95% CI− 27.88, +0.5) decline in cortisol compared to baseline. Women receiving DHEA had a 10.1% (95% CI −15.0, −5.1) decline in high-density lipoprotein and an 18.1% (95% CI −32.2, −3.9) decline in Lp(a) from baseline, but these declines did not significantly differ from women who received placebo. Women receiving DHEA did not have any improvements significantly greater than placebo in the severity of perimenopausal symptoms, mood, dysphoria, libido, cognition, memory, or well-being.
DHEA supplementation significantly effects the endocrine profile, may affect the lipid profile, but does not improve perimenopausal symptoms or well-being compared to placebo.
Brain Natriuretic Peptide and Neutral Endopeptidase Inhibition in Left Ventricular Impairment1
Authors: Lainchbury John G. , Richards A. Mark , Nicholls M. Gary , Espiner Eric A. , Yandle Timothy G. 
Published: January 2014

Brain natriuretic peptide (BNP) is increased in left ventricular impairment and neutral endopeptidase (NEP) is involved in its metabolism. In random order, eight patients with left ventricular impairment received placebo, a 4-h infusion of human BNP (3.0 pmol/kg min), a single oral dose of NEP inhibitor (SCH 42495, 300 mg), and combined BNP and SCH 42495. Plasma BNP, cGMP, and cortisol were significantly increased by all three treatments (P &lt; 0.05–P &lt; 0.001). Combined treatment had a synergistic effect on plasma cGMP. The metabolic clearance rate of exogenous BNP was reduced (25%) by NEP inhibition. Endogenous plasma ANP was augmented more than BNP by NEP inhibition. Plasma aldosterone, unchanged during infusions, rose markedly after BNP and after the combined treatment (P &lt; 0.05 for both). Urine sodium excretion, increased by NEP inhibition (P &lt; 0.05) and by BNP (P = 0.05), was unchanged during combined treatment. Urine cGMP excretion was increased, whereas blood pressure was reduced by all active treatments (P &lt; 0.05–0.01 for all). Heart rate increased only with combined treatment (P = 0.007). Plasma renin activity, norepinephrine, and cardiac output were unaffected.BNP infusion and NEP inhibition both induced significant hemodynamic and renal responses. The augmented hypotensive effect of combined treatments, and consequent fall in renal perfusion pressure, may underly the observed blunting of the natriuretic response that occurred despite greater than additive increments in plasma BNP, ANP, and cGMP.