bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mifepristone-Induced Vaginal Bleeding Is Associated with Increased Immunostaining for Cyclooxygenase-2 and Decrease in Prostaglandin Dehydrogenase in Luteal Phase Endometrium
Authors: Hapangama Dharani K. , Critchley Hilary O. D. , Henderson Teresa A. , Baird David T. 
Published: November 2002

Abstract
The mechanism of mifepristone-induced vaginal bleeding and endometrial shedding was investigated in 13 women who took 200 mg mifepristone in the midluteal phase on d 8 after the onset of the urinary LH surge (LH+8). Endometrial biopsies were collected, 6–24 h after mifepristone (group 1, n = 7) or 36–48 h after mifepristone (group 2, n = 6), and compared with those from a control group in the midluteal phase (n = 7). All women reported vaginal bleeding commencing 36–48 h after taking mifepristone. Treatment with mifepristone significantly reduced serum progesterone levels in all women, when compared with the controls (13.2 nmvs. 34.8 nm, P = 0.001). After mifepristone, a significant increase in cyclooxygenase-2 immunoreactivity was apparent at 36–48 h (P = 0.0018), whereas prostaglandin 15 dehydrogenase enzyme-positive immunostaining declined, to be virtually absent by 36–48 h in both glands and in stroma (P &lt; 0.05). There was no change in intensity or distribution of staining for steroid receptors after mifepristone. The changes in immunostaining for cyclooxygenase-2 and prostaglandin 15 dehydrogenase strongly support the hypothesis that an increase in the local concentration of prostaglandins in the endometrium is involved in the mechanism of bleeding induced by mifepristone in the luteal phase.
Vascular Reactivity in Hypogonadal Men Is Reduced by Androgen Substitution
Authors: Zitzmann Michael , Brune Maik , Nieschlag Eberhard 
Published: November 2002

AbstractThe effect of testosterone (T) substitution therapy on blood vessel functions in relation to cardiovascular disease has not been fully elucidated. In 36 newly diagnosed nonsmoking hypogonadal men (37.5 ± 12.7 yr) endothelium-dependent flow-mediated vasodilatation (FMD; decreased in atherosclerosis) of the brachial artery was assessed before treatment and after 3 months of T substitution therapy (250 mg testosterone enanthate im every 2 wk in 19 men, human chorionic gonadotropin sc twice per week in 17 men). Twenty nonsmoking controls matched for age, low-density lipoprotein cholesterol (LDL-C), body height, and baseline diameter of the artery were selected for repeated measurements from a larger eugonadal control group (n = 113). In hypogonadal men, basal FMD (17.9 ± 4.5%) was significantly higher than in the large (11.9 ± 6.4%) and matched control (11.8 ± 7.1%, both P &lt; 0.001) groups. Grouped multiple linear regression analysis revealed a significant negative association of T levels with FMD within the hypogonadal range, but no significant association was seen within the eugonadal range. During substitution therapy, T levels increased from 5.8 ± 2.3 to 17.2 ± 5.1 nmol/liter and FMD decreased significantly to 8.6 ± 3.1% (P &lt; 0.001, analysis for covariance for repeated measurements including matched controls). LDL-C and advanced age contributed significantly to decrease FMD (P = 0.01, P = 0.04, respectively). Because T substitution adversely affects this important predictor of atherosclerosis, other contributing factors (such as smoking, high blood glucose, and LDL-C) should be eliminated or strictly controlled during treatment of hypogonadal men.
Diurnal Leptin Secretion Is Intact in Male Hypogonadotropic Hypogonadism and Is Not Influenced by Exogenous Gonadotropins
Authors: Kilciler Guldem , Ozata Metin , Oktenli Cagatay , Sanisoglu S.Yavuz , Bolu Erol , Bingol Necati , Kilciler Mete , Ozdemir I. Caglayan , Kutlu Mustafa 
Published: November 2002

Abstract
Circulating leptin shows a pulsatile secretory pattern along with a nocturnal rise. We have previously shown that circulating leptin concentrations are high in males with untreated idiopathic hypogonadotropic hypogonadism (IHH). However, circadian leptin secretion in IHH before and after gonadotropin treatment is not known. Thus, we studied 14 adult males with IHH who had no history of previous hormonal therapy, and 12 age- and body mass index-matched healthy men. Plasma leptin concentrations were measured with 1-h intervals for 24 h before and 6 months after gonadotropin treatment. The 24-h mean leptin concentration showed a significant decrease, from 11.78 ± 1.908 μg/liter at baseline to 10.85 ± 1.939 μg/liter after 6 months of therapy (z = 3.107; P = 0.002). Before and after treatment, 24-h mean leptin concentrations were also significantly higher in the patient group when compared with controls (4.275 ± 0.711 μg/liter) (z = 5.938; P = 0.0001). Hourly leptin levels demonstrated a diurnal pattern in hypogonadal patients, a surge in the midday, and a peak just after midnight, and this pattern did not differ before and after treatment. We observed a similar diurnal pattern in the control subjects too. Leptin levels were negatively and significantly correlated with free testosterone and total testosterone levels both before (r = −0.656, P = 0.011; and r = −0.639, P = 0.014, respectively) and after (r = −0.537, P = 0.048; and r = −0.563, P = 0.036, respectively) gonadotropin administration.
Our observations suggest that the diurnal rhythm of leptin is intact in males with IHH, and short-term gonadotropin treatment does not effect its diurnal rhythm. Moreover, testosterone produced under the influence of the gonadotropin treatment led to decreases in the leptin levels.
Pubertal and Gender-Related Changes in the Sympathoadrenal System in Healthy Children
Authors: Weise Martina , Eisenhofer Graeme , Merke Deborah P. 
Published: November 2002

Abstract
A critical amount of body fat is necessary for the initiation of puberty, and leptin, an adipocyte-derived hormone, is necessary for pubertal development. The sympathoadrenal system modulates body fat stores and leptin secretion and interacts with adrenocortical androgen production, suggesting a possible role in sexual maturation. We studied sympathetic nerve and adrenomedullary activity at rest in 80 healthy children (ages, 5–17 yr; 37 boys and 43 girls) in relation to age, pubertal stage, gender, physical activity, body mass index, and serum levels of sex steroids, dehydroepiandrosterone sulfate, cortisol, leptin, and insulin.
Plasma concentrations of the adrenomedullary hormone, epinephrine (E), and its metabolite metanephrine (MN), decreased significantly with advancing puberty and were higher in boys than in girls. E and MN correlated significantly and inversely with dehydroepiandrosterone sulfate, estradiol, testosterone, leptin, and insulin. Plasma norepinephrine, which is primarily derived from sympathetic nerve endings, increased significantly with advancing puberty and increasing testosterone levels in boys. Stepwise multiple regression analysis revealed that E was best predicted by pubertal stage and leptin, and MN by estradiol and leptin.
Our data suggest that sympathoadrenal hormones may play a role in the complex process of sexual maturation. Further studies are needed to investigate a possible modulatory role of the adrenal medulla in the body weight-related timing of adrenarche and/or gonadarche.
Effects of Above Average Summer Sun Exposure on Serum 25-Hydroxyvitamin D and Calcium Absorption
Authors: Barger-Lux M. Janet , Heaney Robert P. 
Published: November 2002

Abstract
The purpose of this study was to examine the effects of summer sun exposure on serum 25-hydroxyvitamin D [25(OH)D], calcium absorption fraction, and urinary calcium excretion. Subjects were 30 healthy men who had just completed a summer season of extended outdoor activity (e.g. landscaping, construction work, farming, or recreation). Twenty-six subjects completed both visits: after summer sun exposure and again approximately 175 d later, after winter sun deprivation. We characterized each subject’s sun exposure by locale, schedule, and usual attire. At both visits we measured serum 25(OH)D, fasting urinary calcium to creatinine ratio, and calcium absorption fraction. Median serum 25(OH)D decreased from 122 nmol/liter in late summer to 74 nmol/liter in late winter. The median seasonal difference of 49 nmol/liter (interquartile range, 29–67) was highly significant (P &lt; 0.0001). However, we found only a trivial, nonsignificant seasonal difference in calcium absorption fraction and no change in fasting urinary calcium to creatinine ratio. Findings from earlier work indicate that our subjects’ sun exposure was equivalent in 25(OH)D production to extended oral dosing with 70 μg/d vitamin D3 (interquartile range, 41–96) or, equivalently, 2800 IU/d (interquartile range, 1640–3840). Despite this input, at the late winter visit, 25(OH)D was less than 50 nmol/liter in 3 subjects and less than 75 nmol/liter in 15 subjects.
A Mutation in the KCNE3 Potassium Channel Gene Is Associated with Susceptibility to Thyrotoxic Hypokalemic Periodic Paralysis
Authors: Dias Da Silva Magnus R. , Cerutti Janete M. , Arnaldi Liliane A. T. , Maciel Rui M. B. 
Published: November 2002

Abstract
Hypokalemic Periodic Paralyses comprise diverse diseases characterized by acute and reversible attacks of severe muscle weakness, associated with low serum potassium. The most common causes are Familial Hypokalemic Periodic Paralysis (FHypoKPP), an autosomal dominant disease, and Thyrotoxic Hypokalemic Periodic Paralysis (THypoKPP), secondary to thyrotoxicosis. Symptoms of paralysis are similar in both diseases, distinguished by thyrotoxicosis present in THypoKPP. FHypoKPP is caused by mutations in ionic channel genes calcium (CACN1AS), sodium (SCN4A) and potassium (KCNE3). Since both diseases are similar, we tested the hypothesis that THypoKPP could carry the same mutations described in FHypoKPP, being the paralysis a genetically conditioned complication of thyrotoxicosis. In 15 patients with THypoKPP, using target-exon PCR, CSGE screening, and direct sequencing, we excluded known mutations in CACN1AS and SCN4A genes. On the other hand, we were able to identify the R83H mutation in the KCNE3 gene in one sporadic case of THypoKPP, a man who had been asymptomatic until developing thyrotoxicosis caused by Graves’ disease; we confirmed the disease-causing mutation in 2 of 3 descendants. R83H was recently found in two FHypoKPP unrelated families, in which the mutant decreased outward potassium flux, resulting in a more positive resting membrane potential. We, therefore, identified the first genetic defect in THypoKPP, a mutation in the KCNE3 gene.
Assessment of Nondiagnostic Ultrasound-Guided Fine Needle Aspirations of Thyroid Nodules
Authors: Alexander Erik K. , Heering Jenny P. , Benson Carol B. , Frates Mary C. , Doubilet Peter M. , Cibas Edmund S. , Marqusee Ellen 
Published: November 2002

Abstract
Thyroid nodules are common. Evaluation of patients with thyroid nodules typically includes fine needle aspiration biopsy (FNA), an approach that has proven to be accurate for the detection of thyroid cancer. Although the majority of biopsies are adequate for a cytological diagnosis, up to 20% will be insufficient or nondiagnostic. Current opinion suggests that such aspirates should be repeated, although no systematic study has investigated the usefulness of this approach, especially when ultrasound guidance is used to direct the initial FNA. We sought to define the predictors and optimal follow-up strategy for initial nondiagnostic ultrasound-guided FNAs of thyroid nodules.
Data were collected for all patients at the Brigham and Women’s Hospital Thyroid Nodule Clinic between 1995–2000 who underwent ultrasound-guided FNA of a thyroid nodule. All patients with nondiagnostic cytology were advised to return for a repeat ultrasound-guided FNA. Patient age, gender, nodule size, cystic content, solitary vs. multinodular thyroid, and nodule location were documented and evaluated as possible predictors of a nondiagnostic biopsy in a multivariable model. The rate of diagnostic cytology obtained on repeat ultrasound-guided FNA was calculated.
A total of 1128 patients with 1458 nodules were biopsied over a 6-yr period. A total of 1269 aspirations (950 patients) were diagnostic, and 189 (178 patients) were nondiagnostic. The cystic content of each nodule was the only significant independent predictor of nondiagnostic cytology (P &lt; 0.001). The fraction of specimens with initial nondiagnostic cytology increased with greater cystic content (P &lt; 0.001 for trend). A diagnostic ultrasound-guided FNA was obtained on the first repeat biopsy in 63% of nodules and was inversely related to increasing cystic content of each nodule (P = 0.03). One hundred and nineteen patients with 127 nodules returned for follow-up as advised, and malignancy was documented in 5%.
Despite ultrasound-guided FNA, there remains a significant risk of initial nondiagnostic cytology, largely predicted by the cystic content of each nodule. Repeat aspiration is often successful and should be the standard approach to such nodules, given their risk of malignancy.
Transcriptionally Targeted Retroviral Vector for Combined Suicide and Immunomodulating Gene Therapy of Thyroid Cancer
Authors: Barzon Luisa , Bonaguro Roberta , Castagliuolo Ignazio , Chilosi Marco , Gnatta Elisa , Parolin Cristina , Boscaro Marco , Palù Giorgio 
Published: November 2002

Abstract
Gene therapy may be an effective approach to thyroid carcinoma refractory to conventional treatment. A transcriptionally targeted retroviral vector for gene therapy of thyroid carcinomas was generated replacing the viral enhancer with the enhancer sequence of the human thyroglobulin (TG) gene, yielding a chimeric long-terminal repeat. The TG enhancer was used to drive the expression of either a reporter gene (β-galactosidase) or two therapeutic genes, i.e. the prodrug-activating enzyme thymidine kinase of herpes simplex virus (HSV-TK) and human IL-2, separated by an internal ribosome entry site. The corresponding vector having an unmodified long-terminal repeat was used as control. The targeted vector allowed selective transgene expression and cell killing in differentiated thyroid tumor cells but not in anaplastic thyroid carcinoma cells and nonthyroid cells, as demonstrated by quantitative RT-PCR and cytotoxicity assays. Nude mice injected with tumor cells underwent near complete or complete regression of tumors transduced with the control vector after ganciclovir treatment. On the other hand, infection with the thyroid-specific vector led to regression only of TG-expressing tumors. In addition, tumors expressing human IL-2 showed significant growth retardation, compared with nontransduced tumors while exhibiting signs of necrosis and presence of an inflammatory infiltrate. However, HSV-TK/IL-2 plus ganciclovir was significantly more efficient than HSV-TK/IL-2 alone in eradicating tumor masses. Our results indicate that replacement of viral enhancer with TG enhancer confers selectivity of transgene expression in thyroid cells. Thus, the combined thyroid-specific expression of two therapeutic genes (cytokine and suicide genes), although a safe tumor-targeted treatment, would allow an increased anticancer effect.
A NEW BASIS FOR QED BOUND STATE COMPUTATIONS
Authors: PESTIEAU J. , SMITH C. 
Published: November 2002

A simple method to compute QED bound state properties is presented, in which binding energy effects are treated nonperturbatively. It is shown that to take the effects of all ladder Coulomb photon exchanges into account, one can simply perform the derivative of standard QED amplitudes with respect to the external momentum. For example, the derivative of the light-by-light scattering amplitude gives an amplitude for orthopositronium decay to three photons where any number of Coulomb photon exchanges between the e+e-is included.Various applications are presented. From them, it is shown that binding energy must be treated nonperturbatively in order to preserve the analyticity of positronium decay amplitudes.Interesting perspectives for quarkonium physics are briefly sketched.
Semiparametric Bayesian models for human brain mapping
Authors: Fahrmeir L , Gössl C 
Published: November 2002

Functional magnetic resonance imaging (fMRI) has led to enormous progress in human brain mapping. Adequate analysis of the massive spatiotemporal data sets generated by this imaging technique, combining parametric and non-parametric components, imposes challenging problems in statistical modelling. Complex hierarchical Bayesian models in combination with computer-intensive Markov chain Monte Carlo inference are promising tools. The purpose of this paper is twofold. First, it provides a review of general semiparametric Bayesian models for the analysis of fMRI data. Most approaches focus on important but separate temporal or spatial aspects of the overall problem, or they proceed by stepwise procedures. Therefore, as a second aim, we suggest a complete spatiotemporal model for analysing fMRI data within a unified semiparametric Bayesian framework. An application to data from a visual stimulation experiment illustrates our approach and demonstrates its computational feasibility.
A Whole-Genome Linkage Scan Suggests Several Genomic Regions Potentially Containing Quantitative Trait Loci for Osteoporosis
Authors: Deng Hong-Wen , Xu Fu-Hua , Huang Qing-Yang , Shen Hui , Deng Hongyi , Conway Theresa , Liu Yong-Jun , Liu Yao-Zhong , Li Jin-Long , Zhang Hai-Tao , Davies K. M. , Recker Robert R. 
Published: November 2002

AbstractOsteoporosis is an important health problem, particularly in the elderly women. Bone mineral density (BMD) is a major determinant of osteoporosis. For a sample of 53 pedigrees that contain 1249 sibling pairs, 1098 grandparent-grandchildren pairs, and 2589 first cousin pairs, we performed a whole- genome linkage scan using 380 microsatellite markers to identify genomic regions that may contain quantitative trait loci (QTL) of BMD. Each pedigree was ascertained through a proband with BMD values belonging to the bottom 10% of the population. We conducted two-point and multipoint linkage analyses. Several potentially important genomic regions were suggested. For example, the genomic region near the marker D10S1651 may contain a QTL for hip BMD variation (with two-point analysis LOD score of 1.97 and multipoint analysis LOD score of 2.29). The genomic regions near the markers D4S413 and D12S1723 may contain QTLs for spine BMD variation (with two-point analysis LOD score of 2.12 and 2.17 and multipoint analysis LOD score of 3.08 and 2.96, respectively). The genomic regions identified in this and some earlier reports are compared for exploration in extension studies with larger samples and/or denser markers for confirmation and fine mapping to eventually identify major functional genes involved in osteoporosis.
Wild-Type Estrogen Receptor (ERβ1) and the Splice Variant (ERβcx/β2) Are Both Expressed within the Human Endometrium throughout the Normal Menstrual Cycle
Authors: Critchley Hilary O. D. , Henderson Teresa A. , Kelly Rodney W. , Scobie Graeme S. , Evans Lee R. , Groome Nigel P. , Saunders Philippa T. K. 
Published: November 2002

Abstract
Estrogen action is mediated via two subtypes of the estrogen receptor (ER), usually referred to as ERα and ERβ. We have previously compared the spatial and temporal expressions of ERα and ERβ proteins in human endometrium and reported that endothelial cells exclusively express ERβ. In the present study we have extended our investigations to compare the pattern of expression of wild-type (ERβ1) and a newly identified ERβ variant isoform (ERβcx/β2) that lacks the ability to bind steroids.
mRNAs encoding both ERβ1 and ERβcx/β2 receptors were identified in human endometrial extracts by RT-PCR. Quantitative TaqMan R-TPCR demonstrated that levels of total mRNAs were increased significantly premenstrually as circulating progesterone levels declined. ERβ1 and ERβcx/β2 proteins were identified within multiple cell types within the endometrium using isotype-specific monoclonal antibodies; immunoexpression of ERβcx/β2 appeared less intense than that of ERβ1 in endometrial glandular epithelium and endothelial cells. Immunoexpression of ERβ1 appeared unchanged throughout the menstrual cycle. In contrast, levels of ERβcx/β2-specific immunoreactivity were specifically reduced in gland cells within the functional layer, but not in those of the basal layer, in the midsecretory phase. It is possible that coexpression of ERβcx/β2 in cells containing ERβ1 and/or ERα may modulate the effects of estrogens on the endometrium.
Effect of Subcutaneous Leptin Replacement Therapy on Bone Metabolism in Patients with Generalized Lipodystrophy
Authors: Simha Vinaya , Zerwekh Joseph E. , Sakhaee Khashayar , Garg Abhimanyu 
Published: November 2002

Abstract
The adipocyte-derived hormone leptin, which plays an important role in energy homeostasis, has been suggested to have an influence on bone development and remodeling. However, it is not clear from animal studies whether leptin is a stimulator or an inhibitor of bone growth. Cross-sectional studies in humans suggest that serum leptin levels are positively associated with bone mineral density (BMD), but these observations are not consistent, and whether this relationship is independent of obesity remains unclear. We therefore examined the effect of sc leptin administration on BMD and markers of bone turnover in two women, one with congenital generalized lipodystrophy and the other with acquired generalized lipodystrophy. Both patients had regular menstrual cycles. At baseline, the BMD for both patients, measured at the lumbar spine and total hip, was within 1 sd of the peak bone mass. There was no significant change in BMD in both patients after 16–18 months of leptin therapy. Similarly, concentrations of serum osteocalcin and bone-specific alkaline phosphatase or urinary excretion of deoxypyridinoline and N-telopeptides remained unchanged after 6–8 months of leptin therapy, suggesting no effects of leptin on osteoblastic or osteoclastic activity. Our preliminary data suggest that sc leptin replacement in hypoleptinemic patients with generalized lipodystrophy has no effect on the mature adult skeleton.
Neurosteroid Quantification in Human Brain Regions: Comparison between Alzheimer’s and Nondemented Patients
Authors: Weill-Engerer Sébastien , David Jean-Philippe , Sazdovitch Véronique , Liere Philippe , Eychenne Bernard , Pianos Antoine , Schumacher Michael , Delacourte André , Baulieu Etienne-Emile , Akwa Yvette 
Published: November 2002

Abstract
Some neurosteroids have been shown to display beneficial effects on neuroprotection in rodents. To investigate the physiopathological significance of neurosteroids in Alzheimer’s disease (AD), we compared the concentrations of pregnenolone, pregnenolone sulfate (PREGS), dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), progesterone, and allopregnanolone, measured by gas chromatography-mass spectrometry, in individual brain regions of AD patients and aged nondemented controls, including hippocampus, amygdala, frontal cortex, striatum, hypothalamus, and cerebellum. A general trend toward decreased levels of all steroids was observed in all AD patients’ brain regions compared with controls: PREGS and DHEAS were significantly lower in the striatum and cerebellum, and DHEAS was also significantly reduced in the hypothalamus. A significant negative correlation was found between the levels of cortical β-amyloid peptides and those of PREGS in the striatum and cerebellum and between the levels of phosphorylated tau proteins and DHEAS in the hypothalamus. This study provides reference values for steroid concentrations determined by gas chromatography-mass spectrometry in various regions of the aged human brain. High levels of key proteins implicated in the formation of plaques and neurofibrillary tangles were correlated with decreased brain levels of PREGS and DHEAS, suggesting a possible neuroprotective role of these neurosteroids in AD.