bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Genotypic and Histopathological Study of a Large Dutch Kindred with Hyperparathyroidism-Jaw Tumor Syndrome1
Authors: Haven Carola Jose , Wong Fung Ki , van Dam Eveline W. C. M. , van der Luijt Rob , van Asperen Christi , Jansen Joke , Rosenberg Carla , de Wit Mireille , Roijers Janine , Hoppener Jo , Lips Cornelis J. , Larsson Catharina , Teh Bin Tean , Morreau Hans 
Published: January 2014

Familial primary hyperparathyroidism is the main feature of 2 familial endocrine neoplasia syndromes: multiple endocrine neoplasia type 1 (MEN 1) and hyperparathyroidism-jaw tumor syndrome (HPT-JT). The latter is a recently described syndrome that has been associated with ossifying fibroma of the jaw and various types of renal lesions, including benign cysts, Wilms’ tumor, and hamartomas. To further illustrate the natural history of this syndrome, we describe a large, previously unreported Dutch kindred in which 13 affected members presented with either parathyroid adenoma or carcinoma; in 5 affected individuals, cystic kidney disease was found. Additionally, pancreatic adenocarcinoma, renal cortical adenoma, papillary renal cell carcinoma, testicular mixed germcell tumor with major seminoma component, and Hürthle cell thyroid adenoma were also identified. Linkage analysis of the family using MEN1-linked microsatellite markers and mutation analysis excluded the involvement of the MEN1 gene. Using markers from the HPT-JT region in 1q25–31, cosegregation with the disease was found, with a maximum logarithm of odds score of 2.41 obtained for 6 markers using the most conservative calculation. Meiotic telomeric recombination between D1S413 and D1S477 was identified in 3 affected individuals, and when combined with previous reports, delineated the HPT-JT region to 14 centimorgan. Combined comparative genomic hybridization and loss of heterozygosity data revealed complex genetic abnormalities in the tumors, suggesting different possible genetic mechanisms for the disease.
In conclusion, we report a family with hyperparathyroidism linked to chromosome 1q, and exhibiting several types of renal and endocrine tumors that have not been previously described.
Older Men Manifest Multifold Synchrony Disruption of Reproductive Neurohormone Outflow1
Authors: Veldhuis J. D. , Iranmanesh A. , Godschalk M. , Mulligan T. 
Published: January 2014

Under a working clinical hypothesis that aging putatively disrupts neuroendocrine control mechanisms, here we test a specific corollary notion that transitions in sleep stage, oscillations in nocturnal penile tumescence (NPT; a neurogenically organized signal), and the rates of instantaneous secretion of LH and/or testosterone are jointly synchronous in healthy young, but not older, men. To this end, we evaluated 10 young (aged 21–31 yr) and 8 older (aged 65–74 yr) men by intensive overnight multisite monitoring, viz. simultaneous electroencephalogram and NPT recordings (every 30 s) and remote blood sampling (every 2.5 min) to quantitate LH and testosterone release. Waveform-independent deconvolution and cross-correlation analyses of these neurohormone outflow measures revealed that healthy young men sustain four salient physiological linkages overnight: 1) a strong inverse (confirmatory) relationship between sleep stage and NPT activity, such that deeper sleep is accompanied by suppression of NPT; 2) consistent coupling between NPT and testosterone secretion, wherein heightened NPT activity respectively precedes and follows increased testosterone secretion by 12.5–32.5 and 50–60 min; 3) evident synchrony between sleep stage and testosterone secretion, in which testosterone secretion increases over a 30-min window (−2.5 to 25 min) while sleep deepens; and 4) a close temporal linkage between instantaneous LH release and NPT oscillations, whereby LH secretion increases 55–62.5 min before and again 5–30 min after NPT declines. In contrast, older men manifested global loss of expected young adult synchrony; namely, 1) abolition of the inverse relationship between sleep stage and NPT, 2) decorrelation of NPT oscillations and testosterone secretion, 3) decoupling of testosterone release and deep sleep, and 4) abrogation of the linkage between LH secretion and penile detumescence.
In summary, high intensity overnight monitoring of multiple reproductive neuroendocrine outflow measures simultaneously in young men delineates prominent neurophysiological coupling among sleep transitions and NPT activity, LH and testosterone secretion or NPT oscillations, and testosterone secretion and deepening sleep stage. In contrast, healthy older men exhibit near-universal disruption of physiological young adult synchronicity. Thus, we conclude that male reproductive aging is marked by erosion of coordinate regulation among sleep transitions, central nervous system-directed NPT activity, and hypothalamically driven episodic GnRH/LH (and thereby Leydig cell testosterone) secretion. Whether analogous multifold uncoupling of neurohormone signals emerges in the course of reproductive aging in women or in nonhuman species is not yet known.
Plasma Leptin Concentrations and Cardiac Autonomic Nervous System in Healthy Subjects with Different Body Weights
Authors: Paolisso Giuseppe , Manzella Daniela , Montano Nicola , Gambardella Antonio , Varricchio Michele 
Published: January 2014

Abstract
Previous studies have shown that leptin stimulates sympathetic nervous system; heart rate variability (HRV) is a widely used technique for assessing the sympathovagal balance at the cardiac level. The aim of our study was to investigate a possible relationship between plasma leptin levels and the autonomic regulation using spectral analysis of HRV. In 120 healthy nonobese subjects the plasma leptin concentration was determined, and HRV was recorded at baseline and during tilt. All subjects were categorized in quartiles of plasma leptin concentration. Analysis of data showed a significant increase in body mass index, body fat, fasting plasma insulin, triglyceride concentration, and homeostatic model assessment values throughout the different quartiles of plasma leptin concentration. Concerning cardiovascular parameters, heart rate, arterial blood pressures, and RR intervals were not significantly different among the quartiles. Total power and high frequency (HF) in normalized units were significantly decreased, whereas low frequency (LF) normalized units was progressively increased from the first to the fourth quartile. Thus, the LF/HF ratio rose gradually and significantly from the lowest to the highest quartile. Such results were independent of the body fat estimate (P &lt; 0.03 for the trend). The change in the LF/HF ratio was significantly enhanced during tilt (P &lt; 0.001 vs. rest values for all quartiles); the effect was stronger in subjects in the fourth quartile of plasma leptin concentration (P &lt; 0.005 for the trend). The latter parameter was also independent of body fat content and distribution (P &lt; 0.01). Our study shows that increasing fasting plasma leptin concentrations are associated with a shift of the sympathovagal balance toward a progressive increase in sympathetic activation and an increased response to orthostatic stimulus in nonobese subjects with different body fat contents.
Reduced Parathyroid Vitamin D Receptor Messenger Ribonucleic Acid Levels in Primary and Secondary Hyperparathyroidism*
Authors: Carling Tobias , Rastad Jonas , Szabó Eva , Westin Gunnar , Åkerström Göran 
Published: January 2014

Abstract
Vitamin D, via its receptor (VDR), inhibits the hormone secretion and proliferation of parathyroid cells. Vitamin D deficiency and reduced parathyroid VDR expression has been associated with development of hyperparathyroidism (HPT) secondary to uremia. VDR polymorphisms may influence VDR messenger RNA (mRNA) levels and have been coupled to an increased risk of parathyroid adenoma of primary HPT. VDR mRNA relative to glyceraldehyde-3-phosphate dehydrogenase mRNA levels were determined by RNase protection assay in 42 single parathyroid adenomas of patients with primary HPT, 23 hyperplastic glands of eight patients with uremic HPT, and 15 normal human parathyroid glands. The adenomas and hyperplasias demonstrated similar VDR mRNA levels, which were reduced (42 ± 2.8% and 44 ± 4.0%) compared with the normal glands (P &lt; 0.0001). Comparison of parathyroid adenoma with a normal-sized parathyroid gland of the same individual (n = 3 pairs) showed a 20–58% reduction in the tumor. Nodularly enlarged glands represent a more advanced form of secondary HPT and showed greater reduction in the VDR mRNA levels than the diffusely enlarged glands (P &lt; 0.005). The reduced VDR expression is likely to impair the 1,25(OH)2D3-mediated control of parathyroid functions, and to be of importance for the pathogenesis of not only uremic but also primary HPT. Circulating factors like calcium, PTH, and 1,25(OH)2D3 seem to be less likely candidates mediating the decreased VDR gene expression in HPT.
A Comparison of the Effects of Raloxifene and Estrogen on Bone in Postmenopausal Women1
Authors: Prestwood Karen M. , Gunness Michele , Muchmore Douglas B. , Lu Yili , Wong Mayme , Raisz Lawrence G. 
Published: January 2014

Raloxifene HCl, a selective estrogen receptor modulator, has been shown to increase bone mineral density (BMD) and decrease biochemical markers of bone turnover in postmenopausal women without stimulatory effects on the breast and uterus. However, it is not known whether the changes in BMD and bone turnover are associated with changes at the tissue level, nor how changes with raloxifene compare with estrogen. In this randomized, double blind study, we evaluated the effects of raloxifene (Evista, 60 mg/day) or conjugated equine estrogens (CEE; Premarin, 0.625 mg/day) on bone architecture, bone turnover, and BMD. Iliac crest bone biopsies were obtained at baseline and at the end of the study after double tetracycline labeling and were analyzed for standard histomorphometric indexes. Serum and urinary biochemical markers of bone turnover were measured at baseline and at 4, 10, 18, and 24 weeks of treatment. Total body, lumbar spine, and hip BMD were measured at baseline and at the end of the study by dual energy x-ray absorptiometry.
Activation frequency and bone formation rate/bone volume were significantly decreased from baseline in the CEE, but not in the raloxifene, group. Bone mineralization did not change in either group. Most markers of bone resorption and formation decreased in both groups, but to a greater degree in the CEE group (P &lt; .05). Total body and lumbar spine BMD increased from baseline in both groups, with a greater increase in the CEE group (P&lt; 0.05). Hip BMD significantly increased from baseline in the raloxifene group, but the change was not different from that in the CEE group. These results suggest that raloxifene reduces bone turnover and increases bone density, although to a lesser extent than CEE. Thus, raloxifene is an alternative to CEE for the prevention and treatment of osteoporosis in postmenopausal women.
Dynamic Changes in the Intrafollicular Inhibin/Activin/Follistatin Axis during Human Follicular Development: Relationship to Circulating Hormone Concentrations*
Authors: Schneyer Alan L. , Fujiwara Toshihiro , Fox Janis , Welt Corrine K. , Adams Judith , Messerlian Geralyn M. , Taylor Ann E. 
Published: January 2014

Abstract
Previous studies of normal human ovaries suggest that inhibins, activins, and follistatin (FS) are produced in a stage-specific pattern indicative of intraovarian, autocrine/paracrine roles in regulating follicle development. However, these studies relied largely on surgical specimens and thus include little information about the menstrual cycle stage or dominant follicle status at the time follicles or ovaries were obtained. The purpose of this study was to 1) determine the pattern of intrafollicular hormone biosynthesis across antral follicle development in normal women, 2) compare hormone concentrations in dominant and nondominant follicles from the same ovary, and 3) examine the relationship between dominant follicle hormone content and circulating hormone levels. Intrafollicular estradiol, progesterone, and inhibin A concentrations increased significantly with follicle size or maturity, whereas significant inverse relationships were observed for androstenedione and the androstenedione/estradiol (A:E) ratio. In contrast, neither inhibin B, activin A, nor free FS varied consistently with size or maturity. Estradiol, progesterone, and inhibin A levels and A:E ratio were significantly lower in nondominant follicles compared to the dominant follicle aspirated from the same ovary. Although intrafollicular and serum concentrations of each hormone followed the same general pattern as follicles develop, the human follicular fluid/serum gradients changed during the follicular phase and were different for estradiol and inhibin A, suggesting the presence of stage-specific differences in pharmacodynamics. These results are consistent with the hypothesis that the orderly transition from an activin-dominant to an inhibin A/FS-dominant microenvironment is critical for dominant follicle development.
Anisomastia Associated with Interstitial Duplication of Chromosome 16, Mental Retardation, Obesity, Dysmorphic Facies, and Digital Anomalies: Molecular Mapping of a New Syndrome by Fluorescent in Situ Hybridization and Microsatellites to 16q13 (D16S419-D16S503)*
Authors: Stratakis Constantine A. , Lafferty Antony , Taymans Susan E. , Gafni Rachel I. , Meck Jeanne M. , Blancato Jan 
Published: January 2014

AbstractAnisomastia is a common problem among developing adolescent girls. We recently evaluated a 22-yr-old female patient who had severe anisomastia (which had been repaired by surgery), associated with moderate to severe mental retardation, a stocky body habitus with mild obesity, dysmorphic facies (prominent, upslanting palpebral fissures, beaked nose, and a prominent philtrum), webbed neck, low hairline, and severe bilateral clinodactyly of the third, fourth, and fifth fingers with acral (but not large joint) flexion contractures. A peripheral blood high resolution karyotype revealed additional chromosomal material within the long arm of chromosome 16. Densitometric analysis of amplified polymorphic sequence-tagged sites (STS) mapping to 16q suggested that the duplication is defined by the noninvolved markers D16S419 [16q12-cen, 66 centimorgan (cM) from 16p terminus] and D16S421 (16q13-q21, 84.4 cM), encompassing a maximum of 18.4 cM of genetic distance. The STS analysis showed that the duplication was on the maternally derived chromosome 16, resulting in two maternal (and one paternal) copies of that region of chromosome 16. The location was further confirmed by bacterial artificial chromosomes (BACs) that were obtained from a commercially available library, labeled, and used for fluorescence in situ hybridization. The BACs containing STSs D16S408, D16S3137, and D16S3032 (markers that correspond to 16q13) showed two regions of hybridization, indicating that these sites were duplicated, whereas a BAC containing the STS D16S512 (which corresponds to 16q21-q22) revealed one hybridization signal per 16q, indicating that the corresponding region was not involved in the duplication. The distance between the probe signals suggested a tandem duplication. We conclude that even though trisomy 16 is the most common autosomal trisomy in spontaneous abortions, few patients with unbalanced chromosome 16 abnormalities survive to adulthood; in this report we describe one such patient with an interstitial chromosome 16 duplication (at 16q13), who had a specific phenotype associated with abnormal breast size. There are clinical similarities between this patient and patients with other 16q abnormalities, although the breast findings were unique. Molecular cytogenetics, including fluorescence in situ hybridization and densitometric analysis of amplified STSs, provided useful tools for the precise mapping of the syndrome to 16q13, where the gene(s) responsible for this phenotype might be localized.
Increased Fibrinogen Production in Type 2 Diabetic Patients without Detectable Vascular Complications: Correlation with Plasma Glucagon Concentrations
Authors: Barazzoni R. , Zanetti M. , Davanzo G. , Kiwanuka E. , Carraro P. , Tiengo A. , Tessari P. 
Published: January 2014

Abstract
Fibrinogen is a strong cardiovascular risk factor in the general population, and increased fibrinogen plasma concentrations have been reported in type 2 diabetic patients. However, the mechanisms leading to hyperfibrinogenemia in type 2 diabetes are not known. It is also not known whether possible alterations of fibrinogen turnover may precede clinical diabetic micro- and macrovascular complications and therefore potentially contribute to their onset. To address these questions, fibrinogen production was determined in six male type 2 diabetic patients without detectable micro- and macrovascular complications (age, 45 ± 4 yr; body mass index, 27 ± 0.9 kg/m2) and in seven nondiabetic matched controls using leucine isotope precursor-product relationships. Plasma glucose (P &lt; 0.001), insulin (P &lt; 0.05), and glucagon concentrations (P &lt; 0.01) were increased in the patients. Diabetic patients also had increased plasma fibrinogen concentration (+∼50%; P &lt; 0.01) and pool (+∼40%; P &lt; 0.01) as well as fractional (+∼35%; P = 0.08) and absolute (+∼100%; P &lt; 0.01) synthetic rates. The plasma glucagon concentration was positively related (P &lt; 0.005 or less) to the fibrinogen concentration as well as to fractional and absolute synthetic rates. Thus, fibrinogen production is markedly enhanced, and this alteration is likely to determine the observed hyperfibrinogenemia in type 2 diabetic patients. Hyperglucagonemia may contribute to the increased fibrinogen production. These findings in normoalbuminuric patients without clinical complications support the hypothesis that increased fibrinogen production and plasma concentrations may precede and possibly contribute to the onset of clinical cardiovascular complications in type 2 diabetes.
Prognostic Markers in Patients with Typical Bronchial Carcinoid Tumors*
Authors: Granberg Dan , Wilander Erik , Öberg Kjell , Skogseid Britt 
Published: January 2014

Abstract
Typical bronchial carcinoids are usually considered fairly benign tumors. Metastases do however occur, and up to 10% of the patients ultimately die from their disease. To identify prognostic markers, we immunostained 43 typical bronchial carcinoids with antibodies against 8 possibly relevant hormones, oncogenes, tumor suppressor genes, adhesion molecules, and proliferation markers. Altogether 12 patients (28%) had metastatic disease, of whom 10 had regional lymph node metastases at diagnosis. Distant metastases have occurred in 5 patients (12%); all of these have died from their disease. Patients with high expression of Ki-67 had shorter survival time (P &lt; 0.01). None of the immunostained hormones correlated to distant metastases or shorter survival time, but gastrin-releasing peptide correlated to metastatic disease (P &lt; 0.05). All patients who died had CD44-negative tumors (P &lt; 0.001). Nuclear nm23 staining correlated to decreased risk for metastatic disease and distant metastases per se (P &lt; 0.01). Bcl-2 and p53 were associated with increased risk for distant metastases (P &lt; 0.05 and P &lt; 0.01, respectively). We conclude that some patients with typical bronchial carcinoids die from their disease and that gastrin-releasing peptide, Bcl-2, and p53 may be of importance for the malignant transformation of the tumor. Moreover, CD44, nm23, and Ki-67 may give valuable prognostic information and help identify the patients at risk of disease-related death.
Studies of the Synergistic Effect of the Trp/Arg64 Polymorphism of theβ 3-Adrenergic Receptor Gene and the −3826 A→G Variant of the Uncoupling Protein-1 Gene on Features of Obesity and Insulin Resistance in a Population-Based Sample of 379 Young Danish Subjects*
Authors: Urhammer Søren A. , Hansen Torben , Borch-Johnsen Knut , Pedersen Oluf 
Published: January 2014

Abstract
This study examined whether the simultaneous presence of the previously identified Trp/Arg64 polymorphism of theβ 3-adrenergic receptor (BAR) gene and the −3826 A→G nucleotide variant of the uncoupling protein-1 (UCP1) gene are associated with obesity, insulin resistance, or alterations in size at birth in a Danish study population comprising 379 unrelated young Caucasian subjects. All study participants underwent an iv glucose tolerance test with addition of tolbutamide after 20 min. In addition, a number of biochemical and anthropometric measures were performed on each subject. The subjects were genotyped for the 2 polymorphisms by applying PCR-restriction fragment length polymorphism. The subjects were divided into 4 groups according to their BAR and UCP1 genotype: wild-type carriers (n = 184), only Trp/Arg64 carriers (n = 29), only A→G UCP1 carriers (n = 146), and carriers of both genetic variants (n = 20). There were no differences across the genotype groups with respect to body mass index, fat mass, waist to hip ratio, birth weight or length, ponderal index, or weight gain during childhood or adolescence, nor was the combined genotype related to alterations in fasting serum levels of lipids, insulin, or C peptide or the insulin sensitivity index. In conclusion, the present study failed to demonstrate an additive or synergistic effect of the Trp/Arg64 variant of the BAR gene and the −3826 A→G variant of the UCP1 gene on the development of obesity and insulin resistance among randomly recruited Danish Caucasian subjects.
Ontogenetic Pattern of Thyroid Hormone Receptor Expression in the Human Testis
Authors: Jannini Emmanuele A. , Crescenzi Anna , Rucci Nadia , Screponi Emiliano , Carosa Eleonora , De Matteis Anna , Macchia Enrico , d’Amati Giulia , D’Armiento Massimino 
Published: January 2014

Abstract
We studied the spatiotemporal distribution of thyroid hormone nuclear receptors (TRs) α1 and α2 and β messenger RNA (mRNA) levels in normal human testicular tissue during development and in adulthood. Nonpathological specimens from five aborted fetuses (17 and 23 weeks of gestation, three and two cases, respectively) and from four patients undergoing orchiectomy (18 months old and 38-, 42-, and 52-yr-old, respectively) were analyzed by Northern blot, semiquantitative RT-PCR amplification using DNA sequences or specifically designed primers for the TR isoforms, and in situ hybridization.
By using PCR amplification, we found that TRα1 and TRα2 are both expressed at different levels in fetal and adult testis. At all ages TRα2 is found at higher levels. Northern analysis showed hybridization signals corresponding to the expression of TRα2 and TRα1 in a ratio that increased from 2.6 at 17 weeks of gestation to 12.0 in adulthood. In fact, the expression of TRα1 dramatically decreased throughout development, being faintly detectable in the adult testis. Expression of TRβ was not detected at any age studied. This finding was further confirmed by PCR, which did not amplify TRβ either in fetal or in adult testis mRNAs. In situ hybridization studies showed the absence of TRβ and that TRα1 and TRα2 colocalized in Sertoli cells of prepubertal testis, whereas germ and interstitial cells appeared devoid of TR mRNA signals.
From these results it can be concluded that the human testis exclusively expresses TRα, which is localized in Sertoli cells, TRβ being always undetectable. Fetal and prepubertal ages represent the period of maximal expression of TRα1 and TRα2. Theα 2/α1 ratio rises dramatically after development. These results confirm a critical window for the action of thyroid hormone in human testis, in the period of maximal expression of T3 binding isoform TRα1, and may account for the macroorchidism without virilization occurring when hyposecretion of thyroid hormones occurs before puberty.