bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parathyroid MEN1 Gene Mutations in Relation to Clinical Characteristics of Nonfamilial Primary Hyperparathyroidism1
Authors: Carling Tobias , Correa Pamela , Hessman Ola , Hedberg Jakob , Skogseid Britt , Lindberg Daniel , Rastad Jonas , Westin Gunnar , Åkerström Göran 
Published: January 2014

abstract
Biochemical signs and severity of symptoms of primary hyperparathyroidism (pHPT) differ among patients, and little is known of any coupling of clinical characteristics of nonfamilial pHPT to genetic abnormalities in the parathyroid tumors. Mutations in the recently identified MEN1 gene at chromosome 11q13 have been found in parathyroid tumors of nonfamilial pHPT. Using microsatellite analysis for loss of heterozygosity (LOH) at 11q13 and DNA sequencing of coding exons, the MEN1 gene was studied in 49 parathyroid lesions of patients with divergent symptoms, operative findings, histopathological diagnosis, and biochemical signs of nonfamilial pHPT. Allelic loss at 11q13 was detected in 13 tumors, and 6 of them demonstrated previously unrecognized somatic missense and frameshift deletion mutations of the MEN1 gene. Many of the detected mutations would most likely result in a nonfunctional menin protein, consistent with a tumor suppressor mechanism. Clinical and biochemical characteristics of HPT were apparently unrelated to the presence or absence of LOH and the MEN1 gene mutations. However, the demonstration of LOH at 11q13 and MEN1 gene mutations in small parathyroid adenomas of patients with slight hypercalcemia and normal serum PTH levels suggest that altered MEN1 gene function may also be important for the development of mild sporadic pHPT.
Gestational Changes in the Levels of Transforming Growth Factor-β1 (TGFβ1) and TGFβ Receptor Types I and II in the Human Myometrium1
Authors: Hatthachote Panadda , Morgan Joanna , Dunlop William , Europe-Finner G. Nicholas , Gillespie James I. 
Published: January 2014

abstractAs term approaches, a number of key proteins [contraction-associated proteins (CAPs)] are expressed within the human myometrium that are essential for the activation of powerful coordinated contractions during labor. The nature of the signals that switch on the synthesis of CAPs in vivo is not known. The ryanodine-sensitive intracellular Ca2+ release channel (RyR2) is a CAP whose expression in vitro is activated by transforming growth factor-β (TGFβ). The present experiments were performed to determine whether TGFβ and TGFβ receptors are present in the human myometrium at term and to explore the idea that they might form part of a signaling system in vivo. TGFβ receptor types I and II, but not III, were demonstrated in myometrial smooth muscle in tissue taken from nonpregnant, pregnant nonlaboring, and spontaneous laboring women. Western blotting was used subsequently to determine the relative expression of TGFβ receptor types I and II. Using nonpregnant myometrium as a baseline control the levels of expression of receptor types I and II were significantly increased by 168 ± 19% (n = 6) and 162 ± 22% (n = 7) in pregnant nonlaboring myometrium. In spontaneous laboring myometrium the levels of TGFβ receptor type I and II expression were 93 ± 12% (n = 6) and 85 ± 11% (n = 7), respectively, compared to nonpregnant control values and were significantly lower than levels in pregnant nonlaboring tissues. The total TGFβ1 levels in the myometrial tissues were 334 ± 10, 534 ± 73, and 674 ± 106 pg/g tissue wet wt in nonpregnant, pregnant nonlaboring, and spontaneous laboring myometrium (n = 3 in each group), respectively. Thus, the TGFβ signaling system appears to be up-regulated in the myometrium before the onset of parturition. The apparent loss of receptors in the spontaneous laboring samples in the presence of elevated total levels of TGFβ may be indicative of agonist-induced receptor down-regulation. These observations support the idea that cytokines, in particular TGFβ1, may play a role in the normal processes that prepare the myometrium for parturition at term.
Insulin-Like Growth Factor Binding Protein-3: A Novel Biomarker for the Assessment of the Synthetic Capacity of Hepatocytes in Liver Cirrhosis
Authors: Shaarawy Mohamed , Fikry Mohamed Amin , Massoud Baher Aly , Lotfy Samar 
Published: January 2014

The liver is the major source of circulating insulin-like growth factor binding protein-3 (IGFBP-3). Because the hepatic tissue is deranged in cirrhotic patients, we measured serum IGFBP-3 concentrations by two-site immunoradiometric assay in sera from 37 cirrhotic patients with different stages of hepatic dysfunction. These were compared with IGFBP-3 levels from 11 healthy controls. Serum IGFBP-3 levels in patients with chronic liver disease were significantly lower than those of the control group (P &lt; 0.0005). The mean percent decrease in cases of early liver cirrhosis, cirrhosis without, and cirrhosis with ascites were 44%, 59%, and 82% respectively, indicating that serum IGFBP-3 levels decrease as the severity of hepatic dysfunction increases.Moreover, the decrease was more pronounced in cases with hyperbilirubinemia, elevated serum transaminases, hypoalbuminemia, and prolonged prothrombin time. There was a significant positive correlation between serum IGFBP-3 and serum albumin, as well as a significant negative correlation between serum IGFBP-3 and prothrombin time. These results indicate the close correlation of IGFBP-3 levels to worsening of hepatic functions. The determination of serum IGFBP-3 level is a clinically useful marker for the assessment of the synthetic capacity of hepatocytes in cirrhotic patients and an early predictor of impending hepatic dysfunction as well. .
Serum Leptin Levels Correlate with Growth Hormone Secretion and Body Fat in Children*
Authors: Fors Hans , Matsuoka Hisafumi , Bosaeus Ingvar , Rosberg Sten , Wikland Kerstin Albertsson , Bjarnason Ragnar 
Published: January 2014

AbstractThe aim of this study was to investigate the relationship among GH secretion, leptin concentrations, and body composition measured with x-ray absorptiometry (DXA) in children. In total, 71 children were investigated, 51 males and 20 females. Their mean chronological age was 10.8 yr (range, 6.2–17.7 ys), and their mean height (sd) was −2.1 (0.63) sd scores. Their mean weight for height sd scores (WHSDS) was 0.2 (1.18). Body composition was investigated using DXA. Blood samples were taken for analysis of leptin, insulin-like growth factor I (IGF-I), IGF-binding protein-3, and 24-h GH secretion. A positive correlation was found between leptin and total body fat (r = 0.83; P&lt; 0.0001) and when fat was expressed as a percentage of body weight (r = 0.86; P &lt; 0.0001). There were significant (P &lt; 0.0001) relationships between leptin and WHSDS (r = 0.45) and between leptin and body mass index (r = 0.69). A significant gender difference in leptin levels was found, but this disappeared after adjustment for body fat, as measured by DXA. There were significant (P&lt; 0.001) inverse correlations between leptin and the AUCb for GH (r = −0.41), leptin, and GHmax (r =− 0.38), where AUCb is the area under the curve above the calculated baseline, and GHmax is the maximum peak during the 24-h GH profile (percent fat and AUCb for GH, r =− 0.43; percent fat and GHmax, r = −0.39). In a multiple stepwise forward regression analysis with leptin as the dependent variable, the percent trunk fat accounted for 77.7% of the leptin variation. With AUCb for GH as the dependent variable, the percent trunk fat accounted for 20.3% of the variation. With GHmax as the dependent variable, the percent trunk fat accounted for 18.8% of the variation, IGF-binding protein-3 for another 8.5%, and the percentage of fat from arms and legs for another 4.4%.We demonstrated a strong positive correlation between leptin levels and body fat, a significant negative correlation between leptin levels and GH secretion, and a significant negative correlation between body fat and GH secretion. We have also shown that specific regional fat depots have different relationships with leptin and particular markers of GH secretion.
A Possible Role of Immunoglobulin E in Patients with Hyperthyroid Graves’ Disease
Authors: Sato Akira , Takemura Yoshihiro , Yamada Takashi , Ohtsuka Hiromi , Sakai Hideki , Miyahara Yasuhiro , Aizawa Toru , Terao Akira , Onuma Soshin , Junen Kazuhiro , Kanamori Akira , Nakamura Yutaka , Tejima Eizaburo , Ito Yoshiharu , Kamijo Keiichi 
Published: January 2014

Abstract
To investigate the possible participation of immunoglobulin E (IgE) in the autoimmune process of Graves’ disease, incidence of elevation of serum IgE level, TSH receptor antibody (TRAb), and thyroid status were studied in 66 patients with hyperthyroid Graves’ disease, 54 patients with Hashimoto’s thyroiditis, 19 patients with bronchial asthma, and 15 patients with pollen allergy. In hyperthyroid Graves’ patients, elevation of serum IgE levels (≥170 U/mL) was found in 19 of 66 patients (29%), 11 of whom had hereditary and/or allergic conditions. Elevations of serum IgE levels were found in 63% of patients with bronchial asthma and in 40% of patients with pollen allergy. Mean values of serum IgE were the same in patients with hyperthyroid Graves’ disease and with bronchial asthma. During methimazole treatment TRAb decreased without fluctuation of IgE levels in both groups. The decrease in TRAb was significantly greater in patients with normal IgE than in patients with IgE elevation. After prednisone administration, reduction in TRAb was greater in patients with normal IgE than that in patients with IgE elevation.
High incidence of IgE elevation in hyperthyroid Graves’ disease and slower reduction in TRAb in association with IgE elevation suggest a difference in the autoimmune processes in Graves’ disease with and without elevation of IgE.
Two Polymorphisms in the Peroxisome Proliferator-Activated Receptor-γ Gene Are Associated with Severe Overweight among Obese Women*
Authors: Valve R. , Sivenius K. , Miettinen R. , Pihlajamäki J. , Rissanen A. , Deeb S. S. , Auwerx J. , Uusitupa M. , Laakso M. 
Published: January 2014

Abstract
Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor that regulates adipocyte differentiation. Variations in the PPARγ gene may affect the function of the PPARγ and, therefore, body adipocity. We investigated the frequencies of the Pro12Ala polymorphism in exon B and the silent CAC478CAT polymorphism in exon 6 of the PPARγ gene and their effects on body weight, body composition, and energy expenditure in obese Finns. One hundred and seventy obese subjects [29 men and 141 women; body mass index (BMI), 35.7 ± 3.8 kg/m2; age, 43 ± 8 yr; mean ± sd) participated in the study. The frequencies of the Ala12 allele in exon B and CAT478 allele in exon 6 were not significantly different between the obese and population-based control subjects (0.14 vs. 0.13 and 0.19 vs. 0.21, respectively). The polymorphisms were associated with increased BMI [Pro12Pro, 34.5 ± 3.8; Pro12Ala, 34.8 ± 3.1; Ala12Ala, 39.2± 4.6 kg/m2 (P = 0.011); CAC478CAC, 34.5 ± 3.8; CAC478CAT, 34.5 ± 3.3; CAT478CAT, 37.7 ± 4.1 kg/m2 (P = 0.046)]. In addition, the women with both Ala12Ala and CAT478CAT genotypes (n = 5) were significantly more obese compared with the women having both Pro12Pro and CAC478CAC genotypes (n = 85; BMI, 40.6 ± 3.3 vs. 34.4 ± 3.9 kg/m2; P = 0.001), and they had increased fat mass (46.8 ± 9.1 vs. 36.8 ± 7.5 kg; P = 0.005). In conclusion, the Pro12Ala and CAC478CAT polymorphisms in the PPARγ gene are associated with severe overweight and increased fat mass among obese women.
Food-Dependent Cushing’s Syndrome: Possible Involvement of Leptin in Cortisol Hypersecretion*
Authors: Pralong François P. , Gomez Fulgencio , Guillou Louis , Mosimann François , Franscella Sebastiano , Gaillard Rolf C. 
Published: January 2014

Abstract
Stimulation of cortisol secretion by food intake has been implicated in the pathogenesis of some cases of ACTH-independent Cushing’s syndrome, via an aberrant response of the adrenal glands to gastric inhibitory polypeptide (GIP). We report here a novel case of food-dependent Cushing’s syndrome in a patient with bilateral macronodular adrenal hyperplasia. In this patient we were able to confirm a paradoxical stimulation of cortisol secretion by GIP in vivo as well as in vitro on dispersed tumor adrenal cells obtained at surgery. In addition to GIP, in vitro stimulation of these cultured tumor adrenal cells with leptin, the secreted product of the adipocyte, induced cortisol secretion. By comparison, no such stimulation was observed in vitro in adrenal cells obtained from another patient with bilateral macronodular adrenal hyperplasia and Cushing’s syndrome that did not depend on food intake, in tumor cells obtained from a solitary cortisol-secreting adrenal adenoma, and in normal human adrenocortical cells.
These results demonstrate that as in previously described cases of food-dependent Cushing’s syndrome, GIP stimulated cortisol secretion from the adrenals of the patient reported here. Therefore, they indicate that such a paradoxical response probably represents the hallmark of this rare condition. In addition, they suggest that leptin, which normally inhibits stimulated cortisol secretion in humans, participated in cortisol hypersecretion in this case. Further studies in other cases of food-dependent Cushing’s syndrome, however, will be necessary to better ascertain the pathophysiological significance of this finding.
Aromatase Deficiency Caused by a Novel P450arom Gene Mutation: Impact of Absent Estrogen Production on Serum Gonadotropin Concentration in a Boy1
Authors: Deladoëy Johnny , Flück Christa , Bex Marie , Yoshimura Noriko , Harada Nobuhiro , Mullis Primus E. 
Published: January 2014

We identified a new point mutation in the CYP19 gene responsible for aromatase (P450arom) deficiency in a 46,XY male infant with unremarkable clinical findings at birth. This boy is homozygote for a 1-bp (C) deletion in exon 5 of the aromatase gene causing a frame-shift mutation. The frame-shift results in a prematurely terminated protein that is inactive due to the absence of the functional regions of the enzyme.Aromatase deficiency was suspected prenatally because of the severe virilization of the mother during the early pregnancy, and the diagnosis was confirmed shortly after birth. Four weeks after birth, the baby boy showed extremely low levels of serum estrogens, but had a normal level of serum free testosterone; in comparison with the high serum concentration of androstenedione at birth, a striking decrease occurred by 4 weeks postnatally. We previously reported elevated basal and stimulated FSH levels in a female infant with aromatase deficiency in the first year of life. In contrast, in the male infant, basal FSH and peak FSH levels after standard GnRH stimulation tests were normal. This finding suggests that the contribution of estrogen to the hypothalamic-pituitary gonadotropin-gonadal feedback mechanism is different in boys and girls during infancy and early childhood. In normal girls, serum estradiol concentrations strongly correlate with circulating inhibin levels, and thus, low inhibin levels may contribute to the striking elevation of FSH in young girls with aromatase deficiency. In contrast, estradiol levels are physiologically about a 7-fold lower in boys than in girls, and serum inhibin levels remain elevated even though levels of FSH, LH, and testosterone are decreased.
Serum Leptin Concentrations and Expression of Leptin Transcripts in Placental Trophoblast with Advancing Baboon Pregnancy1
Authors: Henson Michael C. , Castracane V. Daniel , O’Neil Jennifer S. , Gimpel Terry , Swan Kenneth F. , Green Amy E. , Shi Wenliang 
Published: January 2014

Leptin is a polypeptide hormone originally thought to be produced exclusively by adipocytes. Recently, however, both leptin messenger ribonucleic acid (mRNA) and leptin protein were identified in human placental trophoblast cells, suggesting a potential role in primate pregnancy. In the present study, venous blood samples were collected at 5-day intervals during gestation from baboons (Papio sp), an established model for the study of human pregnancy, as well as from nonpregnant baboons, and leptin concentrations were determined by RIA. Additionally, placental villous tissue was collected upon cesarean delivery at early (days 60–62; n = 5), mid (days 98–102; n= 5), and late (days 159–167; n = 5) gestation (term = ∼184 days), and leptin mRNA was quantitated by competitive RT-PCR. Finally, in situ hybridization was employed to localize transcripts to specific placental cell types. Results determined that maternal leptin levels (mean ± sem), which were dramatically greater (P &lt; 0.01) than those in nonpregnant cycling baboons (1.4 ± 0.1 ng/mL), increased (P &lt; 0.005) with gestational age from 63.6 ± 10.4 ng/mL on day 60 of gestation to 157.8 ± 16.1 near term. Levels declined to those found in cycling baboons by 15 days postdelivery. In contrast to maternal leptin concentrations, placental leptin mRNA decreased (P &lt; 0.02) with advancing pregnancy, as transcript abundance declined approximately 8-fold from early to late gestation. Maternal peripheral leptin concentrations were positively correlated (r = 0.66; P &lt; 0.001) whereas placental leptin mRNA levels were negatively correlated (r= −0.64; P &lt; 0.01) with gestational age. Expression of leptin mRNA transcripts, as evidenced by RT-PCR in villous tissue, was localized principally within syncytiotrophoblast by in situ hybridization.
In summary, changes in maternal peripheral leptin concentrations and placental leptin mRNA abundance that occur commensurate with advancing gestational age may imply evolving roles for the polypeptide with advancing primate pregnancy. In this capacity, localization of leptin transcripts within the baboon syncytiotrophoblast suggests the potential for autocrine or paracrine interactions within this endocrinologically active tissue. Finally, both the similarities in leptin ontogeny in baboon and human pregnancy and the singular enhancement of maternal leptin levels inherent throughout baboon gestation emphasize the potential of this nonhuman primate model for the study of leptin action in the maternal-fetoplacental unit.
Effects of Intranasal 17β-Estradiol on Bone Turnover and Serum Insulin-Like Growth Factor I in Postmenopausal Women
Authors: Garnero Patrick , Tsouderos Yannis , Marton Istvan , Pelissier Clara , Varin Claire , Delmas Pierre D. 
Published: January 2014

Estrogen therapy, using either oral or transdermal routes, decreases bone turnover and prevents postmenopausal bone loss. It has been suggested that oral and transdermal 17β-estradiol (E2) may have different effects on serum insulin-like growth factor I (IGF-I), a potent bone-forming growth factor. In this study we investigated the effects of a new route of administration, the intranasal E2 spray (S21400), on bone turnover and circulating IGF-I and IGF-binding protein-3 (IGFBP-3). Four hundred and twenty early postmenopausal women (&lt;5 yr since menopause; mean age, 52 yr) were enrolled in a 3-month, double blind, placebo-controlled study of four doses of intranasal E2 (100, 200, 300, and 400μ g/day), two doses of oral E2 valerate (1 or 2 mg/day), and placebo. One hundred and twelve women were further treated for 12 months with intranasal E2 (300 μg/day, i.e. the dose that has been shown to be adequate for the majority of postmenopausal women). Markers of bone resorption (urinary type I collagen C telopeptides) and formation [serum osteocalcin, serum type I collagen N-terminal extension propeptide (PINP), and serum bone alkaline phosphatase (BAP)] were measured at baseline, 1 month, 3 months, and 15 months. Serum IGF-I and IGFBP-3 were measured at baseline, 1 month, and 3 months. Urinary type I collagen C telopeptides decreased significantly in all active treatment groups as soon as 1 month (P &lt; 0.001 vs. placebo) and continued to decrease at 3 months with a dose effect for intranasal E2. Serum osteocalcin and PINP did not change at 1 month for oral E2 (1 and 2 mg), but decreased significantly at 3 months. In contrast, formation markers increased significantly at 1 month for the two highest doses of intranasal E2 (P &lt; 0.01 vs. placebo for osteocalcin and BAP) and did not decrease at 3 months. Oral E2 induced a marked decrease in circulating IGF-I as early as 1 month, which was amplified at 3 months (−29% and −32% for 1 and 2 mg, respectively), whereas no significant change from placebo was observed for intranasal E2 during the 3-month period. Changes in circulating IGF-I correlated significantly (P &lt; 0.01) with changes in osteocalcin, PINP, and BAP at 3 months. Oral and intranasal E2 did not induce any significant change from placebo in serum IGFBP-3 at both 1 and 3 months. After 1 yr of treatment with intranasal E2 (300μ g/day), both resorption and formation markers decreased, reaching the levels in premenopausal women, regardless of the type of treatment during the first 3 months.We conclude that E2 administered by this new nasal route normalizes bone turnover to premenopausal levels. The delayed decrease in bone formation observed with intranasal E2 compared to oral E2 may be related to different effects on serum IGF-I levels.
Heritability of Prostate-Specific Antigen and Relationship with Zonal Prostate Volumes in Aging Twins*
Authors: Bansal Aruna , Murray Darrell K. , Wu James T. , Stephenson Robert A. , Middleton Richard G. , Meikle A. Wayne 
Published: January 2014

AbstractBoth benign prostatic hyperplasia and prostate-specific antigen (PSA) have been shown to increase with age and with prostate volume in men, but the influence of heredity on these relationships is not completely understood. This study has two aims: 1) to investigate the inter-relationships of age, PSA, and various zonal measurements in the prostate; and 2) to assess the impact of heritable influences on total PSA. Eighty-four monozygotic twin pairs and 83 dizygotic twin pairs were studied, and serum total PSA, free PSA, and PSA-∝1-antichymotrypsin were measured. Their prostate volumes [total (TV), transition zone (TZ), and peripheral zone) were quantitated using transrectal ultrasound.Total PSA is significantly correlated with all zonal prostate measurements (TZ, peripheral zone, TV, and TZ/TV) and with age. When linear regression was applied, only age and TZ were retained in the final model. The proportion of variability in total PSA explained by these two factors, however, is below 24%. In contrast, estimates of heritability show that approximately 45% of the variability in total PSA can be explained by inherited factors. Whereas age and TZ are linearly related to total PSA, their influence is much less than that of familial and genetic factors. It is uncertain whether these factors predispose also to prostate cancer or if they are independent of those, whether they confound the accuracy of using total serum PSA level as a diagnostic tool.