bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrittene, Homologous with Somatostatin-28(1–13), Is a Novel Peptide in Mammalian Gut and Circulation
Authors: Ensinck John W. , Baskin Denis G. , Vahl Torsten P. , Vogel Robin E. , Laschansky Ellen C. , Francis Bruce H. , Hoffman Ross C. , Krakover Jonathan D. , Stamm Michael R. , Low Malcolm J. , Rubinstein Marcelo , Otero-Corchon Veronica , D’Alessio David A. 
Published: January 2014

AbstractPreprosomatostatin is a gene expressed ubiquitously among vertebrates, and at least two duplications of this gene have occurred during evolution. Somatostatin-28 (S-28) and somatostatin-14 (S-14), C-terminal products of prosomatostatin (ProS), are differentially expressed in mammalian neurons, d cells, and enterocytes. One pathway for the generation of S-14 entails the excision of Arg13-Lys14 in S-28, leading to equivalent amounts of S-28(1–12). Using an antiserum (F-4), directed to the N-terminal region of S-28 that does not react with S-28(1–12), we detected a peptide, in addition to S-28 and ProS, that was present in human plasma and in the intestinal tract of rats and monkeys. This F-4 reacting peptide was purified from monkey ileum; and its amino acid sequence, molecular mass, and chromatographic characteristics conformed to those of S-28(1–13), a peptide not described heretofore. When extracts of the small intestine were measured by RIA, there was a discordance in the ratio of peptides reacting with F-4 and those containing the C terminus of ProS, suggesting sites of synthesis for S-28(1–13) distinct from those for S-14 and S-28. This was supported by immunocytochemistry, wherein F-4 reactivity was localized in gastrointestinal (GI) endocrine cells and a widespread plexus of neurons within the wall of the distal gut while immunoreactivity to C-terminal domains of S-14 and S-28 in these neurons was absent. Further, F-4 immunoreactivity persisted in similar GI endocrine cells and myenteric neurons in mice with a targeted deletion of the preprosomatostatin gene. We believe that these data suggest a novel peptide produced in the mammalian gut, homologous with the 13 residues of the proximal region of S-28 but not derived from the ProS gene. Pending characterization of the gene from which this peptide is derived, its distribution, and function, we have designated this peptide as thrittene. Its localization in both GI endocrine cells and gut neurons suggests that thrittene may function as both a hormone and neurotransmitter.
High Glucose Stimulates Angiotensinogen Gene Expression via Reactive Oxygen Species Generation in Rat Kidney Proximal Tubular Cells
Authors: Hsieh Tusty-Jiuan , Zhang Shao-Ling , Filep Janos G. , Tang Shiow-Shih , Ingelfinger Julie R. , Chan John S. D. 
Published: January 2014

AbstractThe present studies investigated whether the effect of high glucose levels on angiotensinogen (ANG) gene expression in kidney proximal tubular cells is mediated via reactive oxygen species (ROS) generation and p38 MAPK activation. Rat immortalized renal proximal tubular cells (IRPTCs) were cultured in monolayer. Cellular ROS generation and p38 MAPK phosphorylation were assessed by lucigenin assay and Western blot analysis, respectively. The levels of immunoreactive rat ANG secreted into the media and cellular ANG mRNA were determined by a specific RIA and RT-PCR, respectively. High glucose (25 mm) evoked ROS generation and p38 MAPK phosphorylation as well as stimulated immunoreactive rat ANG secretion and ANG mRNA expression in IRPTCs. These effects of high glucose were blocked by antioxidants (taurine and tiron), inhibitors of mitochondrial electron transport chain complex I (rotenone) and II (thenoyltrifluoroacetone), an inhibitor of glycolysis-derived pyruvate transport into mitochondria (α-cyano-4-hydroxycinnamic acid), an uncoupler of oxidative phosphorylation (carbonyl cyanide m-chlorophenylhydrazone), a manganese superoxide dismutase mimetic, catalase, and a specific inhibitor of p38 MAPK (SB 203580), but were not affected by an inhibitor of the malate-aspartate shuttle (aminooxyacetate acid). Hydrogen peroxide (≥10−5m) also stimulated p38 MAPK phosphorylation, ANG secretion, and ANG mRNA gene expression, but its stimulatory effect was blocked by catalase and SB 203580. These studies demonstrate that the stimulatory action of high glucose on ANG gene expression in IRPTCs is mediated at least in part via ROS generation and subsequent p38 MAPK activation.
Loss of the C Terminus of Melanocortin Receptor 2 (MC2R) Results in Impaired Cell Surface Expression and ACTH Insensitivity
Authors: Hirsch Andrea , Meimaridou Eirini , Fernandez-Cancio Monica , Pandey Amit V. , Clemente María , Audi Laura , Clark Adrian J. L. , Flück Christa E. 
Published: January 2014

Objective: Mutations in melanocortin receptor 2 (MC2R) and its related melanocortin receptor accessory protein (MRAP) cause familial glucocorticoid deficiency. We identified a novel MC2R mutation, K289fs. This unique mutation in the C terminus of MC2R is located in the intracellular part of the protein for which the exact function is unknown.
Setting: A 6-wk-old boy presented with severe hypoglycemia, unmeasurable cortisol, and grossly elevated ACTH but normal electrolytes. Genetic analysis revealed homozygote K289fs mutation in MC2R. His parents and siblings were heterozygous but phenotypically normal.
Intervention and Results: The role of the C terminus of MC2R was studied in two cell systems. Because the K289fs mutant changes the last eight amino acids of the protein and leads to protein elongation, wild-type MC2R and C-terminally mutated constructs were tested for activity to respond to ACTH in an OS3 cell-based reporter assay. Wild-type and alanine-substituted constructs responded normally to ACTH. By contrast K289fs and M290X had a total loss of activity. Cell surface assays and confocal localization studies revealed that K289fs and M290X receptors were not found at the cell surface, indicating that their transport from the endoplasmic reticulum to the cell membrane is disrupted. Interestingly, coimmunoprecipitation experiments showed no alteration in the interaction of mutant MC2R with MRAP, suggesting that interaction between these two proteins does not guarantee normal localization.
Conclusions: Loss of the C terminus of MC2R impairs cell surface expression and ACTH sensitivity but does not disrupt interaction of MC2R with MRAP. These findings highlight the extreme sensitivity of MC2R to structural disruption.
Profiling of Endogenous Estrogens, Their Precursors, and Metabolites in Endometrial Cancer Patients: Association with Risk and Relationship to Clinical Characteristics
Authors: Audet-Walsh Étienne , Lépine Johanie , Grégoire Jean , Plante Marie , Caron Patrick , Têtu Bernard , Ayotte Pierre , Brisson Jacques , Villeneuve Lyne , Bélanger Alain , Guillemette Chantal 
Published: January 2014

Background: Endometrial cancer (EC) predominantly occurs after menopause and is strongly related to steroid hormones, particularly estrogens. However, the relationship between these hormones and clinical characteristics remains unaddressed.
Experimental Design: We analyzed the circulating levels of 18 steroids including adrenal precursors, androgens, estrogens, and their glucuronide metabolites, using specific and validated methods based on tandem mass spectrometry. Our goals were to compare circulating levels in postmenopausal women with EC (n = 126) with those of healthy postmenopausal women (n = 110) and to investigate how these hormonal levels relate to clinical characteristics.
Results: After adjustment for potential confounders, most hormones were significantly elevated in EC patients compared with healthy controls. In women with type I cancer, estrogen levels were up to 3-fold those of healthy women (P &lt; 0.05). These higher levels were associated with an increased risk of cancer, particularly estrogens and their direct precursors, testosterone and androstenedione (odds ratios ranging from 4.4 to 13.3; P ≤ 0.0003). Elevated circulating levels of estrogens and their metabolites were found in cancer cases with type I endometrioid cancer and low-grade and noninvasive tumor, suggesting an association between these hormones and the tumoral estrogenic activity. In addition, levels of estrone sulfate in EC patients with relapse were 2-fold over levels of EC patients without relapse (P &lt; 0.05), and 4.5-fold over those of healthy women (P &lt; 0.001).
Conclusions: Circulating levels of steroids were associated with increased risk of EC. Estrogens may represent novel biomarkers predictive of clinical characteristics, including evidence for an increased risk of relapse.
Sex Differences in Lipid and Lipoprotein Metabolism: It's Not Just about Sex Hormones
Authors: Wang Xuewen , Magkos Faidon , Mittendorfer Bettina 
Published: January 2014

Abstract
It is commonly thought that sex hormones are important regulators of plasma lipid kinetics and are responsible for sexual dimorphism in the plasma lipid profile. Here we discuss the findings from studies evaluating lipid and lipoprotein kinetics in men and women in the context of what we know about the effects of exogenous sex hormone administration, and we conclude that it is more complicated than that. It has become clear that normal physiological alterations in the hormonal milieu (i.e. due to menopause or throughout the menstrual cycle) do not significantly affect plasma lipid homeostasis. Furthermore, parenterally administered estrogens have either no effect or only very small beneficial effects, whereas orally administered estrogens raise plasma triglyceride concentrations—a phenomenon that is not consistent with the observed sex differences and likely results from the hepatic “first-pass effect.” The effects of progestogens and androgens mimic only in part the differences in plasma lipids between men and women. Thus, the underlying physiological modulators of plasma lipid metabolism responsible for the differences between men and women remain to be elucidated.
Prevalence of Goiter and Urinary Iodine Excretion Levels in Children Around Chernobyl*
Authors: Ashizawa Kiyoto , Shibata Yoshisada , Yamashita Shunichi , Namba Hiroyuki , Hoshi Masaharu , Yokoyama Naokata , Izumi Motomori , Nagataki Shigenobu 
Published: January 2014

Abstract
The prevalence of goiter among children living in areas affected by the Chernobyl accident was investigated by analysis of data on approximately 120,000 children examined at five medical diagnostic centers in Belarus, Russia, and the Ukraine. Examinations of thyroid gland were conducted with an arch-automatic ultrasonographic instrument at the five centers under the same protocol. The diagnosis of goiter was established when the thyroid volume exceeded a limit calculated from age, height, and body weight of a child. A considerable variation by region was noted in the prevalence of goiter. Highest in the Kiev region, the prevalence in the five regions was 54% in Kiev, 38% in the Zhitomir regions of the Ukraine, 18% in Gomel, 22% in the Mogilev regions of Belarus, and 41% in the Bryansk region of Russia. Urinary iodine content was measured in approximately 5700 children, and an endemic iodine deficient zone was confirmed in the Bryansk, Kiev, and Zhitomir regions. A significant negative correlation was observed between the prevalence of goiter and the median level of urinary iodine content (Spearman’s rank correlation coefficient was −0.35, P = 0.025).
Increase in Plasma Thyrotropin Levels in Hypothyroid Patients during Treatment due to a Defect in the Commercial Preparation
Authors: Peran S. , Garriga M. J. , Morreale de Escobar G. , Asunción M. , Peran M. 
Published: January 2014

Abstract
Around mid-1995, the Molecular Endocrinology Laboratory of the Regional Hospital (Malaga, Spain) began detecting an increase in TSH levels in the serum of patients under study to control the treatment of hypothyroidism with levothyroxine. Over a period of 5 months, of a total of 467 hypothyroid patients treated with Levothroid, 53% had TSH levels higher than 6 μU/mL. The reliability of the biochemical results was verified by duplicating 56 randomly chosen samples from all those with high TSH levels and by an external control performed in four different laboratories. The amount of levothyroxine in the tablets was analyzed by RIA, high performance liquid chromatography, and their iodine contents. The lowest levels of levothyroxine found in the 50-μg Levothroid tablets were those determined by RIA, with a mean value of 32.3 μg, resulting in a 35.3% loss of activity. The mean value of levothyroxine found in these same tablets by high performance liquid chromatography was 39.3 μg, amounting to a 21.3% loss in activity. The iodine showed no significant loss in these tablets, with a mean experimental value of 48 μg. The commercial laboratory withdrew lot J from the market, the one in which these deficiencies were found.
Keratinocyte Growth Factor Expression in the Mesenchymal Cells of Human Amnion*
Authors: Casey M. Linette , MacDonald Paul C. 
Published: January 2014

AbstractAmnion epithelial and mesenchymal cells were separated by differential protease treatment, and the separated cells were maintained in monolayer culture. Keratinocyte growth factor (KGF) messenger RNA (mRNA) was readily detected by Northern analysis of amnion mesenchymal cell total RNA (10 μg) but not in amnion epithelial cells. Treatment of the amnion mesenchymal cells in serum-free medium with tetradecanoyl phorbol acetate (1 nm) caused an increase in the level of KGF mRNA. Forskolin treatment also caused an increase in KGF mRNA but not to the levels attained with tetradecanoyl phorbol acetate treatment. Dexamethasone (1 nm) treatment of these cells effected a reduction in the level of KGF mRNA. Prolonged maintenance of mesenchymal cells in serum-free medium also was associated with an increase in the level of KGF mRNA. Treatment with a variety of other agents, viz., interleukin (IL)-1, IL-6 plus or minus IL-6 soluble receptor, IL-11, oncostatin M , epidermal growth factor (EGF), and transforming growth factor-β did not modify the level of KGF mRNA. Treatment of amnion epithelial cells with KGF caused an increase in the rate of [3H]thymidine incorporation, but the rate of cell replication induced by KGF was less than that induced by treatment with EGF. Transforming growth factor-β treatment inhibited basal and EGF- and KGF-stimulated amnion epithelial cell replication. The findings of this study are indicative that KGF is expressed in human amnion mesenchymal cells, and that KGF may act on the epithelial cells of this tissue.
The Localization of Androgen Receptors in Human Bone
Authors: Abu E. O. , Horner A. , Kusec V. , Triffitt J. T. , Compston J. E. 
Published: January 2014

Abstract
Androgens have important effects on the human skeleton, and deficiency has been associated with bone loss in both males and females. The skeletal actions of androgens may be mediated directly via the androgen receptor (AR) or indirectly via the estrogen receptor after aromatization to estrogens. The presence of androgen receptors has been demonstrated in bone cells and chondrocytes in vitro, but their presence in human bone in situ has not been reported. In order to provide further evidence for a direct action of androgens on bone via androgen receptors, we have used specific monoclonal antibodies to investigate the expression of human AR in normal developing and osteophytic bone of both sexes.
In the growth plates from the developing bone, androgen receptors were predominantly expressed in hypertrophic chondrocytes and in osteoblasts at sites of bone formation. They were also observed in osteocytes in the bone, and in mononuclear cells and endothelial cells of blood vessels within the bone marrow. In the osteophytes, androgen receptors were widely distributed at sites of endochondral ossification in proliferating, mature, and hypertrophic chondrocytes and at sites of bone remodeling in osteoblasts. They were also expressed in osteocytes and mononuclear cells within the bone marrow. The pattern and number of cells expressing the receptor was similar in both sexes.
Our results show for the first time the presence and distribution of androgen receptors in normal developing human and osteophytic bone in situ and further provide evidence for a direct action of androgens on bone and cartilage cells.
Long-Term and Low-Dose Treatment with Cabergoline Induces Macroprolactinoma Shrinkage
Authors: Colao Annamaria , Di Sarno Antonella , Landi Maria Luisa , Cirillo Sossio , Sarnacchiaro Francesca , Facciolli Giuseppina , Pivonello Rosario , Cataldi Mauro , Merola Bartolomeo , Annunziato Lucio , Lombardi Gaetano 
Published: January 2014

Cabergoline (CAB), a long-lasting dopamine-agonist, specific for the D2 receptor, is effective in normalizing serum PRL levels in most patients with microprolactinoma or idiopathic hyperprolactinemia. Because few data are presently available on the effects of CAB treatment in macroprolactinomas, the aim of this open-label study was to investigate whether this drug was effective in producing tumor shrinkage, as well as in normalizing PRL levels.
Twenty-three patients with macroprolactinoma entered this study: 15 patients had had no treatment, whereas the remaining 8 patients had been previously treated with bromocriptine, which was withdrawn because of intolerance. Three of 23 patients had undergone unsuccessful surgery. Pretreatment serum PRL levels ranged from 100-3860 μg/L.
CAB was administered at a dose of 0.5–3 mg once or twice a week for 12–24 months. Magnetic resonance imaging (MRI) scans were performed before and 3, 6, 12, and 24 months after the beginning of treatment, to evaluate tumor shrinkage, defined as a decrease of at least 80% of baseline tumor volume.
After 3–6 months of treatment with a low dose (0.5–1 mg/week), serum PRL levels normalized in 18 patients. In the remaining 5 patients, whose serum PRL levels were not normalized, the dose was increased to 2–3 mg/week. This schedule caused the normalization of PRL levels in 1 patient, whereas in the remaining 4 patients, PRL levels were reduced to 30–82 μg/L. A tumor volume reduction greater than 80% at MRI occurred in 14 of 23 patients (61%) after CAB treatment (from 2609.4 ± 534.7 to 530.1 ± 141.3 mm3 at the 12–24th month follow-up, P &lt; 0.001). A volume reduction of 41.8 ± 3.4% was already evident after 3 months (1436 ± 285.9 mm3; P &lt; 0.001). The complete disappearance of the tumor mass at MRI occurred after 6 months of treatment with CAB in 1 patient, and in 5 patients after 1 yr of treatment. An improvement of visual field defects was obtained in 9 of the 10 patients presenting visual impairment before CAB treatment. The drug was tolerated well by all patients. Only 1 patient experienced mild nausea, which disappeared spontaneously after the 2nd day of treatment.
Long-term, a low dose of the D2 receptor agonist CAB significantly reduced tumor volume and normalized serum PRL levels in a great majority of patients bearing macroprolactinoma. This treatment met with excellent patient compliance. This study suggests that CAB can be used as a first choice drug treatment in macroprolactinomas, as already shown for microprolactinomas and idiopathic hyperprolactinemia.
Racial Differences in Bone Density between Young Adult Black and White Subjects Persist after Adjustment for Anthropometric, Lifestyle, and Biochemical Differences*†
Authors: Ettinger Bruce , Sidney Stephen , Cummings Steven R. , Libanati Cesar , Bikle Daniel D. , Tekawa Irene S. , Tolan Kimberly , Steiger Peter 
Published: January 2014

AbstractThis study tested whether racial differences in bone density can be explained by differences in bone metabolism and lifestyle. A cohort of 402 black and white men and women, ages 25–36 yr, was studied at the Kaiser Permanente Medical Care Program in Northern California, a prepaid health plan. Body composition (fat, lean, and bone mineral density) was measured using a Hologic-2000 dual-energy x-ray densitometer. Muscle strength, blood and urine chemistry values related to calcium metabolism, bone turnover, growth factors, and level of sex and adrenal hormones were also measured. Medical history, physical activity, and lifestyle were assessed. Statistical analyses using t- and chi-square tests and multiple regression were done to determine whether racial difference in bone density remained after adjustment for covariates. Bone density at all skeletal sites was statistically significantly greater in black than in white subjects; on average, adjustment for covariates reduced the percentage density differences by 42% for men and 34% for women. Adjusted bone density at various skeletal sites was 4.5–16.1% higher for black than for white men and was 1.2–7.3% higher for black than for white women. We concluded that racial differences in bone mineral density are not accounted for by clinical or biochemical variables measured in early adulthood.
Angiotensin II Receptors in Cortical and Medullary Adrenal Tumors1
Authors: Opocher Giuseppe , Rocco Stefano , Cimolato Margherita , Vianello Barbara , Arnaldi Giorgio , Mantero Franco 
Published: January 2014

AbstractSeveral pieces of evidences suggest that angiotensin II (Ang II) has mitogenic effects, and a link between Ang II receptors and adrenal tumors can be suggested. In various adrenal tumors, aldosterone-producing adenoma (APA), Cushing’s adrenal adenomas (Cush), pheochromocytomas (Pheo), and adrenal carcinomas, we studied the density, affinity, and subtype of Ang II receptors. Ang II binding was tested in cell membrane homogenates. [125I]Ang II was used as ligand, and Losartan and CGP 42112 were used as selective Ang II type 1 and type 2 antagonists, respectively. In APA, Ang II receptor density was 178.5 ± 82.7 fmol/mg: however, due to the high degree of variability, the receptor density was not significantly higher than that in nontumorous adrenal cortex (59.3 ± 8.4 fmol/mg). In Cush, the receptor density (27.6 ± 8.2 fmol/mg; P&lt; 0.05) was significantly lower than that in controls, whereas in Pheo and cortical carcinoma, Ang II binding was very low and in several cases almost undetectable. There was no remarkable difference in the Ang II receptor affinity among all tissues tested. The ratio between type 1 and type 2 Ang II receptors showed a large prevalence of type 1 in controls, APA, and three cases of Cush; in two cases of Cush, this ratio was reversed.In conclusion, our data indicate that Ang II receptors are normally expressed in APA and can also be detected in Cush, whereas they have a very low density in Pheo and adrenal carcinoma. Therefore, Ang II receptors are not involved in the lack of response to Ang II that is characteristic of APA; additionally, a reduction of Ang II receptors can be associated with dedifferentiation or malignancy of adrenal tumors. Further investigation of the expression and functional characterization of Ang II receptors is required to better clarify their possible role in adrenal tumorigenesis.