bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Resveratrol and Polyphenol Preparation Suppresses Oxidative and Inflammatory Stress Response to a High-Fat, High-Carbohydrate Meal
Authors: Ghanim Husam , Sia Chang Ling , Korzeniewski Kelly , Lohano Teekam , Abuaysheh Sanaa , Marumganti Anuritha , Chaudhuri Ajay , Dandona Paresh 
Published: January 2014

Abstract

Background:
High-fat, high-carbohydrate (HFHC) meals are known to induce oxidative and inflammatory stress, an increase in plasma endotoxin concentrations, and an increase in the expression of suppressor of cytokine signaling-3 (SOCS-3).

Hypothesis:
The intake of a nutritional supplement containing resveratrol and muscadine grape polyphenols reduces HFHC meal-induced oxidative and inflammatory stress and stimulates the activity of the antioxidant transcription factor, Nrf-2, and its downstream targets.

Methods:
Ten normal, healthy subjects were given a 930-kcal HFHC meal either with placebo or with the supplement. Indices of oxidative stress, inflammation, Nrf-2 binding activity, the concentrations of endotoxin (lipopolysaccharide) and lipoprotein binding protein (LBP), and the expression of TLR-4, CD14, IL-1β, TNFα, SOCS-3, Keap-1, NQO-1, and GST-P1 were measured.

Results:
The intake of the supplement suppressed the meal-induced elevations of plasma endotoxin and LBP concentrations, the expression of p47phox, TLR-4, CD14, SOCS-3, IL-1β, and Keap-1, while enhancing Nrf-2 binding activity and the expression of NQO-1 and GST-P1 genes.

Conclusion:
A supplement containing resveratrol and muscadine polyphenols reduces the magnitude of oxidative stress, increase in lipopolysaccharide and LBP and TLR-4, CD14, IL-1β and SOCS-3 expression after an HFHC meal. It also stimulates specific Nrf-2 activity and induces the expression of the related antioxidant genes, NQO-1 and GST-P1. These results demonstrate the acute antioxidant and antiinflammatory effects of resveratrol and polyphenolic compounds in humans in the postprandial state.
Premature Ovarian Failure in Patients with Autoimmune Addison's Disease: Clinical, Genetic, and Immunological Evaluation
Authors: Reato G. , Morlin L. , Chen S. , Furmaniak J. , Rees Smith B. , Masiero S. , Masiero S. , Albergoni M. P. , Zanchetta R. , Betterle C. 
Published: January 2014

Design
The design of the study was to investigate the prevalence of the following: 1) premature ovarian failure (POF) in patients with autoimmune Addison's disease (AD); 2) steroidproducing cells (StCA) and steroidogenic enzymes (17α-hydroxylase autoantibodies and P450 side-chain cleavage enzyme autoantibodies) in patients with or without POF; and 3) the value of these autoantibodies to predict POF.

Patients
The study included 258 women: 163 with autoimmune polyendocrine syndrome type 2 (APS-2), 49 with APS-1, 18 with APS-4, and 28 with isolated AD.

Methods
StCA were measured by an immunofluorescence technique and 17α-hydroxylase autoantibodies and P450 sidechain cleavage enzyme autoantibodies by immunoprecipitation assays.

Results
Fifty-two of 258 women with AD (20.2%) had POF. POF was diagnosed in 20 of 49 (40.8%) with APS-1, six of 18 (33.3%) with APS-4, 26 of 163 (16%) with APS-2, and none of 28 with isolated AD. In patients with APS-1 and APS-4, POF developed after AD, whereas it preceded AD in patients with APS-2. StCA were detected in 31 of 43 with POF (72%) and 51 of 198 without POF (25.7%). StCA were present in 22 of 38 with APS-1 (57.9%) (11 of 13 with POF); in five of 13 with APS-4 (38.5%) (three of four with POF); in 53 of 162 with APS-2 (32.7%) (17 of 26 with POF), and in one of 28 isolated AD patients (3.6%). Twelve of 13 patients with POF with a duration less than 5 yr (92.3%) and 18 of 25 with duration longer than 5 yr (72%) were StCA positive. Twenty-eight of 31 with POF (90.3%) were positive for at least one steroidogenic antibody. Forty-one women with AD less than 40 yr were followed up for a mean period of 9 yr. Eight of 21 women (38%) positive or seroconverted for steroidogenic autoantibodies developed POF at a mean age of 23 yr (six with APS-1, one with APS-2, and one with APS-4), and none of the 20 patients negative for steroidogenic autoantibodies developed POF.

Conclusions
This study indicates that AD is frequently associated with POF and that steroidogenic antibodies are markers of patients with POF. Steroidogenic autoantibodies are predictive markers of POF in patients with AD.
Thyroid Function in Rubinstein-Taybi Syndrome*
Authors: Olson David P. , Koenig Ronald J. 
Published: January 2014

AbstractRubinstein-Taybi syndrome (RTS) is a genetic syndrome characterized by broad thumbs and halluces, growth retardation, mental retardation, and craniofacial abnormalities. This condition recently was found to be caused by mutations in the gene encoding cAMP response element-binding protein (CREB)-binding protein. As CREB-binding protein has been shown to be a critical coactivator for thyroid hormone receptors, it is plausible that RTS would be characterized by thyroid hormone resistance. In fact, features of RTS, such as mental retardation and short stature, are consistent with thyroid hormone deficiency or resistance. To assess the function of the thyroid axis in RTS, free T4 and TSH were measured in 12 subjects with this syndrome. The free T4 level was normal in all 12 (mean ± sd, 0.97 ± 0.20 ng/dL; normal range, 0.73–1.79), as was the TSH level (2.24 ± 0.87 μU/mL; normal range, 0.3–6.5). Thus, overt thyroid hormone resistance does not appear to be a typical feature of RTS.
G Protein and Thyrotropin Receptor Mutations in Thyroid Neoplasia*
Authors: Esapa Christopher , Foster Sally , Johnson Sarah , Jameson J. Larry , Kendall-Taylor Patricia , Harris Philip E. 
Published: January 2014

AbstractThe cAMP pathway plays a central role in thyroid follicular cell growth and function. Mutations of the TSH receptor (TSHR) or G proteins (gsp) that activate adenylyl cyclase have been identified in autonomously functioning thyroid nodules. Gsp mutations have been identified also in other forms of thyroid neoplasia, but their reported prevalence has been extremely variable. We have studied the prevalence of gsp mutations and activating mutations of Gi2α (gip) in a series of 66 benign and 34 malignant thyroid tumors. Thirty-six tumors were from Boston and 64 from the UK. In addition, we examined the 64 UK tumors for mutations of the TSHR gene. DNA extracted from fresh-frozen or paraffin-embedded tissue was amplified by PCR and examined for mutations using oligonucleotide-specific hybridization and single-strand conformation polymorphism analysis. No G protein gene mutations were identified in the Boston tumors. One gsp mutation, R201C, in a Hürthle cell adenoma and 1 gip mutation, R179C, in a follicular adenoma were demonstrated in tumors from the UK. Oligonucleotide-specific hybridization and single-strand conformation polymorphism analysis of the UK tumors did not demonstrate any mutations of the TSHR gene. Eleven normal thyroid tissue samples were wild-type for Gsα, Gi2α, and the TSHR gene.
Parathyroid Hormone-Related Protein-(1–36) Is Biologically Active When Administered Subcutaneously to Humans1
Authors: Henry Jean G. , Mitnick Maryann , Dann Pamela R. , Stewart Andrew F. 
Published: January 2014

Abstract
PTH-related protein (PTHrP) is responsible for most cases of humoral hypercalcemia of malignancy (HHM). It mimics the actions of PTH as a result of its structural homology with PTH and its ability to bind to and signal via the PTH/PTHrP receptor in bone and kidney. PTHrP-(1–36) appears to be one of several secretory forms of PTHrP. This peptide has been administered iv to normal volunteers previously and has been shown to produce effects that are qualitatively and quantitatively the same as those produced by PTH-(1–34). To determine whether PTHrP-(1–36) could be used sc in humans as a diagnostic reagent for elucidating the differences between HHM and hyperparathyroidism, we performed a 12-h dose-finding study examining whether sc PTHrP-(1–36) could elicit effects on mineral homeostasis.
PTHrP-(1–36) administered sc in three doses (0.82, 1.64, and 3.28μ g/kg) to 21 normal women produced increases in circulating PTHrP-(1–36), reductions in serum phosphorus and the renal phosphorus threshold, increments in fractional calcium excretion and nephrogenous cAMP excretion, and increases in plasma 1,25-dihydroxyvitamin D. These changes were highly significant in statistical terms and were observed at doses that had no effect on serum calcium or endogenous PTH.
These studies demonstrate the feasibility of using PTHrP-(1–36) as a diagnostic probe for future studies aimed at elucidating the differing pathophysiologies of HHM and hyperparathyroidism.
Generation and Characterization of an IGFBP-7 Antibody: Identification of 31kD IGFBP-7 in Human Biological Fluids and Hs578T Human Breast Cancer Conditioned Media
Authors: Wilson Elizabeth M. , Oh Youngman , Rosenfeld Ron G. 
Published: January 2014

Abstract
The cDNA encoding mac25 (IGFBP-7) was first derived from mRNA isolated from leptomeningial and senescent human mammary epithelial cells (1, 2). The open reading frame was shown to predict a protein with homology to the amino terminus of the IGF binding proteins, (IGFBP)1-6. Studies in our laboratory have shown that baculovirus generated mac25 binds IGF-I and-II in a specific manner, leading to the renaming of mac25 as IGFBP-7 (3). Further studies at the cellular level, to identify the involvement of IGFBP-7 in IGF regulation and cell growth, require a specific antibody against the protein, which has yet to be identified in either culture cells or in vivo. We have now generated three polyclonal antibodies against the purified baculovirus peptide, and, by western immunoblots and immunoprecipitation, demonstrated the existence of a specific 31,000 dalton protein. It is a secreted protein and can be identified in the conditioned media of Hs578T breast cancer cells, as well as in normal human urine, cerebrospinal fluid, and amniotic fluid. Subsequent studies with these antibodies should help elucidate the physiological role(s) of this protein.
Heterogeneity of the Human Corticotropin-Releasing Factor-Binding Protein
Authors: Woods R. J. , Kemp C. F. , David J. , Lowry P. J. 
Published: January 2014

AbstractHuman corticotropin-releasing factor (hCRF), secreted by the placenta, principally in the third trimester, is specifically bound in the peripheral circulation to a 37-kDa binding protein (CRF-BP). This complex is cleared from the circulation. We postulate that the protein may be returned to the blood in a form that is immunologically altered and not well recognized by the reported RIAs. We report that a stable isoform can result from temporary denaturation of recombinant CRF-BP by 8 mol/L urea. This isoform, urea-treated binding protein, which can bind CRF, has been found to bind to an antibody raised against a synthetic peptide comprising the first 24 amino acid residues of CRF-BP, but not to a second similar N-terminal antibody, although it was closely matched in titer. Urea-treated binding protein also cross-reacts poorly in the RIA with CRF-BP. It is proposed that as a result of in vivo post-ligand binding events, isoforms may be susceptible to cleavage. After affinity purification, which involves denaturation, recombinant CRF-BP was often found to be cleaved after storage in the presence of protease inhibitors.Here we present evidence for a C-terminally truncated form of the native binding protein in the plasma of subjects suffering from rheumatoid arthritis, which may parallel the in vitro truncation.
Intraoperative Adrenocorticotropin Levels During Transsphenoidal Surgery for Cushing’s Disease Do Not Predict Cure
Authors: Graham Kathryn E. , Samuels Mary H. , Raff Hershel , Barnwell Stanley L. , Cook David M. 
Published: January 2014

Abstract
Recently, intraoperative rapid immunochemiluminometric assay (ICMA) ACTH measurements have been used to evaluate the completeness of resection of ectopic ACTH-secreting tumors. This study evaluates whether this method can be applied to patients undergoing transsphenoidal surgery (TSS) for Cushing’s disease to predict complete pituitary tumor resection.
Eighteen patients with Cushing’s disease undergoing TSS had plasma ACTH concentrations measured by a standard ICMA every 10 min for 1 h immediately after pituitary tumor removal. Patients were evaluated postoperatively for cure by standard criteria. ACTH levels were evaluated for percentage decrease from baseline at each time point.
Patients who were cured (n = 11) had statistically greater decreases in ACTH levels (mean decrease 54%) than patients who were not (n = 7; 26% mean decrease, P &lt; 0.04). By Receiver-Operator Characteristic (ROC) analysis, a reduction of at least 40% best predicted which patients were cured and which were not cured. This level of reduction was observed in 82% of cured patients, and a reduction of less than 40% was observed in 71% of those not cured. The analysis misclassified 4 of the 18 patients, resulting in a diagnostic accuracy of 78%.
Although the mean maximal decrease in ACTH concentrations after tumor removal was significantly different between cured and not cured patients with Cushing’s disease, it was less dramatic than results in the previous ectopic ACTH study. This may relate to incomplete suppression and/or surgical manipulation of normal pituitary corticotrophs in patients with pituitary disease. In summary, in contrast to the ectopic ACTH syndrome, decline of plasma ACTH during TSS does not accurately predict complete tumor resection.
Antiresorptive Therapy in Hyperthyroid Patients: Longitudinal Changes in Bone and Mineral Metabolism
Authors: Jódar Esteban , Muñoz-Torres Manuel , Escobar-Jiménez Fernando , Quesada Miguel , Luna Juan D. , Olea Nicolás 
Published: January 2014

Abstract
The effect of antiresorptive therapy with nasal calcitonin (CT) in recently diagnosed hyperthyroid patients on conventional medical therapy as well as the evolution of bone metabolism were assessed. Forty-five patients with recent-onset hyperthyroidism (&lt;12 weeks) were sex and menopause stratified and randomly allocated to treatment with carbimazole (Neotomizol), carbimazole plus low dose CT (Calsynar; 100 IU/day, 2 days/week), or carbimazole plus high dose CT (Calsynar; 100 IU/day, 14 days/month). Bone mineral density was measured by dual x-ray absorptiometry in lumbar spine, femoral neck, and Ward’s triangle at 0, 9, and 18 months of treatment. We also determined free T4, free T3, TSH, osteocalcin, total and bone alkaline phosphatases, tartrate-resistant acid phosphatase, type I collagen C telopeptide, and urinary hydroxyproline every 3 months of follow-up. No significant difference was observed among treatments. A euthyroid state was attained at 3 months. Bone mass increased significantly at the 9 month evaluation (P &lt; 0.05), with a 5–10% net gain during follow-up. Nevertheless, final bone mass was 4–8% smaller than expected. Bone formation markers were increased at 0 and 3 months, with reductions at 6–9 months; resorption bone markers showed a significant reduction at the 3 month evaluation.
These results indicate that the euthyroid state partially reduces hyperthyroidism-associated osteopenia, with a bone mass recovery period during the 6–9 early months of effective treatment. This recovery phase is characterized by raised bone formation markers and reduced bone resorption markers. The treatment with nasal CT at the doses assayed has no additional effect over that of attainment of the euthyroid state.
Suppression of Tyrosine Kinase Activity Inhibits[ 3H]Thymidine Uptake in Cultured Human Pituitary Tumor Cells1
Authors: Jones T. H. , Justice S. K. , Price A. 
Published: January 2014

Tyrosine kinases are involved in the phosphorylation of proteins that regulate cell growth and proliferation. The mitogenic effect of several growth factors requires tyrosine kinase activity of their receptors. The effect of inhibition of tyrosine kinase activity on thymidine uptake into cultured human pituitary adenoma cells was studied using two inhibitors, genestein and methyl-2,3-dihydroxycinnamate (MDHC).
Of 33 pituitary adenomas, 7 incorporated sufficient[ 3H]thymidine to be investigated in the experiments. Genestein and MDHC both potently inhibited thymidine uptake into these tumors, with a mean inhibition by 74 μmol/L genestein of 61.96± 18.96% (±sd inhibition of basal), by 740 μmol/L genestein of 92.65 ± 8.59%, and by 100 μmol/L MDHC of 93.84 ± 3.85%. The 7 pituitary adenomas were all large with suprasellar extension and secreted interleukin-6 in vitro. They included 2 prolactinomas, 1 somatotropinoma, 1 mammosomatropinoma, and 3 clinically nonfunctioning adenomas. Epidermal growth factor stimulated thymidine uptake in 2 of the 3 clinically nonfunctioning adenomas studied, and this stimulation was inhibited by genestein. Both of these tumors released FSH in cell culture and are probably silent gonadotropinomas. The growth stimulatory effect of conditioned medium from human pituitary cell culture on GH3 cells was inhibited by both genestein and MDHC. We conclude that tyrosine kinase activity is crucial for the integrity and growth of pituitary adenomas in culture. Growth factors released by pituitary adenomas potentially may maintain and promote tumor growth by stimulating tyrosine kinase activity.
The Effect of a Desogestrel-Containing Oral Contraceptive on Glucose Tolerance and Leptin Concentrations in Hyperandrogenic Women*
Authors: Nader Shahla , Riad-Gabriel Maggy G. , Saad Mohammed F. 
Published: January 2014

Abstract
Ovarian hyperandrogenism can be associated with insulin resistance, hyperinsulinemia, glucose intolerance, and obesity. High levels of the lipostatic hormone, leptin, have also been reported in this condition. The purpose of the present study was to examine the effect of an oral contraceptive (OC) of low androgenicity containing desogestrel on glucose tolerance in hyperandrogenic women and the impact of changes in androgenic/estrogenic status on leptin concentrations. Sixteen nondiabetic hyperandrogenic women, aged 29 ± 1 yr with a body mass index (BMI) of 36.8 ± 1.8 kg/m2, underwent an oral glucose tolerance test before and after 6 months of therapy with the OC. Free testosterone decreased and sex hormone-binding globulin increased after therapy (P &lt; 0.001). Glucose tolerance deteriorated significantly, and two women developed diabetes. Body weight, BMI, and leptin did not change significantly. Leptin correlated with BMI before (r = 0.56; P = 0.02) and after (r = 0.51; P = 0.04) treatment, but not with glucose, insulin, total and free testosterone, or sex hormone-binding globulin before or after treatment. In conclusion, 1) glucose tolerance should be monitored in hyperandrogenic women using OC, even those of low androgenicity; and 2) changes in androgenic/estrogenic status had no effect on the leptin concentration, suggesting that its sexual dimorphism is not related to sex steroids.
Mutation Analysis of Glial Cell Line-Derived Neurotrophic Factor, a Ligand for an RET/Coreceptor Complex, in Multiple Endocrine Neoplasia Type 2 and Sporadic Neuroendocrine Tumors
Authors: Marsh Debbie J. , Zheng Zimu , Arnold Andrew , Andrew Scott D. , Learoyd Diana , Frilling Andrea , Komminoth Paul , Neumann Hartmut P.H. , Ponder Bruce A.J. , Rollins Barrett J. , Shapiro Geoffrey I. , Robinson Bruce G. , Mulligan Lois M. , Eng Charis 
Published: January 2014

AbstractCausative germline missense mutations in the RET proto-oncogene have been associated with over 92% of families with the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN 2). MEN 2A is characterized primarily by medullary thyroid carcinoma (MTC) and pheochromocytoma, both tumors of neural crest origin. Parathyroid hyperplasia or adenoma is also seen in MEN 2A, but rarely in MEN 2B, which has additional stigmata, including a marfanoid habitus, mucosal neuromas, and ganglioneuromatosis of the gastrointestinal tract. In familial MTC, MTC is the only lesion present. Somatic RET mutations have also been identified in a subset of sporadic MTCs, pheochromocytomas, and rarely, small cell lung cancer, but not in sporadic parathyroid hyperplasias/adenomas or other neuroendocrine tumors. Glial cell line-derived neurotrophic factor (GDNF) and its receptor molecule GDNFR-α, have recently been identified as members of the RET ligand binding complex. Therefore, the genes encoding both GDNF and GDNFR-α are excellent candidates for a role in the pathogenesis of those MEN 2 families and sporadic neuroendocrine tumors without RET mutations. No mutations were found in the coding region of GDNF in DNA samples from 9 RET mutation negative MEN 2 individuals (comprising 6 distinct families), 12 sporadic MTCs, 17 sporadic cases of parathyroid adenoma, and 10 small cell lung cancer cell lines. Therefore, we find no evidence that mutation within the coding regions of GDNF plays a role in the genesis of MEN 2 and sporadic neuroendocrine tumors.
A New Polymorphic Restriction Site in the Human 11β-Hydroxysteroid Dehydrogenase Type 2 Gene
Authors: Smolenicka Z. , Bach E. , Schaer A. , Liechti-Gallati S. , Frey B.M. , Frey F.J. , Ferrari P 
Published: January 2014

ABTRACT
The 11β-hydroxysteroid dehydrogenase type II enzyme (11βHSD2) inactivates glucocorticoids in the kidney and thus prevents glucocorticoids from occupying the non-selective mineralocorticoid receptor in epithelial tissues. Mutants in the HSD11B2 gene have been found to cause the syndrome of apparent mineralocorticoid excess, a rare autosomal recessive disease characterized by severe hypertension. Thus, this locus could also be an ideal candidate involved in the etiology of primary hypertension. We identified a polymorphism in exon 3 characterized by a GAG to GAA transition at codon 178, with the loss of an Alu I restriction site and analyzed it in an association study using end-stage renal disease patients, diabetic or essential hypertensive patients and control subjects. Two-hundred eighty nine subjects and patients were analyzed; the genotype was determined by amplification of genomic DNA and subsequent digestion with Alu I restriction enzyme. The prevalence of the Alu I allele was 8.6% in healthy control subjects (n = 116). This prevalence was lower (χ2 P = 0.035 vs. controls) than the 18.0% in a group of renal transplant patients (n = 61). The corresponding values for patients with diabetes mellitus (n = 25), hypertension (n = 41) and patients on dialysis (n = 46) were 4.0%, 4.8% and 4.3%, respectively. There was no correlation between blood pressure and the marker in non-ESRD subjects. These data indicate the presence of a polymorphic marker in exon 3 of the HSD11B2 gene; this marker is associated with end-stage renal disease but not with essential hypertension in humans.
Analysis of Loss of Heterozygosity on Chromosome 11 and Infrequent Inactivation of the MEN1 Gene in Sporadic Pituitary Adenomas1
Authors: Tanaka Chisato , Kimura Takehiko , Yang Peng , Moritani Maki , Yamaoka Takashi , Yamada Shozo , Sano Toshiaki , Yoshimoto Katsuhiko , Itakura Mitsuo 
Published: January 2014

abstract
To investigate the role of tumor suppressor genes in sporadic pituitary adenomas, we first analyzed loss of heterozygosity on 11q13 with microsatellite analysis in 31 tumors. Loss of heterozygosity on 11q13 was detected in 1 mixed GH/PRL adenoma, and the somatic 22-bp deletion of the multiple endocrine neoplasia type 1 (MEN1) gene encoding menin was detected in this tumor. Trisomy 11 suggested by the decreased mean allelic ratios of 66% or 65% for 16 or 13 microsatellite markers, respectively, in 2 of 31 pituitary adenomas was confirmed by interphase fluorescence in situ hybridization. Screening for mutations of the MEN1 gene did not find mutations with PCR-single strand conformation polymorphism analysis in other pituitary adenomas retaining heterozygosity on 11q13.
Based on these, it is concluded that inactivation of the MEN1 gene comprises a rare etiology for tumorigenesis of the pituitary gland, and that trisomy 11 or another gene(s) may contribute to the pathogenesis of sporadic pituitary adenomas.