bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for mutations in transcription factors in a Czech cohort of 170 patients with congenital and early-onset hypothyroidism: identification of a novel PAX8 mutation in dominantly inherited early-onset non-autoimmune hypothyroidism
Authors: Al Taji Eva , Biebermann Heike , Límanová Zdeňka , Hníková Olga , Zikmund Jaroslav , Dame Christof , Grüters Annette , Lebl Jan , Krude Heiko 
Published: April 2007

Objective: Mutations in NKX2.1, NKX2.5, FOXE1 and PAX8 genes, encoding for transcription factors involved in the development of the thyroid gland, have been identified in a minority of patients with syndromic and non-syndromic congenital hypothyroidism (CH).
Design: In a phenotype-selected cohort of 170 Czech paediatric and adolescent patients with non-goitre CH, including thyroid dysgenesis, or non-goitre early-onset hypothyroidism, PAX8, NKX2.1, NKX2.5, FOXE1 and HHEX genes were analysed for mutations.
Methods: NKX2.1, NKX2.5, FOXE1 and HHEX genes were directly sequenced in patients with syndromic CH. PAX8 mutational screening was performed in all 170 patients by single-stranded conformation polymorphism, followed by direct sequencing of samples with abnormal findings. The R52P PAX8 mutation was functionally characterized by DNA binding studies.
Results: We identified a novel PAX8 mutation R52P, dominantly inherited in a three-generation pedigree and leading to non-congenital, early-onset, non-goitre, non-autoimmune hypothyroidism with gradual postnatal regression of the thyroid size and function. The R52P PAX8 mutation results in the substitution of a highly conserved residue of the DNA-binding domain with a loss-of-function effect. Conclusions: The very low frequency of genetic defects in a population-based cohort of children affected by non-goitre congenital and early-onset hypothyroidism, even in a phenotype-focussed screening study, suggests the pathogenetic role of either non-classic genetic mechanisms or the involvement of genes unknown so far. Identification of a novel PAX8 mutation in a particular variant of non-congenital early-onset hypothyroidism indicates a key function of PAX8 in the postnatal growth and functional maintenance of the thyroid gland.
Posterior pituitary function in Sheehan’s syndrome
Authors: Atmaca Hulusi , Tanriverdi Fatih , Gokce Cumali , Unluhizarci Kursad , Kelestimur Fahrettin 
Published: April 2007

Objective: We studied posterior pituitary function in 27 patients with Sheehan’s syndrome and 14 controls.
Design: All patients were investigated by water deprivation test and 26 of them by 5% hypertonic saline infusion test. None of the patients had symptoms of diabetes insipidus and all patients were on adequate glucocorticoid and thyroid hormone replacement therapy before testing.
Results: According to dehydration test, 8 (29.6%) patients had partial diabetes insipidus (PDI group) and 19 (70.3%) had normal response (non-DI group). During the 5% hypertonic saline infusion test, the maximal plasma osmolality was higher in PDI (305 ± 4.3) and non-DI (308 ± 1.7) groups when compared with controls (298 ± 1.7 mOsm/kg; P < 0.005), but the maximal urine osmolality was lower in PDI group (565 ± 37) than in non-DI (708 ± 45) and control (683 ± 17 mOsm/kg) groups (P < 0.05). The osmotic threshold for thirst perception was higher in PDI (296 ± 4.3) and non-DI (298 ± 1.4) groups when compared with control group (287 ± 1.5 mOsm/kg) (P < 0.005). Basal plasma osmolalities were also higher in PDI (294 ± 1.0) and non-DI (297 ± 1.1) groups than in controls (288 ± 1.2 mOsm/kg; P < 0.001).
Conclusions: Our findings demonstrated that patients with Sheehan’s syndrome have an impairment of neurohypophyseal function. The thirst center may be affected by ischemic damage and the osmotic threshold for the onset of thirst in patients with Sheehan’s syndrome is increased.
High prevalence of thyroid peroxidase gene mutations in patients with thyroid dyshormonogenesis
Authors: Avbelj Magdalena , Tahirovic Husref , Debeljak Marusa , Kusekova Maria , Toromanovic Alma , Krzisnik Ciril , Battelino Tadej 
Published: April 2007

Objective: Thyroid dyshormonogenesis is a genetically heterogeneous group of inherited disorders in the enzymatic cascade of thyroid hormone synthesis that result in congenital hypothyroidism (CH). Thyroid peroxidase gene (TPO) mutations are one of the most common causes of thyroid dyshormonogenesis. The aim of this study was to identify TPO gene defects in a cohort of patients with thyroid dyshormonogenesis from Slovenia, Bosnia, and Slovakia.
Design and methods: Forty-three patients with permanent CH and orthoptic thyroid glands from 39 unrelated families participated in the study. Mutational analysis of the TPO gene and part of its promoter consisted of single-stranded conformation polymorphism analysis, sequencing, and restriction fragment length polymorphism (RFLP) analysis.
Results: TPO gene mutations were identified in 46% of participants. Seven different mutations were identified, four mutations of these being novel, namely 613C > T (R175X), 1519_1539del (A477_N483del), 2089G > A (G667S), and 2669G > A (G860R). Only a single allele mutation was identified in 65% of the TPO mutation carriers.
Conclusions: The results showed a higher prevalence of TPO gene mutations in thyroid dyshormonogenesis when compared with published studies. The high percentage of single allele mutations implied possible intronic or regulatory TPO gene mutations or monoallelic expression.
Modeling Notch Signaling in Normal and Neoplastic Hematopoiesis: Global Gene Expression Profiling in Response to Activated Notch Expression
Authors: Ganapati Uma , Tan Hongying Tina , Lynch Maureen , Dolezal Milana , de Vos Sven , Gasson Judith C. 
Published: April 2007

Abstract
In normal hematopoiesis, proliferation is tightly linked to differentiation in ways that involve cell-cell interaction with stromal elements in the bone marrow stem cell niche. Numerous in vitro and in vivo studies strongly support a role for Notch signaling in the regulation of stem cell renewal and hematopoiesis. Not surprisingly, mutations in the Notch gene have been linked to a number of types of malignancies. To better define the function of Notch in both normal and neoplastic hematopoiesis, a tetracycline-inducible system regulating expression of a ligand-independent, constitutively active form of Notch1 was introduced into murine E14Tg2a embryonic stem cells. During coculture, OP9 stromal cells induce the embryonic stem cells to differentiate first to hemangioblasts and subsequently to hematopoietic stem cells. Our studies indicate that activation of Notch signaling in flk+ hemangioblasts dramatically reduces their survival and proliferative capacity and lowers the levels of hematopoietic stem cell markers CD34 and c-Kit and the myeloid marker CD11b. Global gene expression profiling of day 8 hematopoietic progenitors in the absence and presence of activated Notch yield candidate genes required for normal hematopoietic differentiation, as well as putative downstream targets of oncogenic forms of Notch including the noncanonical Wnts Wnt4 and 5A.
Disclosure of potential conflicts of interest is found at the end of this article.
Erythropoietin in Cancer: Presumption of Innocence?
Authors: Blau C. Anthony 
Published: April 2007

Abstract
Erythropoietin emerged as the biggest drug in oncology despite never having demonstrated a survival benefit in patients with cancer. Two phase III clinical trials reported more than 3 years ago that erythropoietin adversely affected cancer survival rates, due mainly to tumor progression. Despite changes to the product label for erythropoietins in 2004, clinical practice remained unchanged until recent weeks when, following reports of three new phase III studies and a phase II trial, a “black box warning” for erythropoietin products was issued by the Food and Drug Administration (FDA). Whether erythropoietin products can be considered safe when used for FDA-approved indications is currently at issue; however, addressing this question will be difficult until the mechanisms of erythropoietin-stimulated tumor progression are understood. A thorough evaluation of materials from clinical trials already completed may shed new light on how erythropoietin promotes cancer progression. Until these issues are resolved, oncologists should inform their patients of erythropoietin's potential adverse impact on cancer progression and survival.
Disclosure of potential conflicts of interest is found at the end of this article.
The Effectiveness of State and National Policy on the Implementation of Perinatal HIV Prevention Interventions
Authors: Sarnquist Clea C. , Cunningham Shayna D. , Sullivan Barbara , Maldonado Yvonne 
Published: April 2007

Objectives. The 1994 and 1995 US Public Health Service Guidelines regarding HIV testing and treatment for pregnant women and the resulting 1995 California law mandating an HIV test and treatment offer to every pregnant woman aim to reduce perinatal HIV transmission. However, the effectiveness of such policies after implementation is often unclear. We analyzed the association between these policies and offers of HIV tests and treatment to HIV-infected women in California. Methods. Data from active, population-based surveillance of 496 HIV-infected women and their infants, collected from 1987 to 2002, were analyzed to compare rates of offers of HIV tests and treatment before and after 1996. Results. We found significant increases in offers of HIV tests (P<.001) and offers of treatment (P<.001) when we compared women who delivered between 1987 and 1995 with those who delivered between 1996 and 2002. Receipt of prenatal care was the major predictor of both test and treatment offer. A significant shift in reported HIV risk factors was also evident between the 2 groups. Conclusions. Our findings of increased offers of HIV tests and treatment to HIV-infected pregnant women suggest that the national guidelines and the 1996 California law improved health care for these women, which may lessen the risk of perinatal HIV transmission.
REAL Men: A Group-Randomized Trial of an HIV Prevention Intervention for Adolescent Boys
Authors: DiIorio Colleen , McCarty Frances , Resnicow Ken , Lehr Sally , Denzmore Pamela 
Published: April 2007

Objectives. We tested the efficacy of an intervention among 11- to 14-year-old adolescent boys to promote delay of sexual intercourse, condom use among those who were sexually active, and communication on sexuality between fathers (or father figures) and sons.Methods. Sites were randomly assigned to the intervention and control groups. Assessments were conducted prior to the intervention and at 3-, 6-, and 12-month follow-up interviews.Results. A total of 277 fathers and their sons completed baseline assessments. Most participants were African American, and most fathers lived with their sons. Significantly higher rates of sexual abstinence and condom use and of intent to delay initiation of sexual intercourse were observed among adolescent boys whose fathers participated in the intervention. Fathers in the intervention group reported significantly more discussions about sexuality and greater intentions to discuss sexuality than did control-group fathers.Conclusions. The study demonstrates that fathers can serve as an important educator on HIV prevention and sexuality for their sons.
Bisexual Latino Men and HIV and Sexually Transmitted Infections Risk: An Exploratory Analysis
Authors: Muñoz-Laboy Miguel , Dodge Brian 
Published: April 2007

Objectives. We sought to determine whether there were differences in sexual risk among behaviorally and self-identified bisexual men, men who reported having sex with both men and women without reporting a bisexual identity and men who self-identified as bisexual but reported only recent homosexual behavior over the past 6 months.Methods.secondary data analysis, we conducted stepwise linear regression equation modeling to determine which factors were significant predictors of sexual risk among various subgroups of bisexual Latino men.Results. Having sex with women, regardless of sexual identity, increased the likelihood of insertive unprotected anal intercourse with men. Bisexual identity was not statistically associated with unprotected anal intercourse with men.Conclusions. Future studies should begin to examine differences within groups rather than focusing on group comparisons that yield limited insights into sexual risk predictors for homosexually and bisexually active men. Further research that explores risk and protective factors in the sexual lives of Latino bisexual men is also needed.
Physical Health Complaints Among Lesbians, Gay Men, and Bisexual and Homosexually Experienced Heterosexual Individuals: Results From the California Quality of Life Survey
Authors: Cochran Susan D. , Mays Vickie M. 
Published: April 2007

Objectives. We examined evidence that minority sexual orientation is associated with more-frequent reports of physical health complaints. We also investigated the possible role of HIV infection among gay men and higher rates of psychological distress among lesbians, gay men, and bisexually and homosexually experienced heterosexual individuals in generating these health disparities.Methods. We used data from the California Quality of Life Survey (N=2272 adults) to examine associations between sexual orientation and self-reports about physical health status, common health conditions, disabilities, and psychological distress.Results. Prevalent HIV infection was reported by nearly 18% of gay, bisexual, and homosexually experienced heterosexual men. Gay men and bisexual and homosexually experienced heterosexual individuals had higher levels of psychological distress compared with exclusively heterosexual individuals. Self-reported physical health status varied by gender and by sexual orientation.Conclusions. Lesbians and bisexual and homosexually experienced heterosexual women reported a greater variety of health conditions and limitations compared with exclusively heterosexual women; however, these differences mostly disappeared when distress levels were taken into account. Among men, differences in health complaints appeared to reflect the ongoing burden of HIV and other sexually transmitted diseases in the gay male community.
Overweight and Obesity in Sexual-Minority Women: Evidence From Population-Based Data
Authors: Boehmer Ulrike , Bowen Deborah J. , Bauer Greta R. 
Published: April 2007

Objective. We sought to determine whether lesbians have higher rates of overweight and obesity than women of other sexual orientations. Methods. We compared population estimates of overweight and obesity across sexual orientation groups, using data from the 2002 National Survey of Family Growth. Results. Adjusted multinomial logistic regression analyses showed lesbians have more than twice the odds of overweight (odds ratio [OR]=2.69; 95% confidence interval [CI]=1.40, 5.18) and obesity (OR=2.47; 95% CI=1.19, 5.09) as heterosexual women. Bisexuals and women who reported their sexual orientation as “something else” (besides heterosexual, lesbian, or bisexual) showed no such increase in the odds of overweight and obesity. Conclusions. Lesbian women have a higher prevalence of overweight and obesity than all other female sexual orientation groups. This finding suggests that lesbians are at greater risk for morbidity and mortality linked to overweight and obesity. This finding also highlights the need for interventions within this population.
The Usefulness of the International Diabetes Federation and the National Cholesterol Education Program's Adult Treatment Panel III Definitions of the Metabolic Syndrome in Predicting Coronary Heart Disease in Subjects With Type 2 Diabetes
Authors: Tong Peter C. , Kong Alice P. , So Wing-Yee , Yang Xilin , Ho Chung-Shun , Ma Ronald C. , Ozaki Risa , Chow Chun-Chung , Lam Christopher W. , Chan Juliana C.N. , Cockram Clive S. 
Published: April 2007

OBJECTIVE—The purpose of this study was to compare the predictive value for coronary heart disease (CHD) of the International Diabetes Federation (IDF) definition (with Asian criteria for central obesity) of the metabolic syndrome with existing criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) in Chinese subjects with type 2 diabetes.
RESEARCH DESIGN AND METHODS—Subjects with type 2 diabetes and without macrovascular diseases or end-stage renal disease were categorized by the criteria of the IDF and the NCEP ATP III. CHD was defined as myocardial infarction, ischemic heart disease, coronary revascularization, heart failure, and death related to CHD.
RESULTS—Of 4,350 patients (aged 54.4 ± 13.4 years; median follow-up period 7.1 [interquartile range 5.2–8.5] years), 65.9% had metabolic syndrome according to either IDF or NCEP ATP III criteria. The NCEP ATP III definition identified metabolic syndrome in 786 subjects (18.1%) who did not fulfill the criteria of the IDF. HDL cholesterol and systolic blood pressure were predictors of CHD after adjustment for other confounding factors. Compared with subjects without metabolic syndrome, the IDF criteria failed to predict CHD (hazard ratio 1.13 [95% CI 0.86–1.48], P = 0.374). In contrast, the NCEP ATP III definition (2.51 [1.80–3.50], P &lt; 0.001) predicted an increased risk of CHD with the NCEP-only group having the highest risk (2.49 [1.66–3.73], P &lt; 0.001).
CONCLUSIONS—With established type 2 diabetes, the IDF definition of the metabolic syndrome failed to identify a subgroup of patients who had the highest risk for CHD. Practitioners must recognize the appropriate setting for its application.
Accuracy of the 5-Day FreeStyle Navigator Continuous Glucose Monitoring System
Authors: Weinstein Richard L. , Schwartz Sherwyn L. , Brazg Ronald L. , Bugler Jolyon R. , Peyser Thomas A. , McGarraugh Geoffrey V. 
Published: April 2007

OBJECTIVE—The purpose of this study was to compare the accuracy of measurements of glucose in interstitial fluid made with the FreeStyle Navigator Continuous Glucose Monitoring System with Yellow Springs Instrument laboratory reference measurements of venous blood glucose.
RESEARCH DESIGN AND METHODS—Fifty-eight subjects with type 1 diabetes, aged 18–64 years, were enrolled in a multicenter, prospective, single-arm study. Each subject wore two sensors simultaneously, which were calibrated with capillary fingerstick measurements at 10, 12, 24, and 72 h after insertion. Measurements from the FreeStyle Navigator system were collected at 1-min intervals and compared with venous measurements taken once every 15 min for 50 h over the 5-day period of sensor wear in an in-patient clinical research center. Periods of high rates of change of glucose were induced by insulin and glucose challenges.
RESULTS—Comparison of the FreeStyle Navigator measurements with the laboratory reference method (n = 20,362) gave mean and median absolute relative differences (ARDs) of 12.8 and 9.3%, respectively. The percentage in the clinically accurate Clarke error grid A zone was 81.7% and that in the in the benign error B zone was 16.7%. During low rates of change (&lt;±1 mg · dl−1 · min−1), the percentage in the A zone was higher (84.9%) and the mean and median ARDs were lower (11.7 and 8.5%, respectively).
CONCLUSIONS—Measurements with the FreeStyle Navigator system were found to be consistent and accurate compared with venous measurements made using a laboratory reference method over 5 days of sensor wear (82.5% in the A zone on day 1 and 80.9% on day 5).
The Effect of β-Adrenergic and Peroxisome Proliferator–Activated Receptor-γ Stimulation on Target Genes Related to Lipid Metabolism in Human Subcutaneous Adipose Tissue
Authors: Bogacka Iwona , Gettys Thomas W. , de Jonge Lilian , Nguyen Tuong , Smith Jana M. , Xie Hui , Greenway Frank , Smith Steven R. 
Published: April 2007

OBJECTIVE—The sympathetic nervous system and thiazolidinediones control lipid metabolism and have been implicated in body weight regulation. This study was conducted to determine whether the simultaneous activation of these two signaling systems might synergize to exert beneficial effects on the expression of key genes involved in lipid metabolism and mitochondrial biogenesis in subcutaneous fat in nondiabetic subjects.
RESEARCH DESIGN AND METHODS—A total of 57 women and men were randomized into four groups: 1) placebo/placebo (PP), 2) ephedrine HCl (25 mg, 3 times daily) plus caffeine (200 mg, 3 times daily)/placebo (ECP), 3) placebo/pioglitazone (45 mg) (PPio), and 4) ephedrine plus caffeine/pioglitazone (ECPio) for 16 weeks. Adipose tissue samples were obtained after 12 weeks of treatment to determine gene expression.
RESULTS—Body fat decreased by 6.0 and 4.6% in the ECP and ECPio groups, respectively, while remaining unchanged in the PPio and PP groups. Triglyceride levels decreased by −7.7, −24, −15.2, and −41 mg/dl after 16 weeks treatment in the PP, PPio, ECP, and ECPio groups, respectively. This indicates that pioglitazone groups with or without EC (ephedrine HCl plus caffeine) decreased triglycerides, and EC groups with or without pioglitazone decreased body weight. The mRNA for sirtuin 1 and CD36 increased only in the ECPio group. Carnitine palmitoyltransferase-1, medium-chain acyl CoA dehydrogenase, and malonyl-CoA decarboxylase increased with PPio and ECPio. Stearoyl-CoA desaturase decreased with ECP.
CONCLUSIONS—Combined activation of peroxisome proliferator–activated receptor-γ and β-adrenergic receptors has beneficial effects on body weight, plasma triglycerides, and lipid metabolism in subcutaneous fat by increasing the expression of genes required for fatty acid catabolism.
Motivational Interviewing Improves Weight Loss in Women With Type 2 Diabetes
Authors: West Delia Smith , DiLillo Vicki , Bursac Zoran , Gore Stacy A. , Greene Paul G. 
Published: April 2007

OBJECTIVE—We sought to determine whether adding motivational interviewing to a behavioral weight control program improves weight loss outcomes and glycemic control for overweight women with type 2 diabetes.
RESEARCH DESIGN AND METHODS—We conducted a randomized, controlled, clinical trial in which participants all received an 18-month, group-based behavioral obesity treatment and were randomized to individual sessions of motivational interviewing or attention control (total of five sessions) as an adjunct to the weight control program. Overweight women with type 2 diabetes treated by oral medications who could walk for exercise were eligible. Primary outcomes were weight and A1C, assessed at 0, 6, 12, and 18 months.
RESULTS—A total of 217 overweight women (38% African American) were randomized (93% retention rate). Women in motivational interviewing lost significantly more weight at 6 months (P = 0.01) and 18 months (P = 0.04). Increased weight losses with motivational interviewing were mediated by enhanced adherence to the behavioral weight control program. African-American women lost less weight than white women overall and appeared to have a diminished benefit from the addition of motivational interviewing. Significantly greater A1C reductions were observed in those undergoing motivational interviewing at 6 months (P = 0.02) but not at 18 months.
CONCLUSIONS—Motivational interviewing can be a beneficial adjunct to behavioral obesity treatment for women with type 2 diabetes, although the benefits may not be sustained among African-American women.