bluuebunny/crossref_metadata_2025 huggingface dataset:
Permethrin May Disrupt Testosterone Biosynthesis via Mitochondrial Membrane Damage of Leydig Cells in Adult Male Mouse
Authors: Zhang Shu-Yun , Ito Yuki , Yamanoshita Osamu , Yanagiba Yukie , Kobayashi Miya , Taya Kazuyoshi , Li ChunMei , Okamura Ai , Miyata Maiko , Ueyama Jun , Lee Chul-Ho , Kamijima Michihiro , Nakajima Tamie
Published: April 2007

Permethrin, a popular synthetic pyrethroid insecticide used to control noxious insects in agriculture, forestry, households, horticulture, and public health throughout the world, poses risks of environmental exposure. Here we evaluate the reproductive toxicity of cis-permethrin in adult male ICR mice that were orally administered cis-permethrin (0, 35, or 70 mg/kg·d) for 6 wk. Caudal epididymal sperm count and sperm motility in the treated groups were statistically reduced in a dose-dependent manner. Testicular testosterone production and plasma testosterone concentration were significantly and dose-dependently decreased with an increase in LH, and a significant regression was observed between testosterone levels and cis-permethrin residues in individual mice testes after exposure. However, no significant changes were observed in body weight, reproductive organ absolute and relative weights, sperm morphology, and plasma FSH concentration after cis-permethrin treatment. Moreover, cis-permethrin exposure significantly diminished the testicular mitochondrial mRNA expression levels of peripheral benzodiazepine receptor (PBR), steroidogenic acute regulatory protein (StAR), and cytochrome P450 side-chain cleavage (P450scc) and enzyme and protein expression levels of StAR and P450scc. At the electron microscopic level, mitochondrial membrane damage was found in Leydig cells of the exposed mouse testis. Our results suggest that the insecticide permethrin may cause mitochondrial membrane impairment in Leydig cells and disrupt testosterone biosynthesis by diminishing the delivery of cholesterol into the mitochondria and decreasing the conversion of cholesterol to pregnenolone in the cells, thus reducing subsequent testosterone production.
Lipin1 Regulation by Estrogen in Uterus and Liver: Implications for Diabetes and Fertility
Authors: Gowri P. Mangala , Sengupta Surojeet , Bertera Suzanne , Katzenellenbogen Benita S.
Published: April 2007

Estrogens are essential for fertility and also have important effects on regulation of adiposity and the euglycemic state. We report here that lipin1, a candidate gene for lipodystrophy and obesity that is a phosphatidic acid phosphatase critical in regulation of cellular levels of diacylglycerol and triacylglycerol and a key regulator of lipid utilization, is rapidly and robustly down-regulated in the uterus by estradiol via the estrogen receptor. Lipin1 is expressed predominantly in the uterine luminal and glandular epithelium, and during the estrous cycle, lipin1 is lowest when blood levels of estrogen are highest. Lipin1 is expressed throughout all cells in the liver of ovariectomized female mice, and a sustained down-regulation is observed at the mRNA, protein and immunohistochemical levels after estrogen administration. Because the coupling of proper energy use and availability is central to reproduction, we also investigated expression of lipin1 in the uterus and liver of several mouse models of diabetes. Nonobese diabetic (NOD) mice, which have high blood levels of estrogen and impaired fertility, were severely deficient in lipin1 in the uterus and liver, which, interestingly, could be restored by insulin treatment. By contrast, nonobese diabetic/severe combined immunodeficient (NOD-SCID) mice, which do not develop diabetes, showed normal levels of lipin1. Our findings of lipin1 regulation by estrogen in two key target organs suggest a new role for this lipid-regulating phosphatase not only in central metabolic regulation but also in uterine function and reproductive biology. Estrogen regulation of lipin1 may provide a mechanistic link between estrogens, lipid metabolism, and lipid signaling.
Involvement of Neuropeptide Y Y1 Receptors in the Regulation of Neuroendocrine Corticotropin-Releasing Hormone Neuronal Activity
Authors: Dimitrov Eugene L. , DeJoseph M. Regina , Brownfield Mark S. , Urban Janice H.
Published: April 2007

The neuroendocrine parvocellular CRH neurons in the paraventricular nucleus (PVN) of the hypothalamus are the main integrators of neural inputs that initiate hypothalamic-pituitary-adrenal (HPA) axis activation. Neuropeptide Y (NPY) expression is prominent within the PVN, and previous reports indicated that NPY stimulates CRH mRNA levels. The purpose of these studies was to examine the participation of NPY receptors in HPA axis activation and determine whether neuroendocrine CRH neurons express NPY receptor immunoreactivity. Infusion of 0.5 nmol NPY into the third ventricle increased plasma corticosterone levels in conscious rats, with the peak of hormone levels occurring 30 min after injection. This increase was prevented by pretreatment with the Y1 receptor antagonist BIBP3226. Immunohistochemistry showed that CRH-immunoreactive neurons coexpressed Y1 receptor immunoreactivity (Y1r-ir) in the PVN, and a majority of these neurons (88.8%) were neuroendocrine as determined by ip injections of FluoroGold. Bilateral infusion of the Y1/Y5 agonist, [leu31pro34]NPY (110 pmol), into the PVN increased c-Fos and phosphorylated cAMP response element-binding protein expression and elevated plasma corticosterone levels. Increased expression of c-Fos and phosphorylated cAMP response element-binding protein was observed in populations of CRH/Y1r-ir cells. The current findings present a comprehensive study of NPY Y1 receptor distribution and activation with respect to CRH neurons in the PVN. The expression of NPY Y1r-ir by neuroendocrine CRH cells suggests that alterations in NPY release and subsequent activation of NPY Y1 receptors plays an important role in the regulation of the HPA.
Androgen-Dependent Regulation of Brain-Derived Neurotrophic Factor and Tyrosine Kinase B in the Sexually Dimorphic Spinal Nucleus of the Bulbocavernosus
Authors: Ottem Erich N. , Beck Laurel A. , Jordan Cynthia L. , Breedlove S. Marc
Published: April 2007

Castration of adult male rats causes the dendrites of androgen-sensitive motoneurons of the spinal nucleus of the bulbocavernosus (SNB) to retract. Brain-derived neurotrophic factor (BDNF), via activation of tyrosine receptor kinase B (trkB), has been implicated in mediating androgen effects on SNB dendrites. We used in situ hybridization to demonstrate that SNB motoneurons in gonadally intact adult male rats contain mRNA for both BDNF and trkB. Two weeks after gonadectomy, both transcripts were significantly decreased in SNB motoneurons but not in the non-androgen-responsive motoneurons of the adjacent retrodorsolateral nucleus (RDLN). In a second experiment, target perineal and foot muscles of SNB and RDLN motoneurons, respectively, were injected with the retrograde tracer Fluorogold, and then immunocytochemistry was performed to examine the distribution of BDNF and trkB proteins in SNB and RDLN motoneurons and their glutamatergic afferents. Confocal analysis revealed that gonadectomy induces a loss of BDNF protein in SNB dendrites but not in RDLN dendrites. Testosterone treatment of castrates prevented the loss of BDNF from SNB dendrites. Confocal analysis also revealed trkB protein in SNB and RDLN dendrites and in their glutamatergic afferents. Gonadectomy had no discernable effect on trkB protein in SNB or RDLN motoneurons or in their glutamatergic afferents. These results suggest that androgen maintains a BDNF-signaling pathway in SNB motoneurons that may underlie the maintenance of dendritic structure and synaptic signaling.
Microwave-assisted Fabrication of PS@CdS Core–Shell Nanostructures and CdS Hollow Spheres
Authors: Wang Yongqiang , Wang Guozhong , Wang Hongqiang , Tang Chunjuan , Jiang Zhi , Zhang Lide
Published: April 2007

PS@CdS core–shell nanostructures were fabricated by microwave irradiation at 70 °C from the aqueous solution of CdCl2, TAA, and PVP with PS microspheres without surface modification. The products were investigated by XRD, FE-SEM, TEM, IR, and Raman. CdS hollow spheres were easily obtained by removing the PS cores in toluene solution. The method presented here can be used for the preparation of other PS@II–VI semiconductor core–shell nanostructures and hollow spheres.
Efficient Preparation of vic-Diacetates from Epoxides and Acetic Anhydride in the Presence of Iron(III)-substituted Polyoxometalate as Catalyst
Authors: Yadollahi Bahram , Esfahani Farhad Kabiri
Published: April 2007

Iron(III)-substituted polyoxometalate (TBA)4PFeW11O39·3H2O, has been demonstrated as an efficient catalyst in the ring opening of 1,2-epoxides with acetic anhydride for the one-pot synthesis of 1,2-diol esters in high to excellent yields under solvent-free condition.
Selective Preparation of Zinc Oxide Nanostructures by Electrodeposition on the Templates of Surface-functionalized Polymer Particles
Authors: Watanabe Mitsuru , Aritomo Hiroki , Yamaguchi Ippei , Shinagawa Tsutomu , Tamai Toshiyuki , Tasaka Akimasa , Izaki Masanobu
Published: April 2007

A novel method of controlling zinc oxide (ZnO) nanostructures was developed. The sphere-like ZnO nanostructure was obtained from the electrodeposition on the polymer particle template having anionic surface groups, and under the same electrodeposition condition, microporous ZnO layer was obtained on the polymer particle template having cationic surface groups. These contrasting structures were attributed to the ZnO nucleation site selectivity derived from the specific binding between the polymer particle template surface and Zn2+ ion.
Acid–Base Property of Ethylammonium Nitrate Ionic Liquid Directly Obtained Using Ion-selective Field Effect Transistor Electrode
Authors: Kanzaki Ryo , Uchida Kuniaki , Hara Shota , Umebayashi Yasuhiro , Ishiguro Shin-ichi , Nomura Satoshi
Published: April 2007

Ethylammonium nitrate (EAN) is a protic room-temperature ionic liquid and classified into an amphoteric solvent. The equilibrium constant KS = [EtNH2][HNO3] has directly been obtained for the first time by using an ion-selective field effect transistor (ISFET) electrode. The obtained KS value is of 10−10.0 mol2 dm−6, indicating that the neutral EAN involves HNO3 and EtNH2 molecules as much as 1.0 × 10−5 mol dm−3, or the pH (= −log[HNO3]) is 5 at 298 K.
Predicting change in epistemological beliefs, reflective thinking and learning styles: A longitudinal study
Authors: Phan Huy P.
Published: April 2007

Background

Although extensive research has examined epistemological beliefs, reflective thinking and learning approaches, very few studies have looked at these three theoretical frameworks in their totality.

Aims

This research tested two separate structural models of epistemological beliefs, learning approaches, reflective thinking and academic performance among tertiary students over a period of 12 months.

Sample

Participants were first‐year Arts (N = 616; 271 females, 345 males) and second‐year Mathematics (N = 581; 241 females, 341 males) university students.

Method

Students' epistemological beliefs were measured with the Schommer epistemological questionnaire (EQ, Schommer, 1990). Reflective thinking was measured with the reflective thinking questionnaire (RTQ, Kember et al., 2000). Student learning approaches were measured with the revised study process questionnaire (R‐SPQ‐2F, Biggs, Kember, & Leung, 2001). LISREL 8 was used to test two structural equation models – the cross‐lag model and the causal‐mediating model.

Results

In the cross‐lag model involving Arts students, structural equation modelling showed that epistemological beliefs influenced student learning approaches rather than the contrary. In the causal‐mediating model involving Mathematics students, the results indicate that both epistemological beliefs and learning approaches predicted reflective thinking and academic performance. Furthermore, learning approaches mediated the effect of epistemological beliefs on reflective thinking and academic performance. Results of this study are significant as they integrated the three theoretical frameworks within the one study.
Bullying and victimization at school: The role of mothers
Authors: Georgiou Stelios N.
Published: April 2007

Background

Social learning literature is used in order to describe the contextual parameters of peer aggression, and specifically bullying and victimization.

Aim

The aim of the present study was to examine the influence of maternal characteristics on their child's victimization or bullying experience at school.

Sample

The participants were 252 elementary school students (mean age 11.5 years) and their mothers.

Method

A theoretically driven model was developed and its ability to fit the data was tested. The main factors included in the model were the following: parental style as perceived by the child, self‐reported parental involvement, the mother's emotional state and the degree of victimization experienced by the child at school.

Results

Through confirmatory factor analysis, it was shown that maternal responsiveness was positively related to the child's adjustment at school (i.e. achievement and social adaptation), while the same factor was negatively related to school aggression (bullying and disrupting behaviour). Overprotective mothering was associated with high degrees of victimization experienced by the child, whereas maternal depressiveness was related to both victimization and bullying behaviour on the part of the child.

Conclusions

Parents should be included in the design of intervention plans aiming at the elimination of bullying at school.
Natural Calcium Isotopic Composition of Urine as a Marker of Bone Mineral Balance
Authors: Skulan Joseph , Bullen Thomas , Anbar Ariel D , Puzas J Edward , Shackelford Linda , LeBlanc Adrian , Smith Scott M
Published: April 2007

Background: We investigated whether changes in the natural isotopic composition of calcium in human urine track changes in net bone mineral balance, as predicted by a model of calcium isotopic behavior in vertebrates. If so, isotopic analysis of natural urine or blood calcium could be used to monitor short-term changes in bone mineral balance that cannot be detected with other techniques.

Methods: Calcium isotopic compositions are expressed as δ44Ca, or the difference in parts per thousand between the 44Ca/40Ca of a sample and the 44Ca/40Ca of a standard reference material. δ44Ca was measured in urine samples from 10 persons who participated in a study of the effectiveness of countermeasures to bone loss in spaceflight, in which 17 weeks of bed rest was used to induce bone loss. Study participants were assigned to 1 of 3 treatment groups: controls received no treatment, one treatment group received alendronate, and another group performed resistive exercise. Measurements were made on urine samples collected before, at 2 or 3 points during, and after bed rest.

Results: Urine δ44Ca values during bed rest were lower in controls than in individuals treated with alendronate (P <0.05, ANOVA) or exercise (P <0.05), and lower than the control group baseline (P <0.05, t-test). Results were consistent with the model and with biochemical and bone mineral density data.

Conclusion: Results confirm the predicted relationship between bone mineral balance and calcium isotopes, suggesting that calcium isotopic analysis of urine might be refined into a clinical and research tool.
Treating Stuttering in a Preschool Child With Syllable Timed Speech: A Case Report
Authors: Trajkovski Natasha , Andrews Cheryl , O'Brian Sue , Onslow Mark , Packman Ann
Published: April 2007

In this article we report the use of a simple, nonprogrammed, syllable timed speech procedure to treat stuttering in a 3-year-old boy with a 2-year history of stuttering. The treatment involved the boy and his parents visiting the clinic 7 times, and the parents modelling syllable timed speech 2 to 6 times per day for 5- to 10-minute intervals in and around the home. After 7 weeks, clinic measures and objective, blinded measures of speech beyond the clinic showed stuttering frequency below 1.0% syllables stuttered. Along with low severity ratings made by the parent each day, this meets the stuttering criteria of another, proven treatment for early stuttering intervention. However, in this study reduction in stuttering was achieved with a simpler and more cost efficient procedure. With the caveat that this is a nonexperimental case report, we discuss its potential implications.
Activity-Dependent Presynaptic and Postsynaptic Structural Plasticity in the Mature Cerebellum
Authors: Cesa Roberta , Scelfo Bibiana , Strata Piergiorgio
Published: April 2007

Two models of spine formation have been proposed. Spines can derive from emerging dendritic filopodia that have encountered presynaptic partners, or presynaptic molecules may induce the spine maturation event directly from the dendritic shaft. The first model applies better to the Purkinje cell (PC), because numerous free spines have been described in several conditions, particularly when granule cells degenerate before parallel fiber (PF) synapses are formed. A large number of new spines, many of them being free, appear in the proximal dendritic domain after blockage of electrical activity by tetrodotoxin (TTX). A complete blockage of the AMPA receptors by NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzoquinoxaline-7-sulfonamide), leading to a complete absence of PF- and climbing fiber (CF)-evoked EPSCs and of spontaneous glutamatergic quantal events, mimics the TTX effect. In contrast, metabotropic glutamate receptor blockage by MCPG [(S)-α-methyl-4-carboxyphenylglycine] is ineffective.

In normal conditions, in the proximal dendritic domain of the PC, clusters of a few spines are present only under each CF varicosity. It has been proposed that the active CF is responsible for spine pruning in the territory surrounding the CF synapses. Here, we show that such a pruning is mediated by AMPA but not by metabotropic receptors. Finally, after AMPA receptor blockage, there is a reduced number of spines in each spine cluster underlying CF varicosity. In conclusion, PCs tend to express spines over the entire dendritic territory. CF activity reinforces the CF synaptic contacts and actively suppresses spines in the surrounding territory, which is an effect mediated by AMPA receptors.
Thyroid hormone deficiency and postmenopausal status independently increase serum osteoprotegerin concentrations in women
Authors: Botella-Carretero José I , Alvarez-Blasco Francisco , Millán José Luis San , Escobar-Morreale Héctor F
Published: April 2007

Objective: To study the impact of thyroxine (T4) withdrawal on serum osteoprotegerin concentrations in women, using a healthy euthyroid control group matched for age and postmenopausal status as reference.

Subjects and design: Nineteen women with differentiated thyroid carcinoma were studied the last day on T4 suppressive treatment, 4–7 days after withdrawal and the day before whole body scanning. Eighteen women matched for age and postmenopausal status served as controls. Serum thyroid hormones, urinary bone markers and serum osteoprotegerin concentrations were measured. Statistical methods included repeated measures analysis of variance and one-way analysis of variance.

Results: Patients progressed from subclinical or mild hyperthyroidism at baseline to normal free T4 and triiodothyronine levels 4–7 days later, ending in overt hypothyroidism before scanning. Serum osteoprotegerin increased, and urinary deoxypyridolines/creatinine and pyridolines/creatinine ratios decreased, with acute hypothyroidism (P = 0.026, P = 0.003, and P < 0.001 respectively). Urinary deoxypyridolines/creatinine ratio, pyridolines/creatinine ratio, and serum osteocalcin during hypothyroidism were lower compared with those of healthy controls (P = 0.023, P = 0.019, and P = 0.011 respectively). Serum osteoprotegerin concentrations were higher in postmenopausal patients when compared with premenopausal ones, irrespective of the changes in thyroid function (P = 0.001).

Conclusion: Serum osteoprotegerin concentrations increase following acute hypothyroidism after T4 withdrawal in women with differentiated thyroid carcinoma, and also with postmenopausal status.
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

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

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 Inevitability of Infidelity: Sexual Reputation, Social Geographies, and Marital HIV Risk in Rural Mexico
Authors: Hirsch Jennifer S. , Meneses Sergio , Thompson Brenda , Negroni Mirka , Pelcastre Blanca , del Rio Carlos
Published: April 2007

Marriage presents the single greatest risk for HIV infection among women in rural Mexico. We drew on 6 months of participant observation, 20 marital case studies, 37 key informant interviews, and archival research to explore the factors that shape HIV risk among married women in one of the country’s rural communities. We found that culturally constructed notions of reputation in this community lead to sexual behavior designed to minimize men’s social risk (threats to one’s social status or relationships), rather than viral risk and that men’s desire for companionate intimacy may actually increase women’s risk for HIV infection. We also describe the intertwining of reputation-based sexual identities with structurally patterned sexual geographies (i.e. the social spaces that shape sexual behavior). We propose that, because of the structural nature of men’s extramarital sexual behavior, intervention development should concentrate on sexual geographies and risky spaces rather than risky behaviors or identities.
Modern Marriage, Men’s Extramarital Sex, and HIV Risk in Southeastern Nigeria
Authors: Smith Daniel Jordan
Published: April 2007

For women in Nigeria, as in many settings, simply being married can contribute to the risk of contracting HIV. I studied men’s extramarital sexual behavior in the context of modern marriage in southeastern Nigeria. The results indicate that the social organization of infidelity is shaped by economic inequality, aspirations for modern lifestyles, gender disparities, and contradictory moralities. It is men’s anxieties and ambivalence about masculinity, sexual morality, and social reputation in the context of seeking modern lifestyles—rather than immoral sexual behavior and traditional culture—that exacerbate the risks of HIV/AIDS.
The Response of Bovine Spermatozoa to Bicarbonate and Its Use to Assess the Influence of Added Oviductal Epithelial Proteins on Cryopreservation
Authors: Prathalingam Niledran S. , Watson Paul F. , Revell Stuart G. , Busby Jennifer , Holt William V.
Published: April 2007

ABSTRACT: The oviduct is a crucial organ for fertilization and has been demonstrated to perform a variety of interactions with spermatozoa ranging from sperm storage, to stabilizing sperm membranes and reducing free radicals. The oviduct is separated into 2 anatomically and physiologically distinct regions: the isthmus, in which sperm are stored, and the ampulla where fertilization occurs. We aimed to investigate whether proteins derived from different regions of the bovine oviduct had beneficial effects on bovine sperm membrane integrity, osmotic resistance, and motility following cryopreservation. The extent to which sperm motility could be activated by bicarbonate was demonstrated and used as a novel approach to postthaw sperm assessment. While oviductal proteins did not increase the degree of postthaw sperm viability, spermatozoa exposed to the isthmic proteins before freezing showed higher osmotic resistance after thawing. The presence of bicarbonate increased the proportion of spermatozoa with high curvilinear (VCL) and straight line velocity (VSL) in all treatment groups. After thawing, spermatozoa exposed to isthmic proteins had higher VCL and VSL than spermatozoa exposed to the ampullar proteins. We conclude that proteins derived from the isthmus can stabilize and protect spermatozoa during cryopreservation.
Breast Cancer from Oral and Transdermal Estradiol: A Cohort Study of Finnish Women
Authors: Wong Tanping , Shah Nirav R
Published: April 2007

Evaluation of: Lyytinen H, Pukkala E, Ylikorkala O: Breast cancer risk in postmenopausal women using estrogen-only therapy. Obstet. Gynecol. 108(6), 1354–1360 (2006) [ 1 ]. A cohort study of 84,729 Finnish women over the age of 50 years who used oral or transdermal estradiol for at least 6 months, followed for the incidence of breast cancer using a national cancer registry. The study was conducted to evaluate whether the risk of breast cancer with estrogen-only therapy varies by dose, constituents or route of administration. A total of 2171 women developed breast cancer, with no increased risk observed for less than 5 years of use, and some risk for greater than 5 years of use for both oral and transdermal routes of administration.
Behavioral Approaches to Weight Control: A Review of Current Research
Authors: Pinto Angela Marinilli , Gokee-LaRose Jessica , Wing Rena R
Published: April 2007

Weight management is a salient issue for women. Studies of behavioral, pharmacological and surgical interventions indicate that women comprise the majority of patients presenting for weight-loss treatment. In this review we discuss the health impact of obesity for women, review behavioral treatments for adult overweight and obesity, and address topics of particular relevance for women, including concerns that weight-loss treatment may precipitate the development of eating pathology, as well as time periods of high risk for weight gain such as pregnancy and menopause.
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 < 0.001) predicted an increased risk of CHD with the NCEP-only group having the highest risk (2.49 [1.66–3.73], P < 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 (<±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.