bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of COX-2–mediated signaling by α3 type IV noncollagenous domain in tumor angiogenesis
Authors: Boosani Chandra Shekhar , Mannam Arjuna P. , Cosgrove Dominic , Silva Rita , Hodivala-Dilke Kairbaan M. , Keshamouni Venkateshwar G. , Sudhakar Akulapalli 
Published: April 2007

AbstractHuman α3 chain, a noncollagenous domain of type IV collagen [α3(IV)NC1], inhibits angiogenesis and tumor growth. These biologic functions are partly attributed to the binding of α3(IV)NC1 to αVβ3 and α3β1 integrins. α3(IV)NC1 binds αVβ3 integrin, leading to translation inhibition by inhibiting focal adhesion kinase/phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 pathways. In the present study, we evaluated the role of α3β1 and αVβ3 integrins in tube formation and regulation of cyclooxygenase-2 (COX-2) on α3(IV)NC1 stimulation. We found that although both integrins were required for the inhibition of tube formation by α3(IV)NC1 in endothelial cells, only α3β1 integrin was sufficient to regulate COX-2 in hypoxic endothelial cells. We show that binding of α3(IV)NC1 to α3β1 integrin leads to inhibition of COX-2–mediated pro-angiogenic factors, vascular endothelial growth factor, and basic fibroblast growth factor by regulating IκBα/NFκB axis, and is independent of αVβ3 integrin. Furthermore, β3 integrin–null endothelial cells, when treated with α3(IV)NC1, inhibited hypoxia-mediated COX-2 expression, whereas COX-2 inhibition was not observed in α3 integrin–null endothelial cells, indicating that regulation of COX-2 by α3(IV)NC1 is mediated by integrin α3β1. Our in vitro and in vivo findings demonstrate that α3β1 integrin is critical for α3(IV)NC1-mediated inhibition of COX-2–dependent angiogenic signaling and inhibition of tumor progression.
Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V>F) mutation
Authors: Passamonti Francesco , Randi Maria Luigia , Rumi Elisa , Pungolino Ester , Elena Chiara , Pietra Daniela , Scapin Margherita , Arcaini Luca , Tezza Fabiana , Moratti Remigio , Pascutto Cristiana , Fabris Fabrizio , Morra Enrica , Cazzola Mario , Lazzarino Mario 
Published: April 2007

Abstract
Essential thrombocythemia (ET) may occur in women of childbearing age. To investigate the risk of pregnancy complications, we studied 103 pregnancies that occurred in 62 women with ET. The 2-tailed Fisher exact test showed that pregnancy outcome was independent from that of a previous pregnancy. The rate of live birth was 64%, and 51% of pregnancies were uneventful. Maternal complications occurred in 9%, while fetal complications occurred in 40% of pregnancies. The Mantel-Haenszel method showed that fetal loss in women with ET was 3.4-fold higher (95% confidence interval [CI]: 3-3.9; P < .001) than in the general population. Half of the women studied carried the JAK2 (617V>F) mutation, and a multivariate logistic regression model identified this mutation as an independent predictor of pregnancy complications (P = .01). Neither the platelet count nor the leukocyte count was a risk factor. JAK2 (617V>F)–positive patients had an odds ratio of 2.02 (95% CI: 1.1 - 3.8) of developing complications in comparison with JAK2 (617V>F)–negative patients. Aspirin did not prevent complication in JAK2 (617V>F)–positive patients and appeared to worsen outcome in JAK2 (617V>F)–negative patients. A relationship was found between JAK2 (617V>F) and fetal loss (P = .05). This study indicates that patients carrying the JAK2 (617V>F) mutation have higher risk of developing pregnancy complications.
Anterior and Posterior Pituitary Function Testing with Simultaneous Insulin Tolerance Test and a Novel Copeptin Assay
Authors: Katan Mira , Morgenthaler Nils G. , Dixit Kashinath C. S. , Rutishauser Jonas , Brabant Georg E. , Müller Beat , Christ-Crain Mirjam 
Published: April 2007

Abstract
Context: Posterior pituitary function in patients with suspected diabetes insipidus is usually assessed by a water deprivation test. Alternatively, a nonosmotic stimulus such as hypoglycemia may be used to stimulate vasopressin [arginine vasopressin (AVP)] secretion. Plasma AVP measurement may aid in the diagnosis and, especially, differential diagnosis of diabetes insipidus and polydipsia. However, AVP measurement is cumbersome. Copeptin, the stable C-terminal glycopeptide of the AVP prohormone, is stoichiometrically secreted from the posterior pituitary.
Objective: The aim was to study the value of copeptin levels in the diagnosis of diabetes insipidus during insulin-induced hypoglycemia.
Patients and Methods: A total of 38 patients were studied during insulin-induced hypoglycemia as part of a combined pituitary function test for possible anterior pituitary disease. There were 29 patients who had normal posterior pituitary function, and nine had central diabetes insipidus. Blood sampling was done before and 30, 45, and 90 min after iv insulin injection. Copeptin was measured with a new sandwich immunoassay.
Results: Patients with intact posterior pituitary function had basal copeptin levels of 3.7 ± 1.5 pm, with a maximal increase to 11.1 ± 4.6 pm 45 min after insulin injection. Copeptin levels in patients with diabetes insipidus were 2.4 ± 0.5 pm before insulin injection, with a maximum increase to 3.7 ± 0.7 pm. Both basal and stimulated copeptin levels were lower in patients with diabetes insipidus as compared with patients with intact posterior pituitary function. A stimulated copeptin level 45 min after insulin injection of less than 4.75 pm had an optimal diagnostic accuracy to detect diabetes insipidus.
Conclusion: Copeptin measurement may be used to assess posterior together with anterior pituitary function during insulin-induced hypoglycemia.
Associations of Adiponectin with Body Fat Distribution and Insulin Sensitivity in Nondiabetic Hispanics and African-Americans
Authors: Hanley Anthony J. G. , Bowden Donald , Wagenknecht Lynne E. , Balasubramanyam Aarthi , Langfeld Carl , Saad Mohammed F. , Rotter Jerome I. , Guo Xiuqing , Chen Yii-Der I. , Bryer-Ash Michael , Norris Jill M. , Haffner Steven M. 
Published: April 2007

Abstract
Context: Hypoadiponectinemia has emerged as an independent risk factor for type 2 diabetes and cardiovascular disease. Although associations of adiponectin with central obesity and insulin resistance have been reported, very little data are available from studies using detailed measures of insulin sensitivity (SI) and/or body fat distribution in ethnic groups at high risk for metabolic disease.
Objective: The aim of the study was to identify the correlates of adiponectin in 1636 nondiabetic Hispanics and African-Americans.
Design: A cross-sectional analysis of participants in the Insulin Resistance Atherosclerosis Family Study was conducted. SI was determined from frequently sampled iv glucose tolerance tests with minimal model analysis. Subcutaneous and visceral adipose tissues (SAT, VAT, respectively) were determined with computed tomography. Triglyceride, high-density lipoprotein, C-reactive protein, and adiponectin were measured in fasting samples. Generalized estimating equation (GEE) models were used to identify factors associated with adiponectin concentration.
Setting: A multicenter study using a family-based design was conducted.
Participants: A total of 1636 nondiabetic Hispanic and African-American subjects participated.
Main Outcome Measures: Circulating adiponectin concentration was measured.
Results: Age, female gender, high-density lipoprotein, SAT, and SI were positive independent correlates of adiponectin, whereas glucose, CRP, and VAT were negative independent correlates (all P &lt; 0.05). Ethnicity was not an independent correlate of adiponectin in this model (P = 0.27); however, an ethnicity by VAT interaction term was retained, indicating a stronger negative association of VAT with adiponectin in African-Americans compared with Hispanics.
Conclusion: Directly measured SI, VAT, and SAT were independently correlated with adiponectin in Hispanic and African-American subjects. The inverse association of VAT with adiponectin was stronger in African-Americans compared with Hispanics, a finding that suggests possible ethnic differences in the effects of visceral obesity.
Effects of Combined Recombinant Insulin-Like Growth Factor (IGF)-I and IGF Binding Protein-3 in Type 2 Diabetic Patients on Glycemic Control and Distribution of IGF-I and IGF-II among Serum Binding Protein Complexes
Authors: Clemmons D. R. , Sleevi M. , Allan G. , Sommer A. 
Published: April 2007

Abstract
Context: Administration of recombinant human IGF-I (rhIGF-I)/recombinant human IGF binding protein-3 (rhIGFBP-3) to patients with type 2 diabetes improves blood glucose and enhances insulin sensitivity. The changes in various components of the IGF system that occur in response to rhIGF-I/rhIGFBP-3 as well as the minimum effective dose have not been determined.
Objectives: The aim was to determine the dose of rhIGF-I/rh-IGFBP-3 necessary to achieve a significant decrease in glucose and to determine the changes that occur in the IGF-II and acid labile subunit in response to treatment.
Design: A total of 39 insulin-requiring type 2 diabetics were randomized to placebo or one of six groups that received different dosages of rhIGF-I/rhIGFBP-3. After 3 d in which insulin doses were adjusted to improve glucose control, a variable insulin dosage regimen was continued, and either placebo or one of six dosages (0.125–2.0 mg/kg·d) of rhIGF-I/rhIGFBP-3 was administered for 7 d. All subjects were hospitalized, and dietary intake as well as insulin dosage were controlled with instructions to treat to normal range targets.
Results: Fasting glucose was reduced in the groups that received either 1 (32 ± 5% reduction) or 2 mg/kg·d (40 ± 6% reduction) of the complex. Mean daily glucose (four determinations) was reduced by 26 ± 4% in the 1 mg/kg group and by 33 ± 5% in the 2 mg/kg group compared with 18 ± 4% in the placebo group. Total serum IGF-I increased between 2.0 ± 0.3- and 5.7 ± 1.3-fold by d 8. IGFBP-3 concentrations increased significantly only in the 2 mg/kg group. IGF-II concentrations declined to values that were between 27 ± 4% and 64 ± 7% below baseline. Acid labile subunit concentrations declined significantly in the three highest dose groups. The sum of the IGF-I + IGF-II concentrations was significantly increased at the two highest dosages. There were very few drug-associated adverse events reported in this study with the exception of hypoglycemia, which occurred in 15 subjects who had received rhIGF-I/rhIGFBP-3 treatment.
Conclusions: Administration of rhIGF-I/rhIGFBP-3 resulted in a redistribution of the amount of IGF-I and IGF-II that bound to IGFBP-3. Fasting and mean daily blood glucose were reduced significantly in the two highest dosage groups. The results suggest that both the total concentration of IGF-I as well as its distribution in blood may determine the extent to which insulin sensitivity is enhanced.
Effects of Testosterone Therapy on Cardiovascular Risk Markers in Androgen-Deficient Women with Hypopituitarism
Authors: Miller K. K. , Biller B. M. K. , Schaub A. , Pulaski-Liebert K. , Bradwin G. , Rifai N. , Klibanski A. 
Published: April 2007

Abstract
Context: Low-dose testosterone replacement therapy in women with relative androgen deficiency has been shown to have beneficial effects on body composition, bone mass, and psychosexual function. However, the safety of chronic testosterone administration on cardiovascular risk and insulin resistance is unknown.
Objective: The aim of the study was to determine the effects of physiological testosterone replacement on cardiovascular risk markers and insulin resistance in women.
Design: A 12-month, randomized, placebo-controlled study was conducted.
Setting: A General Clinical Research Center was the setting for the study.
Study Participants: A total of 51 women of reproductive age with androgen deficiency due to hypopituitarism participated.
Intervention: Study participants were randomized to physiological testosterone administration, 300 μg daily, or placebo, by patch.
Main Outcome Measures: We measured fasting glucose, fasting insulin, insulin-resistance homeostasis model of assessment (IRHOMA), quantitative insulin sensitivity check index (QUICKI), high-sensitivity C-reactive protein, vascular cell adhesion molecule (VCAM), leptin, lipoprotein (a), apolipoprotein A1, and homocysteine.
Results: At 12 months, fasting insulin and IRHOMA were significantly lower in the testosterone compared with the placebo group, and there was a trend toward a higher QUICKI level at 12 months in the testosterone compared with the placebo group. These differences were no longer significant after controlling for baseline levels. We observed no effect, either positive or negative, of testosterone administration on high-sensitivity C-reactive protein, VCAM leptin, lipoprotein (a), or apolipoprotein A1.
Conclusions: Our data suggest that physiological testosterone replacement in women with hypopituitarism for 12 months does not increase, and may improve, insulin resistance. Chronic low-dose testosterone administration does not increase markers of cardiovascular disease reflecting several different mechanistic pathways. Large, randomized, placebo-controlled, long-term prospective studies are needed to determine whether low-dose testosterone replacement affects cardiovascular risk and event rates in women.
Signal Transducer and Activator of Transcription (Stat) 5b-Mediated Inhibition of Insulin-Like Growth Factor Binding Protein-1 Gene Transcription: A Mechanism for Repression of Gene Expression by Growth Hormone
Authors: Ono Mitsuru , Chia Dennis J. , Merino-Martinez Roxana , Flores-Morales Amilcar , Unterman Terry G. , Rotwein Peter 
Published: April 2007

Abstract
GH plays a central role in controlling somatic growth, tissue regeneration, and intermediary metabolism in most vertebrate species through mechanisms dependent on the regulation of gene expression. Recent studies using transcript profiling have identified large cohorts of genes whose expression is induced by GH. Other results have demonstrated that signal transducer and activator of transcription (Stat) 5b, a latent transcription factor activated by the GH receptor-associated protein kinase, Jak2, is a key agent in the GH-stimulated gene activation that leads to somatic growth. By contrast, little is known about the steps through which GH-initiated signaling pathways reduce gene expression. Here we show that Stat5b plays a critical role in the GH-regulated inhibition of IGF binding protein-1 gene transcription by impairing the actions of the FoxO1 transcription factor on the IGF binding protein-1 promoter. Additional observations using transcript profiling in the liver indicate that Stat5b may be a general mediator of GH-initiated gene repression. Our results provide a model for understanding how GH may simultaneously stimulate and inhibit the expression of different cohorts of genes via the same transcription factor, potentially explaining how GH action leads to integrated biological responses in the whole organism.
Hes1 and Hes5 Control the Progenitor Pool, Intermediate Lobe Specification, and Posterior Lobe Formation in the Pituitary Development
Authors: Kita Aya , Imayoshi Itaru , Hojo Masato , Kitagawa Masashi , Kokubu Hiroshi , Ohsawa Ryosuke , Ohtsuka Toshiyuki , Kageyama Ryoichiro , Hashimoto Nobuo 
Published: April 2007

AbstractThe pituitary gland is composed of two distinct entities: the adenohypophysis, including the anterior and intermediate lobes, and the neurohypophysis, known as the posterior lobe. This critical endocrine organ is essential for homeostasis, metabolism, reproduction, and growth. The pituitary development requires the control of proliferation and differentiation of progenitor cells. Although multiple signaling molecules and transcription factors are required for the proper pituitary development, the mechanisms that regulate the fate of progenitor cells remain to be elucidated. Hes genes, known as Notch effectors, play a crucial role in specifying cellular fates during the development of various tissues and organs. Here, we report that mice deficient for Hes1 and Hes5 display severe pituitary hypoplasia caused by accelerated differentiation of progenitor cells. In addition, this hypoplastic pituitary gland (adenohypophysis) lacks the intermediate lobe and exhibits the features of the anterior lobe only. Hes1 and Hes5 double-mutant mice also lack the neurohypophysis (the posterior lobe), probably due to incomplete evagination of the diencephalon. Thus, Hes genes control not only maintenance of progenitor cells but also intermediate vs. anterior lobe specification during the adenohypophysis development. Hes genes are also essential for the formation of the neurohypophysis.
Terbinafine-Induced Acute Autoimmune Hepatitis in the Setting of Hepatitis B Virus Infection
Authors: Paredes Angelo H , Lewis James H 
Published: April 2007

Objective: To report a case of terbinafine-induced autoimmune hepatitis in a patient with chronic hepatitis B infection. Case Summary: A 57-year-old Taiwanese male with chronic hepatitis 8 virus (HBV) began an oral regimen of terbinafine 250 mg once daily for dermatophyte toenail onychomycosis, despite the manufacturer's recommendation not to use the drug in patients with liver dysfunction. The patient's liver enzyme levels were within normal limits at initiation of therapy. Immediately prior to concluding the 12 week treatment course, he became anorexic with malaise and subsequently developed ascites and jaundice. After a visit to an outside emergency department and positively trending liver function test levels, he was referred to our liver clinic. The patient was taking no other medications or herbal supplements, did not drink alcohol, and did not appear to suffer a flare of HBV infection. The diagnosis was supported by the presence of transient autoantibodies and a liver biopsy consistent with acute autoimmune drug injury. Three weeks after terbinafine was discontinued, peak levels of aspartate aminotransferase (1282 IU/L), alanine aminotransferase (1044 IU/L), and bilirubin (5.9 mg/dL) were noted; his platelet level had decreased to 77 × 103/mm3. He was treated with supportive care that included vitamin K for coagulopathy, diuretics for ascites, and adefovir to prevent hepatitis B exacerbation. The patient's liver function studies began to normalize 6 weeks after terbinafine was discontinued. Discussion: Terbinafine-induced hepatobiliary dysfunction, due to hepatocellular injury, cholestasis, or mixed form, has been reported, but this is the first case of autoimmune hepatitis supported by serologic, biochemical, and biopsy results. Use of the Naranjo probability scale revealed a probable relationship between the patient's hepatitis and terbinafine. Furthermore, the Roussel Uclaf Causality Assessment Method, a scoring system that specifically assesses the likelihood of drug-induced elevated levels of liver-associated enzymes, also supported a probable relationship. The pathogenesis of most drug-induced autoimmune hepatitis remains speculative, likely involving hapten-carrier complex and the cytochrome P450 isoenzymes. In this patient, his chronic HBV carrier state may have predisposed him to this autoimmune reaction. Conclusions: Healthcare practitioners should heed the manufacturer's warning that terbinafine not be used in patients with underlying hepatic disease.
Bazedoxifene: A Third-Generation Selective Estrogen Receptor Modulator for Treatment of Postmenopausal Osteoporosis
Authors: Stump Amy L , Kelley Kristi W , Wensel Terri M 
Published: April 2007

Objective: To review clinical studies and other available literature regarding the development, pharmacology, toxicology, pharmacokinetics/pharmacodynamics, adverse effects, and place in therapy of bazedoxifene, a selective estrogen receptor modulator (SERM), currently in Phase III clinical trials for the treatment and prevention of postmenopausal osteoporosis. Data Sources: A literature search was performed of PubMed (1966–February 2007). International Pharmaceutical Abstracts (1970–February 2007), Web of Science (1975–February 2007), Biological Abstracts (1926–2007), and Google Scholar (2001–February 2007) databases, using the search terms bazedoxifene, TSE-424, Indole-33, WAY-140424, selective estrogen receptor modulator, and SERM. In addition, product information was requested from the manufacturer, and www.clinicaltrials.gov was searched for unpublished Phase III clinical trials in progress. Study Selection and Data Extraction: Articles on Phase I and II trials were selected for review, as well as articles discussing preclinical development of bazedoxifene. At the time of writing, no articles on Phase III trials were available for review. Abstracts of unpublished data were reviewed, as was information provided by the manufacturer. Data Synthesis: Bazedoxifene is a third-generation SERM currently in Phase III clinical trials. It has been found to act as an agonist on skeletal tissue, with bone turnover reduced by 20–25% with doses of 20 or 40 mg daily. In addition, bazedoxifene has been found to be an antagonist on breast tissue and uterine tissue, demonstrating inhibition of breast tissue proliferation and decreased endometrial stimulation as the dose is increased. Conclusions: Current literature suggests that bazedoxifene will likely be safe and effective when used in the treatment of postmenopausal osteoporosis. Completion of Phase III clinical trials will more fully elucidate the safety and efficacy profile of bazedoxifene, as well as more clearly define its place in therapy.
Drug-Induced Sweet's Syndrome
Authors: Thompson Dennis F , Montarella Kristin E 
Published: April 2007

Objective: To systematically review the pertinent literature on drug-induced Sweet's syndrome (SS). Data Sources: MEDLINE (1966–December 2006), International Pharmaceutical Abstracts (1970–December 2006), Science Citation Index (1945–December 2006), and EMBASE (1980–December 2006) were searched using the key terms Sweet's syndrome, drug-induced, and acute neutrophilic dermatitis. Study Selection and Data Extraction: All case reports of drug-induced SS located using the above databases were collected for causality assessment. In addition, relevant articles regarding the various causes and presentations of SS were selected to provide background information. Bibliographies of all relevant articles were reviewed for additional citations. Data Synthesis: All case reports of drug-induced SS were evaluated against an expanded Naranjo scale with specific criteria for SS. Tables were developed listing key criteria for evaluating the case reports for causality. Data were evaluated by quantity and quality of evidence, and an assessment was made as to whether there was a feasible pharmacologic mechanism to explain causality. Conclusions: Granulocyte colony-stimulating factor (G-CSF), all-trans retinoic acid (ATRA), and vaccines met 2 of 3 criteria for an association with SS. There are sufficient data and a plausible pharmacologic mechanism for G-CSF and ATRA. Vaccines meet the qualitative criteria and also have a plausible pharmacologic mechanism. The evidence regarding minocycline is of high quality; however, the quantity of evidence and a reasonable pharmacologic mechanism are lacking. A host of miscellaneous drugs have also been implicated in causing the disorder, all without sufficient evidence.