bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peroxisome Proliferator-Activated Receptor α L162V Polymorphism in Nonalcoholic Steatohepatitis and Genotype 1 Hepatitis C Virus-Related Liver Steatosis
Authors: Verdi Hasibe , Sare Koytak Elif , Önder Oğuz , Arslan Ergül Ayça , Cinar Kubilay , Idilman Ramazan , Erden Esra , Mithat Bozdayi Abdurrahman , Yurdaydin Cihan , Uzunalimoglu Özden , Bozkaya Hakan 
Published: August 2007

BackgroundPeroxisome proliferator-activated receptor α (PPARα) plays important roles in lipid metabolism. A recently discovered L162V polymorphism of the PPARα gene is associated with enhanced transcriptional activity. In this study, the frequency of L162V was investigated in nonalcoholic steatohepatitis (NASH) and genotype 1 hepatitis C virus (HCV)-related liver steatosis.MethodsSeventy-two NASH and 141 HCV-infected patients (54 with steatosis, 87 without steatosis) and 119 healthy controls were included. L162V polymorphism of the PPARα gene was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).ResultsPCR and RFLP analysis of the related gene segment was successful in 93%, 96%, and 100% of NASH and HCV-infected patients and controls, respectively. The frequency of the L162V polymorphism was similar in the NASH and HCV-infected patients and controls (5.9%, 3.6%, and 2.5%, respectively). No difference in the frequency of this polymorphism was observed in HCV-infected patients with or without significant liver steatosis. L162V was not associated with obesity, type 2 diabetes mellitus, hypercholesterolemia, or hypertriglyceridemia.ConclusionsNeither NASH nor genotype 1 HCV-related liver steatosis seems to be associated with the PPARα L162V polymorphism. This polymorphism may have no association with the presence of type 2 diabetes mellitus, obesity, or various blood lipid alterations in NASH and HCV-infected patients.
Supportive Programs Increase Medical Students’ Research Interest and Productivity
Authors: Zier Karen , Friedman Erica , Smith Lawrence 
Published: August 2007

Background Advances in biomedical research during the last decade have highlighted the necessity of attracting greater numbers of physicians to careers that include a research component. Physician participation in research is essential to increase the number of clinical and translational studies performed, as well as to educate the public about the importance of clinical trials and to assist in recruiting participants. We hypothesized that attractive research opportunities that included faculty mentoring, recognition of participation, and rewards for accomplishments would encourage medical student participation. Methods The Medical Student Research Office was created at Mount Sinai School of Medicine in 1996 to develop structured research programs and advise students looking to undertake a research project. Data from students participating in the summer research program and Medical Student Research Day, from the research section of the Medical Student Performance Evaluation, were collected from 1996 to 2004. Results For the last 4 years, the majority of medical students did research following the first year of school. Students did basic and clinical research, although most preferred clinically oriented or translational projects. Participation in Research Day and the number of publications suggest that interest is growing, including that by traditionally underrepresented groups. Conclusion Although it is too early to assess the long-term effects, the research programs offered led to greater numbers of students who did research, including those in traditionally underrepresented groups. Moreover, students were highly satisfied with their experiences, with 80% feeling that it increased their interest in applying principles they learned to the practice of medicine.
Proinflammatory Reaction and Cytoskeletal Alterations in Endothelial Cells after Shock Wave Exposure
Authors: Sondén Anders , Johansson Anne-Sofie M. , Palmblad Jan , Kjellström Thomas B. 
Published: August 2007

Background Although the effects on human organs by shock waves (SWs) induced by medical treatments or high-energy trauma are well recognized, little is known about the effects on the cellular level. Since blood vessel injury is a common finding after SW exposure, we assessed the in vitro effects of SWs on human umbilical vein endothelial cells (HUVECs). Methods An in vitro trauma model was used to expose HUVEC monolayers to focused SWs or to shock waves plus cavitation (SWC), a subsequent phenomenon that is often considered the main cause of SW vascular injury. Results SWs alone did not cause any changes in the studied variables. In contrast, HUVEC monolayers exposed to SWC exhibited discrete central lesions with extensive cell death. Cells peripheral to the main lesion area displayed disassembly of dense peripheral bands and formation of actin stress fibers, indicating increased intercellular gaps. Expression of P-selectin was enhanced 11-fold compared with controls, whereas expression of E-selectin and intercellular adhesion molecule 1 was enhanced 8-fold ( p < .05) and 1.5-fold ( p < .01), respectively. The latter responses were preceded by nuclear translocation of nuclear factor κB subunit p65 by 16% ( p < .01). When compared with mechanically produced lesions used as controls, SWC lesions exhibited an impaired regeneration rate of the endothelial cell layer ( p < .001). Redistribution of centrosomes toward the lesion borders was less effective in the SWC samples compared with the mechanically produced lesions ( p < .01). Conclusions SWC lesions were associated with a switch to an endothelial proinflammatory phenotype, with an impaired regeneration rate and changes in cytoskeletal functions.
Does Waiver of Written Informed Consent from the Institutional Review Board Affect Response Rate in a Low-Risk Research Study?
Authors: Krousel-Wood Marie , Muntner Paul , Jannu Ann , Hyre Amanda , Breault Joseph 
Published: August 2007

Background Requiring written informed consent for a minimal-risk survey may result in limited participation rates. Methods Data from a cross-sectional survey of 177 older patients (87 blacks and 90 whites) with hypertension enrolled in the managed care Medicare risk product were used to assess participation rates pre- and postwaiver of written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization. Prior to the waivers being granted, patients were contacted two times via mail with an introductory letter and an informed consent document. Those who completed and returned the informed consent document were administered the questionnaire. After 6 weeks, a waiver of written informed consent and HIPAA authorization was obtained from the Institutional Review Board. Nonparticipants were reapproached and asked to complete the questionnaire. Participation rates were recorded before and after receiving the waivers. Results Participation rates increased from 21.5% in the prewaiver period to 57.4% in the postwaiver period ( p < .001). Prewaiver participation differed by demographic subgroup and was higher among whites (26.7%) versus blacks (16.1%; p = .087), men (31.6%) versus women (16.7%; p = .024), and participants ≥ 75 years old (28.4%) versus < 75 years old (14.6%; p = .025). In contrast, the postwaiver participation rate did not differ significantly across race, gender, or age subgroupings. Significant increases in participation rates from the pre- to the postwaiver time period were noted within each demographic subgroup (all p < .01). Conclusions We identified a substantial increase in participation rates postwaiver of written informed consent and HIPAA authorization in a minimal-risk survey. The need for written documentation for minimal-risk surveys may negatively impact recruitment of blacks, women, and patients < 75 years old.
Changes in Central Arterial Pressure Waveforms during the Normal Menstrual Cycle
Authors: Ounis-Skali Nadia , Mitchell Gary F. , Solomon Caren G. , Solomon Scott D. , Seely Ellen W. 
Published: August 2007

Background Changes in estradiol and progesterone during the human menstrual cycle may impact vascular and cardiac function. Renin-angiotensin-aldosterone system (RAAS) hormones increase during the luteal phase of the menstrual cycle and may antagonize the vascular effects of estradiol. This study was designed to investigate central arterial changes, cardiac function, and RAAS activity in response to gonadal steroid variations during the menstrual cycle. Methods We studied 15 women during the follicular and midluteal phases with determination of estradiol, progesterone, hormones of the RAAS, and spot urine sodium and creatinine levels. Central pulsatile hemodynamics was evaluated using calibrated carotid tonometry and central aortic Doppler flow. Systolic ejection period (SEP) and systolic pressure time integral (SPTI) were computed from carotid pressure waveforms. Results Levels of estradiol, progesterone, and RAAS hormones were higher in the luteal phase. SEP and SPTI were lower during the luteal phase, whereas central and peripheral blood pressures and measures of arterial stiffness were unchanged between the two phases. The urine sodium-to-creatinine ratio was similar at both phases. Conclusion Central arterial stiffness does not differ between the follicular and midluteal phases of the menstrual cycle in healthy women, despite significant changes in estradiol and progesterone levels. Systole was shortened during the midluteal phase. RAAS activation during the luteal phase may be responsible for a lack of the expected estradiol-mediated reduction in arterial stiffness between the two phases of the menstrual cycle. Because load was unchanged, the decrease in SEP and SPTI may represent a direct effect of estrogen, progesterone, or RAAS activation on ventricular function.
Effects of Antenatal Betamethasone on Maternal and Fetoplacental Matrix Metalloproteinases 2 and 9 Activities in Human Singleton Pregnancies
Authors: Gharraee Zahra , Beharry Kay D.A. , Valencia Arwin M. , Cho Steve , Guajardo Leonel , Nageotte Michael P. , Modanlou Houchang D. 
Published: August 2007

Background A single course of antenatal betamethasone is administered to women at risk of preterm labor to advance fetal lung maturation. Matrix metalloproteinases (MMPs) are collagen-degrading enzymes that remodel extracellular matrix components during lung development. We tested the hypothesis that the effects of betamethasone on fetal lung maturation involve changes in MMP activity. Methods We conducted a prospective, observational pilot study of three groups of singleton pregnancies. Group 1 ( n = 21) was composed of women who were antenatally treated with a single course of betamethasone and who delivered < 37 weeks of gestation, group 2 ( n = 7) was composed of matched untreated women who delivered < 37 weeks of gestation, and group 3 ( n = 15) was composed of untreated women who delivered > 37 weeks of gestation. Maternal blood, mixed cord blood, and placental samples were collected at the time of delivery for MMP-2 and MMP-9 activity and tissue inhibitor of metalloproteinases (TIMP)-1 and -2 levels. Results MMP-2 activity was significantly higher in the maternal, placental, and fetal compartments in group 1 compared with group 2 ( p < .05). TIMP-2 levels were lower in groups 1 and 2 compared with group 3. Maternal TIMP-2 levels were higher ( p < 0.003), whereas fetal TIMP-1 ( p < .01) and MMP-9 to TIMP-1 ratios ( p < .05) were lower when delivery was delayed more than 2 weeks following betamethasone treatment. Conclusion We conclude that elevated MMP-2 activity in the maternal and fetoplacental compartments may suggest a mechanism, in part, for betamethasone-induced fetal lung maturation.
Relationship of Serum Interleukin-6 and Tumor Necrosis Factor α Levels with Abdominal Fat Distribution Evaluated by Ultrasonography in Overweight or Obese Postmenopausal Women
Authors: Fenkci Semin , Rota Simin , Sabir Nuran , Sermez Yurdaer , Guclu Aydin , Akdag Beyza 
Published: August 2007

Background The objective of this study was to measure associations of circulating interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels with anthropometric and abdominal fat distribution in overweight or obese postmenopausal women. Methods One hundred eight overweight or obese postmenopausal were evaluated. Demographic and anthropometric measurements were done. Serum IL-6, TNF-α, glucose, and insulin levels were measured. Insulin resistance was calculated by using homeostasis model assessment-insulin resistance (HOMA-IR). The assessment of abdominal fat distribution was performed by ultrasonography. Statistical analysis was made with Pearson and partial correlation analysis. Results There was a positive correlation between serum IL-6 and TNF-α ( r = .19; p = .047). IL-6 was positively correlated with body mass index (BMI) ( r = .43; p = .0001), waist circumference ( r = .41; p = .0001), and visceral fat layer ( r = .33; p = .0001) measurements and HOMA-IR index ( r = .31, p = .001). A positive relationship between HOMA-IR and visceral fat layer thickness was observed ( r = .320; p = .0001). TNF-α was positively associated with BMI but not with any measures of central obesity. When adjustment for BMI was performed, there were no significant relationships between the studied parameters. Conclusions There are no significant correlations between abdominal fat distributions measured by ultrasonography and circulating IL-6 and TNF-α levels. BMI may have a stronger association with circulating inflammatory cytokine concentrations than with different measures of central obesity in overweight or obese postmenopausal women.
Embryonic Exposure to Low-Dose 17β-Estradiol Decreases Fetal Mass Sex Specifically in Male Mice and Does Not Cause Hypospadias
Authors: Blaschko Sarah D. , Willingham Emily J. , Baskin Laurence S. 
Published: August 2007

Background Endocrine-disrupting compounds are synthetic and natural compounds in the environment that can alter endocrine-governed developmental processes. Among these are the natural estrogens genistein, a plant isoflavone, and 17β-estradiol (E2), which is present in dietary animal products, such as eggs and meat. In addition, natural and synthetic steroids are administered to beef cattle to promote growth, and low levels of the estrogens can persist in the beef. Most previous work using E2 has involved injection; however, oral administration results in a different suite of hormone products following first-pass metabolism in the liver. Methods Low doses of E2 were administered orally to pregnant dams to determine embryonic effects. As end points of effects, we examined whether embryonic exposure produced hypospadias, an endocrine-linked abnormality of the male genitalia, and we assessed fetal mass. Results Male fetuses from the two highest dosage groups were significantly smaller than their control male counterparts, and males from the highest dosage group were also significantly smaller than control females. Control males were significantly larger than all females, and there was no difference in mass among control and treated females. Additionally, the E2 dose was inversely correlated with mass overall. No effect of these doses of E2 on hypospadias was seen. Conclusions These results indicate a sex-specific fetal effect of low-dose, orally administered E2, which appears to exert androgen-inhibiting effects on mass in males.
Cell Biology of Pathologic Renal Calcification: Contribution of Crystal Transcytosis, Cell-Mediated Calcification, and Nanoparticles
Authors: Kumar Vivek , Farell Gerard , Yu Shihui , Harrington Sean , Fitzpatrick Lorraine , Rzewuska Ewa , Miller Virginia M. , Lieske John C. 
Published: August 2007

Introduction The earliest lesion in the kidneys of idiopathic calcium oxalate stone formers is deposition of calcium phosphate in the interstitium, termed a Randall's plaque. Yet the cellular and molecular factors leading to their formation are unknown. Methods The influence of urinary proteins on adhesion of preformed calcium oxalate crystals to rat continuous inner medullary collecting duct (cIMCD) cells was studied in vitro, and cIMCD cells were also exposed to calcifying media containing β-glycerophosphate for up to 28 days. Renal tissue was obtained from a stone-forming and non-stone-forming individual at the time of nephrectomy. These nanoparticles, isolated from renal stones obtained at the time of surgical resection, were analyzed and propagated in standard cell culture medium. Results Urinary proteins influence crystal adhesion to renal epithelial cells, and this activity is abnormal in the urine of stone-forming patients. cIMCD cells assumed an osteoblastic phenotype when exposed to the calcifying medium, expressing two bone matrix proteins (osteopontin and bone sialoprotein) that were also identified in the kidney of the stone-forming patient and associated with crystal deposition. Nanoparticles were propagated from the majority of renal stones. Isolates were susceptible to selected metabolic inhibitors and antibiotics and contained conserved bacterial proteins and deoxyribonucleic acid (DNA). Conclusions These results suggest new paradigms for Randall's plaque formation and idiopathic calcium oxalate stone disease. It seems unlikely that these events are driven solely by physical chemistry; rather, they are critically influenced by specific proteins and cellular responses, and understanding these events will provide clues toward novel therapeutic targets.
Etiology of Decreased Gastric Nitric Oxide in the Critically Ill
Authors: Boivin Michel A. , Fiack Christopher A. , Kennedy John C. , Iwamoto Gary K. 
Published: August 2007

Background Nitric oxide (NO) is present in the gas phase of the normal human stomach at a high concentration (1-10 ppm). The majority of this NO is produced from the reduction of dietary nitrate to nitrite and finally NO. Generation of this nonenzymatically produced gastric NO occurs only in an acidic environment. We examined NO concentrations in critically ill subjects and the mechanism for the observed perturbations. Methods Seven critically ill, intubated intensive care unit (ICU) patients (mean APACHE II score 16) and seven control patients were studied. Gastric NO concentrations were measured with a Sievers NO analyzer (GE, Boulder, CO). Nitrate and nitrite concentrations were determined by a modified Griess assay. Bacterial counts were determined by optical density at 600 nm. Results Gastric NO concentration was significantly lower in the critically ill group (102.7 ppb) compared with the control group (953.2 ppb), although this difference was abolished by treating the control group with omeprazole (54 ppb). Gastric nitrate and nitrite concentrations were similar in the control and ICU groups, suggesting that substrate deficiency was not a cause of the low intragastric NO. Gastric pH was significantly lower in the control subjects (3.0) compared with the ICU patients (6.3) and the control subjects after receiving omeprazole (6.5). ICU patients had a trend toward higher gastric bacterial load. Conclusion In critically ill patients, markedly decreased NO concentrations are found in the gas of the stomach owing to a failure of gastric acidification.
Regulation of Vascular Proteoglycan Synthesis by Metabolic Factors Associated with Diabetes
Authors: Wilson Patricia , Drennon Katherine , Tannock Lisa R. 
Published: August 2007

Background Diabetes is associated with accelerated atherosclerosis, but the mechanisms responsible for this are not known. Proteoglycans have been shown to play a critical role in the initiation of atherosclerosis owing to their ability to bind and retain atherogenic lipoproteins in the artery wall. Proteoglycan structure and composition are altered in atherosclerotic lesions compared with adjacent normal regions of the artery wall, and this is exaggerated in diabetes. The purpose of this study was to determine if metabolic factors associated with diabetes lead to altered proteoglycan structure and composition. Methods Vascular smooth muscle cells, endothelial cells, and macrophages were exposed to normal (5.6 mmol/L) or high (25 mmol/L) glucose levels, various insulin and free fatty acid levels, and the cytokines transforming growth factor β (TGF-β1) and platelet-derived growth factor, alone or in combination, and proteoglycan synthesis was determined. Results Glucose concentrations, insulin, and free fatty acids did not alter proteoglycan synthesis, size, or relative distribution. The effect of TGF-β to increase biglycan and versican synthesis, increase sulfate incorporation, and increase the size of the secreted proteoglycans was not altered by the ambient glucose level in the culture medium, nor did high glucose increase levels of active TGF-β. Conclusion Vascular proteoglycan synthesis is not affected by metabolic factors associated with diabetes. We suggest that elevated TGF-β levels in diabetes are responsible for the altered proteoglycan synthesis observed in diabetes.
Plasma Cytokines, Metabolic Syndrome, and Atherosclerosis in Humans
Authors: Reilly Muredach P. , Rohatgi Anand , McMahon Kimberly , Wolfe Megan L. , Pinto Shailesh C. , Rhodes Thomas , Girman Cynthia , Rader Daniel J. 
Published: August 2007

Background Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) integrate inflammatory and adipose signaling but also have direct vascular effects. We hypothesized that plasma levels of IL-6 and soluble tumor necrosis factor α receptor 2 (sol-TNFR2) would be related to coronary atherosclerosis beyond established risk factors and the metabolic syndrome. Methods We examined the association of IL-6 and sol-TNFR2 with metabolic syndrome, C-reactive protein (CRP), and coronary artery calcification (CAC) in 875 asymptomatic participants in the Study of Inherited Risk of Coronary Atherosclerosis. Results IL-6 levels were 56% higher ( p < .001) and sol-TNFR2 levels 16% higher ( p < .001) in subjects with metabolic syndrome compared with those without. Both cytokines were associated with CAC beyond age, gender, Framingham risk scores, family history, metabolic syndrome, and CRP (odds ratio and 95% confidence interval of higher CAC for 1 SD increase in log-transformed cytokine levels: 1.23 [1.06-1.43], p = .006 for IL-6 and 1.15 [1.01-1.31], p = .04 for sol-TNFR2). In fact, cytokine levels were independently associated with CAC scores in the subgroup with metabolic syndrome and were additive to the homeostasis model assessment of insulin resistance in predicting CAC. Conclusions Plasma IL-6 and sol-TNFR2 levels were independently associated with CAC, suggesting a role in integrating innate immune and adipose signaling in promoting atherosclerosis and cardiovascular risk. Measurement of their levels may facilitate cardiovascular risk prediction and targeting of therapeutic strategies.