bluuebunny/crossref_metadata_2025 huggingface dataset:
Putative Association of Fas and FasL Gene Polymorphisms with Clinical Outcomes of Hepatitis B Virus Infection
Authors: Jung Yong Jin , Kim Yoon Jun , Kim Lyoung Hyo , Lee Soo Ok , Park Byung Lae , Shin Hyoung Doo , Lee Hyo-Suk
Published: October 2007

Objective:Fas/FasL polymorphisms, which are related to apoptosis, might influence the clearance of hepatitis B virus (HBV) infection and the occurrence of hepatocellular carcinoma (HCC). This study was performed to determine whether Fas and FasL promoter polymorphisms are associated with clinical outcome in chronic HBV infection. Methods: A total of 1,095 Korean subjects were prospectively allocated to two different groups: ‘the chronic carrier group’ (CC; n = 666), who were repeatedly hepatitis B surface antigen (HBsAg)-positive, and ‘the spontaneous recovery group’ (SR; n = 429), who were HBsAg-negative with antibodies to HBsAg and hepatitis B core antigen. In addition, the CC group was subcategorized into chronic hepatitis and HCC subgroups. Fas promoter polymorphisms at –1377G>A and –670A>G and the FasL promoter polymorphism at –844C>T were analyzed for and the genotype distributions of subjects were compared. Results: There were no significant associations between Fas or FasL promoter polymorphism with the HBV clearance and HBeAg clearance. However, –1377G>A in Fas promoter region showed protective effect to HCC occurrence (RH = 0.70, p = 0.03). Conclusions:Fas–1377G>A polymorphisms might be involved in the pathogenesis of human HCC.
The Heritability of Abstract Reasoning in Caribbean Latinos with Familial Alzheimer Disease
Authors: Johnson Beverly , Santana Vincent , Schupf Nicole , Tang Ming-X , Stern Yaakov , Mayeux Richard , Lee Joseph H.
Published: October 2007

Background: Alzheimer disease (AD) is under substantial genetic influence. To better understand the genetic influence on component phenotypes of AD, we estimated the heritability (h2) of abstract reasoning and examined its relation with apolipoprotein Ε4 (APOE-Ε4). Methods: We studied abstract reasoning in 1,116 individuals from 210 Caribbean Hispanic families with late onset AD, using the similari- ties subtest scores from the Wechsler Adult Intelligence Scale. We computed h2, then performed analysis of variance to examine the effect of APOE-Ε4. Results: Abstract reasoning was highly heritable (h2unadjusted = 79.9%). After adjusting for covariates, the h2 was reduced to 32.6%, with education accounting for 40.8% of the variance. The APOE-Ε4 allele had no effect. Conclusion: Abstract reasoning was strongly influenced by genetic factors and education. Genes other than APOE contribute to the inheritance of abstract reasoning ability.
Validation of Neutron Activation as a Novel Method to Determine Glomerular Filtration Rate
Authors: Mandelbrot Didier A. , Dhaliwal Simarjit K. , Evan Norfolk R. , Licho Robert , Reinhardt Christopher P. , Jaffry Saatiah
Published: October 2007

Background/Aims: Despite widespread interest in determining the glomerular filtration rate (GFR) of patients, current methods all have significant limitations. Therefore, a compelling need exists for new tests of GFR that are both accurate and easy to perform. We have previously reported that the technique of neutron activation (NA) accurately measures iohexol in vitro. In this study, we demonstrate that NA can be used to determine GFR by measuring the clearance of iohexol, and directly compare these results to a gold-standard method based on 99mTc-DTPA. Methods: We studied 57 patients with mild to moderate chronic kidney disease and normal volunteers. Subjects were simultaneously injected with iohexol and 99mTc-DTPA. Blood and urine samples were collected over 4 h to calculate GFR by the UV/P method. Results: The range of GFRs was 28–212 ml/min. GFRs obtained using iohexol and 99mTc-DTPA correlated closely (R = 0.95). The bias between the 2 techniques was 0.96 ml/min, and precision (defined as the standard deviation of the mean of the difference between the 2 values for each patient) was 10.6 ml/min. Accuracy was such that 98% of subjects had NA GFRs within 20% of the reference 99mTc-DTPA measurements. Conclusions: We conclude that NA is an excellent technique to measure GFR. NA has several advantages over current methods to directly measure GFR, including the ability to reassay samples, high throughput and the avoidance of patient and hospital radioactivity exposure. In the future, NA could be applied to GFR agents that do not contain iodine, such as Gd-DTPA, and to the simultaneous measurement of agents that reflect renal blood flow, such as iodohippurate. Therefore, NA holds great potential to improve the measurement of renal function in a safe, easily obtainable way.
Renal Sodium-Glucose Cotransporter Activity and Aquaporin-2 Expression in Rat Kidney during Chronic Nitric Oxide Synthase Inhibition
Authors: Albertoni Borghese María F. , Majowicz Mónica P. , Ortiz María C. , Delgado María F. , Sterin Speziale Norma B. , Vidal Noberto A.
Published: October 2007

Background/Aims: The renal sodium glucose cotransporter (SGLT2) and the water channel aquaporin-2 (AQP2) play a critical role in tubular sodium and water reabsorption and in the regulation of extracellular fluid volume both in physiologic and pathophysiologic conditions. However, there is little information about SGLT2 and AQP2 expression and/or activity in hypertension and there are no reports during hypertension induced by chronic nitric oxide synthase (NOS) inhibition. Methods: Hypertension was induced in rats by oral administration of NG-nitro-L-arginine methyl ester (L-NAME) (20 mg/kg/24 h) for 6 (H6) or 12 (H12) weeks. SGLT2 activity was measured using α-14C-methylglucose active uptake. The expression level of transporters was assessed by immunohistochemistry and/or immunoblotting. Results: SGLT2 activity was reduced in both H6 and H12; this was due neither to a decrease in SGLT2 expression nor to a change in membrane phospholipid composition. In H6, AQP2 expression diminished only in the inner medulla (IM), while in H12 it diminished in both outer (OM) and IM. This reduced expression of AQP2 may partially account for the increased urinary volume and decreased urinary osmolality in H12, since we obtained a strong correlation between AQP2 expression and these urinary parameters in both OM and IM. Conclusion: We propose that in rats in which hypertension is induced by NOS inhibition, SGLT2 activity and AQP2 expression are modified to compensate for the elevated arterial pressure. However, we cannot discount the possibility that the observed changes are due to the decrease in NO production itself.
Second Primary Tumors following a Diagnosis of Meningioma in Sweden, 1958–1997
Authors: Davis Faith , Tavelin Björn , Grutsch James , Malmer Beatrice
Published: October 2007

This study quantifies the risk of second primary tumors following a diagnosis of meningioma. 12,012 meningiomas and 926 second primary cancers were identified (ICD7, path code 461) between1958 and 1997 using Swedish Cancer Registry data. Standardized incidence ratios (SIRs) and exact 95% confidence intervals (CIs) were calculated. An elevated risk of any second primary cancer diagnosis (SIR = 1.2, 95% CI = 1.1–1.3) was observed. Elevated and statistically significant SIRs were observed for renal cancer (SIR = 1.6), melanoma (SIR = 1.7), thyroid cancer (SIR = 2.6) and brain tumors (SIR = 2.6). A consistent pattern of risk over time supports the evaluation of common risk factor profiles for renal, melanoma and thyroid cancers. Radiation exposures increase the risk of these rare tumors, so quantifying the cumulative and shared effects of environmental and treatment exposures is of further interest.
Headache 22 Years after Hospitalization for Head Injury Compared with Matched Community Controls
Authors: Nestvold Knut , Stavem Knut
Published: October 2007

Objectives: Little information is available on long-term headache following head injury. We compared the prevalence of headache in a cohort with previous hospitalization for head injury and matched controls. Materials and Methods: A questionnaire about headache was sent to 361 patients who were hospitalized for head injury in 1974–1975 and 722 matched community controls. Results: In multivariate conditional regression analysis among 192 responding case/control pairs, there was no evidence of higher odds of headache ≥1 day per month (odds ratio, OR 1.04, 95% CI 0.56–1.92, p = 0.90) compared with controls. However, there was a tendency to higher odds of headache ≥1 day per month among female cases than among controls (OR 2.03, 95% CI 0.94–4.39, p = 0.07). Conclusions: The study could not show increased odds of headache in a cohort 22 years following hospitalization for head injury, but it is possible that females are more likely to report long-term headache following head injury than matched controls.
HIV-Related Peripheral Neuropathy and Glucose Dysmetabolism: Study of a Public Dataset
Authors: Sheth Soham G. , Rao Chitharanjan V. , Tselis Alexandros , Lewis Richard A.
Published: October 2007

Aims and Methods: The authors analyzed the public dataset of Multicenter AIDS Cohort Study to examine the association of glucose dysmetabolism with HIV-related peripheral neuropathy. Results: Among 5,622 participants in the data, 282 (5%) had peripheral neuropathy, of which 225 had sensory neuropathy. Of 225 participants with sensory neuropathy, 191 (84.8%) had exposure to highly active antiretroviral therapy. Of 225 with sensory neuropathy, 46 had fasting sugars measured; 26 of them (56.5%) had either impaired fasting glucose (fasting glucose ≥110 mg/dl) or diabetes (fasting glucose ≥126 mg/dl). Among 693 participants without neuropathy, who had fasting sugars measured, 441 (63.7%) had glucose dysmetabolism (p = 0.33). The mean HbA1c levels in participants with sensory neuropathy (5.1 ± 1.02, n = 51) were significantly higher than in those without sensory neuropathy (4.8 ± 0.6, n = 164, p = 0.02), though its clinical relevance is unclear. Among 739 participants who had fasting sugars measured, 63.2% had glucose dysmetabolism, showing high prevalence of glucose dysmetabolism among participants with HIV infection. Conclusions: Except for slightly higher HbA1c levels, there was no significant difference in prevalence of glucose dysmetabolism among participants with and without sensory neuropathy. The study brings up important aspects of using public datasets for epidemiologic studies including its limitations and a unique opportunity for pilot studies for new investigators.
Visuospatial Planning and Problem Solving in Alzheimer’s Disease Patients: A Study with the Tower of London Test
Authors: Franceschi Massimo , Caffarra Paolo , De Vreese Luc , Pelati Oriana , Pradelli Samantha , Savarè Rita , Cerutti Renata , Grossi Enzo
Published: October 2007

Background: Executive dysfunction in Alzheimer’s disease (AD) has been recently recognized as an early and prominent clinical sign. The Tower of London (ToL), a task specifically devised to test executive functions of visuospatial planning and problem solving, has frequently been used in neuropsychological experiments, but rarely in the clinical ground. Methods: One hundred and sixty-one AD patients and 212 nondemented healthy controls were administered a simplified ToL version. Results: AD patients were significantly impaired (p < 0.0001) in all ToL scores and in the total execution time. The ‘accuracy’ score of ToL at a cut off of ≤29/36 yielded a sensitivity of 71.2% and a specificity of 76.4% (AUC 0.79) for the diagnosis of AD versus controls. Conclusions: Visuospatial planning and problem solving are significantly impaired in early dementia of the Alzheimer’s type. A successful sensitivity/specificity ratio, the independence of education and the simplicity of this version of ToL make it a useful executive functioning screening test for early AD.
Preliminary Evidence for Genetic Selection of 677T-MTHFR by Natural Annual Cycle of Folate Abundance
Authors: Lucock Mark , Yates Zoë , Ng Xiaowei , Veysey Martin , Blades Barbara , Travers Cheryl , Lewis Peter , Sturm Jonathon , Roach Paul
Published: October 2007

Background/Aims: Folic acid mediates transfer of one-carbon units into methionine and DNA-thymine biosynthesis. Discretionary and mandatory use of synthetic folic acid (SFA) to reduce spina bifida is on the increase. We show that historically, the seasonal cycle of abundance of folate-rich foods may have regulated embryo viability by acting as a selection factor for a significant polymorphism within a gene encoding 5,10-methylenetetrahydrofolate reductase (677C→T-MTHFR). Methods: Blood was collected from 150 UK and 118 Australian subjects born prior to discretionary or mandatory use of SFA. 677C→T-MTHFR genotype was determined using PCR. Results: The highest prevalence for 677T-MTHFR occurred 9 months post-harvest in UK subjects and was significantly higher at this time of year (July–Sept.) compared with Jan.-Mar. (OR = 2.0, 95% CI 1.03–3.87, p = 0.039) and Oct.–Dec. (OR = 2.2, 95% CI 1.12–4.31, p = 0.021). This effect was not detected in an Australian population subject to more moderate seasonality. Conclusions: Dietary folate may confer significant genetic buffering within populations dependent upon seasonal food sources that modify an individual’s vitamin status at the time of conception.
Role of Calcitriol and Cortisol on Human Adipocyte Proliferation and Oxidative and Inflammatory Stress: A Microarray Study
Authors: Sun Xiaocun , Morris Kristin L. , Zemel Michael B.
Published: October 2007

Dietary calcium inhibits adiposity, and a key underlying mechanism is suppression of calcitriol, which modulates Ca2+ signaling and mitochondrial uncoupling in adipocytes. We demonstrated that calcitriol directly regulates adipocyte 11β-HSD-1 expression and cortisol production in human adipocytes in vitro and dietary calcium inhibits visceral adipose tissue 11β-HSD-1 expression in mice, indicating an interaction of calcitriol and cortisol in obesity. Consequently, we have evaluated the gene expression profile of human subcutaneous adipocytes treated with calcitriol and/or cortisone. Data analysis demonstrated significant calcitriol modulation of gene expression toward inhibition of the adipocyte apoptosis (e.g., VEGF and STC-2) and promotion of adipocyte proliferation (e.g., IGF-1 and IGF-1R). Calcitriol also up-regulated oxidative stress and inflammatory genes such as NOX-4 and TLR-3. The calcitriol/cortisone combination resulted in significant additional up-regulation of 11β-HSD-1 and down-regulation of adiponectin expression, while cortisone exerted little independent effect in the absence of calcitriol. Overall, calcitriol stimulated a pattern of adipocyte gene expression which favored adipocyte proliferation, oxidative and inflammatory stress and visceral adiposity, and these effects were amplified in the presence of cortisone; however, this conclusion must be tempered by the adipocyte source (subcutaneous) and requires confirmation in visceral adipocytes.
Role of Proteomics in the Study of Nutrition
Authors: Velázquez-Arellano Antonio , Encarnación Sergio
Published: October 2007

With the advent of nutrigenomics, a more mechanistic view of the variable host responses to nutrients is beginning to emerge. Proteomics is central to nutrigenomics since studies on the effect of nutrients on the proteome have the potential to explain, at the molecular level, many of the physiological changes associated with nutritional stimuli. Proteomics aims at the resolution, identification and quantitation of complex protein mixtures, discovery of interactions of proteins with other molecules, as well as their cellular localization and their role in metabolism. In this article, recent studies on proteomic effects of two vitamins, biotin and folic acid, will be considered as examples of this novel approach to nutriology.
Apoptotic Phenotype Alters the Capacity of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand to Induce Human Vascular Endothelial Activation
Authors: Chen Pei-Lin , Easton Alexander
Published: October 2007

Background/Aims: The ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to activate vascular endothelium is unclear. This study investigates the link between endothelial apoptosis and activation in response to TRAIL. Methods and Results: Endothelial cell apoptosis was modeled with the immortalized human endothelial cell line EA.hy926, and with primary human umbilical vein endothelial cells (HUVEC) sensitized with the phosphatidylinositol 3-kinase inhibitor LY294002 in 1% serum. EA.hy926 expressed greatest levels of TRAIL receptors R1 and R2, and HUVEC of R2 and R3, determined by flow cytometry. Recombinant human (rh)TRAIL induced apoptosis in both models, reducing cell numbers preventable with caspase inhibitors, and confirmed by annexin V staining. In EA.hy926, rhTRAIL activated NF-ĸB (1 h) with increased ICAM-1 expression (24 h). rhTRAIL also increased adhesion of human neutrophils, blocked with an antibody to neutrophil CD18, a ligand for ICAM-1, and with antibodies to TRAIL and TRAIL-R1 and R2. rhTRAIL increased neutrophil adhesion to sensitized HUVEC, without effect on unmodified HUVEC. rhTRAIL did not increase surface labeling of ICAM-1 or E-selectin in sensitized HUVEC. Conclusions: TRAIL increases neutrophil adhesion when it concurrently induces apoptosis both in EA.hy926 and in sensitized HUVEC. TRAIL may therefore induce endothelial activation in concert with endothelial apoptosis.
Increased Saliva Cortisol Awakening Response in Patients with Mild Cognitive Impairment
Authors: Lind Karin , Edman Åke , Nordlund Arto , Olsson Tommy , Wallin Anders
Published: October 2007

Background: It is unknown whether HPA-axis dysfunction is present in patients with mild cognitive impairment (MCI). The aim of the present study was to investigate whether cortisol levels are elevated among patients with MCI and/or whether the individuals have adequate feedback control of their HPA axis. Material and Methods: 27 patients with MCI and 15 healthy controls were included in the study. Saliva samplings were performed 5 times a day before intake of 0.5 mg dexamethasone, and 5 times a day after intake of dexamethasone, respectively. Results: Significantly higher cortisol levels were found 15 min after awakening among patients with MCI in comparison with the controls, both before and after dexamethasone administration (p < 0.05). Also, the ratio between cortisol at awakening time and 15 min after awakening was lower in the patient group after dexamethasone administration (p < 0.05). There were no significant differences in basal cortisol levels before or after dexamethasone between groups. Conclusion: The results indicate that there is an HPA-axis disturbance, with normal basal cortisol levels and increased awakening response among patients with MCI. The dissociation between basal values and the awakening response may be of pathophysiological importance for the cognitive impairment.
Neural Connectivity in the Mediobasal Hypothalamus of the Sheep Brain
Authors: Qi Y. , Iqbal J. , Oldfield B.J. , Clarke I.J.
Published: October 2007

The ventromedial nucleus of the hypothalamus (VMN) and the arcuate nucleus (ARC) are two centres regulating energy balance and food intake, but inter-connectivity of these nuclei is not well defined in non-rodent species. In this study, we performed retrograde tracing and immunohistochemistry in the ovine brain with ewes receiving FluoroGold® (FG) injections into either ARC or VMN for the mapping of retrogradely labelled cells. Strong reciprocal connections were found between the two regions. The distribution of the FG labelled neurons in other regions of the hypothalamus and brain stem was also mapped. Some of the cells projecting from ARC to VMN were immunopositive for neuropeptide Y, galanin, adrenocorticotropin (marker of pro-opiomelanocortin cells) or tyrosine hydroxylase (marker of dopaminergic cells). Melanin-concentrating hormone and orexin neurons in the lateral hypothalamic area were also found to provide input to the VMN and ARC. This observed interconnectivity between regions important for metabolic regulation and other neuroendocrine functions presumably allows coordinated functions. Input to both the ARC and VMN from other brain regions, such as brain stem cell groups, provides a further level of regulation. These data provide a substrate upon which further understanding of appetite regulation and neuroendocrine function can be derived in this species.
Association of Prohepcidin and Hepcidin-25 with Erythropoietin Response and Ferritin in Hemodialysis Patients
Authors: Kato Akihiko , Tsuji Takayuki , Luo Jinghui , Sakao Yukitoshi , Yasuda Hideo , Hishida Akira
Published: October 2007

Hepcidin is a key regulator of iron metabolism. In this study, we examined whether measurement of hepcidin is useful in assessing recombinant human erythropoietin (rHuEPO) responsiveness in regular hemodialysis (HD) patients in a cross-sectional fashion. We examined the association between serum prohepcidin, a prohormone of hepcidin, and rHuEPO dosage and the rHuEPO/hemoglobin (Hb) ratio in 75 HD patients. We also semiquantatively measured the peak intensity of serum hepcidin-25, the major form of mature hepcidin, in 24 HD patients by using surface-enhanced laser desorption ionization time of flight time mass spectrometry, and compared those between rHuEPO-hyporesponsive (rHuEPO 192 ± 10 [126–252] IU/kg/week, n = 15) and responsive patients (rHuEPO 40 ± 9 [0–81] U/kg/week, n = 9). A significant but weak relationship was found between serum prohepcidin and rHuEPO dosage (r = 0.24, p < 0.05) and rHuEPO/Hb ratio (r = 0.22, p = 0.06). However, prohepcidin did not become an indicator of hematopoietic parameters by multiple regression analysis. Serum hepcidin-25 intensity was significantly and positively correlated with ferritin (r = 0.51, p < 0.01) but not with log-transformed C-reactive protein. There was no difference in the intensities of serum hepcidin-25 between rHuEPO-hyporesponsive and responsive patients (64 ± 10 vs. 52 ± 16 AU, p = NS). It follows from these findings that the assessment of serum hepcidin using currently available assays was not valid in predicting rHuEPO responsiveness in chronic HD patients.
Brain Natriuretic Peptide in Hemodialysis Patients: Predictive Value for Hemodynamic Change during Hemodialysis and Cardiac Function
Authors: Matayoshi Tetsutaro , Kato Toako , Nakahama Hajime , Nakata Hiroto , Yoshihara Fumiki , Kamide Kei , Horio Takeshi , Nakamura Satoko , Kawano Yuhei
Published: October 2007

Background: Though brain natriuretic peptide (BNP) is widely used as a clinical marker of cardiac function, there is considerable confusion in the interpretation of its value in hemodialysis (HD) patients whose BNPs are often elevated without cardiac diseases. The aim of the present study is to examine the predictive value of BNP for blood pressure (BP) fall during HD and cardiac function. Methods: Subjects consisted of 205 (160 males, 45 females; age 66.5 ± 10.5 years) consecutive uremic patients requiring maintenance HD who were admitted to our hospital during 2001–2004. One hundred and eleven cases had a history of ischemic heart disease. We measured BNP in all cases and collected clinical data including age, sex, duration of HD, blood examination and echocardiography. Results: BNP of all 205 cases ranged from 6 to 16,097 pg/ml (median 831). During HD, the average BP change was –24.5 ± 20.5 mm Hg, and 111 cases showed a systolic BP reduction >20 mm Hg. BNP did not predict the degree of BP fall. After adjusting confounding factors, the presence of ischemic heart disease, ultrafiltration rate, systolic BP before HD and serum sodium concentration showed a significant correlation with BP change (t = –2.84, –2.76, –4.68 and 2.90; p = 0.005, <0.01, <0.0001 and <0.005, respectively). In relation to echocardiographic indices, BNP >785 pg/ml could predict left ventricular dysfunction (fractional shortening of the left ventricle <30%, sensitivity 73%, specificity 65%). Conclusion: The level of BNP could not predict BP fall during HD. However, BNP is a good indicator of cardiac function even in uremic patients.
Investigating the Possible Effects of Trauma Experiences and 5-HTT on the Dissociative Experiences of Patients with OCD Using Path Analysis and Multiple Regression
Authors: Lochner Christine , Seedat Soraya , Hemmings Sian M.J. , Moolman-Smook Johanna C. , Kidd Martin , Stein Dan J.
Published: October 2007

Dissociation is defined as the disruption of the usually integrated functions of consciousness, such as memory, identity, and perceptions of the environment. Causes include various psychological, neurological and neurobiological mechanisms, none of which have been consistently supported. To our knowledge, the role of gene-environment interactions in dissociative experiences in obsessive-compulsive disorder (OCD) has not previously been investigated. Eighty-three Caucasian patients (29 male, 54 female) with a principal diagnosis of OCD were included. The Dissociative Experiences Scale was used to assess dissociation. The role of childhood trauma (assessed with the Childhood Trauma Questionnaire), and a functional 44-bp insertion/deletion polymorphism in the promoter region of the serotonin transporter, or 5-HTT, in mediating dissociation, was investigated using multiple regression analysis and path analysis using the partial least squares model. Both analyses indicated that an interaction between physical neglect and the S/S genotype of the 5-HTT genesignificantly predicted dissociation in patients with OCD. Dissociation may be a predictor of poorer treatment outcome in patients with OCD; therefore, a better understanding of the mechanisms that underlie this phenomenon may be useful. Here, two different but related statistical techniques (multiple regression and partial least squares), confirmed that physical neglect and the 5-HTT genotype jointly play a role in predicting dissociation in OCD.
Birth during Autumn Is a Risk for Adolescent Self-Mutilative Behavior
Authors: Riala Kaisa , Hakko Helinä , Räsänen Pirkko
Published: October 2007

Background: A season of birth tendency has been shown for several psychiatric disorders and suicidal behavior. Our aim was to examine the association between season of birth and self-mutilative behavior (SMB) among adolescent psychiatric inpatients. Methods: The study sample consisted of 508 (40.9% males) 12- to 17-year-old adolescents consecutively admitted to the Department of Psychiatry of Oulu University Hospital, Finland, between April 2001 and May 2006. The birth month of each adolescent was categorized into one of the four seasons: spring (March–May), summer (June–August), autumn (September–November) or winter (December–February). The information on SMB was based on the K-SADS-PL interview, which included an item on nonsuicidal physical self-damaging acts without intent to die. A total of 144 adolescents (27 males, 117 females) met the criteria for SMB. The association between season of birth and SMB was assessed with a logistic regression analysis after controlling for each adolescent’s age, previous suicide attempts and DSM-IV-diagnosed psychiatric disorders. Results: The monthly distribution of births of adolescents with SMB differed statistically significantly from that observed in the general population of the same age. An association between season of birth and SMB was seen in girls, but not in boys. The likelihood for SMB was significantly increased (adjusted OR 2.9; 95% CI 1.4–6.2) among girls born in autumn compared to those born in winter. Conclusions: Birth during autumn may predispose girls to SMB via dysfunctional serotonergic or other neurotransmitter systems. These findings may also be related to seasonal rhythms in parental mood and poor early care of the offspring.
Association between Monoamine Oxidase A Polymorphisms and Anger-Related Personality Traits in Korean Women
Authors: Yang Jae-Won , Lee So-Hee , Ryu Seung-Ho , Lee Boung-Chul , Kim Seung-Hyun , Joe Sook-Haeng , Jung In-Kwa , Choi Ihn-Geun , Ham Byung-Joo
Published: October 2007

It has been suggested that polymorphisms in the monoamine oxidase A (MAO-A) gene are associated with aggressive and impulsive behaviors. In the present study, we investigated the association of the MAO-A variable number of tandem repeat polymorphism in the promoter region (MAO-A uVNTR) with anger-related personality traits. Specifically, MAO-A uVNTR polymorphisms were examined for associations with the State-Trait Anger Expression Inventory (STAXI) scores in 211 normal Korean women. All subjects were assessed using the STAXI and genotyped for MAO-A uVNTR status. The scores on the STAXI subscales differed significantly among the MAO-A uVNTR polymorphism genotypes in terms of anger expression-out (AX-Out) scores. Post hoc comparisons revealed significant differences between the 3/3 and 4/4, and between 3/4 and 4/4 polymorphisms. However, no significant difference was observed in other STAXI subscale scores among these genotypes. Subjects with the high-activity MAO-A uVNTR had significantly higher AX-Out scores than subjects with other genotypes. MAO-A uVNTR polymorphisms may contribute in part to the expression of anger. These findings support the hypothesis that this polymorphism in the MAO-A gene may be associated with anger-related personality traits in Korean women.
Association between Arterial Stiffness and Peritoneal Fluid Kinetics
Authors: Zhe Xing-wei , Tian Xin-kui , Chen Wei , Guo Li-juan , Gu Yue , Chen Hui-min , Tang Li-jun , Wang Tao
Published: October 2007

Background: A high peritoneal transport status in continuous ambulatory peritoneal dialysis (CAPD) patients is associated with a markedly increased morbidity and mortality. While the causes are as yet unknown, overall the proportion of deaths due to cardiovascular disease is estimated at 40–50% among dialysis patients. Arterial stiffness has been established as a cardiovascular risk factor, while the links between peritoneal transport status and aortic stiffness have not yet been investigated. Methods: We included 65 prevalent CAPD patients (24 males/41 females) from our center in a cross-sectional study. Arterial stiffness was assessed by brachial pulse pressure (PP) and carotid-femoral pulse wave velocity (C-F PWV). The patients’ peritoneal fluid transport was assessed by kinetic modeling. The patients’ peritoneal small solute transport rate was assessed by D/Pcr at 4 h. Extracellular water to total body water (E/T) ratio was assessed by means of bioimpedance analysis. C-reactive protein was also measured. Results: C-F PWV was positively correlated with patients’ age (r = 0.489, p < 0.01), diabetic status (r = 0.327, p < 0.01), peritoneal fluid absorption rate (Ke; r = 0.251, p < 0.05), PP (r = 0.483, p < 0.01), and E/T (r = 0.517, p < 0.01). Multivariate regression analysis showed that C-F PWV was independently related to E/T (p < 0.01), PP (p < 0.01), age (p < 0.05), and Ke (p < 0.05). Conclusion: Peritoneal fluid transport (Ke), as well as E/T, age and PP were found to be independent predictors of elevated C-F PWV in CAPD patients, suggesting that there might be a link between high aortic stiffness and increased Ke rate, hypothetically through generalized vasculopathy.
Atypical Fundus Lesions in Juvenile Pseudoxanthoma Elasticum
Authors: Aydin Erdinc , Demir Helin Deniz , Batioglu Figen , Sezer Engin
Published: October 2007

Background: To report two cases with previously undescribed fundus lesions as early ocular signs of pseudoxanthoma elasticum (PXE). Methods: Clinical work-up including color photography and fundus fluorescein angiography (FFA). Results: A 10-year-old girl and an 8-year-old boy (siblings) presented with dermatological exacerbations of PXE. On ophthalmological examination, both patients showed multiple, round, and yellowish white lesions located from the perifoveal area through to the midperipheral retina. FFA revealed hyperfluorescence without leakage during any phase, in accordance with the location of the lesions on the fundus. Conclusion: Atypical fundus lesions in early childhood may be early ocular signs of PXE, in contrast to other well-known manifestations that appear in later decades.
Nebivolol Induces a Hyperpolarizing Effect on Smooth Muscle Cells in the Mouse Renal Artery by Activation of Beta-2-Adrenoceptors
Authors: Georgescu A. , Pluteanu F. , Flonta M.-L. , Badila E. , Dorobantu M. , Popov D.
Published: October 2007

Nebivolol is a highly selective β1-adrenoceptor antagonist with vasodilator properties involving the vascular endothelium, but its effect on the smooth muscle cells (SMC) is still unclear. In this paper, we tested the effect of nebivolol on renal artery smooth muscle cells and investigated the cellular mechanism involved. To this purpose, the denuded renal arteries isolated from mice were studied in vitro using the myograph and the nitric oxide (NO) sensor techniques, while the SMC in culture were analyzed by the patch-clamp technique. The myograph technique was used to assay the vasodilator effect of nebivolol on the arterial muscular layer, and to establish the optimal dose of the drug to be tested on single SMC by the patch-clamp technique. Using both the myograph and the patch-clamp techniques, we examined the potential contribution of β2-adrenoceptors and Ca2+-activated K+ channels to the nebivolol-induced effects, by exposing the denuded arteries and SMC cultures to specific inhibitors such as butoxamine (100 µmol/l), tetraethylammonium (TEA, 1 mmol/l), and iberiotoxin (100 nmol/l). The direct measurement of NO using the NO sensor enabled us to evaluate if nebivolol induces/or not the release of NO in denuded renal arteries. The results of this study show that nebivolol exerts vasodilator effects on the SMC in the denuded renal arteries and the maximal response is achieved at a concentration of 50 µmol/l. Nebivolol effects involve binding to the β2-adrenoceptors and the subsequent activation of Ca2+-activated K+ channels in SMC, with no contribution of NO. Taken together, the study brings new insights into the mechanism underlying the nebivolol-induced arterial vasodilation.
Prevalence of Ovarian Cancer among Women with a CA125 Level of 35 U/ml or Less
Authors: Kobayashi Hiroshi , Yamada Yoshihiko , Sado Toshiyuki , Sakata Mariko , Yoshida Shozo , Kawaguchi Ryuji , Kanayama Seiji , Shigetomi Hiroshi , Haruta Shoji , Tsuji Yoriko , Ueda Sachiyo , Kitanaka Takashi , Oi Hidekazu
Published: October 2007

Background: The optimal upper limit of the normal range for CA125 in ovarian cancer screening is unknown. We investigated the prevalence of ovarian cancer among women in the Shizuoka Cohort Study on Ovarian Cancer Screening (SCSOCS) trial who had an abnormal ultrasound (US) and a CA125 level of 35 U/ml or less. Methods: Of 48,027 women enrolled in the SCSOCS trial, 40,801 women never had a CA125 level of more than 35 U/ml, and underwent transvaginal US. Results: Among the 40,801 women (age range 45–85 years), 4,859 women had an abnormal transvaginal US examination (category 1 [simple morphology], 4,741 women, and category 2 [complex morphology], 118 women). Of the 4,859 women, 981 (912 with the category 1 and 69 with the category 2) had a surgery. Of the 981 women, ovarian cancer was diagnosed in 8 (0.815%), and 5 of these 8 cancers (63%) were in stage I. The prevalence of ovarian cancer with abnormal US was 0.207% among women with a CA125 level of up to 15 U/ml, 0.488% among those with values of 15–20 U/ml, 0.685% among those with values of 20–25 U/ml, 2.04% among those with values of 25–30 U/ml, and 6.12% among those with values of 30–35 U/ml. Conclusions: Surgery-detected ovarian cancer is not rare among women with CA125 levels of 35 U/ml or less – levels generally thought to be in the normal range.
Glomerular Regeneration Is Delayed in Nephritic α8-Integrin-Deficient Mice: Contribution of α8-Integrin to the Regulation of Mesangial Cell Apoptosis
Authors: Hartner Andrea , Marek Ines , Cordasic Nada , Haas Christian , Schocklmann Harald , Hulsmann-Volkert Gudrun , Plasa Isabel , Rascher Wolfgang , Hilgers Karl F. , Amann Kerstin
Published: October 2007

Background/Aims: α8β1-Integrin is expressed in mesangial cells. In vitro studies suggest a role for α8-integrin in the regulation of cell proliferation and apoptosis. We tested the hypothesis that α8-integrin is essential for the healing process after mesangioproliferative glomerulonephritis. Methods: Mice homozygous for a deletion of the α8-integrin chain were compared with wild-type mice. To study glomerular healing, we used the habu toxin model of reversible mesangioproliferative glomerulonephritis. Animals received 6 mg/kg habu toxin intravenously; controls received saline only. Results: Early mesangiolysis occurred in wild-type and α8-integrin-deficient mice. However, mesangiolysis was no longer detectable after 7 days in wild types but persisted after 14 days in α8-integrin-deficient animals. Mesangial activation marker α-smooth muscle actin was detectable only at day 7 in wild-type mice but persisted until day 14 in α8-integrin-deficient mice. In wild types, glomerular cell proliferation and apoptosis peaked at day 7 and decreased thereafter but remained elevated in α8-integrin-deficient mice until day 28. In cultivated mesangial cells, α8-integrin expression was associated with increased cell survival. Conclusion: Interactions between α8-integrin and the mesangial matrix may contribute to healing of glomerular injury by influencing cell proliferation and apoptosis.
Is Systemic Heparin a Risk Factor for Catheter-Related Sepsis in Dialysis Patients?
Authors: Diskin Charles J. , Stokes Thomas J. , Dansby Linda M. , Radcliff Lautrec , Carter Thomas B.
Published: October 2007

Background: Biofilms are dense aggregates of surface adherent microorganisms embedded in a polysaccharide matrix. Intravenous iron and heparin are thought to promote the formation of biofilm. Both are commonly employed during hemodialysis treatments which might affect the incidence of catheter-related sepsis. Methods: 559 patients who underwent hemodialysis treatment with a catheter were reviewed. Episodes of sepsis were analyzed for the use of systemic heparin and intravenous iron as well as all other risk factors for sepsis. Results: Sepsis developed in 141 of the 796 catheters. Analysis of variance revealed that the number of days that the catheter remained in place was the most significant variable (p < 0.0001) associated with catheter-related sepsis along with multiple other variables, but a Cox proportional hazards analysis revealed that only the two biofilm risk factors (intravenous iron [p < 0.001], and mid-treatment bolus of heparin [p = 0.046]) along with previously reported factor of a depressed serum albumin (p = 0.001) are of significance. Conclusion: In addition to duration of catheter use, we found three significant risk factors for sepsis and two of those three have been associated with the development of biofilm.
Decompensated Heart Failure in the Setting of Kidney Dysfunction: A Community-Wide Perspective
Authors: Ismailov Rovshan M. , Goldberg Robert J. , Lessard Darleen , Spencer Frederick A.
Published: October 2007

Background: Patients with heart failure (HF) and kidney disease have a poor long-term outlook which has provided impetus for the identification of factors of prognostic importance and more fully understanding the impact of kidney dysfunction in patients with HF. Objectives: Our objectiveswere to describe the characteristics, hospital treatment practices, as well as hospital and long-term outcomes in patients with varying degrees of kidney dysfunction who were hospitalized with acute HF at all medical centers in a large New England metropolitan area. Methods: Residents of the Worcester metropolitan area hospitalized with clinical findings of decompensated HF at 11 greater Worcester medical centers during 1995 and 2000 comprised the study sample. Kidney function was classified into 4 categories of estimated glomerular filtration rate (eGFR) for purposes of analysis: <30 (n = 569), 30–44 (n = 725), 45–59 (n = 763), and ≧60 (n = 2,293) ml/min per 1.73 m2. Results: The average age of the study sample was 76 years and 57% were women. Patients with severe kidney dysfunction were less likely to receive angiotensin-converting enzyme inhibitors, diuretics and digoxin during hospitalization for acute HF compared to patients with more normal kidney function. Patients with lower eGFR levels had higher in-hospital and post-discharge death rates in comparison to those with higher levels of eGFR. Conclusion: Our results demonstrate the impact of renal impairment on the prognosis of patients with decompensated HF. Our findings highlight the less than optimal management of these high-risk patients. Increased surveillance and enhanced treatment of patients with HF and kidney dysfunction remains warranted to improve the survival outlook of these patients.
Essential Role of Smad3 in Infarct Healing and in the Pathogenesis of Cardiac Remodeling
Authors: Bujak Marcin , Ren Guofeng , Kweon Hyuk Jung , Dobaczewski Marcin , Reddy Anilkumar , Taffet George , Wang Xiao-Fan , Frangogiannis Nikolaos G.
Published: October 2007

Background—

Postinfarction cardiac repair is regulated through timely activation and repression of inflammatory pathways, followed by transition to fibrous tissue deposition and formation of a scar. The transforming growth factor-β/Smad3 pathway is activated in healing infarcts and may regulate cellular events critical for the inflammatory and the fibrotic responses.

Methods and Results—

We examined the effects of Smad3 gene disruption on infarct healing and the pathogenesis of cardiac remodeling. In the absence of injury, Smad3-null hearts had comparable function to and similar morphology as wild-type hearts. Smad3-null animals had suppressed peak chemokine expression and decreased neutrophil recruitment in the infarcted myocardium but showed timely repression of inflammatory gene synthesis and resolution of the inflammatory infiltrate. Although myofibroblast density was higher in Smad3-null infarcts, interstitial deposition of collagen and tenascin-C in the remodeling myocardium was markedly reduced. Compared with wild-type animals, Smad3
−/−
mice exhibited decreased dilative remodeling and attenuated diastolic dysfunction; however, infarct size was comparable between groups. Transforming growth factor-β–mediated induction of procollagen type III and tenascin-C in isolated cardiac fibroblasts was dependent on Smad3, which suggests that decreased fibrotic remodeling in infarcted Smad3-null hearts may be due to abrogation of the profibrotic transforming growth factor-β responses.

Conclusions—

Smad3 loss does not alter the time course of resolution of inflammation in healing infarcts, but it prevents interstitial fibrosis in the noninfarcted myocardium and attenuates cardiac remodeling. Thus, the Smad3 cascade may be a promising therapeutic target for the treatment of myocardial infarction.
Hypertension In Sub-Saharan Africa
Authors: Addo Juliet , Smeeth Liam , Leon David A.
Published: October 2007

Hypertension is an important public health challenge worldwide. Information on the burden of disease from hypertension is essential in developing effective prevention and control strategies. An up-to-date and comprehensive assessment of the evidence concerning hypertension in sub-Saharan Africa is lacking. A literature search of the PUBMED database was conducted and supplemented by a manual search of bibliographies of retrieved articles. The search was restricted to population based studies on hypertension in sub-Saharan Africa published between January 1975 and May 2006. Data were extracted after a standard protocol and using standard data collection forms. Thirty-seven publications met the inclusion criteria. The prevalence of hypertension varied extensively between and within studies. Prevalence of hypertension was higher in urban than rural studies in all studies that covered both types of area, and also increased with increasing age in most studies. In most studies less than 40% of people with blood pressure above the defined normal range had been previously detected as hypertensive. Of people with previously diagnosed hypertension, less than 30% were on drug treatment in most studies, and less than 20% had blood pressure within the defined normal range. Hypertension is of public health importance in sub-Saharan Africa, particularly in urban areas, with evidence of considerable under-diagnosis, treatment, and control. There is an urgent need to develop strategies to prevent, detect, treat, and control hypertension effectively in the African region.
Clandestine Agent: The Real Agnes Smedley
Authors: Eckstein Arthur M.
Published: October 2007

This essay reviews a new biography of Agnes Smedley, a radical American writer and journalist who secretly worked for the Soviet Union and the Chinese Communist Party on various endeavors, including espionage. When Smedley was accused in the late 1940s of having been a Soviet spy, she staunchly denied the allegations and depicted herself as an innocent victim of a McCarthyite smear. Ruth Price, the author of the new biography, initially expected to find that Smedley had indeed been unjustly accused of spying for the Soviet Union. But as Price sifted through newly available materials from Russia and China, she made the disconcerting discovery that Smedley had in fact eagerly served as an agent of influence and spy for the Soviet Union and the Chinese Communists. This case illustrates some of the complexities that arise when assessing why certain Western intellectuals and government officials decided to become spies for the Soviet Union.
Sino-Soviet Relations and the Emergence of the Chinese Communist Regime, 1946–1950: New Documents, Old Story
Authors: Radchenko Sergey
Published: October 2007

Andrei Ledovskii, a long-time Soviet diplomat with a particular expertise on East Asian affairs, and several other Russian specialists on Soviet policy in the Far East have published a massive collection of declassified documents about Soviet policy vis-à-vis China in the first five years after World War II. The authors seek to show that the Communist victory in the Chinese civil war was attributable to Soviet fraternal help, that Josif Stalin wholeheartedly embraced the Chinese Communists' struggle for power, and that the Sino-Soviet alliance from beginning to end enjoyed unstinting Soviet support. But in fact the documents reveal that Stalin's policy toward the Chinese Communists was opportunistic and utilitarian, that he refrained from decisively supporting the Communists in the Civil War until almost the end, and that all the talk of proletarian internationalism in the Sino-Soviet alliance was but a cloak for Soviet expansionist ambitions in East Asia.
In the Shadow of the Bomb: U.S.-Soviet Biomedical Relations in the Early Cold War, 1944–1948
Authors: Krementsov Nikolai
Published: October 2007

The deterioration of U.S.-Soviet scientific relations in 1946–1948 traditionally has been seen as simply a consequence of the growing political conflict between the United States and the Soviet Union. Scientific activities with direct military applications—most clearly manifested in the nuclear bomb—have been depicted as the primary motive for a variety of Cold War science policies, ranging from restrictions on international cooperation to the veil of secrecy placed over military-related scientific research. This article explores U.S.-Soviet relations in oncology in 1944–1948 and shows that science became an integral part and an instrument, rather than a mere reflection, of the Cold War confrontation. Science played a central role in the formulation of certain Cold War policies and informed Soviet decision-making on a wide range of policy issues that were essential to the growth of the Cold War. In this context, the symbolic value of science as a propaganda tool became no less important than its military applications.