bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin C therapy ameliorates vascular endothelial dysfunction in treated patients with homocystinuria
Authors: Pullin C. H. , Bonham J. R. , McDowell I. F. W. , Lee P. J. , Powers H. J. , Wilson J. F. , Lewis M. J. , Moat S. J.
Published: March 2003

Objectives: We sought to investigate the effects of short‐ and long‐term vitamin C therapy on endothelial dysfunction in patients with homocystinuria.

Background: Untreated homocystinuria due to cystathionine β‐synthase deficiency is associated with premature atherothrombotic disease; 25% of untreated patients suffer a vascular event by the age of 16 years and 50% by 29 years. Treatment directed at reducing homocysteine accumulation significantly reduces this risk. However, despite ‘optimal’ treatment and compliance, hyperhomocysteinaemia usually persists and individuals exhibit endothelial dysfunction indicative of an adverse cardiovascular prognosis. Additional intervention is therefore required to further reduce cardiovascular risk.

Methods: We investigated the endothelial effects of acute (2 g single dose) and chronic (1 g/day for 6 months) administration of oral vitamin C in 5 patients with homocystinuria (mean age 26 years, 1 male) and 5 age‐ and sex‐matched controls. Brachial artery endothelium‐dependent flow‐mediated dilatation (FMD) and endothelium‐independent responses to nitroglycerin (NTG) were measured using high‐resolution ultrasonic vessel wall‐tracking.

Results:Baseline: Plasma total homocysteine was 100.8 ± 61.6 and 9.2 ± 1.9 μmol/L in the patient and control groups, respectively (p < 0.001). FMD responses were impaired in the patient group (20 ± 40 μm) compared with the controls (116 ± 30 μm) (p < 0.001). Vitamin C administration: FMD responses in the patient group improved both acutely, 160 ± 65 μm at 4 h (p < 0.001), and chronically, 170 ± 70 μm at 2 weeks (p < 0.001) and 170 ± 40 μm at 6 months (p < 0.001). FMD responses in the control group were unaltered (p = 0.526). Within both groups, neither the vascular response to NTG nor plasma homocysteine was altered (p > 0.4).

Conclusions: Vitamin C ameliorates endothelial dysfunction in patients with homocystinuria, independent of changes in homocysteine concentration and should therefore be considered as an additional adjunct to therapy to reduce the potential long‐term risk of atherothrombotic disease.
Male war‐zone veterans' perceived relationships with their children: The importance of emotional numbing
Authors: Ruscio Ayelet Meron , Weathers Frank W. , King Lynda A. , King Daniel W.
Published: March 2003

Despite growing recognition of substantial interpersonal impairment among many war‐zone veterans with posttraumatic stress disorder (PTSD), little is known about the association between PTSD symptomatology and veterans' relationships with their children. This study examined the differential pattern of associations between the symptom clusters of PTSD and the perceived father–child relationships of 66 male Vietnam veterans. Analyses revealed that only the emotional numbing cluster was significantly related to perceived quality of all relationship domains. The association between emotional numbing and perceived relationship quality remained significant in regression analyses even after controlling for fathers' family‐of‐origin stressors, combat exposure, depression, and substance abuse. Findings suggest that emotional numbing may be the component of PTSD most closely linked to interpersonal impairment in war‐zone veterans.
Towards an Understanding of Complex Biological Membranes from Atomistic Molecular Dynamics Simulations
Authors: Saiz Leonor , Bandyopadhyay Sanjoy , Klein Michael L.
Published: March 2003

Computer simulation has emerged as a powerful tool for studying the structural and functional properties of complex biological membranes. In the last few years, the use of recently developed simulation methodologies and current generation force fields has permitted novel applications of molecular dynamics simulations, which have enhanced our understanding of the different physical processes governing biomembrane structure and dynamics. This review focuses on frontier areas of research with important biomedical applications. We have paid special attention to polyunsaturated lipids, membrane proteins and ion channels, surfactant additives in membranes, and lipid–DNA gene transfer complexes.
Effect of Isoproterenol on the L-type Ca2+ Current in Cardiac Cells from Rats and Hybernating Ground Squirrels
Authors: Kokoz Yu. M. , Grichenko A. S. , Korystova A. F. , Lankina D. A. , Markevich N. I.
Published: March 2003

The perforated patch clamp method was used to study the effect of the agonist of beta-adrenoreceptors isoproterenol on L-type Ca2+ current in cardiocytes of rats and ground squirrels in two states: active and hibernating. It is shown that isoproterenol exerts a dual effect on Ca2+ currents of rats and ground squirrels in the active state: at Vh = −50 mV, the current increases, whereas at Vh = −30 mV, it decreases. In hibernating ground squirrels, the dual effect of isoproterenol is not observed: isoproterenol increases Ca2+ current at any Vh values. The hypothesis is put forward that, during the entrance of ground squirrels into hibernation, the phosphorylation of one of the sites (not cAMP-dependent) of L-type Ca2+ channels is blocked.
Interleukin-6 Induced Suppression of Bovine Parathyroid Hormone Secretion
Authors: Carlstedt E. , Ridefelt P. , Lind L. , Rastad J.
Published: March 2003

Calcium disturbances in the critically ill coincide with elevations of proinflammatory cytokines. The effects of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) on parathyroid hormone (PTH) secretion were investigated. IL-6 and TNF-α had no acute effect on PTH secretion in extracellular Ca2+ concentrations of 0.5, 1.25 and 3.0 mM. In contrast to TNF-α, cultures for 24 h in the presence of 10 ng/mL of IL-6 showed decreased PTH secretion by 51% and 29% in 0.5 mM and 1.25 mMCa2+ respectively. Neither IL-6 nor TNF-α, affected cytoplasmic Ca2+ of the cells. We conclude that PTH secretion in vitro can be suppressed by IL-6 at clinically relevant concentrations. This suppression may aggravate hypocalcemia of the critically ill and attenuate the conventionally strong stimulation of the PTH release by reduction in serum calcium.
Liposomal Delivery of CTL Epitopes to Dendritic Cells
Authors: Chikh Ghania , Schutze-Redelmeir Marie-Paule
Published: March 2003

The induction of strong and long lasting T-cell response, CD4+ or CD8+, is a major requirement in the development of efficient vaccines. An important aspect involves delivery of antigens to dendritic cells (DCs) as antigen presenting cells (APCs) for the induction of potent antigen-specific CD8+ T lymphocyte (CTLs) responses. Protein or peptide-based vaccines become an attractive alternative to the use of live cell vaccines to stimulate CTL responses for the treatment of viral diseases or malignancies. However, vaccination with proteins or synthetic peptides representing discrete CTL epitopes have failed in most instances due to the inability for exogenous antigens to be properly presented to T cells via major histocompatibility complex (MHC) class I molecules. Modern vaccines, based on either synthetic or natural molecules, will be designed in order to target appropriately professional APCs and to co-deliver signals able to facilitate activation of DCs. In this review, we describe the recent findings in the development of lipid-based formulations containing a combination of these attributes able to deliver tumor- or viral-associated antigens to the cytosol of DCs. We present in vitro and pre-clinical studies reporting specific immunity to viral, parasitic infection and tumor growth.
The relative contribution of war experiences and exile‐related stressors to levels of psychological distress among Bosnian refugees
Authors: Miller Kenneth E. , Weine Stevan M. , Ramic Alma , Brkic Nenad , Bjedic Zvezdana Djuric , Smajkic Amer , Boskailo Esad , Worthington Greg
Published: March 2003

This study examined the relative contribution of 2 exile‐related variables—social isolation and daily activity level—and war experiences of violence and loss, to levels of PTSD and depressive symptomatology in 2 groups of Bosnian refugees, 1 clinical group (N = 59) and the other a nonclinical community (N = 40) group. As hypothesized, exposure to war‐related violence was highly predictive of PTSD symptoms in both groups: in addition, social isolation was significantly related to PTSD symptomatology in the community group. In contrast, depressive symptomatology was accounted tor primarily by the exile‐related stressors. For the clinical group, depressive symptoms were also accounted for by experiences of war‐related loss. The implications of these findings for mental health interventions with refugees are considered.
Secondary traumatic stress and vicarious trauma: A validational study
Authors: Jenkins Sharon Rae , Baird Stephanie
Published: March 2003

Vicarious trauma (VT) and secondary traumatic stress (STS) or compassion fatigue both describe effects of working with traumatized persons on therapists. Despite conceptual similarities, their emphases differ: cognitive schemas vs. posttraumatic symptoms and burnout, respectively. The TSI Belief Scale (TSI‐BSL) measures VT; the Compassion Fatigue Self‐Test (CFST) for Psychotherapists measures STS. Neither has substantial psychometric evidence yet, nor has their association been studied. Results for 99 sexual assault and domestic violence counselors show concurrent validity between TSI‐BSL, and CFST, moderate convergence with burnout but useful discrimination, and strong convergence with general distress, but adequate independent shared variance. Counselors with interpersonal trauma histories scored higher on CFST, but not TSI‐BSL or burnout, consistent with the CFST's emphasis on trauma symptomatology.
Tetramethyl Rhodamine Methyl Ester (TMRM) is Suitable for Cytofluorometric Measurements of Mitochondrial Membrane Potential in Cells Treated with Digitonin
Authors: Floryk Daniel , Houštêk Josef
Published: March 2003

A new method for cytofluorometric analysis of mitochondrial membrane potential ΔΨ has been developed by using TMRM as a cationic, mitochondrial selective probe. The method is based on limited treatment of cultured cells with digitonin which permeabilises the plasma membrane and leaves mitochondria intact. The resulting signal of TMRM-stained cells thus represents only the probe accumulated in mitochondria. Fibroblasts and cybrids were used as a model cell systems and optimal conditions for digitonin treatment and staining by TMRM were described. The TMRM signal collapsed by valinomycin, KCN and antimycin A and FCCP titration was used to gradually lower ΔΨ and characterise the stability of ΔΨ. The method is suitable for sensitive measurement of ΔΨ in different types of cultured cells.
Delivery of Protein Antigens to the Immune System by Fusion-Active Virosomes: A Comparison with Liposomes and ISCOMs
Authors: Bungener Laura , Huckriede Anke , Wilschut Jan , Daemen Toos
Published: March 2003

The induction of effective cellular and humoral immune responses against protein antigens is of major importance in vaccination strategies against infectious diseases and cancer. Immunization with protein alone in general does not result in efficient induction of cytotoxic T lymphocyte (CTL) and antibody responses. Numerous other immunization strategies have been explored. In this review we will discuss a number of lipid-based antigen delivery systems suitable for the induction of CTL responses. These systems comprise reconstituted virus envelopes (virosomes), liposomes, and immune-stimulating complexes (ISCOMs). We will concentrate on delivery of the protein antigen ovalbumin (OVA) since extensive studies with this antigen have been performed for all of the systems discussed, allowing direct comparison of antigen delivery efficiency. Stimulation of CTL activity requires processing of the antigen in the cytosol of antigen-presenting cells (APCs) and presentation of antigenic peptides on surface major histocompatibility class I complexes (MHC class I). In vitro, the ability of antigen delivery systems to induce MHC class I presentation indeed correlates with their capacity to deliver antigen to the cytosol of cells. This capacity appears to be less important for the induction of cytotoxic T lymphocytes in vivo. Instead, other properties of the antigen delivery system like activation of APCs and induction of T helper cells play a more prominent role. Fusion-active virosomes appear to be a very potent system for induction of CTL activity, most likely since virosomes combine efficient delivery of antigen with general stimulation of the immune system.
Promoting Political Empowerment: Evaluation of an Intervention with University Students
Authors: Angelique Holly Lizotte , Reischl Thomas M. , Davidson William S.
Published: March 2003

The aim of this research is to examine the effects of an intervention, focusing on the development of political empowerment, with university students. Undergraduates were randomly assigned to one of two conditions (intervention/control) and were surveyed at two time points: before implementation of the intervention and upon completion of the intervention (or the equivalent two semester period). ANCOVA analyses reveal that individuals who participated in the empowering intervention had increased feelings of political commitment and a decreased sense of political efficacy compared to individuals who were randomly assigned to a waiting list/control group. Finally, limitations of this study are discussed and suggestions for future research are presented.
Synthetic Peptide Fragments as Probes for Structure Determination of Potassium Ion-Channel Proteins
Authors: Haris Parvez I.
Published: March 2003

Potassium channels are a diverse class of transmembrane proteins that are responsible for diffusion of potassium ion across cell membranes. The lack of large quantities of these proteins from natural sources, is a major hindrance in their structural characterization using biophysical techniques. Synthetic peptide fragments corresponding to functionally important domains of these proteins provide an attractive approach towards characterizing the structural organization of these ion-channels. Conformational properties of peptides from three different potassium channels (Shaker, ROMK1 and minK) have been characterized in aqueous media, organic solvents and in phospholipid membranes. Techniques used for these studies include FTIR, CD and 2D-NMR spectroscopy. FTIR spectroscopy has been a particularly valuable tool for characterizing the folding of the ion-channel peptides in phospholipid membranes; the three different types of potassium channels all share a common transmembrane folding pattern that is composed of a predominantly α-helical structure. There is no evidence to suggest the presence of any significant β-sheet structure. These results are in excellent agreement with the crystal structure of a bacterial potassium channel (Doyle, D. A. et al. (1998) Science280:69–77), and suggest that all potassium channel proteins may share a common folding motif where the ion-channel structure is constructed entirely from α-helices.
The Religious Support Scale: Construction, Validation, and Cross‐Validation
Authors: Fiala William E. , Bjorck Jeffrey P. , Gorsuch Richard
Published: March 2003

Cutrona and Russell's social support model was used to develop a religious support measure (C. E. Cutrona & D. W. Russell, 1987), including 3 distinct but related subscales respectively measuring support from God, the congregation, and church leadership. Factor analyses with the main sample's data (249 Protestants) and cross‐validation (93 additional Protestants) supported the scales' reliability and validity. All 3 types of religious support were related to lower depression and greater life satisfaction. Moreover, several relationships between the 3 subscales and psychological functioning variables remained significant after controlling for variance because of church attendance and social support. Results suggest that religious attendance does not automatically imply religious support, and that religious support can provide unique resources for religious persons, above and beyond those furnished by social support. Findings are discussed regarding relevance to community psychology.
Guanylyl Cyclase C Receptor: Regulation of Catalytic Activity by ATP
Authors: Bhandari Rashna , Suguna K. , Visweswariah Sandhya S.
Published: March 2003

Guanylyl cyclase C (GCC), a member of the family of membrane bound guanylyl cyclases is the receptor for the heat-stable enterotoxin (ST) peptides and the guanylin family of endogenous peptides. GCC is activated upon ligand binding to increase intracellular cGMP levels, which in turn activates other downstream signalling events in the cell. GCC is also activated in vitro by nonionic detergents. We have used the T84 cell line as a model system to investigate the regulation of GCC activity by ATP. Ligand-stimulated GCC activity is potentiated in the presence of ATP, whereas detergent-stimulated activity is inhibited. The potentiation of GCC activity by ATP is dependent on the presence of Mg2+ ions, and is probably brought about by a direct binding of Mg-ATP to GCC. The protein kinase-like domain of GCC, which has earlier been shown to play a critical role in the regulation of GCC activity, may be a possible site for the binding of Mg-ATP to GCC.
Successful Transfection of Lymphocytes by Ternary Lipoplexes
Authors: Simões S. , Slepushkin V. , Gaspar R. , de Lima M. C. Pedroso , Düzgünes N.
Published: March 2003

Transgene expression in lymphoid cells may be useful for modulating immune responses in, and gene therapy of, cancer and AIDS. Although cationic liposome-DNA complexes (lipoplexes) present advantages over viral vectors, they have low transfection efficiency, unfavorable features for intravenous administration, and lack of target cell specificity. The use of a targeting ligand (transferrin), or an endosome-disrupting peptide, in ternary complexes with liposomes and a luciferase plasmid, significantly promoted transgene expression in several T- and B-lymphocytic cell lines. The highest levels of luciferase activity were obtained at a lipid/DNA (±) charge ratio of 1/1, where the ternary complexes were net negatively charged. The use of such negatively charged ternary complexes may alleviate some of the drawbacks of highly positively charged plain lipoplexes for gene delivery.
Auxiliary Photosynthetic Functions of Arabidopsis thaliana—Studies in vitro and in vivo
Authors: Norén Hanna , Svensson Per , Andersson Bertil
Published: March 2003

An improved cultivation system for Arabidopsis thaliana was developed, allowing advanced biochemical studies in vitro and in vivo of this important model plant. Highly functional Arabidopsis thylakoids were isolated and used to study both basic and regulatory photosynthetic functions with the aim to create a platform for the characterization of mutants deficient in auxiliary proteins. Light-induced proteolytic degradation of the D1 protein could be followed and shown to be a subsequent event to photoinactivation of electron transport. The phosphorylation and dephosphorylation of thylakoid proteins resembled that seen in spinach leaves although phospho-CP43 revealed an unusual regulatory behavior.
Multigroup Confirmatory Component and Factor Analyses of the Italian Version of the Aggression Questionnaire1
Authors: Fossati Andrea , Maffei Cesare , Acquarini Elena , Di Ceglie Antonella
Published: March 2003

Summary Multisample confirmatory factor analyses were carried out in samples of Italian university and high school students in order to assess the replicability of the factor structure in the Italian version of the Aggression Questionnaire by Buss and Perry. Item-level multiple-group component analysis confirmed Buss and Perry's 4-factor structure of the Aggression Questionnaire items in both samples. The results of multisample maximum likelihood confirmatory factor analysis of scale scores supported the hypothesis of single aggression latent dimension underlying the four Aggression Questionnaire scales, the structure of which was invariant across the two samples.
Hepatocyte Growth Factor Activates Ccaat Enhancer Binding Protein and Cell Replication Via Pi3–Kinase Pathway
Authors: Cho Min Kyung , Kim Sang Geon
Published: March 2003

Hepatocyte growth factor (HGF), a ligand of c–Met receptor, stimulates activation of cellular kinases via phosphatidylinositol 3–kinase (PI3–kinase). CCAAT/enhancer binding protein (C/EBP) controls cell cycle progression. The present study was designed to determine whether HGF activates C/EBP in association with the S–phase entrance for cell replication and whether PI3–kinase contributes to the activation of C/EBP. Treatment of H4IIE cells, a hepatocyte–derived cell line, with HGF increased protein binding to the C/EBP binding site at an early time. Immunodepletion, subcellular fractionation, and confocal microscopic analyses showed that the HGF–induced C/EBP DNA binding activity depended on nuclear translocation of C/EBPβ. Whereas stable transfection of the p110 catalytic subunit of PI3–kinase enhanced HGF–mediated nuclear translocation of C/EBPβ and DNA binding, stable transfection of p85 subunit or chemical inhibition of PI3–kinase completely blocked C/EBP activation. HGF increased luciferase reporter activity in cells transfected with a mammalian cell expression vector containing -1.65 kilobase rGSTA2 promoter comprising C/EBP response element (pGL–1651). Whereas transfection with pCMV500, a control vector, allowed pGL–1651 to respond to HGF, expression of dominant negative mutant C/EBP completely inhibited the ability of HGF to stimulate the reporter gene expression. Flow cytometric analysis showed that HGF caused an increase in the area of S phase with a reciprocal decrease in that of G1 phase, suggesting that HGF promoted cell cycle progression to S phase. In conclusion, HGF induces nuclear translocation of C/EBPβ via the PI3–kinase pathway and stimulates C/EBP DNA binding and gene transcription and that the PI3–kinase-mediated C/EBP activation by HGF may contribute to cell replication.
Prospective Analysis of Risk Factors for Hepatocellular Carcinoma in Patients With Liver Cirrhosis
Authors: Velázquez Rosario F. , Rodríguez Manuel , Navascués Carmen A. , Linares Antonio , Pérez Ramón , Sotorríos Nieves G. , Martínez Isabel , Rodrigo Luis
Published: March 2003

Better knowledge of the risk factors associated with the appearance of hepatocellular carcinoma (HCC) could improve the efficacy of surveillance programs. A total of 463 patients aged 40 to 65 years with liver cirrhosis in Child–Pugh class A or B were included in a program of early diagnosis. The predictive value of different risk factors was evaluated using the Kaplan–Meier method and Cox regression model. Thirty–eight patients developed HCC. In the multivariate analysis, 4 variables showed an independent predictive value for the development of HCC: age 55 years or older, antibody to hepatitis C virus (anti–HCV) positivity, prothrombin activity 75% or less, and platelet count less than 75 × 103/mm3. According to the contribution of each of these factors to the final model, a score ranging between 0 and 4.71 points was constructed to allow the division of patients into 2 different risk groups. The low–risk group included those with a score of 2.33 points or less (n = 270; 4 with HCC; cumulative incidence of HCC at 4 years, 2.3%), and the high–risk group included those with a score greater than 2.33 (n = 193; 34 with HCC; cumulative incidence of HCC at 4 years, 30.1%) (P= .0001). In conclusion, a simple score made up of 4 clinical and biological variables allowed us to distinguish 2 groups of cirrhotic patients at high and low risk for the development of HCC. We believe this score can be useful in establishing a subset of cirrhotic patients in whom a surveillance program for early detection of HCC could be unjustified.
Influence of Ethnicity in the Outcome of Hepatitis C Virus Infection and Cellular Immune Response
Authors: Sugimoto Kazushi , Stadanlick Jason , Ikeda Fusao , Brensinger Colleen , Furth Emma E. , Alter Harvey J. , Chang Kyong-Mi
Published: March 2003

This study was performed to examine the immunologic basis for the apparent ethnic difference in clinical outcome of hepatitis C virus (HCV) infection between African Americans (AA) and Caucasian Americans (CA). To this end, we recruited 99 chronically HCV–infected and 31 spontaneously HCV–cleared subjects for clinical, virologic, and immunologic analysis. In particular, CD4–proliferative T–cell response to genotype 1-derived HCV antigens (core, NS3–NS5) was examined in 82 patients chronically infected with genotype 1 (54 AA, 28 CA) and in all HCV–cleared subjects (14 AA, 17 CA). HCV–specific Th1 response also was examined in 52 chronic and 13 recovered subjects. Our results showed that HCV clearance was associated with a vigorous HCV–specific Th1 response irrespective of ethnic origin. Although the HCV–specific CD4 T–cell response clearly was weaker during chronic infection, AA ethnicity in this setting was associated with a significantly greater CD4–proliferative T–cell response to HCV, particularly to the nonstructural antigens (22% AA vs. 0% CA, P = .007) as well as better clinical parameters of liver disease. Interestingly, most HCV–specific CD4 T–cell proliferative responses in AA patients were unaccompanied by concurrent interferon γ (IFN–γ) production, suggesting a dysregulated virus–specific, CD4 T–cell effector function during chronic HCV infection. In conclusion, our results suggest that host ethnicity does influence the clinical outcome and antiviral T–cell response during HCV infection. AA ethnicity is associated with a more robust antiviral CD4 T–cell response than CA ethnicity, although these T cells are limited in direct virus or disease control due to their dysfunctional nature.
Cyclins and Cyclin–Dependent Kinases: Comparative Study of Hepatocellular Carcinoma Versus Cirrhosis
Authors: Masaki Tsutomu , Shiratori Yasushi , Rengifo William , Igarashi Kouichi , Yamagata Michiko , Kurokohchi Kazutaka , Uchida Naohito , Miyauchi Yoshiaki , Yoshiji Hitoshi , Watanabe Seishiro , Omata Masao , Kuriyama Shigeki
Published: March 2003

Increasing evidence has indicated that perturbation of cyclins is one of the major factors leading to cancer. The aim of this study was not only to investigate various cell cycle–related kinase activities in hepatocellular carcinoma (HCC), but also to analyze the difference of cell cycle–related kinase activity levels between hepatitis C virus (HCV)–induced HCC and HCV–induced cirrhosis. The protein levels of cyclins D1, E, A, and H, and of cyclin dependent kinase 1 (Cdk1), Cdk2, Cdk4, Cdk6, and Cdk7 in HCC and in surrounding nontumorous cirrhosis were determined by Western blot. The enzymatic activities of cyclins D1, E, A, Cdk1, Cdk4, Cdk6, Cdk7, and Wee1 were measured using in vitro kinase assays. Protein levels and kinase activities of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 were significantly elevated in HCC compared with surrounding cirrhotic tissues. The enhanced cyclin D1–related kinase activity in HCC was accompanied by the up–regulation of Cdk4 activity, but not Cdk6 activity. The kinase activities of Cdk6, Cdk7, and Cdk1 did not differ between HCC and surrounding cirrhotic tissues. In addition, the protein levels and kinase activities of cyclin D1, Cdk4, and cyclin E were higher in poorly differentiated HCC and advanced HCC. In conclusion, the increases of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 play an important role in the development of HCC from cirrhosis. Cyclin D1, Cdk4, and cyclin E activation may be closely related to the histopathologic grade and progression of HCC.
Thrombopoietin in Acute Liver Failure
Authors: Schiødt Frank V. , Balko Jody , Schilsky Michael , Harrison Edwyn M. , Thornton Annelise , Lee William M.
Published: March 2003

Thrombopoietin (TPO) is the primary regulator of platelet production. TPO is produced in the liver and levels are low in patients with cirrhosis. Because thrombocytopenia is common in patients with acute liver failure (ALF), we measured TPO concentrations (normal TPO range, 31 to 136 pg/mL) in 51 patients with ALF to determine if low levels were associated with thrombocytopenia. TPO levels from hospital day 2 were elevated in 43% of patients, normal in 47%, and decreased in 10% of patients. Levels were higher in acetaminophen–induced than in non-acetaminophen–induced ALF, 160 (12 to 549) pg/mL versus 73 (18 to 563) pg/mL, respectively, P = .031. TPO levels did not correlate with platelet count and were not related with survival or infection. We analyzed daily TPO levels for the first week of hospitalization in 12 patients with acetaminophen–induced ALF and observed a gradual increase from a median admission level of 50 (5 to 339) pg/mL to a median peak level of 406 (125 to 1,081) pg/mL occurring on day 5 (3 to 6). Platelets were reduced in 11 of the 12 patients with a nadir platelet count of 52 (19 to 156) × 109 cells/L occurring on day 5.5 (1 to 6). The peak TPO level did not correlate with the nadir platelet count (P = .43). In conclusion, the normal inverse relationship between platelet count and TPO levels was not observed in ALF. Despite severe hepatic dysfunction, serum TPO levels were initially normal and increased during hospitalization in acetaminophen–induced ALF, but did not prevent the development of thrombocytopenia.
Novel Cd4+ and Cd8+ T–Cell Determinants Within the Ns3 Protein in Subjects With Spontaneously Resolved Hcv Infection
Authors: Wertheimer Anne M. , Miner Camette , Lewinsohn David M. , Sasaki Anna W. , Kaufman Ezra , Rosen Hugo R.
Published: March 2003

Spontaneous resolution of hepatitis C virus (HCV) infection is a relatively infrequent event, and these individuals provide a unique opportunity to characterize correlates of protective immunity as an important first step in the development of vaccine candidates. The aim of this study was to directly and comprehensively enumerate HCV–nonstructural protein 3 (NS3) specific CD4+ and CD8+ T cells ex vivo from HLA diverse individuals who had been successful in spontaneously resolving HCV infection. We measured interferon gamma (IFN–γ) production with an ELISPOT assay using magnetic bead–separated CD4+ or CD8+ T cells in response to autologous DCs that had been pulsed with 15mer per peptides overlapping by 11 amino acids and spanning all of the NS3 protein (150 total peptides). All subjects with spontaneously recovered HCV infection demonstrated vigorous and multispecific CD4+ T–cell responses to NS3 peptides, and 6 of 10 subjects demonstrated CD8+ T–cell responses. More importantly, we identified novel, previously unpredicted antigenic regions, which in most cases elicited high frequencies within a given individual. In conclusion, subjects who have spontaneously eradicated HCV infection up to 35 years earlier demonstrate persistent CD4+ and CD8+ T–cell responses specific to NS3. By providing a comprehensive screening of all potential T–cell epitopes contained in the NS3 region, our strategy defines the breadth of the T–cell response and identifies novel, unpredicted specificities.
Culture and conflict: Japanese managers and Thai subordinates
Authors: Swierczek Fredric William , Onishi Jun
Published: March 2003

This article presents the findings of research on the application and adaptability of Japanese management practices in a different cultural context, Thailand. The national characteristics of Japan and Thailand based on Hofstede's conceptual framework, Japanese human resource management approaches and the specific Japanese business practices and social concepts were analyzed. Possible conflicts between the Japanese management and Thai staff based on the different perceptions of the Japanese management style were assessed. Data were collected from ten Japanese manufacturers using a sample of 100 employees (50 Japanese managers and 50 Thai subordinates from the same group of companies). The results shows an interesting pattern of Japanese managers adapting more to Thai culture and as well as Thai subordinates adapting to the Japanese style of management and human resource system.
Prognostic Value of Abnormal Vasoreactivity of Epicardial Coronary Arteries to Sympathetic Stimulation in Patients With Normal Coronary Angiograms
Authors: Schindler Thomas H. , Hornig Burkhard , Buser Peter T. , Olschewski Manfred , Magosaki Nobuhisa , Pfisterer Matthias , Nitzsche Egbert U. , Solzbach Ulrich , Just Hanjörg
Published: March 2003

Objective—

We aimed to evaluate prospectively whether patients with normal coronary angiogram but abnormal epicardial vasoreactivity to cold pressor test (CPT) are at increased risk for cardiovascular events.

Methods and Results—

Vasoreactivity in response to CPT and dilation of epicardial arteries to intracoronary application of nitroglycerin were assessed quantitatively (percent change of luminal area, ΔLA%) in 130 patients with normal coronary angiograms. Cardiovascular events (cardiovascular death, acute coronary syndrome, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary bypass grafting, ischemic stroke, or peripheral revascularization) were assessed as clinical outcome parameters over a mean follow-up period of 45±9 months. Based on their vascular responses to CPT, patients were assigned into the following 3 groups: group 1, patients with normal vasodilator response (ΔLA >0%; n=37); group 2, patients with moderate vasoconstrictor response (ΔLA between 0% and −15%; n=42); and group 3, patients with severe vasoconstrictor response (ΔLA ≤−15%; n=51). Although patients from groups 2 and 3 had significantly increased vasoconstrictor response to CPT (group 2, ΔLA −6±3% and group 3, ΔLA −24±6% versus group 1, ΔLA 11±9%;
P
≤0.0001), they showed normal endothelial-independent epicardial vasodilation to intracoronary application of nitroglycerin similar to patients from group 1 (ΔLA 39±16% and 34±14% versus 41±14%;
P
=NS, respectively). During follow-up, none of the patients from group 1 developed cardiac events. However, 7 cardiovascular events occurred in group 2 and 30 occurred in group 3 in 4 and 22 patients, respectively (
P
≤0.0001, univariate by log-rank test). After adjustment for known risk factors for coronary artery disease, impaired epicardial coronary vasoreactivity to CPT remained significantly associated with the risk of developing cardiovascular events (
P
=0.040, multivariate by Cox regression model).

Conclusions—

In patients with normal coronary angiogram, abnormal vasoreactivity of epicardial coronary arteries in response to sympathetic stimulation is associated with the risk of developing cardiovascular events.
Origin of Vascular Smooth Muscle Cells and the Role of Circulating Stem Cells in Transplant Arteriosclerosis
Authors: Hillebrands Jan-Luuk , Klatter Flip A. , Rozing Jan
Published: March 2003

To date, clinical solid-organ transplantation has not achieved its goals as a long-term treatment for patients with end-stage organ failure. Development of so-called chronic transplant dysfunction (CTD) is now recognized as the predominant cause of allograft loss long term (after the first postoperative year) after transplantation. CTD has the remarkable histological feature that the luminal areas of intragraft arteries become obliterated, predominantly with vascular smooth muscle cells (VSMCs) intermingled with some inflammatory cells (transplant arteriosclerosis, or TA). The development of TA is a multifactorial process, and many risk factors have been identified. However, the precise pathogenetic mechanisms leading to TA are largely unknown and, as a result, adequate prevention and treatment protocols are still lacking. This review discusses the origin (donor versus recipient, bone marrow versus nonbone marrow) of the VSMCs in TA lesions. Poorly controlled influx and subsequent proliferative behavior of these VSMCs are considered to be critical elements in the development of TA. Available data show heterogeneity when analyzing the origin of neointimal VSMCs in various transplant models and species, indicating the existence of multiple sites of origin. Based on these findings, a model considering plasticity of VSMC origin in TA in relation to severity and extent of graft damage is proposed.
Mouse Macrophage Paraoxonase 2 Activity Is Increased Whereas Cellular Paraoxonase 3 Activity Is Decreased Under Oxidative Stress
Authors: Rosenblat Mira , Draganov Dragomir , Watson Catherine E. , Bisgaier Charles L. , La Du Bert N. , Aviram Michael
Published: March 2003

Objective—To determine whether paraoxonases (PONs) are expressed in macrophages and to analyze the oxidative stress effect on their expression and activities.

Methods and Results—We demonstrated the presence (mRNA, protein, activity) of PON2 and PON3 but not PON1 in murine macrophages, whereas in human macrophages, only PON2 was expressed. Under oxidative stress as present in mouse peritoneal macrophages (MPMs) from apoE-deficient (E0) mice as well as in C57BL6 mice, MPMs that were incubated with buthionine sulfoximine, with angiotensin II, with 7-ketocholesterol, or with oxidized phosphatidylcholine, PON2 mRNA levels and lactonase activity toward dihydrocoumarin significantly increased (by 50% to 130%). In contrast, PON3 lactonase activity toward lovastatin was markedly reduced (by 29% to 57%) compared with control cells. The supplementation of E0mice with dietary antioxidants (vitamin E, pomegranate juice) significantly increased macrophage PON3 activity (by 23% to 40%), suggesting that oxidative stress was the cause for the reduced macrophage PON3 activity. Incubation of purified PON2 or PON3 with E0mice MPMs resulted in reduced cellular lipid peroxides content by 14% to 19% and inhibition of cell-mediated LDL oxidation by 32% to 39%.

Conclusions—Increased macrophage PON2 expression under oxidative stress could represent a selective cellular response to reduce oxidative burden, which may lead to attenuation of macrophage foam cell formation.
Report of eight children with amitraz intoxication
Authors: Çaksen Hüseyin , Odabaş Dursun , Arslan Şükrü , Akgün Cihangir , Ataş Bülent , Akbayram Sinan , Tuncer Oguz
Published: March 2003

Many pesticides are formulated in organic solvents. An example is amitraz, one of the formamidine groups of pesticidal chemicals. It is commonly used for the treatment of generalized demodicosis in dogs and for the control of ticks and mites in cattle and sheep. In this article, the clinical and laboratory findings of eight children with amitraz intoxication are reviewed. The purpose was to enlighten the findings of amitraz intoxication in children. Of the eight patients, five (62.5%) were boys, three (37.5%) were girls, and the ages ranged from 1 to 4 years. All children accidentally ingested amitraz orally, with no dermal exposure. The most common observed signs were decreased consciousness and bradycardia. Leukocytosis, hyperglycemia, hypernatremia, increased serum aspartate transaminase level, and prolonged partial prothrombin time were diagnosed in children. None of the children had hypothermia, hypotension, or convulsion and none of the patients died. The findings show that the initial signs and symptoms of acute amitraz intoxication appeared severe but they disappeared, with only supportive care needed in most cases within a few days.
The influence of amitraz on biochemical parameters in mice
Authors: Filazi Ayhan , Sireli Meltem , Kalkan Faruk
Published: March 2003

In this study, the effect of amitraz on biochemical parameters of mice was studied. Mice were given amitraz by gavage at 15 or 45 mg/kg body weight. Since the drug was diluted with dimethylsulphoxide (DMSO), it was administered to another experimental animal group in order to determine its own effects on biochemical parameters. Following drug administration, 48 hours passed to let hepatic lesions develop and after that 1 mL of blood was taken from each mouse. They were killed by ether euthanasia for histopathological examination. The result of the analyses revealed that amitraz had no effect on serum glucose concentration, whereas DMSO led to a significant decrease in blood sugar concentration. Increase in urea, phosphorous, aspartate transaminase and alanine amino transferase values were observed only in the group given 45 mg/kg body weight amitraz. A decrease in creatinine and alkaline phosphatase concentrations was observed in all groups. No differences were observed in serum calcium and bilirubin concentrations. No pathological changes were detected in the kidneys and livers. It was concluded that, even in asymptomatic amitraz toxicity cases, adverse effects on kidney and liver functions were likely to develop.
Tape‐assisted reciprocal teaching: Cognitive bootstrapping for poor decoders
Authors: Le Fevre Deidre M. , Moore Dennis W. , Wilkinson Ian A. G.
Published: March 2003

Background: Students who have limited skills in decoding and comprehension and who lack motivation to read present difficulties for practitioners. Difficulties may be compounded when these students lack access to age‐appropriate and interesting text and have lost the notion of reading as a process of obtaining meaning from print.

Aims: This research examined the effects of a modified reciprocal teaching intervention for readers with poor decoding skills and poor comprehension. Tapeassisted reciprocal teaching was used to help students with poor decoding skills develop cognitive and metacognitive strategies and improve their comprehension of high interest expository texts.

Methods: Two single‐subject research design studies involving four groups of students were conducted. Study I involved one experimental group and Study II was a multiple baseline design involving three experimental groups.

Sample: Each experimental group comprised a heterogeneous mix of six students, three with poor decoding skills and three with adequate decoding skills, all of whom showed poor comprehension.

Results: As a result of the tape‐assisted reciprocal teaching, the poor decoders demonstrated improved application of cognitive and metacognitive strategies and improved comprehension. These improvements were shown on both researcherdeveloped and standardised tests as well as on maintenance and transfer measures. The students with adequate decoding skills also showed improvements in comprehension.

Conclusions: The success of the intervention for poor decoders suggests that tape assisted reciprocal teaching may be seen as a form of ‘cognitive bootstrapping’ to enable poor readers to escape the cycle of reading failure and engage more meaningfully in the process of reading.
Tendon Transfer to Reconstruct Wrist Extension in Children with Obstetric Brachial Plexus palsy
Authors: Al-QATTAN M. M.
Published: March 2003

This study reports on 20 children with obstetric brachial plexus palsy who underwent a tendon transfer to reconstruct wrist extension. The mean age at the time of tendon transfer was 8 years. There were seven patients with Erb’s palsy and the remaining 13 had total palsy. The flexor carpi ulnaris was utilized 15 times and the flexor carpi radialis five times. The transferred tendon was sutured to the tendon of the extensor carpi radialis brevis. The result of the transfer was assessed according to a modified Medical Research Council (MRC) muscle grading system. A good result was obtained in 18 patients (modified MRC grade of 4) and a fair result (modified MRC grade of 3) in two. The choice of tendon transfer to reconstruct the wrist drop deformity in various conditions including adult traumatic brachial plexus injuries is discussed.
The ‘Pillared-Privatisation’ of Pension Provision in the European Union: The Case of the United Kingdom
Authors: Ring Patrick , McKinnon Roddy
Published: March 2003

Across the European Union, national governments are re-assessing the institutional mechanisms through which pension provision is delivered. This articles sets the debate within the wider context of the ‘pillared’ structural analysis often adopted by international institutions when discussing pensions reform. It then sets out a detailed discussion of developments in the UK, arguing that the UK is moving towards a model of reform akin to that promoted by the World Bank – referred to here as ‘pillared-privatisation’. The themes of this model indicate more means-testing, greater private provision, and a shift of the burden of risk from the government to individuals. An assessment is then made of the implications of UK developments for other EU countries. It is suggested that while there are strong reasons to think that other countries will not travel as far down the road of ‘pillared-privatisation’ as the UK, this should not be taken as a ‘given’.
Ethical Dilemmas in Testing for Late Onset Conditions: Reactions to Testing and Perceived Impact on Other Family Members
Authors: Chapman Elizabeth
Published: March 2003

This paper examines some of the ethical dilemmas that arise when testing for the late onset, untreatable condition of Huntington disease (HD) specifically now that technology allows us to test younger generations of the family for the mutant gene. Drawing on interview data from families with Huntington disease, the reactions to testing and perceived impact on other family members are considered. These are discussed in the light of the possible lowering of the age of test applicants. This potentially raises problems for a younger generation as they are confronted with reproductive decisions that the older generation did not have to face. It also means that individuals have the prospect of living with knowledge of a future illness for much longer.
Mental health status of human rights workers, Kosovo, June 2000
Authors: Holtz Timothy H. , Salama Peter , Cardozo Barbara Lopes , Gotway Carol A.
Published: March 2003

Human righls workers in humanitarian relief settings may be exposed to traumatic events that put them at risk for psychiatric morbidity. We conducted a cross‐sectional survey in June 2000 to study the prevalence of psychiatric morbidity among 70 expatriate and Kosovar Albanian staff collecting human rights data in Kosovo. Among those surveyed, elevated levels of anxiety, depression, and posttraumatic stress disorder symptoms were found in 17.1, 8.6, and 7.1% respectively. Multiple regression analysis revealed that human rights workers at risk for elevated anxiety symptoms were those who had worked with their organization longer than 6 months, those who had experienced an armed attack, and those who experienced local hostility. Our study indicates that human rights organizations should consider mental health assessment, care, and prevention programs for their staff.
Neurological, cognitive and attributional predictors of posttraumatic stress symptoms after traumatic brain injury
Authors: Williams W. Huw , Evans Jonathan J. , Needham Paul , Wilson Barbara A.
Published: March 2003

We investigated the relationship between the reporting of symptoms of posttraumatic stress disorder (PTSD) in a community sample of 66 survivors of severe traumatic brain injury (TBI) and measures of injury severity, memory, insight, and index‐event attributions. Correlational analyses revealed that report ing of PTSD symptoms was related to level of insight and not associated with the severity of survivors' injury, educational background, premorbid or current IQ, or memory impairment. The severity of PTSD symptoms was also associated with external attributions to others of causality for the event.