bluuebunny/crossref_metadata_2025 huggingface dataset:
Wfs1 gene deletion causes growth retardation in mice and interferes with the growth hormone pathway
Authors: Kõks S. , Soomets U. , Paya-Cano J. L. , Fernandes C. , Luuk H. , Plaas M. , Terasmaa A. , Tillmann V. , Noormets K. , Vasar E. , Schalkwyk L. C.
Published: March 2009

The aim of present study was to describe changes in gene expression in the temporal lobe of mice induced by deletion of the Wfs1 gene. Temporal lobes samples were analyzed using Affymetrix Mouse Genome 420 2 GeneChips and expression profiles were functionally annotated with GSEA and Ingenuity Pathway Analysis. We found that Wfs1 mutant mice are significantly smaller (20.9 ± 1.6 g) than their wild-type counterparts (31.0 ± 0.6 g, P < 0.0001). This difference existed in 129S6 and C57B6 backgrounds. Interestingly, microarray analysis identified upregulation of growth hormone (GH) transcripts and functional analysis revealed activation of GH pathways. In line with microarray data, the level of IGF-1 in the plasma of Wfs1 mutant mice was significantly increased ( P < 0.05). Thus, Wfs1 deletion induces growth retardation, whereas the GH pathway is activated. To test the interaction between the Wfs1 deletion and genomic background, mutant mice were backcrossed to two different genetic backgrounds. In line with previous studies, an interaction between a gene knockout and genetic background was found in gene expression profiles in the congenic region. However, genetic background did not alter the effect of the Wfs1 mutation on either body weight or GH pathway activation. Further studies are needed to describe biochemical and molecular changes of the growth hormone axis as well as in other hormones to clarify their role in growth retardation in the Wfs1 mutant mice.
Thermal Hydraulic Analysis of a Passive Residual Heat Removal System for an Integral Pressurized Water Reactor
Authors: Gou Junli , Qiu Suizheng , Su Guanghui , Jia Douna
Published: March 2009

A theoretical investigation on the thermal hydraulic characteristics of a new type of passive residual heat removal system (PRHRS), which is connected to the reactor coolant system via the secondary side of the steam generator, for an integral pressurized water reactor is presented in this paper. Three‐interknited natural circulation loops are adopted by this PRHRS to remove the residual heat of the reactor core after a reactor trip. Based on the one‐dimensional model and a simulation code (SCPRHRS), the transient behaviors of the PRHRS as well as the effects of the height difference between the steam generator and the heat exchanger and the heat transfer area of the heat exchanger are studied in detail. Through the calculation analysis, it is found that the calculated parameter variation trends are reasonable. The higher height difference between the steam generator and the residual heat exchanger and the larger heat transfer area of the residual heat exchanger are favorable to the passive residual heat removal system.
Chemokine Expression in Melanoma Metastases Associated with CD8+ T-Cell Recruitment
Authors: Harlin Helena , Meng Yuru , Peterson Amy C. , Zha Yuanyuan , Tretiakova Maria , Slingluff Craig , McKee Mark , Gajewski Thomas F.
Published: March 2009

Despite the frequent detection of circulating tumor antigen–specific T cells, either spontaneously or following active immunization or adoptive transfer, immune-mediated cancer regression occurs only in the minority of patients. One theoretical rate-limiting step is whether effector T cells successfully migrate into metastatic tumor sites. Affymetrix gene expression profiling done on a series of metastatic melanoma biopsies revealed a major segregation of samples based on the presence or absence of T-cell–associated transcripts. The presence of lymphocytes correlated with the expression of defined chemokine genes. A subset of six chemokines (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10) was confirmed by protein array and/or quantitative reverse transcription-PCR to be preferentially expressed in tumors that contained T cells. Corresponding chemokine receptors were found to be up-regulated on human CD8+ effector T cells, and transwell migration assays confirmed the ability of each of these chemokines to promote migration of CD8+ effector cells in vitro. Screening by chemokine protein array identified a subset of melanoma cell lines that produced a similar broad array of chemokines. These melanoma cells more effectively recruited human CD8+ effector T cells when implanted as xenografts in nonobese diabetic/severe combined immunodeficient mice in vivo. Chemokine blockade with specific antibodies inhibited migration of CD8+ T cells. Our results suggest that lack of critical chemokines in a subset of melanoma metastases may limit the migration of activated T cells, which in turn could limit the effectiveness of antitumor immunity. [Cancer Res 2009;69(7):3077–85]
Circulating B-Cell Chronic Lymphocytic Leukemia Cells Display Impaired Migration to Lymph Nodes and Bone Marrow
Authors: Hartmann Tanja Nicole , Grabovsky Valentin , Wang Wei , Desch Petra , Rubenzer Gabriele , Wollner Stefan , Binsky Inbal , Vallon-Eberhard Alexandra , Sapoznikov Anita , Burger Meike , Shachar Idit , Haran Michal , Honczarenko Marek , Greil Richard , Alon Ronen
Published: March 2009

Homing to secondary lymphoid organs and bone marrow (BM) is a central aspect of leukemic pathophysiology. We investigated the roles of the two major lymphocyte integrins LFA-1 and VLA-4 on B-cell chronic lymphocytic leukemia (CLL) cells in these processes. We found that the majority of CLL cells expressed significantly reduced LFA-1 due to low β2 integrin transcripts. VLA-4 expression was heterogenous but underwent rapid activation by the BM chemokine CXCL12. CLL cells failed to transmigrate across VCAM-1–expressing, ICAM-1–expressing, and CXCL12-expressing endothelium, whereas when LFA-1 expression was regained in subsets of CLL cells, these lymphocytes rapidly transmigrated the endothelium. Furthermore, when injected into tail veins of immunodeficient mice, normal B cells rapidly homed to lymph nodes (LN) in a LFA-1–dependent manner, whereas CLL cells did not. Nevertheless, only residual CLL subsets could reenter BM, whereas both normal and CLL cells homed to the mice spleen in an LFA-1–independent and VLA-4–independent manner. Our results suggest that CLL cells have a reduced capacity to adhere and transmigrate through multiple vascular endothelial beds and poorly home to lymphoid organs other than spleen. Integrin blocking could thus be an efficient strategy to prevent circulating CLL cells from reaching prosurvival niches in LNs and BM but not in spleen. [Cancer Res 2009;69(7):OF3121–30]
Evaluation of T- and NK-Cell-Targeted Therapies: Is There a Role for Rituximab Prophylaxis?
Authors: Ambinder Richard F.
Published: March 2009

Splizimomab, an antibody that targets CD2, was studied in the treatment of T and natural killer cell lymphoma and was found to be associated with Epstein-Barr virus lymphoproliferative disease. B cell depletion may provide a platform for further evaluation of this and other promising antibody approaches that result in T cell depletion.
Can Routine Posttransplant HPV Vaccination Prevent Commonly Occurring Epithelial Cancers after Allogeneic Stem Cell Transplantation?
Authors: Savani Bipin N. , Goodman Stacey , Barrett A. John
Published: March 2009

The association between squamous cell carcinoma (SCC) of the oral cavity, female genital tract, and skin with human papilloma virus (HPV) subtypes is well established in the general population and in solid organ transplant recipients, but no consistent link has been reported between HPV infection and SCC after allogeneic stem cell transplantation (allo-SCT). Studies are needed to determine if SCC, the most common secondary malignancy after allo-SCT, which is linked to chronic graft versus host disease and immunosuppressive therapy, is HPV related. Consideration should be given to assessing pretransplant HPV antibodies to identify patients at risk for HPV reactivation. If a strong relationship between HPV and second malignancies after SCT exists, studies to evaluate the immunogenicity and efficacy of quadrivalent HPV vaccine (subtypes 6, 11, 16, and 18) should be considered in both male and female long-term survivors after allo-SCT.
Clinico-Immunochemical Studies on Airborne Areca catechu L. Pollen, a Probable Risk Factor in Emergency Asthma Hospitalization from Eastern India
Authors: Chakraborty Pampa , Mandal Jyotshna , Sarkar Eva , Chowdhury Indrani , Gupta-Bhattacharya Swati
Published: March 2009

Background: The pollen grain of the Areca catechu L. tree is airborne and allergenic. This study aimed to know the role of this pollen as a source of aeroallergen with effect on emergency asthma hospitalization, to isolate its important allergic fraction and to check its cross-reaction with betel nut. Methods:Areca pollen was monitored with a Burkard sampler. Determination of allergenic activities was studied by in vivo and in vitro analyses. Asthma hospitalization data were collected from two nearby hospitals. The pollen extract was fractionated by a combination of DEAE-Sephadex and Sephacryl S-200 column. The protein components were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cross-reactivity of Areca pollen and betel nut was shown by IgE enzyme-linked immunosorbent assay (ELISA) inhibition. Results: The Areca pollen was perennially airborne. Skin test results of respiratory allergic patients showed 38.6% positivity. The detected aeroallergen spots in particle immunoblotting correlated significantly with airborne pollen count. Areca pollen showed a significant positive correlation with asthma hospitalization. There are 6 IgE-reactive protein components in the whole-pollen extract. IgE-reactive fraction 1 was resolved into 4 subfractions. Subfraction 1a showing IgE reactivity contained 3 protein components, among which 2 of 48 and 118 kDa were IgE reactive. The 48-kDa component was reported to be cross-reactive with other palm pollen types. In IgE ELISA inhibition, the betel nut extract showed 50% inhibition with about 110 ng/ml concentration. Conclusion:A. catechu pollen is a significant contributor to the aeroallergen load in India. Its partially purified IgE-reactive fraction may be useful in therapeutics. The betel nut extract showed remarkable cross-reactivity with Areca pollen.
Therapeutic Surfactants Modulate the Viability of Eosinophils and Induce Inflammatory Mediator Release
Authors: Erpenbeck Veit J. , Fischer Ina , Wiese Kathrin , Schaumann Frank , Schmiedl Andreas , Nassenstein Christina , Krug Norbert , Hohlfeld Jens M.
Published: March 2009

Background: There is increasing interest in testing surfactant preparations for asthma therapy. Previously, Curosurf was demonstrated to increase inflammation in allergic asthmatics. So far, little is known about the immunomodulatory effects of therapeutic surfactants, in particular concerning the interaction of surfactant components with eosinophils as key effector cells of the allergic airway inflammation. The aim of the present study was to determine the effect of different therapeutic surfactants on cellular functions of eosinophils. Methods: Eosinophils were isolated from peripheral blood of atopic volunteers and incubated with the natural animal-derived surfactants Curosurf or Alveofact or the synthetic recombinant human surfactant Venticute at different concentrations for up to 42 h. Results: Curosurf and Venticute modulated the viability of eosinophils. While incubation with Curosurf increased the number of necrotic eosinophils after 1, 20 and 42 h, Venticute increased the number of apoptotic and necrotic cells after 1 h, but there were no differences compared with control cells at later time points. All surfactant preparations increased the levels of eosinophil cationic protein after 20 h and, in addition, Curosurf enhanced eosinophil cationic protein release after 42 h. The supernatant of eosinophils induced chemotaxis against autologous eosinophils, and the presence of Curosurf, but not Alveofact or Venticute, augmented the chemotactic effect. Chemotaxis was partly blocked by inhibition of eotaxin but not by inhibition of leukotrienes or platelet-activating factor. Conclusions: Therapeutic surfactants differ in their effects on eosinophil viability and the accompanying release of inflammatory mediators and chemotactic signals. Proinflammatory effects were most pronounced for the natural surfactant Curosurf.
Aspirin-Induced COX-2 Overexpression in Monocytes of Aspirin-Intolerant Patients
Authors: Morgan Tina , Bajrovic Nissera , Silar Mira , Kosnik Mitja , Korosec Peter
Published: March 2009

Background: We hypothesize that alternate regulation of cyclooxygenase-2 (COX-2) may predispose patients to aspirin-induced exacerbations.Therefore, we want to examine the dynamics of COX-2 up-regulation in whole blood monocytes in the presence and absence of aspirin. Methods: COX-2 expression was evaluated by flow cytometry through intracellular staining of whole blood monocytes with antiCOX-2 antibodies. Enzyme up-regulation was monitored after in vitrostimulation with lipopolysaccharide (LPS) and/or aspirin in 19 aspirin-intolerant (AI) patients (8 aspirin-sensitive asthmatics and 11 urticaria-angioedema patients) and 14 healthy controls. Results: We found significantly higher COX-2 expression levels after stimulation with LPS and aspirin (mean 78.8, range 44.9–92.3; p = 0.0002) in comparison to LPS alone (mean 65.9%, range 33.6–82.6) in AI patients. A comparable, but lower up-regulation was also observed after aspirin stimulation alone (median 2.1%, range 0.5–15.9; p = 0.004) in comparison with baseline values (median 1%, range 0.1–5.4). There was no significant difference in COX-2 expression between LPS and aspirin stimulation (mean 61.8%, range 26.8–89.2; p = 0.09) and LPS stimulation (mean 55.5%, range 28.1–74.3) nor between aspirin stimulation alone (median 0.5%, range 0–8.6; p = 0.8) and baseline values (median 0.4%, range 0–5.4) in healthy control subjects. Conclusions: The main finding of this study is that COX-2 appears to be differentially regulated in aspirin-sensitive patients. What is really new is the observation that aspirin and LPS increase COX-2 expression on blood monocytes of AI asthmatics, a finding in contrast with the lack of an effect of the same stimuli on COX-2 expression on monocytes from healthy subjects.
Amusia and Musical Functioning
Authors: Alossa Nicoletta , Castelli Lorys
Published: March 2009

Music, as language, is a universal and specific trait to humans; it is a complex ability with characteristics that are unique compared to other cognitive abilities. Nevertheless, several issues are still open to debate, such as, for example, whether music is a faculty that is independent from the rest of the cognitive system, and whether musical skills are mediated by a single mechanism or by a combination of processes that are independent from one another. Moreover, the anatomical correlations of music have yet to be clarified. The goal of this review is to illustrate the current condition of the neuropsychology of music and to describe different approaches to the study of the musical functions. Hereby, we will describe the neuropsychological findings, suggesting that music is a special function carried out by different and dedicated processes that are probably subserved by different anatomical regions of the brain. Moreover, we will review the evidence obtained by working with brain-damaged patients suffering from music agnosia, a selective impairment in music recognition.
Encephalitis after Influenza in Sweden 1987–1998: A Rare Complication of a Common Infection
Authors: Hjalmarsson Anders , Blomqvist Paul , Brytting Maria , Linde Annika , Sköldenberg Birgit
Published: March 2009

The aim of this study was to investigate the incidence of influenza-related encephalitis in Sweden during 11.5 years. Studies from Japan report an increased incidence of influenza-related encephalitis/encephalopathy. Few other studies are available. We conducted a retrospective register-based study on the Swedish National Inpatient Register, which covers all Swedish hospitals. In 1987–1998, a total number of 14,250 hospitalized individuals had an influenza diagnosis (population incidence: 137 per million personyears). In-hospital mortality was 4.1%. Using three different approaches, only 21 cases of influenza-related encephalitis were found, corresponding to a rate of 1.5 per 1,000 hospitalized persons with an influenza diagnosis (population incidence 0.21 per million person-years). We conclude that encephalitis following influenza occurs rarely, or is an infrequently recognized, diagnosed or reported complication. The cases we studied in detail have all recovered without sequels.
Clinical Identification of Dysarthria Types among Neurologists, Residents in Neurology and Speech Therapists
Authors: Van der Graaff M. , Kuiper T. , Zwinderman A. , Van de Warrenburg B. , Poels P. , Offeringa A. , Van der Kooi A. , Speelman H. , De Visser M.
Published: March 2009

Background: Classification of dysarthria types comprises flaccid, spastic, ataxic, hypo- and hyperkinetic and mixed dysarthria. This study focussed on the ability of neurologists to clinically identify the correct type of dysarthria in neurological patients. Methods: Eighteen patients with dysarthria and 4 healthy controls were enrolled in the study. The gold standard for dysarthria type was the underlying neurological disease. Recordings of a standard reading passage and free speech were made. Raters were neurologists, residents in neurology and speech therapists, whose scores were compared. Results: Neurologists correctly identified 40% of the recordings, residents 41%, and speech therapists 37%. Interrater agreement was fair among all 3 groups; intrarater agreement was fair to moderate. Conclusion: This study suggests that neurologists should be aware of the unreliability of identifying the dysarthria type without the use of additional validated instruments or rating scales in a clinical setting.
Clinical Features, Neuroimaging and Treatment of Spontaneous Intracranial Hypotension and Magnetic Resonance Imaging Evidence of Blind Epidural Blood Patch
Authors: Su Chen-San , Lan Min-Yu , Chang Yung-Yee , Lin Wei-Che , Liu Kuan-Ting
Published: March 2009

Background and Purpose: Spontaneous intracranial hypotension (SIH) is an uncommon, but not rare, cause of headache. We analyzed a series of patients with SIH and attempted to establish a clinical procedure. Methods: We retrospectively reviewed 11 patients with SIH who were admitted between January 2004 and May 2007. Data recorded from patients included basic data, clinical symptoms, neurological imaging studies and treatment. Results: Orthostatic headache was the most common symptom, but there were still 2 patients without orthostatic headache. Diffuse pachymeningeal enhancement was the most common finding in brain MRI study and engorgement of the spinal epidural venous plexus was the most common finding in spinal MRI study. Eight of our patients received epidural blood patches in the lumbar area and 6 of these were symptom-free within 2 weeks. Two patients received spinal MRI immediately after administering the epidural blood patch, and this revealed that most of the blood had spread to the upper cervical area from the lumbar injection. Conclusion: A blind epidural blood patch from the lumbar area is an acceptable procedure even if the area of leakage is unknown. A reasonable clinical procedure for the patients of SIH may minimize the rate of repeat puncture.
Physical Activity, High-Density Lipoprotein Cholesterol Subfractions and Lecithin:Cholesterol Acyltransferase in Dialysis Patients
Authors: Masuda Reika , Imamura Hiroyuki , Mizuuchi Keiko , Miyahara Keiko , Kumagai Harumitsu , Hirakata Hideki
Published: March 2009

Background/Aims: Although a low level of high-density lipoprotein cholesterol (HDL-C) is an independent risk factor for atherosclerotic heart disease, the mechanism of HDL-C abnormality in hemodialysis (HD) as well as peritoneal dialysis (PD) patients is not fully understood. The purpose of this study was to investigate the relationship of physical activity with HDL-C subfractions and lecithin:cholesterol acyltransferase activity in HD and PD patients. Methods: Thirty-five HD and 26 PD patients were studied. Physical activity was estimated as the average number of steps taken per day over 7 days (steps/day). Results: When possible confounding factors were included in the stepwise multiple regression analyses, in HD patients, steps/day was significantly positively related to HDL2-C and apolipoprotein (Apo) A-I, while it was significantly positively related to HDL3-C in PD patients. When subjects were subdivided into 3 groups according to steps/day, in HD patients, the highest category of steps/day had significantly higher HDL2-C and Apo A-I than the lowest category, while such results were not observed in PD patients. Conclusion: These results suggest that the associations of physical activity with HDL-C subfractions and Apo A-I that are known in the general population are more pronounced in HD patients than PD patients.
Comparison of Antibody Monitoring System with Flow Cytometric Crossmatch Test in Renal Transplant Recipients with High Panel-Reactive Antibody
Authors: Hwang Hyeon Seok , Hyoung Bok Jin , Lee So Young , Jeon Youn Joo , Yoon Hye Eun , Kim Jin Young , Choi Bum Soon , Oh Eun Jee , Kim Yong Soo , Bang Byung Kee , Yang Chul Woo
Published: March 2009

Background/Aims: The antibody monitoring system (AMS) is a recently developed enzyme-linked immunosorbent assay (ELISA) crossmatch assay to detect donor-specific anti-HLA immunoglobulin G antibodies (DS-HLA Abs). This study was conducted to compare the AMS with the flow cytometric crossmatch (FCXM) test in renal transplant recipients with high panel-reactive antibody (PRA). Methods: Thirty-two sera were obtained from 10 patients with panel reactivity above 50%. When anti-HLA Ab was detected by ELISA PRA and the matched donor had the corresponding HLA antigen, it was considered to indicate DS-HLA Ab. The results of the AMS assay and FCXM were compared with the DS-HLA Abs. Results: Twenty-three (71.9%) sera were positive for DS-HLA Abs by ELISA PRA. The AMS assay showed that the number of compatible sera with DS-HLA Abs was 27 (84.4%), and it was significantly concordant (κ = 0.649, p < 0.0001). For FCXM, the number of compatible sera with DS-HLA Abs was 26 (81.3%), and it was also significantly concordant (κ = 0.614, p < 0.0001). There was a significant degree of concordance between the AMS assay and FCXM in detection of DS-HLA Abs (κ = 0.452, p = 0.010). Conclusion: The AMS assay is comparable to FCXM in detecting DS-HLA Abs in high PRA recipients.
Giant Pulmonary Sequestration: The Rare Case Requiring the EXIT Procedure with Resection and ECMO
Authors: Mychaliska George B. , Bryner Benjamin S. , Nugent Clark , Barks John , Hirschl Ronald B. , McCrudden Kimberly , Chames Mark , Gomez-Fifer Carlen , Servin Monica N. , Chiravuri S. Devi
Published: March 2009

Although most prenatally diagnosed pulmonary sequestrations (PS) are asymptomatic, large lesions are associated with pleural effusions and pulmonary hypoplasia. We present the first reported case of a prenatally diagnosed giant extralobar pulmonary sequestration that required the ex utero intrapartum treatment (EXIT) procedure with resection and extracorporeal membrane oxygenation (ECMO). We discuss the compelling rationale for performing EXIT-resection-ECMO in the setting of a large thoracic mass and anticipated severe respiratory failure at birth.
Agreement in Cognitive and Clinical Assessments in Alzheimer’s Disease
Authors: Tractenberg Rochelle E. , Aisen Paul S.
Published: March 2009

Aims: To estimate agreement among scores on three common assessments of cognitive function. Method: Baseline responses on the Alzheimer’s Disease Assessment Scale – Cognitive, Clinical Dementia Rating, and the Mini-Mental State Examination were obtained from two clinical trials (n = 138 and n = 351). A graphical method of examining agreement, the means-difference or Bland-Altman plot, was followed by Levene’s test of the equality of variance corrected for multiple comparison within each sample. Results: 70–78% of variability was shared by one factor, suggesting that all three instruments reflect cognitive impairment. However, agreement among tests was significantly worse for individuals with greater-than-average, relative to individuals with less-than-average, cognitive impairment. Conclusions: Worse agreement between tests, as a function of increasing cognitive impairment, implies that interpretation of these tests and selection of coprimary cognitive impairment outcomes may depend on impairment level.
Early Helicobacter pylori Eradication Restores Sonic Hedgehog Expression in the Gastric Mucosa of Mongolian Gerbils
Authors: Nishizawa Toshihiro , Suzuki Hidekazu , Nakagawa Izumi , Minegishi Yuriko , Masaoka Tatsuhiro , Iwasaki Eisuke , Hibi Toshifumi
Published: March 2009

Background and Aim: Sonic hedgehog (Shh) is a morphogen involved in the homeostasis of the gastric fundic glands. Alterations of gastric mucosal Shh expression after eradication of Helicobacter pylori were examined. Method: Mongolian gerbils were inoculated with H. pylori at the age of 5 weeks. H. pylori eradication was then carried out at 12, 24 or 48 weeks after the inoculation, and the gerbils were examined at 10 weeks after the eradication. Gastric inflammation was evaluated by the tissue myeloperoxidase activity and the histological scoring. Immunohistochemistry and in situ hybridization were performed for determining the Shh expression. Results: Significant decrease of the myeloperoxidase activity and scores for acute and chronic inflammation as well as atrophy were observed in the H. pylori-eradicated gerbils as compared with the findings in the non-H. pylori-eradicated gerbils. Significant increase of the horizontal length of the area positive for Shh expression was noted in the H. pylori-eradicated gerbils as compared with that in the non-H. pylori-eradicated gerbils. Earlier eradication promoted better restoration of Shh expression. 50% of the animals of the 24-week eradication group and all animals in the 48-week eradication group exhibited heterotopic proliferative glands. In the animals showing heterotopic proliferative glands, the front line of Shh regeneration was cut off at the point of development of heterotopic proliferative glands. Conclusion:H. pylori-associated deregulation of Shh expression that could be linked to gastric atrophy and the associated preneoplastic transformation appears to be reversible with early H. pylori eradication.
Joint Use of Drugs and Alcohol
Authors: Hakkarainen Pekka , Metso Leena
Published: March 2009

Aims: To determine the relationships between the different patterns of drinking and drug use in the general population. Design: The data from three nationwide surveys conducted in Finland in 1998, 2002 and 2004 were pooled into one dataset (n = 7,227). Participants: Population aged 15–69. Measurements: Use of illicit drugs was analyzed in relation to annual alcohol consumption, heavy episodic drinking, frequenting of pubs and restaurants, and the misuse of prescribed drugs. Respondents were divided into five different groups according to their involvement in drug cultures, i.e. ‘no contact with drug cultures’, ‘some contact with drug cultures’, ‘drug experimenters and ex-users’, ‘cannabis users’ and ‘multidrug users’. Findings: The prevalence of drug use increased along with the annual alcohol consumption, and polysubstance use was most prevalent among heavy drinkers. Heavy episodic drinking and frequenting of pubs and restaurants increased in parallel with involvement in drug cultures. Misuse of prescribed drugs was most prevalent among multidrug users. Conclusions: Polysubstance use patterns reveal an interlacing of alcohol and drug cultures. However, standard measures employed in alcohol and drug research are insufficient to capture the phenomenon in detail, and more research and the development of new approaches are needed.
Calcium and Phosphate Control by Dialysis Treatments
Authors: Messa Piergiorgio , Cerutti Roberta , Brezzi Brigida , Alfieri Carlo , Cozzolino Mario
Published: March 2009

Calcium and phosphate changes, besides their involvement in bone disease, have been claimed to also be involved in the increased vascular morbidity and mortality of dialysis patients. Even after the recent advances of therapeutic options, their control still remains a challenging problem. Dialysis treatment is a basic approach to the control of these two electrolytes. Calcium control by dialysis is mainly dependent on its mass balance, which is variably influenced by the calcium concentration difference between blood and dialysis solutions (either dialysate or infusion fluids) and by the duration of the treatment. There is no full agreement on the ideal calcium concentration in dialysis fluids, since this choice is also mostly influenced by the concomitant medical therapy. However, there is some consensus in suggesting a lower calcium concentration in standard hemodialysis (HD) treatment (1.25–1.50 mmol/l) than in dialysis treatments characterized by high convective transport. In peritoneal dialysis, calcium balance is affected by its blood dialysate concentration difference and dialysate glucose concentration, with ideal calcium concentration probably being >1.25 and <1.75 (which are the most commonly used concentrations). Phosphate dialysis balance is also a critical and challenging problem, since the possibility to reach an always desired null or possibly negative balance relies on this. Even though some increased phosphate removal can be obtained with the highest efficiency techniques, such as hemodiafiltration as compared with traditional HD, the most impacting factor still remains the duration of dialysis treatment. However, some experimental attempts at increasing phosphate removal independently of increasing dialysis duration are mentioned.
Flanking Markers of Cystatin C (CST3) Gene Do Not Show Association with Alzheimer’s Disease
Authors: Helisalmi Seppo , Väkevä Antti , Hiltunen Mikko , Soininen Hilkka
Published: March 2009

Background: In the present study we determined whether the cystatin c gene (CST3) is genetically associated with late-onset Alzheimer’s disease (AD). Methods: Two informative flanking single nucleotide polymorphisms (SNP), rs2424577 and rs3827143, of the CST3 gene and apolipoprotein E (APOE) gene were assessed in 568 Finnish AD patients and 688 cognitively healthy controls. Samples were genotyped with the TaqMan technique, and we conducted a single allele and genotypic distribution comparison as well as an estimation of haplotype frequencies between cases and controls. Results: The APOE genotype distribution differed as expected between the AD cases and controls (p < 0.001). On the whole, any significant differences in AD risk were not found in single SNP and haplotype analyses for the CST3 gene between the whole study cohorts or in the stratified subgroups. Interestingly, AG-genotype carriers of rs3827143 showed a significant difference (p = 0.04) between cases and controls when compared to AA-genotype carriers, but this finding remained insignificant in the adjusted model. Conclusion: Although flanking SNP cover the whole gene transcript with strong linkage disequilibrium, our data show that the CST3 gene is not associated with AD risk in the Finnish population.
Urinary GADD45γ Expression Is Associated with Progression of lgA Nephropathy
Authors: Yu Sukyong , Cho Jinhee , Park Inwhee , Kim Seung Jung , Kim Heungsoo , Shin Gyu-Tae
Published: March 2009

Background: Growth arrest and DNA damage-45γ (GADD-45γ) is induced in response to environmental stresses and functions in the regulation of cell cycles. Previous findings by our group suggested that GADD45γ contributed to renal tubular cell damage through induction of inflammatory and fibrogenic molecules. We examined the effects of urinary GADD45γ expression on the decline in renal function with IgA nephropathy in the present study. Methods: Patients (n = 62) were followed for a total of 710.3 ± 287.5 days. The rate of renal function decline was assessed by the slopes of inverse serum creatinine and estimated glomerular filtration rate (GFR) plotted against time. Renal survival was calculated by Kaplan-Meier analysis and the primary endpoint was an increase in serum creatinine levels by 50% or more. Results: Kidney function declined more rapidly in the GADD45γ-positive group compared to the GADD45γ-negative group. Kidney survival estimates at the end of the study period were 82.9% in the GADD45γ-positive group and 100% in the negative group (p = 0.03). This difference remained significant in the group with GFR values <90 ml/min/1.73 m2 when adjusted to stratification factors. Conclusion: The results suggest that urinary GADD45γ expression is associated with progression of renal disease.
The LDL Receptor
Authors: Goldstein Joseph L. , Brown Michael S.
Published: March 2009

In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.
Behavioral and Electrophysiological Evidence of Motor Cortex Activation Related to an Amputated Limb: A Multisensorial Approach
Authors: Touzalin-Chretien Pascale , Ehrler Solange , Dufour André
Published: March 2009

Phantom limb sensations may be linked to motor activities in the deafferented cortices of amputees, with artificial visual feedback of an amputated limb leading to enhanced phantom sensations. The present study was designed to verify if cortical motor activity related to an amputated limb can be triggered by visual input using an objective behavioral measure and with a neurophysiological correlate. Trauma amputees and normally limbed subjects showed superior performance in a mirror-drawing task when the mirror was placed sagittally (giving visual feedback of the amputated/inactive limb) compared with when it was placed frontally. Measurement of lateralized movement-related brain potentials showed that, under the lateral mirror condition, contralateral motor activity of the viewed hand was observed in both normal subjects and trauma amputees. In contrast, this activity was not observed in subjects with congenital limb absence. These findings suggest that, in traumatic amputees, motor enhancement due to visualization of the movements of the missing limb reflects the effectiveness of motor commands to the missing limb, strengthening the hypothesis of the functional survival of deafferented cortical motor areas.
Neural Signatures of Semantic and Phonemic Fluency in Young and Old Adults
Authors: Meinzer Marcus , Flaisch Tobias , Wilser Lotte , Eulitz Carsten , Rockstroh Brigitte , Conway Tim , Gonzalez-Rothi Leslie , Crosson Bruce
Published: March 2009

As we age, our ability to select and to produce words changes, yet we know little about the underlying neural substrate of word-finding difficulties in old adults. This study was designed to elucidate changes in specific frontally mediated retrieval processes involved in word-finding difficulties associated with advanced age. We implemented two overt verbal (semantic and phonemic) fluency tasks during fMRI and compared brain activity patterns of old and young adults. Performance during the phonemic task was comparable for both age groups and mirrored by strongly left-lateralized (frontal) activity patterns. On the other hand, a significant drop of performance during the semantic task in the older group was accompanied by additional right (inferior and middle) frontal activity, which was negatively correlated with performance. Moreover, the younger group recruited different subportions of the left inferior frontal gyrus for both fluency tasks, whereas the older participants failed to show this distinction. Thus, functional integrity and efficient recruitment of left frontal language areas seems to be critical for successful word retrieval in old age.
The Sea That is No More Rev 21:1 and the Function of Sea Imagery in the Apocalypse of John
Authors: Moo Jonathan
Published: March 2009

The enigmatic phrase in Rev 21:1, “the sea is no more”, has yet to be adequately explained or related cogently to the rest of the book. In this article I categorise the multiple roles in which αλασσα appears in Rev 4-20 and address the potential implications of each use of sea imagery for explaining its absence from John's vision of the new heaven and earth. Along the way, the various theories that have been proposed by other interpreters are assessed; this is followed by a brief consideration of the potential relevance of several parallels that have been suggested. On the basis of these investigations and an analysis of the context of Rev 21-22, it is proposed that the difficult phrase in 21:1c is best explained in terms of the use of a new-creation typology that serves to highlight the way in which this new creation differs from that described in Gen 1.
“Pagane” Zitate im Neuen Testament
Authors: Wittkowsky Vadim
Published: March 2009

In the New Testament there are quotations from pagan texts which are normally explained as a sign of Paul and Luke's acquaintance with Greek literature. A more accurate examination of the relevant texts shows, however, that each of these quotations makes more sense if considered against the background of early Jewish practice. The connection with pagan literature serves at the same time as an intertextual reference to Jewish polemics against paganism. This conclusion confirms once more the well-known thesis of M. Hengel, namely that there is no direct dependence of early Christianity on non-Jewish thought.
Kein Gewinn = Gewinn Die kynisch geprägte Struktur der Argumentation in 1 Tim 6:3-12
Authors: Neumann Nils
Published: March 2009

In the last chapter of 1 Timothy there is one passage arguing passionately and polemically against differently minded teachers. It calls on its readers to beware of the different teaching (1 Tim 6:3-12). This New Testament text brings forward a train of thought that shows far reaching parallels to the Cynic Philosophy of the 1st and 2nd centuries A.D. The criticism which 1 Timothy passes on its opponents corresponds to the criticism of the contemporary Cynics against their adversaries. It mainly concerns the hypocritical motivations that lead the differently minded teachers to preach their message: according to the view of their critics they only aim to make money out of their teachings. In this reasoning polemical and paraenetical components unite. The careful consideration of this New Testament passage's similarity to the cynic world of thought also faciliates the description of the specific character in the intention of 1 Timothy against the cynic background, i.e. the christological accentuation of the favoured good teaching and lifestyle.
The Construction and Subversion of Patriarchal Perfection: Abraham and Exemplarity in Philo, Josephus, and the Testament of Abraham
Authors: Reed Annette Yoshiko
Published: March 2009

In dialogue with recent research on the Roman discourse of exemplarity, this article explores representations of Abraham in selected sources from the first and early second centuries C.E. In the first part of the article, references to the patriarch in the writings of Philo and Josephus are considered in light of the transformation of Greek ideas about exempla by Roman authors like Polybius, Livy, and Valerius Maximus. In the second part, the inversion of Abraham's exemplarity in the Testament of Abraham is investigated in relation to the treatment of famous figures in the Apocolocyntosis and in Juvenal's 10th Satire. By juxtaposing the use of exempla in contemporaneous Roman and Jewish writings, the article explores their parallel reflections on the power of the past and shows how Romans and Jews alike appropriated of elements of Greek culture for the articulation of new expressions of local pride, ethnic specificity, and cultural resistance.
The Rabbinic Polemic against Sanctification of Sites
Authors: Eliyahu Eyal Ben
Published: March 2009

The attribution of holiness to various sites in antiquity was confined neither to a particular ethnic or religious group, nor to one particular geographical locale, but was rather practiced by a wide range of groups vis-à-vis many locations. Contrary to these views, the rabbis made a very clear and sharp statement regarding the sanctity of Jerusalem and the Temple Mount and negated the idea of the existence of holy places outside Jerusalem. The rabbis struggled against the sanctity of the biblical “holy mountain,” as well as against sites that could have been regarded as holy on the basis of the biblical narrative. The discovery of this polemic illuminates and offers an explanation for many surprising passages in early rabbinic literature that belittle high mountains and biblical “memorial sites” in the Land of Israel. The examples, drawn from the various strata of early rabbinic literature, demonstrate surprising rabbinic consensus on this issue.
Denial of Chronic Illness and Disability
Authors: Livneh Hanoch
Published: March 2009

Denial has been an integral part of the psychological and disability literature for more than 100 years. Yet, denial is an elusive concept and has been associated with mixed, indeed conflicting, theoretical perspectives, clinical strategies, and empirical findings. In this two-part article, the author provides an overview of the existing literature on denial that addresses the most prominent and rehabilitation-relevant features of it. Part I provides a generic yet clinically based discussion of denial and focuses on the following: historical perspective of denial, the definitions of denial, the types or forms of denial most often encountered in the literature, the functions served by denial, the indicators or markers most frequently associated with denial, the dynamics and processes inherent in the operation of denial, and the costs and benefits of denial.
Towards the re-verification of process tank calibrations
Authors: Howell J.
Published: March 2009

Re-verification is needed to ensure that the calibration (the relationship between measured level and measured volume) that is obtained during commissioning has not changed over time. This can be achieved, in part, by metering in solution and correlating with marks identified a priori. Mark identification and correlation are discussed and possible error sources are outlined.
Flagellated Magnetotactic Bacteria as Controlled MRI-trackable Propulsion and Steering Systems for Medical Nanorobots Operating in the Human Microvasculature
Authors: Martel Sylvain , Mohammadi Mahmood , Felfoul Ouajdi , Zhao Lu  , Pouponneau Pierre
Published: March 2009

Although nanorobots may play critical roles for many applications in the human body, such as targeting tumoral lesions for therapeutic purposes, miniaturization of the power source with an effective onboard controllable propulsion and steering system have prevented the implementation of such mobile robots. Here, we show that the flagellated nanomotors combined with the nanometer-sized magnetosomes of a single magnetotactic bacterium can be used as an effective integrated propulsion and steering system for devices, such as nanorobots, designed for targeting locations only accessible through the smallest capillaries in humans while being visible for tracking and monitoring purposes using modern medical imaging modalities such as magnetic resonance imaging. Through directional and magnetic field intensities, the displacement speeds, directions, and behaviors of swarms of these bacterial actuators can be controlled from an external computer.
Algorithms and Software for Nanomanipulation with Atomic Force Microscopes
Authors: Requicha A.A.G. , Arbuckle D.J. , Mokaberi B. , Yun J.
Published: March 2009

Interactive manipulation of nanoparticles by mechanically pushing them with the tip of an Atomic Force Microscope (AFM) is now performed routinely at many laboratories around the world. However, a human in the loop introduces significant inaccuracies and results in a very slow process, mostly because of the need to locate the particles before and after the manipulation operations in the presence of large spatial uncertainties, which are often comparable to the size of the particles. In this paper we describe the nanomanipulation systems developed at USC's Laboratory for Molecular Robotics during the last decade, culminating in a fully automatic system that is capable of accurately positioning small nanoparticles, with diameters of around 10 nm. This system uses software compensators for the non-linearities inherent in the piezoelectric actuators used in most AFMs. The planner and execution systems are described, as well as the software architecture of the systems. Experimental results are presented that validate the approach and show that nanoparticle patterns that would take hours to build interactively can now be built in minutes. Automatic operation makes it possible to use manipulation to construct much more complex nanostructures than those built in the past.
Obama: the new contours of power
Authors: Harris Jerry , Davidson Carl
Published: March 2009

Barack Obama's election as US president marks a historic cultural shift in US political life, and is a major victory for progressive forces. But what is the nature of the broad-based alliance that placed him in the White House, how was it forged and from what did it derive its strength? The global economic crisis has shockingly exposed the bankruptcy of hitherto dominant and unfettered neoliberalism and opened the way for setting a genuinely progressive social and economic agenda. This article analyses the challenges that face the new administration and the balance of progressive forces that could make a profound and lasting difference to US society.
The Horror of the Mob
Authors: Buur Lars
Published: March 2009

Images of uncontrolled mob violence continue to influence political concerns and float media reportage in South Africa. The images resemble those of angry and destructive black `struggle' youth toyi-toying in front of burning tyres, cleansing the township of its enemies and attacking state officials during the apartheid era. Today, such actions are portrayed as the manoeuvres of a lost generation destroying the fruits of democracy and undermining their own black government. Nevertheless, the image of the angry, uncontrolled mob has its roots in resistance to both colonialism and apartheid, where large crowds and mobs descended on cities or operated in the city's Other (its adjacent black townships). This article explores the ways in which the images and horrors of uncontrolled mob violence continue to haunt the imagination of the new democracy. Further, it links collective fantasies about mobs to the constitution of sovereignty.