bluuebunny/crossref_metadata_2025_split huggingface dataset:
The dysbindin gene in major depression: An association study
Authors: Zill Peter , Baghai Thomas C. , Engel Rolf , Zwanzger Peter , Schüle Cornelius , Eser Daniela , Behrens Stefanie , Rupprecht Rainer , Möller Hans‐Jürgen , Ackenheil Manfred , Bondy Brigitta 
Published: June 2004

AbstractThe pathophysiological mechanisms, as well as the molecular loci of antidepressant drug action have not yet been established, but recent models proposed that several adaptive mechanisms in signal transduction cascades beyond the receptor and reuptake systems are involved in antidepressant action and play an important role in the etiology of affective disorders. In this context, the dysbindin gene (dystrobrevin‐binding‐protein 1, DTNBP1), which was recently reported to be associated with schizophrenia seems to be an interesting candidate gene for affective disorders. Dysbindin is widely expressed in the human brain and binds to the dystrophin‐associated protein complex (DPC) which appears to be involved in signal transduction pathways, which have been repeatedly investigated and described as altered or disturbed in affective disorders [McLeod et al. [2003: Psychopharmacol Bull 35:24–41]; Brambilla et al. [2003: Mol Psychiatry 8:721–737]]. Therefore, we investigated whether five SNPs in the dysbindin gene could be susceptibility factors in the ethiology of major depression or for the response to antidepressant treatment in a sample of 293 patients compared to 220 healthy controls. Applying single SNP evaluation, as well as haplotype analysis we could not detect an association between the dysbindin polymorphisms and major depression or the response to antidepressant treatment. In conclusion, our results suggest that SNPs in the dysbindin gene are unlikely to play a major role in the pathophysiology of major depression or are in linkage disequilibrium (LD) with a neighboring mutation or gene. Further analysis are needed to confirm these results. © 2004 Wiley‐Liss, Inc.
Congenital malformations in offspring of Hispanic and African‐American women in California, 1989–1997
Authors: Carmichael Suzan L. , Shaw Gary M. , Kaidarova Zhanna 
Published: June 2004

AbstractBACKGROUNDLittle is known about risks of most specific birth defects among infants born to U.S.‐born and foreign‐born Hispanic or African‐American women.METHODSUsing data from a large population‐based registry, we explored risks of selected congenital malformation phenotypes in offspring of U.S.‐born and foreign‐born Hispanic and African‐American women, relative to non‐Hispanic white women, in California. Approximately 2.2 million live births and stillbirths occurred during the ascertainment period, 1989–1997. Information on maternal racial‐ethnic background and other covariates was obtained from birth certificate and fetal death files.RESULTSAdjusted relative risks (ARRs) for the 20 groupings of malformations designated by three‐digit British Pediatric Association (BPA) codes ranged from 0.6 (genital organ malformations, among infants born to foreign‐born Hispanics) to 1.7 (anencephaly, also among infants born to foreign‐born Hispanics). Grouping by four‐digit BPA codes revealed that among infants born to U.S.‐born Hispanics, 46 of the ARRs were ≤0.8 and 12 were ≥1.3; among infants born to foreign‐born Hispanics, 75 of the ARRs were ≤0.8 and 15 were ≥1.3; and among infants born to African‐American women, 45 ARRs were ≤0.8 and 25 were ≥1.3. For each racial‐ethnic group of women, the observed variability in risks covered most organ systems.CONCLUSIONSAlthough the results suggested that (in comparison with non‐Hispanic whites) each racial‐ethnic group was more likely to have reduced risk for specific defects (rather than elevated risk), in general, the range of the relative risks was comparatively narrow. Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.
A common ABCC2 promoter polymorphism is not a determinant of the risk of spina bifida
Authors: Jensen Liselotte E. , Wall Amelia M. , Cook Michelle , Hoess Katy , Thorn Caroline F. , Whitehead Alexander S. , Mitchell Laura E. 
Published: June 2004

AbstractBACKGROUNDThere is compelling evidence that the risk of spina bifida, a malformation of the caudal neural tube, is associated with maternal and/or embryonic disturbances in folate/homocysteine metabolism. Hence, functional variants of genes that influence folate/homocysteine metabolism constitute a biologically plausible group of candidate risk factors for spina bifida and other neural tube defects. One such candidate is ABCC2, the gene encoding ABCC2, (a.k.a. canalicular multispecific organic anion transporter [cMOAT], multidrug resistance related protein 2 [MRP2]), a member of the ABC transporter family that effluxes natural folates and anti‐folate drugs such as methotrexate.METHODSThe association between the risk of spina bifida and both the maternal and embryonic ABCC2 C(–24)T genotype was evaluated by using the transmission disequilibrium test and log‐linear modeling.RESULTSThese analyses provided no evidence that the risk of spina bifida was significantly related to either the maternal or embryonic ABCC2 C(–24)T genotype.CONCLUSIONSThe results of the present analyses suggest that the C(–24)T variant of the ABCC2 gene is not a major determinant of spina bifida risk. Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.
Immunocytochemical localization of polyamines during attachment and spreading of retinal pigment epithelial and intestinal epithelial cells
Authors: Johnson Dianna A. , Sharma Rajesh K. , Allan Katherine , Ray Ramesh , Johnson Leonard R. 
Published: June 2004

AbstractIn order to form and maintain a protective barrier for photoreceptors, the retinal pigment epithelium relies on integrin signaling and related pathways to form adhesion complexes, undergo cell spreading, and establish a confluent cellular monolayer. Polyamines are multifunctional polycations that are essential for cell attachment and spreading, although their exact mechanisms of action are as yet unclear. We report new immunocytochemical evidence suggesting that in the cells of retinal pigment epithelium and also the intestinal epithelium, polyamines are present in a population of intracellular vesicles that appear transiently during initial stages of cell spreading. In newly attached cells with minimal spreading, the vesicles are seen near the nucleus, whereas in more highly spread cells, the vesicles are localized to the plasma membrane, near, but not precisely co‐localized with an enzyme marker for adhesion complexes, focal adhesion kinase. We also observe pronounced nuclear staining in newly attached cells that have not spread, whereas this staining is decreased in cells that have spread. Nuclear staining has been previously reported in other cell types and has been attributed to DNA binding of polyamines, which is known to stabilize chromatin structure. We hypothesize that the appearance of polyamine vesicles near focal adhesions of cells undergoing attachment and spreading may reflect the mechanism by which polyamine pools are targeted to appropriate interaction sites necessary for the assembly of adhesion complexes. Alternatively, the vesicles could represent the mechanism by which polyamines are removed from the nucleus and possibly released from the cell. Cell Motil. Cytoskeleton 58:269–280, 2004. © 2004 Wiley‐Liss, Inc.
Folate, colorectal carcinogenesis, and DNA methylation: Lessons from animal studies
Authors: Kim Young‐In 
Published: June 2004

AbstractFolate, a water‐soluble B vitamin and cofactor in one‐carbon transfer, is an important nutritional factor that may modulate the development of colorectal cancer (CRC). Epidemiologic and clinical studies indicate that dietary folate intake and blood folate levels are inversely associated with CRC risk. Collectively, these studies suggest an ∼ 40% reduction in the risk of CRC in individuals with the highest dietary folate intake compared with those with the lowest intake. Animal studies using chemical and genetically predisposed rodent models have provided considerable support for a causal relationship between folate depletion and colorectal carcinogenesis as well as a dose‐dependent protective effect of folate supplementation. However, animal studies also have shown that the dose and timing of folate intervention are critical in providing safe and effective chemoprevention; exceptionally high supplemental folate levels and folate intervention after microscopic neoplastic foci are established in the colorectal mucosa promote, rather than suppress, colorectal carcinogenesis. These animal studies, in conjunction with clinical observations, suggest that folate possesses dual modulatory effects on carcinogenesis depending on the timing and dose of folate intervention. Folate deficiency has an inhibitory effect, whereas folate supplementation has a promoting effect on the progression of established neoplasms. In contrast, folate deficiency in normal epithelial tissues appears to predispose them to neoplastic transformation, and modest levels of folate supplementation suppress the development of tumors in normal tissues. Notwithstanding the limitations associated with animal models, these studies suggest that the optimal timing and dose of folate intervention must be established for safe and effective chemoprevention in humans. Folate is an important factor in DNA synthesis, stability, and integrity, the repair aberrations of which have been implicated in colorectal carcinogenesis. Folate may also modulate DNA methylation, which is an important epigenetic determinant in gene expression (an inverse relationship), in the maintenance of DNA integrity and stability, in chromosomal modifications, and in the development of mutations. A mechanistic understanding of how folate status modulates colorectal carcinogenesis further strengthens the case for a causal relationship and provides insight into a possible chemopreventive role of folate. Environ. Mol. Mutagen. 44:10–25, 2004. © 2004 Wiley‐Liss, Inc.
Goeldi's monkeys: A primate paradox?
Authors: Porter Leila M. , Garber Paul A. 
Published: June 2004

Abstract“A primate with the skull of aCallicebus, the mandible and feet of a marmoset and the tail and teeth ofPseudocebus[=Cebus] ….” (Riberio, 1941 as cited in Hershkovitz1p. 866). Goeldi's monkeys are the least understood species of platyrrhine. The monkeys' small body size, black coloration, tendency to forage in the low forest understory, and cryptic nature, make them difficult to observe in the wild. Until recently, they had never been the focus of a long‐term field study and as a result, little was known of the monkeys' behavior and ecology. Goeldi's monkeys comprise only one recognized species,Callimico goeldii, and have an unusual suite of anatomical and reproductive traits. These traits have created considerable confusion for taxonomists and physical anthropologists.
Inverse expression of dihydrodiol dehydrogenase and glutathione‐S‐transferase in patients with esophageal squamous cell carcinoma
Authors: Wang Liang‐Shun , Chow Kuan‐Chih , Wu Yu‐Chung , Lin Tze‐Yi , Li Wing‐Yin 
Published: June 2004

AbstractWe investigated the significances of the expressions of dihydrodiol dehydrogenase (DDH) and glutathione‐S‐transferase (GST) in patients with esophageal squamous cell carcinoma (ESCC). By using immunohistochemistry, we measured expressions of DDH, GST, COX‐2, nm23‐H1, HER‐2/neu and mdr‐1 in 145 patients with ESCC. Expression of DDH was confirmed by immunoblotting and reverse transcription‐polymerase chain reaction. Relation between DDH expression and clinicopathological parameters was analyzed by statistical analysis. Difference of survivals between different groups was compared by a log rank test. DDH overexpression was detected in 66.9% of pathological sections (97/145) and in 41.6% of metastatic lymph nodes (37/89). The nucleotide sequencing of DNA fragments from 16 tumorous specimens showed that the major isoform was DDH2 for ESCC. GST expression, however, was only detected weakly in 24 patients (16.6%). For patients with ESCC, DDH overexpression was positively correlated with smoking habit, tumor stage, number of metastatic lymph nodes, lymphovascular invasion and COX‐2 expression, and inversely correlated with GST and nm23‐H1 expressions, but not related to mdr‐1 or HER‐2/neu expressions. As compared to DDH overexpressed group, patients with low DDH expression had significantly lower incidence of tumor recurrences and better survival (p = 0.026). Using univariate analysis, prognostic factors included tumor stage, number of metastatic lymph nodes, cell differentiation, lymphovascular invasion and expressions of DDH and nm23‐H1. Multivariate analysis showed significant correlation of tumor stage, number of metastatic lymph nodes and nm23‐H1 expression with patient's survival. In conclusion, inverse expressions of DDH and GST may be associated with carcinogenesis and disease progression for ESCC patients, but their biological function and pathophysiological regulation in tumors require additional studies. © 2004 Wiley‐Liss, Inc.
Evaluation of a selectively oncolytic adenovirus for local and systemic treatment of cervical cancer
Authors: Bauerschmitz Gerd J. , Kanerva Anna , Wang Minghui , Herrmann Isabell , Shaw Denise R. , Strong Theresa V. , Desmond Renee , Rein Daniel T. , Dall Peter , Curiel David T. , Hemminki Akseli 
Published: June 2004

AbstractTreatment options for disseminated cervical cancer remain inadequate. Here, we investigated a strategy featuring Ad5‐Δ24RGD, an oncolytic adenovirus replication‐competent selectively in cells defective in the Rb‐p16 pathway, such as most cervical cancer cells. The viral fiber contains an αvβ3 and αvβ5 integrin‐binding RGD‐4C motif, allowing coxsackie‐adenovirus receptor‐independent infection. These integrins have been reported to be frequently upregulated in cervical cancer. Oncolysis of cervical cancer cells was similar to a wild‐type control in vitro. In an animal model of cervical cancer, the therapeutic efficacy of Ad5‐Δ24RGD could be demonstrated for both intratumoral and intravenous application routes. Biodistribution was determined following intravenous administration to mice. Further preclinical safety data were obtained by demonstrating lack of replication of the agent in human peripheral blood mononuclear cells. These results suggest that Ad5‐Δ24RGD could be useful for local or systemic treatment of cervical cancer in patients with disease resistant to currently available modalities. © 2004 Wiley‐Liss, Inc.
Signaling pathways required for matrix metalloproteinase‐9 induction by betacellulin in head‐and‐neck squamous carcinoma cells
Authors: O‐charoenrat Pornchai , Wongkajornsilp Adisak , Rhys‐Evans Peter H. , Eccles Suzanne A. 
Published: June 2004

AbstractThe mechanisms by which c‐erbB‐dependent signaling contribute to the invasive potential of HNSCC remain to be fully elucidated. We have previously shown that c‐erbB autocrine and/or paracrine stimulation upregulates MMP‐9 but has no effect on the related gelatinase, MMP‐2. BTC, a major c‐erbB ligand, has the ability to efficiently activate all c‐erbB receptors and to bind directly to EGFR and c‐erbB‐4. BTC is commonly expressed in HNSCC cells and exerts the most potent effects in terms of MMP induction relative to other c‐erbB ligands so far tested. In the present study, we explored the contribution of major downstream events triggered by BTC/c‐erbB receptor signaling to the regulation of MMP‐9 and in vitro invasiveness of HNSCC cells. In human HNSCC cell lines, SIHN‐006 and Detroit‐562, BTC treatment resulted in rapid tyrosine phosphorylation of all c‐erbB receptors whereas both endogenous MMP‐9 and BTC‐stimulated MMP‐9 were predominantly mediated via EGFR. BTC induced ERK1/2, JNK/SAPK and Akt phosphorylation with differing kinetics but not p38 kinase. The BTC‐dependent activation of JNK and PI3K/Akt pathways occurred predominantly via EGFR, whereas activation of the MEK‐1/ERK pathway occurred via all 4 c‐erbB receptors, although again predominantly via EGFR. Selective inhibition of ERK/MAPK (by PD98059 or U0126) and PI3K (by LY294002 or wortmannin) led to marked reduction of both basal and BTC‐induced MMP‐9 activity and invasive ability of HNSCC cells. In contrast, inhibition of p38 kinase with SB203580 produced no such effects. A specific inhibitor of NF‐κB, BAY 11‐7085, also blocked the stimulatory effect of BTC. No remarkable inhibition of MMP‐9 and invasion was observed on targeting other cellular activities, such as PKA, PKC and PLC‐γ. Taken together, our data show that BTC induces MMP‐9 production and invasion primarily through activation of EGFR, MAPK and PI3K/Akt in HNSCC cells. © 2004 Wiley‐Liss, Inc.
Inhibition of spontaneous development of liver tumors by inoculation with dendritic cells loaded with hepatocellular carcinoma cells in C3H/HeNCRJ mice
Authors: Irie Masaki , Homma Sadamu , Komita Hideo , Zeniya Mikio , Kufe Donald , Ohno Tsuneya , Toda Gotaro 
Published: June 2004

AbstractWe attempted to prevent spontaneous development of liver tumors by s.c. inoculation with DCs loaded with syngeneic HCC cells in C3H/HeNCrj mice. A new cell line, MIH‐2, was established from an HCC that had developed spontaneously in a C3H/HeNCrj mouse. Bone marrow–derived DCs were loaded with irradiated MIH‐2 cells by treatment with PEG. Fluorescence microscopy and flow‐cytometric analysis showed that about 45% of PEG‐treated DCs and MIH‐2 cells (DC/MIH‐2) were DCs loaded with MIH‐2 cells. Thirteen‐month‐old mice received inoculations of DC/MIH‐2 (9 × 105/mouse) 4 times at 6‐day intervals and were killed at 16 months of age to assess liver tumors. The incidence of liver tumors in these mice was significantly lower than that in mice not receiving inoculations (p < 0.05) but similar to that in 13‐month‐old mice (the age at which inoculation started), indicating that inoculation inhibited the development of new tumors. Splenocytes from inoculated mice, but not those from uninoculated mice, showed cytotoxic activity against MIH‐2 cells. Cytotoxic activity was not elicited by CD4+ T cells, CD8+ T cells, or DX5+ cells isolated from splenocytes but was elicited by adherent cells, identified as CD11b+ macrophages. CD4+ T cells, but not CD8+ T cells, from inoculated mice produced IFN‐γ by incubation with DC/MIH‐2. Cytotoxicity by splenocytes was attenuated by anti‐IFN‐γ antibody. Immunization with DCs loaded with syngeneic HCC cells induces CD4+ T cells that produce IFN‐γ by response to antigen of HCC, which would lead to macrophage activation to kill liver tumor cells at an early stage. © 2004 Wiley‐Liss, Inc.
Prognostic implications of loss of heterozygosity at 8p21 and 9p21 in head and neck squamous cell carcinoma
Authors: Coon Steven W. , Savera Adnan T. , Zarbo Richard J. , Benninger Michael S. , Chase Gary A. , Rybicki Benjamin A. , Van Dyke Daniel L. 
Published: June 2004

AbstractLoss of heterozygosity (LOH) in chromosomal regions that harbor tumor suppressor genes from tumor tissue may lead to decreased survival time in cancer patients with squamous cell carcinoma of the head and neck (HNSCC). We studied 8 regions frequently lost in HNSCC in 150 patients having a primary diagnosis of HNSCC. Tumor and normal tissue DNA were genotyped for microsatellite repeat markers in 8 unlinked chromosomal regions. The association between LOH and death from HNSCC was investigated, weighted by number of informative markers per region and adjusted for age at diagnosis, self‐reported race, tumor stage and current smoking status. LOH at 3 chromosomal regions were independently associated with reduced survival. A greater risk for cancer mortality was observed for LOH at chromosomal regions 3p24.3‐p14.3 (p = 0.02), 8p21.3‐p11.21 (p = 0.02) and 9p24.2‐p21.2 (p = 0.03). In these regions, LOH at one or more markers was observed in 66.9%, 43.3% and 60.6% of patients, respectively. Survival times were significantly shorter for those with LOH at marker NEFL on 8p21.2 (relative risk = 6.15; p = 0.0002) and at D9S126 on 9p21.2 (relative risk = 5.96; p = 0.0003). Our results indicate that LOH at several chromosomal sites may offer additional independent prognostic information beyond traditional indicators such as tumor stage and age. © 2004 Wiley‐Liss, Inc.
Anticancer agent CHS 828 suppresses nuclear factor‐κB activity in cancer cells through downregulation of IKK activity
Authors: Olsen Lone Stengelshøj , Hjarnaa Pernille‐Julia Vig , Latini Scilla , Holm Pernille Kaae , Larsson Rolf , Bramm Erik , Binderup Lise , Madsen Mogens Winkel 
Published: June 2004

AbstractCHS 828, a pyridyl cyanoguanidine, has been shown to exert a significant antitumor effect in preclinical tests in vitro and in vivo, and CHS 828 is in phase I/II clinical trials. We have investigated the effect of CHS 828 on the nuclear factor‐κB (NF‐κB) because of its well‐known role in the control of cell division and apoptosis. CHS 828 is able to inhibit the lipopolysaccharide (LPS)‐induced nuclear localization as well as the transcriptional activity of NF‐κB in human THP‐1 leukemia cells. Moreover, CHS 828 has also been shown to inhibit the LPS‐induced degradation of the IκBα and IκBβ in THP‐1 cells, leading us to identify the IκB kinase complex as a molecular target of CHS 828. The IKK activity is inhibited by CHS 828 with an IC50 of 8 nM. The inhibition of the IKK activity by different CHS 828 analogues correlates well with the inhibition of NYH small cell lung cancer cell proliferation in vitro and in vivo. Moreover, the inhibition of NF‐κB transcriptional activity in different cancer cell lines by CHS 828 correlates to some extent with the reduction by CHS 828 of the size of the corresponding xenografts. Activation of NF‐κB has been shown to induce expression of antiapoptotic proteins, and cancer cells have been shown to have high levels of constitutively active NF‐κB. Therefore, we hypothesize that the anticancer activity of CHS 828 is due to inhibition of the IKK activity by which the antiapoptotic protection of NF‐κB is removed, leading to the promotion of apoptosis. © 2004 Wiley‐Liss, Inc.
Non‐Hodgkin's lymphoma among asthmatics exposed to pesticides
Authors: Lee Won Jin , Cantor Kenneth P. , Berzofsky Jay A. , Zahm Shelia H. , Blair Aaron 
Published: June 2004

AbstractWe conducted a pooled analysis of population‐based case‐control studies in Iowa, Minnesota and Nebraska to investigate whether asthma modifies risk of non‐Hodgkin's lymphoma (NHL) associated with pesticide exposures. Cases (n = 872) diagnosed with NHL from 1980 to 1986 and frequency‐matched controls (n = 2,381) randomly selected from the same geographic areas as the cases were included. Information on use of pesticides and history of asthma was based on interviews. Unconditional logistic regression was used to calculate ORs, adjusted for age, state and vital status. Of all subjects, 177 (45 cases, 132 controls) reported having been told by their doctor that they had asthma. Subjects with an asthma history had a nonsignificantly lower risk of NHL than nonasthmatics (OR = 0.6, 95% CI 0.3–1.4), and there was no main effect of pesticide exposure (OR = 1.0, 95% CI 0.8–1.2). However, asthmatics tended to have larger ORs associated with exposure to pesticides than nonasthmatics. The OR among asthmatics was 1.8 (95% CI 1.1–3.2) for ever‐use of crop insecticides, 2.7 (95% CI 1.0–7.2) for chlordane, 2.4 (95% CI 1.0–5.7) for lindane and 3.7 (95% CI 1.3–10.9) for fonofos. Among nonasthmatics, ORs were 1.1 (0.9–1.3), 1.5 (1.1–2.2), 1.3 (0.97–1.8) and 1.6 (1.0–2.4), respectively. Although there is limited power for assessing interaction, our results suggest that the risk of NHL among asthmatics with pesticide exposure may be higher than among nonasthmatics with pesticide exposure. © 2004 Wiley‐Liss, Inc.