bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG‐fMRI of focal epileptic spikes: Analysis with multiple haemodynamic functions and comparison with gadolinium‐enhanced MR angiograms
Authors: Bagshaw Andrew P. , Aghakhani Yahya , Bénar Christian‐G. , Kobayashi Eliane , Hawco Colin , Dubeau François , Pike G. Bruce , Gotman Jean 
Published: March 2004

AbstractCombined EEG‐fMRI has recently been used to explore the BOLD responses to interictal epileptiform discharges. This study examines whether misspecification of the form of the haemodynamic response function (HRF) results in significant fMRI responses being missed in the statistical analysis. EEG‐fMRI data from 31 patients with focal epilepsy were analysed with four HRFs peaking from 3 to 9 sec after each interictal event, in addition to a standard HRF that peaked after 5.4 sec. In four patients, fMRI responses were correlated with gadolinium‐enhanced MR angiograms and with EEG data from intracranial electrodes. In an attempt to understand the absence of BOLD responses in a significant group of patients, the degree of signal loss occurring as a result of magnetic field inhomogeneities was compared with the detected fMRI responses in ten patients with temporal lobe spikes. Using multiple HRFs resulted in an increased percentage of data sets with significant fMRI activations, from 45% when using the standard HRF alone, to 62.5%. The standard HRF was good at detecting positive BOLD responses, but less appropriate for negative BOLD responses, the majority of which were more accurately modelled by an HRF that peaked later than the standard. Co‐registration of statistical maps with gadolinium‐enhanced MRIs suggested that the detected fMRI responses were not in general related to large veins. Signal loss in the temporal lobes seemed to be an important factor in 7 of 12 patients who did not show fMRI activations with any of the HRFs. Hum. Brain Mapp. 22:179–192, 2004. © 2004 Wiley‐Liss, Inc.
Postsynaptic injection of calcium‐independent phospholipase A2 inhibitors selectively increases AMPA receptor‐mediated synaptic transmission
Authors: St‐Gelais Fannie , Ménard Caroline , Congar Patrice , Trudeau Louis‐Eric , Massicotte Guy 
Published: April 2004

AbstractThe calcium‐independent form of phospholipase A2 (iPLA2), an enzyme known to generate arachidonic acid (AA), was recently identified as the predominant constitutive phospholipase in the hippocampus. The present study shows that the iPLA2 inhibitor bromoenol lactone, when introduced into hippocampal CA1 pyramidal cells through a patch pipette, generated a dose‐dependent increase in the amplitude of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptor‐mediated excitatory postsynaptic currents (EPSCs). The iPLA2 inhibitor by itself interfered with neither paired pulse facilitation nor N‐methyl‐D‐aspartate (NMDA) receptor‐mediated EPSCs, suggesting that its influence on synaptic transmission is postsynaptic in origin and specific to the AMPA subtype of glutamate receptors. Comparable results were obtained with palmitoyl trifluoromethyl ketone, a second structurally distinct iPLA2 inhibitor. The ability of iPLA2 inhibitors to increase AMPA receptor‐mediated currents was also reproduced by MK‐866, an inhibitor recognized to interfere with the generation of 5‐lipoxygenase by‐products of AA. At the biochemical level, we found that AMPA, but not NMDA glutamate receptor subunits, were upregulated in rat brain sections pre‐incubated with the iPLA2 inhibitors. Collectively, these results provide the first experimental evidence that constitutive iPLA2 and/or its metabolites play an important role in the postsynaptic modulation of neurotransmission in CA1 pyramidal cells of the hippocampus. © 2004 Wiley‐Liss, Inc.
Role of hepatitis C virus infection in malignant lymphoma in Spain
Authors: de Sanjose Silvia , Nieters Alexandra , Goedert James J. , Domingo‐Domenech Eva , Fernandez de Sevilla Alberto , Bosch Ramon , Herrera Pilar , Domingo Alicia , Petit Jose , Bosch Xavier , Kallinowski Birgit 
Published: March 2004

AbstractHepatitis C virus (HCV) has been implicated in the etiology of malignant lymphomas. We estimated the risk of lymphoma associated with detection of HCV infection. Cases (n = 529) were consecutive patients newly diagnosed with a lymphoid malignancy between 1998 and 2002 in 4 centers in Spain. Lymphomas were diagnosed and classified using the WHO Classification. Controls (n = 600) were hospitalized patients matched to the cases by 5‐year age group, gender and study center. Several medical conditions associated with severe immunosuppression precluded the eligibility of controls. Patients underwent a personal interview and blood sampling. HCV positive subjects were considered those with antibody response to third generation ELISA or detection of HCV RNA with Amplicor 2.0. Cases were systematically tested for HIV antibodies. We used the χ2 test and unconditional logistic regression to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for lymphoma associated with HCV. HCV infection was detected in 40 cases (7.5%) and 23 (3.8%) control subjects. Six of 16 patients with HIV‐related lymphomas and 4 of 8 organ‐recipient‐related lymphomas were HCV positive. The analysis, excluding HIV‐infected subjects and organ recipients, led to a prevalence of HCV of 5.9% among cases and 3.8% among controls. The age‐, gender‐ and center‐adjusted OR for all lymphomas was 1.58 (95% CI = 0.89–2.79). Among all lymphoma categories, HCV was associated with an increased risk of low grade B‐cell lymphomas not otherwise specified (NOS) (OR = 35.98, 95% CI = 4.70–275.4). A 2‐fold excess risk associated to HCV was observed for marginal B‐cell lymphomas, diffuse large B‐cell lymphoma and lymphoma B NOS but the associations were not statistically significant. HCV infection is associated with an increased risk of a broad spectrum of lymphoid neoplasms among non severely immunocompromised subjects in Spain. © 2004 Wiley‐Liss, Inc.
Hepatitis C virus infection and non‐hodgkin lymphoma: Results of the NCI‐seer multi‐center case‐control study
Authors: Engels Eric A. , Chatterjee Nilanjan , Cerhan James R. , Davis Scott , Cozen Wendy , Severson Richard K. , Whitby Denise , Colt Joanne S. , Hartge Patricia 
Published: March 2004

AbstractSeveral studies have noted elevated hepatitis C virus (HCV) prevalence among patients with non‐Hodgkin lymphoma (NHL), suggesting that HCV infection increases NHL risk through chronic immune stimulation. Population‐based data from the U.S. are lacking. In a population‐based case‐control study of NHL in the United States, we identified HCV infection using an enzyme immunoassay, confirmed by recombinant immunoblot assay or HCV RNA detection. The association between HCV and NHL was assessed using logistic regression, adjusting for demographic factors, illicit drug use or medical history. Thirty‐two of 813 (3.9%) NHL cases and 14 of 684 (2.1%) controls were HCV‐infected [odds ratio (OR) 1.96, 95%CI 1.07–4.03]. For separate NHL subtypes, numbers were limited. Nonetheless, positive associations were noted for follicular (OR 2.46, 95%CI 1.01–5.81), marginal zone (3.99, 0–13.6) and mucosa‐associated lymphoid tissue (2.04, 0–7.20) NHLs. For all NHLs combined, the HCV‐NHL association changed little after adjustment for sex, age, race and study center (OR 1.89, 95%CI 1.00–4.00). HCV was common in controls who had injected drugs (40%) or used other illicit drugs (6.5%), but adjustment for drug use did not affect the HCV‐NHL association (OR 1.87, 95%CI 0.95–4.10). Transfusion history was unrelated to HCV status, and adjustment for this exposure did not attenuate the HCV‐NHL association (OR 2.15, 95%CI 1.12–4.76). Excluding 4 subjects with a history of hemodialysis or 3 subjects with organ transplants also did not affect the results. Our study demonstrates an association between HCV infection and NHL in the United States. HCV infection may be a cause of NHL. © 2004 Wiley‐Liss, Inc.
Correlation of hMLH1 and HPP1 hypermethylation in gastric, but not in esophageal and cardiac adenocarcinoma
Authors: Geddert Helene , Kiel Sibylle , Iskender Erol , Florl Andrea R. , Krieg Thomas , Vossen Sandra , Gabbert Helmut E. , Sarbia Mario 
Published: March 2004

AbstractUsing methylation‐specific real‐time PCR, we determined the prevalence of aberrant methylation in the mismatch repair gene hMLH1 and in the recently described HPP1 gene among 50 esophageal, 50 cardiac and 50 gastric ADCs. Additionally, expression of hMLH1 protein was detected immunohistochemically and correlated with DNA MSI. Hypermethylation of hMLH1 was found in 14% of esophageal, 28% of cardiac and 32% of gastric ADCs, whereas HPP1 hypermethylation was found more frequently in the 3 tumor types (64% vs. 38% vs. 54%). In gastric ADC, HPP1 hypermethylation was found more frequently in tumors with concomitant hMLH1 hypermethylation (81%) than in those without hMLH1 hypermethylation (41%, p = 0.008). Complete loss of hMLH1 protein expression, which was present in 10 carcinomas (5 cardiac and 5 gastric), was invariably correlated with hMLH1 hypermethylation and MSI. In conclusion, our data indicate that MSI and loss of the mismatch repair protein hMLH1, which is mainly caused by hMLH1 gene hypermethylation, are more prevalent in stomach and cardia carcinogenesis than in that of the esophagus. Moreover, in gastric cancer, hMLH1 hypermethylation is correlated with hypermethylation of the HPP1 gene. © 2004 Wiley‐Liss, Inc.
Attenuation by cyclic phosphatidic acid of peritoneal metastasis of azoxymethane‐induced intestinal cancers in Wistar rats
Authors: Ishihara Ryu , Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako , Uedo Noriya , Higashino Koji , Mukai Mutsuko , Ishiguro Shingo , Kobayashi Susumu , Murakami‐Murofushi Kimiko 
Published: March 2004

AbstractThe effect of cyclic phosphatidic acid, a unique analogue of lysophosphatidic acid, on the induction of bombesin‐enhanced peritoneal metastases from intestinal adenocarcinomas induced by azoxymethane was investigated in male Wistar rats. Rats were given 10 weekly injections of azoxymethane (7.4 mg/kg body weight, s.c.) and of bombesin (40 μg/kg body weight, s.c.) every other day from the start of the experiment, and from week 16, they received injections of cyclic phosphatidic acid (3 or 6 mg/kg body weight, s.c.) every other day until the end of the experiment in week 45. Cyclic phosphatidic acid at both dosages significantly decreased the incidence of bombesin‐enhanced cancer metastases to the peritoneum but had little or no effect on the location, histologic type, depth of involvement or infiltrating growth patterns of the tumors. Cyclic phosphatidic acid at either dose decreased significantly the incidence of lymphatic vessel invasion of adenocarcinomas and the activity of RhoA protein in the tumors, both of which were enhanced by bombesin. Our findings indicate that cyclic phosphatidic acid inhibits cancer metastasis through inhibition of RhoA protein activation. © 2004 Wiley‐Liss, Inc.
Glutathione S‐transferase T1 null‐genotype is associated with an increased risk of lung cancer
Authors: Sørensen Mette , Autrup Herman , Tjønneland Anne , Overvad Kim , Raaschou‐Nielsen Ole 
Published: March 2004

AbstractGlutathione S‐transferases (GSTs) are involved in detoxification of carcinogens, e.g., from tobacco smoke. Therefore, polymorphisms in the GST genes have been considered as potential modifiers of individual cancer risk. In a population‐based case‐cohort study where cases and the subcohort sample were matched on duration of smoking, we investigated the occurrence of lung cancer and histological subtypes of lung cancer in relation to deletion polymorphism in both GSTM1 and GSTT1, single nucleotide polymorphisms (SNPs) in GSTP1 (Ile105Val and Ala114Val) and a 3 base pair deletion polymorphism in GSTM3. We further investigated the effects of the GST polymorphisms on lung cancer risk within subgroups of subjects defined by gender and age. The results showed a 2.4‐fold (CI = 1.31–4.41) increased risk of lung cancer in GSTT1 null‐genotype carriers but no significant effects of the polymorphisms in GSTM1, GSTM3, GSTP1‐105 or GSTP1‐114. The association was strongest in lower age groups, with a 9.6‐fold increase in risk for subjects with the GSTT1 null‐genotype in the 50–55 years age interval (CI = 3.03–30.59). Positive associations were found for GSTT1 within all major histological subtypes. Squamous cell carcinoma was the histological type most strongly associated with the GSTT1 genotype, with a 5.0‐fold (CI = 2.26–11.18) increase in risk for subjects carrying the GSTT1 null‐genotype. The effects of the GSTT1 null‐genotype seemed stronger in the presence of the GSTM1 null‐genotype or the GSTP1‐105 variant allele. These results suggest that the GSTT1 null‐genotype is associated with an increased risk of lung cancer, especially in younger individuals. © 2004 Wiley‐Liss, Inc.
Comparison of K‐ras point mutation distributions in intraductal papillary‐mucinous tumors and ductal adenocarcinoma of the pancreas
Authors: Kitago Minoru , Ueda Masakazu , Aiura Koichi , Suzuki Keiichi , Hoshimoto Sojun , Takahashi Shin , Mukai Makio , Kitajima Masaki 
Published: March 2004

AbstractIntraductal papillary‐mucinous tumors (IPMT) consist of cells with varying histologic degrees of severity and exhibit multiple tumor loci; however, whether or not these lesions exhibit the same genetic changes has not been clarified. To investigate this point, we analyzed K‐ras mutations in multiple IPMT lesions from each patient enrolled in our study and compared our findings to those for patients with ductal adenocarcinoma of the pancreas (DC). Twenty IPMT specimens and 7 DC specimens were resected, microdissected and analyzed for the presence of K‐ras mutations. The mutated genes were then sequenced using a genetic analyzer. K‐ras mutations were observed in 80% of IPMT and 100% of DC patients. More than 2 types of K‐ras mutation were observed in the main tumors of 43.8% of IPMT and 0% of DC patients. K‐ras mutations in peritumoral and separated lesions were observed in 66.7% and 62.5% of IPMT patients, respectively. At least one identical mutation between the main tumor and the peritumoral or separated lesions was recognized in all of the IPMT patients with those lesions. Different mutations from those in the main tumor were observed in 40% of IPMT patients with separated lesions. The survival curve of IPMT‐carcinoma patients with more than 2 types of K‐ras mutation in the main tumor was better than that with one type of K‐ras mutation. IPMT patients exhibit a remarkably genetic heterogeneity in main tumor and have good prognosis. © 2004 Wiley‐Liss, Inc.
A prospective study of dietary lactose and ovarian cancer
Authors: Fairfield Kathleen M. , Hunter David J. , Colditz Graham A. , Fuchs Charles S. , Cramer Daniel W. , Speizer Frank E. , Willett Walter C. , Hankinson Susan E. 
Published: March 2004

AbstractThe milk sugar lactose is an hypothesized risk factor for epithelial ovarian cancer because of possible direct toxic effects of its metabolites on oocytes or by compensatory gonadotropin stimulation. Women are presently encouraged to consume dairy products as a source of calcium to prevent osteoporosis. The objective of our study was to prospectively assess lactose, milk and milk product consumption in relation to ovarian cancer risk among 80,326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin cancer. Participants in the Nurses' Health Study reported on known and suspected ovarian cancer risk factors in questionnaires mailed biennially from 1976 to 1996. Food frequency questionnaires were included in the years 1980, 1984, 1986 and 1990. Newly reported ovarian cancer was documented by review of medical records. During 16 years of follow‐up (1980–1996), 301 cases of invasive epithelial ovarian cancer were confirmed. Pooled logistic regression was used to control for age, body mass index (kg/m2), caffeine intake, oral contraceptive use, smoking history, parity and tubal ligation. For all subtypes of invasive ovarian cancer combined, we observed a nonsignificant 40% greater risk for women in the highest category of lactose consumption compared to the lowest (multivariate relative risk (RR) 1.40, 95% confidence interval (CI), 0.98–2.01). We observed a 2‐fold higher risk of the serous ovarian cancer subtype among those in the highest category of lactose consumption compared to the lowest (RR 2.07, 95% CI, 1.27–3.40). For each 11‐gram increase in lactose consumption (the approximate amount in one glass of milk), we observed a 20% increase in risk of serous cancers (RR 1.20, 95% CI, 1.04–1.39). Skim and low‐fat milk were the largest contributors to dietary lactose. Women who consumed one or more servings of skim or low‐fat milk daily had a 32% higher risk of any ovarian cancer (RR 1.32, 95% CI, 0.97–1.82) and a 69% higher risk of serous ovarian cancer (RR 1.69, 95% CI, 1.12–2.56) compared to women consuming 3 or less servings monthly. Controlling for fat intake did not change our findings. Our findings provide some support for the hypothesis that lactose intake increases risk of epithelial ovarian cancer. However, the observed excess risk appeared limited to the serous subtype of ovarian cancer in our study. © 2004 Wiley‐Liss, Inc.
Thalidomide reduces serum C‐reactive protein and interleukin‐6 and induces response to IL‐2 in a fraction of metastatic renal cell cancer patients who failed IL‐2‐based therapy
Authors: Kedar Igal , Mermershtain Wilmosh , Ivgi Hefziba 
Published: March 2004

AbstractInterleukin‐2 (IL‐2) has some antitumor activity in patients with renal cell carcinoma. It has been noted that response to IL‐2 and prognosis may be adversely affected by elevated serum levels of C‐reactive protein (CRP) or interleukin‐6 (IL‐6). We used thalidomide to treat patients with cancer‐induced cachexia and noted that the drug significantly reduced serum levels of CRP and IL‐6 to normal or near normal levels in a substantial fraction of patients. We tested whether thalidomide might potentiate the response of patients with renal cell carcinoma to IL‐2. Four patients with metastatic renal cell carcinoma and high serum levels of CRP and IL‐6 who had experienced disease progression on IL‐2 were retreated with the same IL‐2 regimen combined with thalidomide 300 mg p.o. daily. Two patients achieved good partial responses and 2 patients had prolonged disease stabilization with the combination of IL‐2 plus thalidomide. The regimen was well tolerated without increased IL‐2‐associated toxicity. Reduction of serum CRP or IL‐6 levels with thalidomide may enhance the responsiveness of renal cell carcinoma to IL‐2. A Phase II study of the combination is in order. It is possible that the thalidomide‐induced normalization of serum acute phase proteins might improve the response of other types of malignancy to IL‐2 or other immune‐based therapies. © 2004 Wiley‐Liss, Inc.
Familial risks of cancer as a guide to gene identification and mode of inheritance
Authors: Hemminki Kari , Li Xinjun 
Published: March 2004

AbstractOccurrence of cancer in parents and offspring may be due to dominant causes, whereas cancer affecting only siblings may indicate a recessive causation. Systematic comparisons of mode of inheritance have not been available for most types of cancer. Using the Swedish Family‐Cancer Database, standardized incidence ratios (SIR) were calculated for offspring whose parents or siblings were diagnosed with the same cancer. The degree of environmental causation was assessed by spouse correlation and by comparing risks among siblings of different ages. We identified reliable familial risks for all common neoplasms, SIRs ranging from 1.6 to 4.3 when only a parent was affected and up to 8.5 when only a sibling was effected. Risks between siblings were particularly high for renal cancer. Spouse correlation was found only for lung and stomach cancer, but the analysis of sibling risks by their age difference suggested that even for some other cancers environmental effects in childhood may contribute to familial aggregation. The results from these analysis suggest that familial cluster of cancer at most sites is heritable, caused by dominant effects; for renal cancer recessive effects may be most important. © 2004 Wiley‐Liss, Inc.
Case‐control study of anthropometric measures and prostate cancer risk
Authors: Friedenreich Christine M. , McGregor S. Elizabeth , Courneya Kerry S. , Angyalfi Steven J. , Elliott Frederick G. 
Published: March 2004

AbstractA population‐based case‐control study of 988 stage T2 or greater prostate cancer cases and 1,063 controls was conducted in Alberta from November 1997 to December 2000 to examine the influence of anthropometric risk factors on the risk of prostate cancer using several different measures. An in‐person interview was conducted, and all anthropometric measurements were taken using standardized methods. Respondents also recalled their body weight at each decade from age 20 to the referent year. Several anthropometric variables were derived, and unconditional logistic regression analyses were performed. The multivariable odds ratios, when comparing the highest to the lowest quartile were: for body mass index, OR = 1.12 (95% CI 0.85–1.47); for waist‐hip ratio, OR = 1.07 (0.83–1.38); for height, OR = 0.78 (0.60–1.02); for weight, OR = 0.91 (0.70–1.18); for weight gain since age 20, OR = 0.91 (0.70–1.19); and for difference between minimum and maximum adult weight, OR = 0.89 (0.69–1.16). Our study provides evidence for no association between any measures of anthropometry including several derived measures of changes in weight over lifetime and prostate cancer risk. © 2004 Wiley‐Liss, Inc.
Attenuated type II TGF‐β receptor signalling in human malignant oral keratinocytes induces a less differentiated and more aggressive phenotype that is associated with metastatic dissemination
Authors: Huntley Suzy P. , Davies Maria , Matthews John B. , Thomas Gareth , Marshall John , Robinson C. Max , Eveson John W. , Paterson Ian C. , Prime Stephen S. 
Published: March 2004

AbstractWe examined the effect of stable transfection of dominant negative TβR‐II (dn TβR‐II) cDNA in a human oral carcinoma cell line that contained normal Ras and was growth inhibited by TGF‐β1. Two clonal cell lines containing dn TβR‐II were isolated and compared to the vector‐only control and parent cell line. The treatment of cells with exogenous TGF‐β1 resulted in a decrease in ligand‐induced growth inhibition and loss of c‐myc downregulation in test cells compared to controls; transcriptional activation of certain genes including fra‐1 and collagenase was retained. Cells containing dn TβR‐II grew faster in monolayer culture, expressed less keratin 10 and exhibited increased motility and invasion in vitro compared to control cell lines. Endogenous TGF‐β1 production and the regulation of MMP‐2 and MMP‐9 by TGF‐β1 remained unchanged. After orthotopic transplantation to the floor of the mouth in athymic mice, cells containing dn TβR‐II formed comparable numbers of primary tumours at the site of inoculation as controls but the tumours were less differentiated as demonstrated by the absence of keratin 10 immunostaining. Further, metastatic dissemination to the lungs and lymphatics was more evident in grafts of cells containing dn TβR‐II than controls. Taken together, the results demonstrate that attenuation of TGF‐β signalling through transfection of dn TβR‐II cDNA leads to an enhanced growth rate, a loss of tumour cell differentiation and an increase in migration and invasion, characteristics that corresponded to the development of the metastatic phenotype. © 2004 Wiley‐Liss, Inc.