bluuebunny/crossref_metadata_2025_split huggingface dataset:
GABAergic and glutamatergic axons innervate the axon initial segment and organize GABAA receptor clusters of cultured hippocampal pyramidal cells
Authors: Christie Sean B. , De Blas Angel L. 
Published: January 2003

AbstractWe have studied γ‐aminobutyric acid (GABA)A receptor (GABAAR) clustering within the axon initial segment (AIS) in low‐density cultures of hippocampal pyramidal cells following GABAergic and glutamatergic innervation of the AIS. Large, intensely fluorescent, and postsynaptic GABAAR clusters were present in the AIS. More than 95% of these clusters colocalized with presynaptic GABAergic or glutamatergic terminals, forming matched or mismatched synapses, respectively. Less than 5% of the GABAAR clusters of the AIS did not colocalize with GABAergic or glutamatergic terminals, suggesting that GABAARs normally do not form clusters unless the AIS received GABAergic or glutamatergic innervation. Few or no clusters of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionate (AMPA) receptors or the postsynaptic density‐95 protein (PSD‐95) were found in the AIS, even when the AIS was innervated by glutamatergic axons. Glutamatergic innervation of the AIS that formed mismatched synapses with postsynaptic GABAAR clusters mainly occurred when the AIS did not receive GABAergic innervation. However, when the AIS was innervated by GABAergic axons, the formation of matched GABAergic synapses predominated and coincided with large reductions in both the density of glutamatergic terminals from the AIS and the mismatching of GABAAR clusters. A similar effect was observed at axo‐dendritic synapses, where GABAergic innervation also led to a large decrease in mismatched GABAAR clusters and a smaller, but significant, decrease in glutamatergic terminal density in dendrites that received GABAergic innervation. We hypothesize that competition between GABAergic and glutamatergic innervation of the AIS in the intact hippocampus leads to the exclusive presence of GABAergic inhibitory synapses in the AIS of pyramidal cells. J. Comp. Neurol. 456:361–374, 2003. © 2003 Wiley‐Liss, Inc.
PDAPP; YFP double transgenic mice: A tool to study amyloid‐β associated changes in axonal, dendritic, and synaptic structures
Authors: Brendza Robert P. , O'Brien Cara , Simmons Kelly , McKeel Daniel W. , Bales Kelly R. , Paul Steven M. , Olney John W. , Sanes Joshua R. , Holtzman David M. 
Published: January 2003

AbstractNeuritic plaques are one of the stereotypical hallmarks of Alzheimer's disease (AD) pathology. These structures are composed of extracellular accumulations of fibrillar forms of the amyloid‐β peptide (Aβ), a variety of other plaque‐associated proteins, activated glial cells, and degenerating nerve processes. To study the neuritic toxicity of different structural forms of Aβ in the context of regional connectivity and the entire cell, we crossed PDAPP transgenic (Tg) mice, a model with AD‐like pathology, to Tg mice that stably express yellow fluorescent protein (YFP) in a subset of neurons in the brain. In PDAPP; YFP double Tg mice, markedly enlarged YFP‐labeled axonal and dendritic varicosities were associated with fibrillar Aβ deposits. These varicosities were absent in areas where there were nonfibrillar Aβ deposits. Interestingly, YFP‐labeled varicosities revealed changes that corresponded with changes seen with electron microscopy and the de Olmos silver staining technique. Other silver staining methods and immunohistochemical localization of phosphorylated neurofilaments or phosphorylated tau were unable to detect the majority of these dystrophic neurites. Some but not all synaptic vesicle markers accumulated abnormally in YFP‐labeled varicosities associated with neuritic plaques. In addition to the characterization of the effects of Aβ on axonal and dendritic structure, YFP‐labeled neurons in Tg mice should prove to be a valuable tool to interpret the localization patterns of other markers and for future studies examining the dynamics of axons and dendrites in a variety of disease conditions in living tissue both in vitro and in vivo. J. Comp. Neurol. 456:375–383, 2003. © 2003 Wiley‐Liss, Inc.
Are there gender differences in the prescribing of hypnotic medications for insomnia?
Authors: Brownlee K. , Devins G. M. , Flanigan M. , Fleming J. A. E. , Morehouse R. , Moscovitch A. , Plamondon J. , Reinish L. , Shapiro C. M. 
Published: January 2003

AbstractGender differences in the prescribing patterns of general classes of medications for insomnia were examined. The classes of medications included: zopiclone, antidepressants, benzodiazepines, antihistamines and no medication. The sample comprised a sub‐set of respondents from 2620 questionnaires of the Canadian Multicentre Sleep Database. Respondents for this database were contacted through physicians, announcements in the media and local pharmacies. The results indicated that gender alone was not associated with differential prescribing for insomnia, nor was gender associated with patterns of medication use such as frequency of taking medication, length of use, taking more or less medication than prescribed or attempts to stop taking medication. Demographic factors were included in the analysis and age and marital status were associated with different prescribing patterns for men and women with insomnia. It is possible that physicians refer to stereotypic expectations when prescribing hypnotics. Copyright © 2002 John Wiley & Sons, Ltd.
Cognitive effects of long‐term benzodiazepine use in older adults
Authors: Pat McAndrews Mary , Weiss Rachel T. , Sandor Paul , Taylor Ann , Carlen Peter L. , Shapiro Colin M. 
Published: January 2003

AbstractThis study examined the potential for cognitive morbidity associated with the long‐term use of benzodiazepine (BZ) sedative‐hypnotics in a sample of healthy older adults. Tests of memory, attention and processing speed were conducted prior to and 1 month after drug discontinuation for 25 BZ‐users and at similar intervals for 26 healthy control subjects. After controlling for differences in affective status between BZ‐users and controls, there were no significant group differences in cognitive performance. However, BZ‐users showed greater gains on tests of attention and speed of processing at repeat testing compared with controls this improvement was not attributable to a change in affective status. These findings suggest that there may be subtle and reversible effects of long‐term BZ use on speed‐dependent tasks in older adults. However, the magnitude of these effects is quite small and may be of little clinical significance in the healthy elderly. Copyright © 2002 John Wiley & Sons, Ltd.
Adverse effects of temazepam in older adults with chronic insomnia
Authors: Morin Charles M. , Bastien Celyne H. , Brink Douglas , Brown Timothy R. 
Published: January 2003

AbstractBackgroundBenzodiazepine‐hypnotics are frequently used for treating insomnia in older adults; however, there is little information about adverse effects associated with their usage over several weeks, particularly in this segment of the population.ObjectiveThis study reports on the incidence of adverse effects of temazepam in older adults with chronic insomnia and examines whether the addition of cognitive‐behaviour therapy (CBT) is associated with less drug used and fewer adverse effects.MethodSixty patients with chronic and primary insomnia were randomized to temazepam (n = 20), placebo (n = 20) or temazepam plus CBT (n = 20). Data from the physicians' weekly assessments and patients' sleep diaries were used to evaluate adverse effects, the dose (7.5–30 mg) at which they occurred, and drug use patterns over the 8‐week course of treatment.ResultsThe incidence of adverse effects was infrequent, as shown by the low percentages of complaints reported by patients in the temazepam (7.8%), placebo (10.8%) and combination groups (8.3%). The severity of adverse events was mild and decreased over the course of treatment. The maximum dose was reached by 10 patients receiving temazepam, 14 placebo and 7 in the combined treatment. The average nightly dosage used was 20 mg for both the temazepam and placebo groups and 16 mg for the combined condition. Patients receiving temazepam plus CBT used less drugs, with approximately the same incidence of adverse effects.ConclusionTemazepam is a safe hypnotic for use by older adults over an 8‐week treatment period. There are few adverse effects and behavioural tolerance to those effects develop over time. The addition of cognitive‐behavioural intervention reduced both the amount of medication used and the incidence of adverse effects, with comparable sleep improvements. Copyright © 2003 John Wiley & Sons, Ltd.
Deguelin suppresses the formation of carcinogen‐induced aberrant crypt foci in the colon of CF‐1 mice
Authors: Murillo Genoveva , Kosmeder Jerome W. , Pezzuto John M. , Mehta Rajendra G. 
Published: January 2003

AbstractDeguelin [(7aS,BaS)‐13,13a‐dihydro‐9,10‐dimethoxy‐3,3‐dimethyl‐3H‐Bis[1]benzopyrano[3,4‐b:6′,5′‐e]pyran‐7(7aH)‐one], a naturally occurring rotenone, has shown chemopreventive efficacy in several in vivo and in vitro models. In this report, the effectiveness of deguelin at inhibiting the development of AOM‐induced colonic ACF was investigated in CF‐1 mice. Loss of hex activity was assessed as a second biomarker. In an initial experiment, animals were given s.c. injections of AOM (10 mg/kg body weight) once a week for 2 weeks to induce ACF. Deguelin and vehicle (corn oil) were administered i.g. 7 days a week. Treatment was initiated 2 weeks prior to the first dose of carcinogen and continued for the duration of the study. The mean number of ACF for the control group was 29.0 ± 4.3, whereas the mean numbers of ACF in the deguelin groups were 24.8 ± 2.7, 7.2 ± 1.5 and 4.6 ± 1.4 at doses of 2.5, 5.0 and 10.0 mg/kg body weight, respectively. In a similar manner, treatment with deguelin significantly (p < 0.001) suppressed the appearance of hex− crypts in a dose‐dependent manner. In a second study, the ability of deguelin to block the initiation and promotion stages of colon carcinogenesis was investigated. Greatest inhibition was observed when deguelin was administered during the promotional stage (73.3%, p < 0.001). These results demonstrate that deguelin is an efficacious chemopreventive agent against colon carcinogenesis. © 2002 Wiley‐Liss, Inc.
GLUT‐1 and CAIX as intrinsic markers of hypoxia in carcinoma of the cervix: Relationship to pimonidazole binding
Authors: Airley Rachel E. , Loncaster Juliette , Raleigh James A. , Harris Adrian L. , Davidson Susan E. , Hunter Robert D. , West Catharine M.L. , Stratford Ian J. 
Published: January 2003

AbstractThe presence of hypoxia in tumours results in the overexpression of certain genes, which are controlled via the transcription factor HIF‐1. Hypoxic cells are known to be radioresistant and chemoresistant, thus, a reliable surrogate marker of hypoxia is desirable to ensure that treatment may be rationally applied. Recently, the HIF‐1‐regulated proteins Glut‐1 and CAIX were validated as intrinsic markers of hypoxia by comparison with pO2 measured using oxygen electrodes. We compare the expression of Glut‐1 and CAIX with the binding of the bioreductive drug hypoxia marker pimonidazole. Pimonidazole was administered to 42 patients with advanced carcinoma of the cervix, 16 hr before biopsy. Sections of single or multiple biopsies were then immunostained for Glut‐1 and CAIX, and the area of staining scored by eye, using a “field‐by‐field” semi‐quantitative averaging system. Using 1 biopsy only, Glut‐1 (r = 0.54, p = <0.001) correlated with the level of pimonidazole binding, and Glut‐1 and CAIX expression also correlated significantly (r = 0.40, p = <0.009). Thus, our study has shown that HIF‐1 regulated genes have potential for future use as predictors of the malignant changes mediated by hypoxia, and warrant further investigation as indicators of response to cancer therapy. © 2002 Wiley‐Liss, Inc.
Very low concentrations of arsenite suppress poly(ADP‐ribosyl)ation in mammalian cells
Authors: Hartwig Andrea , Pelzer Anke , Asmuss Monika , Bürkle Alexander 
Published: January 2003

AbstractArsenite is a naturally occurring environmental pollutant of major concern, since adverse health effects including cancer of skin and internal organs have been attributed to chronic arsenic exposure especially via drinking water. Arsenite is not a significant inducer of point mutations but exerts clastogenic activities and interferes with various DNA repair systems at concentrations in the low micromolar range. Nevertheless, no single DNA repair protein exquisitely sensitive to arsenic has been identified. Here we report that poly(ADP‐ribosyl)ation, which is predominantly mediated by poly(ADP‐ribose) polymerase‐1 (PARP‐1), is inhibited at concentrations as low as 10 nM in cultured HeLa cells, closely matching arsenic concentrations in blood and urine of the general population. Since poly(ADP‐ribosyl)ation is an immediate cellular response to DNA damage, playing a major role in DNA base excision repair and the maintenance of genomic stability, its inhibition by arsenite may add to the risk of cancer formation under low‐exposure conditions. © 2002 Wiley‐Liss, Inc.
Molecular basis of basal cell carcinoma: Analysis of differential gene expression by differential display PCR and expression array
Authors: Welss Thomas , Papoutsaki Marina , Michel Günter , Reifenberger Julia , Chimenti Sergio , Ruzicka Thomas , Abts Harry F. 
Published: January 2003

AbstractBasal cell carcinoma (BCC) is the most common tumor in the Caucasian population. Although BCC rarely metastasize and cause death, they are problematic due to their destructive growth and the frequent localization on the face. Until now the knowledge of genes differentially expressed in BCC has been incomplete. To elucidate the complex alterations in BCC‐associated gene expression, we took advantage of 2 techniques: the differential display RT‐PCR (DD‐PCR) and the differential hybridization of cDNA arrays. Using DD‐PCR, we showed differential expression of genes known from other biological contexts (e.g., rac, ubiquitin hydrolase), which could now be associated with BCC. In addition, we detected unknown genes possibly contributing to the carcinogenesis of BCC. Of the 588 genes screened by differential hybridization of the Atlas™ human cDNA array, differences in the expression levels of BCC were observed for 10 genes. These data were obtained with RNA probes pooled from several BCC of different donors and were subsequently confirmed by semiquantitative RT‐PCR for Janus protein tyrosine kinase 3 (Jak3), microsomal glutathione S‐transferase 1 (GST 12), teratocarcinoma‐derived growth factor cripto, glutaredoxin and the monocyte chemoattractant protein 1 (MCP‐1) in 10 individual BCC specimens, 2 squamous cell carcinoma (SCC), the cell line HaCaT and cultured normal human keratinocytes (NHK) in comparison to normal skin. These genes are candidates from gene families with known association to tumors, but they have not been reported in the carcinogenesis of BCC yet. In summary, both approaches allow the detection of differentially expressed genes possibly involved in the carcinogenesis of BCC. © 2002 Wiley‐Liss, Inc.
Prognostic value of tumor‐infiltrating dendritic cells expressing CD83 in human breast carcinomas
Authors: Iwamoto Mitsuhiko , Shinohara Hisashi , Miyamoto Akiko , Okuzawa Masaaki , Mabuchi Hideaki , Nohara Takehiro , Gon Goki , Toyoda Masao , Tanigawa Nobuhiko 
Published: January 2003

AbstractDCs are the most potent antigen‐presenting cells that play a major role in initiating the antitumor immune response. Although the clinical significance of TIDCs has been investigated in a variety of human cancers, few studies have focused on the in situ maturation status of DCs. We have analyzed the maturation‐specific significance of TIDCs in the prognosis of patients with breast carcinoma. We evaluated 130 breast carcinomas for the presence of TIDCs using immunohistochemistry with an anti‐CD1a antibody for immature DCs and an anti‐CD83 antibody for mature DCs. Intratumoral expression of immunosuppressive cytokines was also examined. All samples contained CD1a+ TIDCs, and 82 (63.1%) samples contained CD83+ TIDCs. The number of CD83+ TIDCs was inversely correlated with lymph node metastasis and with tissue expression of VEGF and TGF‐β, whereas the number of CD1a+ TIDCs was not. Kaplan‐Meier analysis (log rank statistics) revealed a significant association of increasing number of CD83+ TIDCs with longer relapse‐free (p = 0.002) and overall (p < 0.001) survival. Furthermore, among patients with lymph node metastasis, the survival rate of those with larger numbers of CD83+ TIDCs was significantly better than that of patients with fewer CD83+ TIDCs. Multivariate analysis revealed that CD83+ TIDCs had independent prognostic relevance in breast carcinomas. The infiltration of tumors by mature DCs expressing CD83 may be of great importance in initiating the primary antitumor immune response and is confirmed as an independent, immunologic prognostic parameter for survival in patients with breast cancer. © 2002 Wiley‐Liss, Inc.
Immune enhancement of nitroreductase‐induced cytotoxicity: Studies using a bicistronic adenovirus vector
Authors: Green Nicola K. , McNeish Iain A. , Doshi Rajeev , Searle Peter F. , Kerr David J. , Young Lawrence S. 
Published: January 2003

AbstractThe nitroreductase (NR)/CB1954 enzyme prodrug system has given promising results in preclinical studies and is currently being assessed in phase I clinical trials. It is well established that there is an immune component to the bystander effect observed with other systems such as thymidine kinase and cytosine deaminase; however, such an effect has not previously been described using NR. We have preliminary data suggesting an immune bystander effect with NR to further examine these effects and their potential enhancement by cytokines, an adenoviral vector containing CMV‐NR, an internal ribosome entry site (IRES) and the gene for murine GM‐CSF (mGM‐CSF) was constructed. The NR‐GM‐CSF virus was validated in 2 experimental models and demonstrated increased therapeutic efficacy in the MC26 murine colorectal tumour model. These data illustrate that the combination of suicide gene therapy using NR and CB1954 with immune stimulation via GM‐CSF gives an improved response compared to either modality alone and suggests that the immune component of this response may be beneficial in combating unresectable, metastatic disease and preventing tumour recurrence. © 2002 Wiley‐Liss, Inc.
Effects of E‐cadherin transfection on gene expression of a gallbladder carcinoma cell line: Repression of MTS1/S100A4 gene expression
Authors: Kohya Naohiko , Kitajima Yoshihiko , Jiao Wan , Miyazaki Kohji 
Published: January 2003

AbstractE‐cadherin is important in cell‐to‐cell adhesion and controls cell polarity and tissue morphology. Loss of E‐cadherin expression occurs in various human tumors and is the first step in cancer invasion and metastasis. We demonstrate that the exogenous expression of E‐cadherin transfected into G‐415 GB cells not only increases cell‐to‐cell adhesion but also reduces in vitro cell proliferation, motility and invasion. Our aim was to determine what genes are most affected by the exogenous expression of E‐cadherin in GB cancer cells. We analyzed gene expression pertaining to cell proliferation, motility and invasion. Conventional RT‐PCR was performed for these genes; quantitative RT‐PCR was carried out on genes exhibiting altered expression. Conventional RT‐PCR revealed that E‐cadherin transfection suppressed expression of mts1 mRNA and increased that of c‐myc and MT1‐MMP. In quantitative RT‐PCR analysis, levels of c‐myc and MT1‐MMP mRNA were elevated by to 2.56‐ and 2.22‐fold, respectively, in the E‐cadherin transfectant, whereas mts‐1 was 7.14‐fold suppressed compared to parental cells. These results indicated that expression of mts1 mRNA was most affected by E‐cadherin transfection. Immunocytochemical analysis of transfectant and parental cells demonstrated an inverse correlation in E‐cadherin and mts1 expression. Immunohistochemical analysis of 37 GB cancer specimens confirmed this observation in vivo. Loss of E‐cadherin expression followed by expression of the mts1 gene may be an important event for increasing cell proliferation, motility and invasion activity in the progression of GB cancer. © 2002 Wiley‐Liss, Inc.
Sodium selenite, dietary micronutrient, prevents the lymphocyte DNA damage induced by N‐nitrosodiethylamine and phenobarbital promoted experimental hepatocarcinogenesis
Authors: Thirunavukkarasu C. , Sakthisekaran D. 
Published: January 2003

AbstractSelenium (Se), a micronutrient, has a long history in chemoprevention of mammary and colon cancers in rodent models. Se is a current clinical trial, having shown promise in prevention of prostate and other human cancers. The mechanisms involved in the in vivo anti‐carcinogenic activity of Se remain to be elucidated. In the present study, we examined the effect of sodium selenite supplementation in lymphocytes, obtained from hepatoma bearing rats on DNA damage in correlation with oxidative stress. In addition, this study examined the supplementation of Se at 4‐ppm levels in the form of sodium selenite either before initiation or during initiation and/or promotion phase's increases lymphocyte Se concentrations. This in turn improves lymphocyte resistance to oxidative stress and protection against the lymphocytes DNA damage. Supplementation of Se increased lymphocyte Se concentration and reduced lymphocytes DNA damage as determined by single cell gel electrophoresis. The enzymatic antioxidants such as superoxide dismutase, glutathione peroxidase, and catalase were found to be decreased while the thiobarbituric acid reactive substances level was increased in the lymphocytes of hepatoma bearing rats. Furthermore, the reactive oxygen species such as superoxide radicals and hydroxyl radicals were also found to be high in lymphocytes. Our present results explain the understanding of unique association between anti‐peroxidative effect of Se and ultimately the capability of Se to prevent cancer. © 2002 Wiley‐Liss, Inc.
Nuclear matrix localization of high mobility group protein I(Y) in a transgenic mouse model for prostate cancer
Authors: Leman Eddy S. , Madigan Michael C. , Brünagel Gisela , Takaha Natsuki , Coffey Donald S. , Getzenberg Robert H. 
Published: January 2003

AbstractNuclear shape and the underlying nuclear structure, the nuclear matrix in cancer cells. Since the NM composition is considered to maintain nuclear shape and architecture, nuclear matrix proteins (NMPs) may be involved in transformation. Our laboratory has recently characterized a subset of NMPs that are associated with prostate cancer development in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. One of the identified NMPs, E3E, has a similar molecular weight (22 kDa) with a protein known as HMGI(Y). HMGI(Y) belongs to a group of non‐histone and chromatin‐associated proteins, high‐mobility‐group (HMG) proteins, and it has been shown to associate with the NM. HMGI(Y) has been reported to be elevated in different types of cancer including prostate cancer. In this study, we examined the expression of HMGI(Y) protein in the NMP composition of the TRAMP model during the progression from normal to neoplasia. The expression of HMGI(Y) in the NMP extracts of three prostatic epithelial cell lines derived from a 32‐week TRAMP mouse: TRAMP‐C1, TRAMP‐C2, and TRAMP‐C3 was also examined. Using both one‐dimensional and high‐resolution two‐dimensional immunoblot analyses, we found that: (i) HMGI(Y) is a nuclear matrix protein expressed as two protein bands with MW of 22–24 kDa and (ii) HMGI(Y) expression is correlated with neoplastic and malignant properties in late stage TRAMP prostate tumors. Overall, these findings support the evidence that HMGI(Y) can be utilized as a marker and prognostic tool for prostate cancer. © 2002 Wiley‐Liss, Inc.