bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma sex steroid hormones and breast cancer risk in Chinese women
Authors: Yu Herbert , Shu Xiao‐Ou , Shi Runhua , Dai Qi , Jin Fan , Gao Yu‐Tang , Li Benjamin D.L. , Zheng Wei 
Published: March 2003

AbstractEstrogens regulate the growth and differentiation of mammary cells and play an important role in the development of breast cancer. High circulating levels of estrogens are associated with increased risk of breast cancer in Caucasian women. Because Asian women have low estrogens in the circulation compared with their Caucasian counterparts, the effect of estrogens on breast cancer risk in populations with low circulating estrogens remains to be elucidated. We conducted a population‐based case‐control study in China to evaluate the association of sex steroid hormones with breast cancer risk in Chinese women. Our study included 300 incident cases with primary breast cancer and 300 age‐ and menopausal status‐matched healthy controls randomly selected from the general population in Shanghai. Fasting blood samples were collected from cases prior to any treatment and from their matched controls. Commercial immunoassays were used to measure plasma concentrations of estradiol, estrone, estrone sulfate, testosterone, progesterone, dehydroepiandrosteindian sulfate (DHEA‐S) and steroid hormone‐binding globulin (SHBG). Conditional logistic regression analysis was performed to examine the association between steroid hormones and breast cancer risk. The results showed that breast cancer risk was elevated with increasing levels of estrone and testosterone (p for trend < 0.05) but not with DHEA‐S, estradiol, estrone sulfate, progesterone or SHBG. The estimated relative risks between upper and lower tertiles were 2.07 (95% confidence interval [CI] 0.97–4.41) for estrone in postmenopausal women, 2.01 (95% CI 0.96–4.21) for testosterone in premenopausal women, and 2.40 (95% CI 1.11–5.21) for testosterone in postmenopausal women, after adjusting for age at first live birth, waist‐to‐hip ratio, total calorie intake, a history of fibroadenoma, a family history of breast cancer and SHBG. These results, in general, are consistent with the findings in Caucasian women and indicate that high sex steroid hormones in the circulation, both androgen and estrogen, are associated with increased risk of breast cancer even in populations with relatively low sex hormones. © 2003 Wiley‐Liss, Inc.
Predictors of metachronous colorectal neoplasms in sporadic adenoma patients
Authors: Bertario Lucio , Russo Antonio , Sala Paola , Pizzetti Paolo , Ballardini Giovanni , Andreola Salvatore , Spinelli Pasquale 
Published: March 2003

AbstractOur objective was to assess the overall risk of subsequent colorectal neoplasms (cancer or adenoma) in relation with the various characteristics of the index lesion in a cohort of patients who underwent endoscopic polypectomies of colorectal adenomas. A total of 1,086 patients with adenomas of the large bowel were reported between 1979 and 1999 at the National Cancer Institute of Milan during a screening program for colorectal carcinoma. Data on patients who had colonoscopic examinations and treatments were collected prospectively. The relation between colorectal cancer (CRC) and adenoma features was assessed by computing the hazard ratio (HR) values and corresponding confidence intervals (95% CI) according to Cox proportional hazard models. Of the 1,086 eligible patients (487 females, 579 males), 736 had single adenomas (67.7%) and 350 had multiple adenomas (32.3%). Histologic examination revealed 772 cases of tubular adenoma (73%), 205 cases of tubulovillous adenoma and 80 cases of villous adenoma (7.5%). Severe dysplasia was found in 3.3% of the cases. During the 11,393 person‐years of follow‐up, with an average time of surveillance of 10.5 years, colorectal carcinomas developed in 10 patients (0.8%) and a new adenoma in 323 patients (29%). Multivariate analysis showed that male gender (HR 1.6; 95% CI 1.3–2.0), multiple polyps (HR 1.6; 95% CI 1.3–2.0), polyps larger than 2 cm (HR 1.5; 95% CI 1.1–2.1), tubulovillous and villous histology (HR 1.3; 95% CI 1.0–1.6 and HR 1.8; 95% CI 1.2–2.6, respectively) at index polypectomy were statistically significant risk factors for developing metachronous adenomatous polyps. The standardized incidence rates (SIR) for CRC was 0.52 (95% CI 0.25–0.95). The SIR was increased in subjects with severe dysplasia (2.8; 95% CI 0.34–1.02). Some features of large bowel adenomas are strongly correlated with an increased risk of metachronous adenomas and colorectal cancer. However, the endoscopic polypectomy is able to reduce by 50% the incidence of CRC in patients with large bowel adenomas. © 2003 Wiley‐Liss, Inc.
Cancer risks in hairdressers: Assessment of carcinogenicity of hair dyes and gels
Authors: Czene Kamila , Tiikkaja Sanna , Hemminki Kari 
Published: March 2003

AbstractMore than a decade ago, an increased risk for bladder cancer among male hairdressers was established. Frequent changes of hair dye formulations together with their widespread use call for safety guarantees. We carried out a follow‐up study of a cohort of 38,866 female and 6,824 male hairdressers from Sweden and analyzed all of their malignancies over a period of 39 years. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for 28 cancer sites were calculated using the economically active population as a reference. During the years 1960–1998 a total of 1,043 cancer cases were recorded in male hairdressers. Excess risks for cancers of the upper aerodigestive tract and lung and colorectal adenocarcinoma were observed. Additionally, male hairdressers working in 1960 had an increased risk for urinary bladder cancer, which was highest in the 1960s with an SIR of 2.56 (95% CI 1.36–4.39) and decreased with the follow‐up time. A total of 2,858 cancers were recorded in female hairdressers. An increased risk was observed for cancers of the pancreas, lung and cervix and in situ cancer of the skin. The increased risk for in situ skin cancer specifically affected the scalp and neck, sites of contact for hair dyes, with an SIR of 2.43 (95% CI 1.14–4.44). The increase in lung cancer, the only site for which cancer was increased in either sex, may depend on confounding from smoking. Bladder cancer was not increased among hairdressers in the recent decades and is therefore not likely to be associated with modern hair dyes. © 2003 Wiley‐Liss, Inc.
Phenotypic reversion of rat neoplastic liver nodules is under genetic control
Authors: De Miglio Maria R. , Simile Maria M. , Muroni Maria R. , Calvisi Diego F. , Virdis Patrizia , Asara Giuseppina , Frau Maddalena , Bosinco Giovanni M. , Seddaiu Maria A. , Daino Lucia , Feo Francesco , Pascale Rosa M. 
Published: March 2003

AbstractLow DNA synthesis and high redifferentiation (remodeling) characterize neoplastic nodules induced by chemical carcinogens in hybrid BFF1 rats, generated by crossing the susceptible F344 and resistant BN strains. We performed whole‐genome scanning of BFF2 rats to identify loci controlling remodeling of nodules induced, 32 weeks after initiation with diethylnitrosamine, by the RH protocol. Remodeling nodules were identified as areas lacking uniformity of GST‐P immunostaining and with irregular margins. Two loci in suggestive linkage with the percentage of remodeling nodules were identified on chromosomes 7 and 1 (LOD scores 3.85 and 2.9 at D7Rat25 and D1Mgh14). Significant dosage‐negative effect of the B allele on remodeling and additive interaction between these loci were found. Significant epistatic interactions, showing a recessive, remodeling‐enhancing effect of B alleles, occurred between D1Mit3 and D11Rat11 (corrected p = 0.0013) and between D6Rat14 and D8Rat46 (corrected p = 0.028). These data show that remodeling of neoplastic nodules during rat hepatocarcinogenesis is under genetic control. Loci affecting remodeling map to chromosomal regions syntenic to chromosomal segments of human HCC showing structural abnormalities. © 2003 Wiley‐Liss, Inc.
Organization and modifications of sperm acrosomal molecules during spermatogenesis and epididymal maturation
Authors: Yoshinaga Kazuya , Toshimori Kiyotaka 
Published: March 2003

AbstractThe mammalian acrosome is a highly specialized organelle overlying the anterior part of the sperm nucleus and contains a variety of proteins, including hydrolytic enzymes and matrix molecules. Functionally, the anterior acrosome is involved in the acrosome reaction or sperm–zona pellucida interaction, while the equatorial segment (posterior acrosome) is involved in sperm–egg fusion. The acrosome is formed during spermiogenesis, during which associated molecules are transported from the Golgi apparatus and organized. Many of the molecules thus arranged gradually become compartmentalized during sperm passage through the epididymis. Some of them are further modified during the fertilization process. The findings indicate that acrosomal molecules are not only restricted to a specific region (domain) of the acrosome but also undergo ongoing relocation in a stage‐specific manner during sperm maturation in the testis and epididymis. Such maturation‐associated modifications are considered essential for sperm molecules to reach the correct or final site before fertilization. This review focuses on the organization and modifications of the acrosomal molecules as well as their compartmentalization within the acrosome. Microsc. Res. Tech. 61:39–45, 2003. © 2003 Wiley‐Liss, Inc.
Expression of mammalian spermatozoal nucleoproteins
Authors: Dadoune Jean‐Pierre 
Published: March 2003

AbstractA dramatic remodeling of sperm chromatin occurs during mammalian spermiogenesis. Nuclear elongation and chromatin condensation are concomitant with modifications in the basic protein complement associated with DNA. A number of biochemical events accompany the displacement of histones and the appearance of protamines in elongating spermatids. The mRNAs of transition proteins and protamines are transcribed and stored in the cytoplasm of spermatids until days later when they are translated. The intrinsic regulation of the expression of the transition protein and protamine genes occurs at three levels: transcription, translation, and posttranslation. The aim of this review is to cover most of the morphological, biochemical, and functional events which concern nuclear protein transitions during spermiogenesis and which are thereby involved in the nuclear status of ejaculated sperm cells. Microsc. Res. Tech. 61:56–75, 2003. © 2003 Wiley‐Liss, Inc.
Ca2+/calmodulin‐dependent protein kinases II and IV both promote survival but differ in their effects on axon growth in spiral ganglion neurons
Authors: Hansen Marlan R. , Bok Jinwoong , Devaiah Anand K. , Zha Xiang‐Ming , Green Steven H. 
Published: March 2003

AbstractSpiral ganglion neuron (SGN) survival in vitro can be maintained by neurotrophins, permeant cAMP analogs, and depolarization in an additive manner, with depolarization being the most efficacious. Therefore, we used cultured SGNs to determine the mechanism by which depolarization promotes neuronal survival. Our data implicate Ca2+/calmodulin‐dependent protein kinase (CaMK) activity by showing that it is induced by depolarization, that CaMK activity is necessary for at least part of the survival‐promoting effect of depolarization, and that CaMKII or CamKIV activity suffices to support neuronal survival in the absence of other trophic stimuli. First, that depolarization of SGNs activates CaMKs is evidenced by observation of increased CaMKII phosphorylation and of CaMK‐dependent CREB phosphorylation. Second, the requirement for CaMKs is shown by a reduction of SGN survival under depolarizing conditions in the presence of CaMK inhibitors. Third, transfection of COOH‐terminal‐truncated (lacking regulatory domain), constitutively active CaMKII or CaMKIV, but not of normal, full‐length CAMKs, promotes SGN survival in the absence of other trophic stimuli, indicating that CaMK activity is sufficient to promote survival. The survival‐promoting effect of truncated CaMKs is additive with that of depolarization, neurotrophins, or cyclic AMP. Although both CaMKII and CaMKIV activities converge in promoting survival, their actions on axon growth are markedly different: Transfection of truncated CaMKII, but not of truncated CaMKIV, into SGNs prevents axon outgrowth. © 2003 Wiley‐Liss, Inc.
Axons of alpha ganglion cells regenerate faster than other types into a peripheral nerve graft in adult cats
Authors: Maki Hideki , Watanabe Masami , Tokita Yoshihito , Saito Kiyoshi , Yoshida Jun 
Published: March 2003

AbstractWe reported previously that alpha ganglion cells in the cat retina have the highest ability in axonal regeneration. To examine whether alpha cells regenerate axons faster, we estimated the rate of axonal regeneration of retinal ganglion cells (RGCs) with transplantation of a peripheral nerve (PN) segment. After 4, 6, and 8 weeks of survival, regenerated RGCs were double‐labeled with two fluorescent dyes injected separately at 10 mm and 20 mm from the connected site. From a scatter diagram of double‐labeling ratios, we estimated that axons reached 20 mm by 3.2 weeks. Immunostaining suggested that first axon sprouts entered a PN segment on Day 4. These values enabled us to estimate average rates of axonal regeneration as 1.1 mm/day for all the RGCs. Proportions of cell types of regenerated RGCs were obtained with Lucifer yellow injections, and those of alpha cells were higher than those in normal retinas in any periods. From analysis of scatter diagrams, we estimated axonal growth rate of alpha, beta, and non‐alpha/beta cells as 1.4, 1.1, 1.0 mm/day, respectively. The higher regeneration rate of alpha cells may reflect greater regenerative ability compared to other cell types. The present system also provides control values when a method to promote axonal regeneration is developed. © 2003 Wiley‐Liss, Inc.
Activation of protein kinase C inhibits retrograde transport of neurotrophins in mice
Authors: Ozsarac Nesrin , Weible Michael , Reynolds Anna J. , Hendry Ian A. 
Published: March 2003

AbstractRetrograde axonal transport of neurotrophins from nerve terminal to cell body requires a number of key processes, including internalization of the receptor‐neurotrophin complex into vesicles and formation of multivesicular bodies and their transport along the axon. Previous studies have shown that each of these processes can be regulated by kinases. In this study, we looked at the role of protein kinase C (PKC) in retrograde transport by injecting labeled neurotrophins together with relevant pharmacological agents into the eye and measuring the accumulation of radioactivity in the trigeminal and superior cervical ganglia. Inhibitors of PKC, Ro‐31‐8220 and rottlerin, did not affect the retrograde transport of nerve growth factor (NGF); however, phorbol ester activation of classical and novel PKCs blocked retrograde transport. The effect of phorbol esters was partially reversed by rottlerin and Ro‐31‐8220. Activation of PKC has been shown to be involved in the disorganization of actin filaments. In this study, we show that Ro‐31‐8220 reverses growth cone collapse by phorbol 12‐myristate 13‐acetate and suggest that one of the effects of activating PKC on retrograde transport is to disrupt the actin filaments. © 2003 Wiley‐Liss, Inc.
Altered gene expression in frontal cortex and midbrain of 3,4‐methylenedioxymethamphetamine (MDMA) treated mice: Differential regulation of GABA transporter subtypes
Authors: Peng Weiping , Simantov Rabi 
Published: March 2003

AbstractChanges in gene expression were examined in the brain of mice treated with a drug of abuse, 3,4‐methylenedioxymethamphetamine (MDMA, also called Ecstasy). Frontal cortex and midbrain mRNA, analyzed by differential display polymerase chain reaction (DD‐PCR) method, showed an altered expression of several cDNAs, 11 of which were isolated, cloned and sequenced. The sequence of one MDMA‐induced mRNA corresponds (99.3%) to the mouse γ‐amino butyric acid (GABA) transporter 1 (mGAT1). The established involvement of GABA neurotransmission in the activity of several abused drugs prompted us to focus herein on MDMA effect on the GABA transporter gene family. Semi‐quantitative PCR analysis with primers selective to the reported mGAT1 sequence confirmed that MDMA treatment increased mGAT1 expression. Time‐course study of the expression of the three GABA transporter subtypes showed that MDMA induced a differential temporal activation of mGAT1 and mGAT4, but had no effect on mGAT2. Quantitative real‐time PCR further proved the increased expression of mGAT1 and mGAT4 upon MDMA treatment. Western immunoblotting with anti‐GAT1 antibodies showed that MDMA also increased GAT1 protein levels, suggesting that neurotransmission of GABA was altered. MDMA effect was also verified in serotonin transporter knockout (−/−) mice that are insensitive behaviorally to MDMA; the drug did not increase GAT1 protein level in these mutants. In mice, tiagabine and NO‐711, inhibitors of GABA transporters, restrained MDMA‐induced acute toxicity and death. These results should facilitate novel approaches to prevent deleterious effects, including fatality, induced by MDMA and similar abused psychostimulants. © 2003 Wiley‐Liss, Inc.
Modulation of perch connexin35 hemi‐channels by cyclic AMP requires a protein kinase A phosphorylation site
Authors: Mitropoulou Georgia , Bruzzone Roberto 
Published: March 2003

AbstractRetinal neurons are coupled via gap junctions, which function as electrical synapses that are gated by ambient light conditions. Gap junctions connecting either horizontal cells or AII amacrine cells are inhibited by the neurotransmitter dopamine, via the activation of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway. Fish connexin35 (Cx35) and its mouse ortholog, Cx36, are good candidates to undergo dopaminergic modulation, because they have been detected in the inner plexiform layer of the retina, where Type II amacrine cells establish synaptic contacts. We have taken advantage of the ability of certain connexins to form functional connexons (hemi‐channels), when expressed in Xenopus oocytes, to investigate whether pharmacological elevation of cAMP modulates voltage‐activated hemi‐channel currents in single oocytes. Injection of perch Cx35 RNA into Xenopus oocytes induced outward voltage‐dependent currents that were recorded at positive membrane potentials. Incubation of oocytes with 8‐bromoadenosine 3′,5′‐cyclic monophosphate (8‐Br‐cAMP), a membrane permeable cAMP analog, resulted in a dose‐dependent and reversible inhibition of hemi‐channel currents at the more positive voltage steps. In contrast, treatment with 8‐Br‐cAMP did not have any effect on hemi‐channel currents induced by skate Cx35. Amino acid sequence comparison of the two fish connexins revealed, in the middle cytoplasmic loop of perch Cx35, the presence of a PKA consensus sequence that was absent in the skate connexin. The results obtained with two constructs in which the putative PKA phosphorylation site was either suppressed (perch Cx35R108Q) or introduced (skate Cx35Q108R) indicate that it is responsible for the inhibition of hemi‐channel currents. These studies demonstrate that perch Cx35 is a target of the cAMP/PKA signaling pathway and identify a consensus PKA phosphorylation site that is required for channel gating. © 2003 Wiley‐Liss, Inc.
Influence of the frequency parameter on extracellular glutamate and γ‐aminobutyric acid in substantia nigra and globus pallidus during electrical stimulation of subthalamic nucleus in rats
Authors: Windels François , Bruet Nicolas , Poupard Annie , Feuerstein Claude , Bertrand Anne , Savasta Marc 
Published: March 2003

AbstractHigh‐frequency stimulation (HFS) of the subthalamic nucleus (STN) proves to be an efficient treatment for alleviating motor symptoms in Parkinson's disease (PD). However, the mechanisms of HFS underlying these clinical effects remain unknown. Using intracerebral microdialysis, we previously reported that HFS induces, in normal rats, a significant increase of extracellular glutamate (Glu) in the globus pallidus (GP in rats or GPe in primates) and the substantia nigra pars reticulata (SNr), whereas γ‐aminobutyric acid (GABA) was increased only in the SNr. Bradykinesia can be improved by STN stimulation in a frequency‐dependent manner, a plateau being reached around 130 Hz. The aim of the present study was to determine whether neurochemical changes are also frequency dependent. Electrical STN stimulation was applied at various frequencies (10, 60, 130, and 350 Hz) in normal rats. The results show that, for Glu, the amplitude of increase detected in GP and SNr is maximal at 130 Hz and is maintained at 350 Hz. No modifications of GABA were observed in GP whatever the frequency applied, whereas, in SNr, GABA increased from 60 to 350 Hz. Our results provide new neurochemical data implicating STN target structures in deep‐brain‐stimulation mechanisms. © 2003 Wiley‐Liss, Inc.
NFAT4 is expressed in primary astrocytes and activated by glutamate
Authors: Jones Elizabeth A. , Sun Doug , Kobierski Linda , Symes Aviva J. 
Published: March 2003

AbstractCalcium signaling is a critical component of astrocyte activation but little information is available regarding the identity and function of transcriptional targets of calcium signaling in these cells. As a first step in elucidating the mechanisms that astrocytes use to regulate transcription in response to raised intracellular calcium concentrations, we have investigated expression and activation of the calcium activated transcription factors of the NFAT family. We report here that NFAT4 is expressed in U373 astrocytoma cells and in primary cultures of astrocytes. Treatment of U373 cells or primary astrocytes with the calcium ionophore A23187, or the neurotransmitter glutamate, leads to NFAT nuclear translocation and increased DNA binding to a NFAT consensus site through a cyclosporin A‐sensitive process. These data suggest that NFAT4 functions as a calcium‐responsive transcription factor in astrocytes. Published 2003 Wiley‐Liss, Inc.