bluuebunny/crossref_metadata_2025 huggingface dataset:
An Unusually Low Microsatellite Mutation Rate in Dictyostelium discoideum, an Organism With Unusually Abundant Microsatellites
Authors: McConnell Ryan , Middlemist Sara , Scala Clea , Strassmann Joan E , Queller David C
Published: October 2007

The genome of the social amoeba Dictyostelium discoideum is known to have a very high density of microsatellite repeats, including thousands of triplet microsatellite repeats in coding regions that apparently code for long runs of single amino acids. We used a mutation accumulation study to see if unusually high microsatellite mutation rates contribute to this pattern. There was a modest bias toward mutations that increase repeat number, but because upward mutations were smaller than downward ones, this did not lead to a net average increase in size. Longer microsatellites had higher mutation rates than shorter ones, but did not show greater directional bias. The most striking finding is that the overall mutation rate is the lowest reported for microsatellites: ∼1 × 10−6 for 10 dinucleotide loci and 6 × 10−6 for 52 trinucleotide loci (which were longer). High microsatellite mutation rates therefore do not explain the high incidence of microsatellites. The causal relation may in fact be reversed, with low mutation rates evolving to protect against deleterious fitness effects of mutation at the numerous microsatellites.
Detection of Quantitative Trait Loci Influencing Recombination Using Recombinant Inbred Lines
Authors: Dole Jefferey , Weber David F
Published: October 2007

The genetic basis of variation in recombination in higher plants is polygenic and poorly understood, despite its theoretical and practical importance. Here a method of detecting quantitative trait loci (QTL) influencing recombination in recombinant inbred lines (RILs) is proposed that relies upon the fact that genotype data within RILs carry the signature of past recombination. Behavior of the segregational genetic variance in numbers of chromosomal crossovers (recombination) over generations is described for self-, full-sib-, and half-sib-generated RILs with no dominance in true crossovers. This genetic variance, which as a fraction of the total phenotypic variance contributes to the statistical power of the method, was asymptotically greatest with half sibbing, less with sibbing, and least with selfing. The statistical power to detect a recombination QTL declined with diminishing QTL effect, genome target size, and marker density. For reasonably tight marker linkage power was greater with less intense inbreeding for later generations and vice versa for early generations. Generational optima for segregation variance and statistical power were found, whose onset and narrowness varied with marker density and mating design, being more pronounced for looser marker linkage. Application of this method to a maize RIL population derived from inbred lines Mo17 and B73 and developed by selfing suggested two putative QTL (LOD > 2.4) affecting certain chromosomes, and using a canonical transformation another putative QTL was detected. However, permutation tests failed to support their presence (experimentwise α = 0.05). Other populations with more statistical power and chosen specifically for recombination QTL segregation would be more effective.
Quantitative Trait Loci for the Circadian Clock in Neurospora crassa
Authors: Kim Tae-Sung , Logsdon Benjamin A , Park Sohyun , Mezey Jason G , Lee Kwangwon
Published: October 2007

Neurospora crassa has been a model organism for the study of circadian clocks for the past four decades. Among natural accessions of Neurospora crassa, there is significant variation in clock phenotypes. In an attempt to investigate natural allelic variants contributing to quantitative variation, we used a quantitative trait loci mapping approach to analyze three independent mapping populations whose progenitors were collected from geographically isolated locations. Two circadian clock phenotypes, free-running period and entrained phase, were evaluated in the 188 F1 progeny of each mapping population. To identify the clock QTL, we applied two QTL mapping analyses: composite interval mapping (CIM) and Bayesian multiple QTL analysis (BMQ). When controlling false positive rates ≤0.05, BMQ appears to be the more sensitive of the two approaches. BMQ confirmed most of the QTL from CIM (18 QTL) and identified 23 additional QTL. While 13 QTL colocalize with previously identified clock genes, we identified 30 QTL that were not linked with any previously characterized clock genes. These are candidate regions where clock genes may be located and are expected to lead to new insights in clock regulation.
Revisiting the X:A Signal That Specifies Caenorhabditis elegans Sexual Fate
Authors: Gladden John M , Farboud Behnom , Meyer Barbara J
Published: October 2007

In Caenorhabditis elegans, sex is determined by the opposing actions of X-signal elements (XSEs) and autosomal signal elements (ASEs), which communicate the ratio of X chromosomes to sets of autosomes (X:A signal). This study delves more deeply into the mechanism by which XSEs transmit X chromosome dose. We determined the relative contributions of individual XSEs to the X:A signal and showed the order of XSE strength to be sex-1 > sex-2 > fox-1 > ceh-39 ≥ region 1 XSE. sex-1 exerts a more potent influence on sex determination and dosage compensation than any other XSE by functioning in two separate capacities in the pathway: sex-1 acts upstream as an XSE to repress xol-1 and downstream as an activator of hermaphrodite development and dosage compensation. Furthermore, the process of dosage compensation affects expression of the very XSEs that control it; XSEs become fully dosage compensated once sex is determined. The X:A signal is then equivalent between XO and XX animals, causing sexual differentiation to be controlled by genes downstream of xol-1 in the sex-determination pathway. Prior to the onset of dosage compensation, the difference in XSE expression between XX and XO embryos appears to be greater than twofold, making X chromosome counting a robust process.
The Role of Stn1p inSaccharomyces cerevisiaeTelomere Capping Can Be Separated From Its Interaction With Cdc13p
Authors: Petreaca Ruben C , Chiu Huan-Chih , Nugent Constance I
Published: October 2007

The function of telomeres is twofold: to facilitate complete chromosome replication and to protect chromosome ends against fusions and illegitimate recombination. In the budding yeast Saccharomyces cerevisiae, interactions among Cdc13p, Stn1p, and Ten1p are thought to be critical for promoting these processes. We have identified distinct Stn1p domains that mediate interaction with either Ten1p or Cdc13p, allowing analysis of whether the interaction between Cdc13p and Stn1p is indeed essential for telomere capping or length regulation. Consistent with the model that the Stn1p essential function is to promote telomere end protection through Cdc13p, stn1 alleles that truncate the C-terminal 123 residues fail to interact with Cdc13p and do not support viability when expressed at endogenous levels. Remarkably, more extensive deletions that remove an additional 185 C-terminal residues from Stn1p now allow cell growth at endogenous expression levels. The viability of these stn1-t alleles improves with increasing expression level, indicating that increased stn1-t dosage can compensate for the loss of Cdc13p–Stn1p interaction. However, telomere length is misregulated at all expression levels. Thus, an amino-terminal region of Stn1p is sufficient for its essential function, while a central region of Stn1p either negatively regulates the STN1 essential function or destabilizes the mutant Stn1 protein.
Developmental and Cell Cycle Progression Defects in Drosophila Hybrid Males
Authors: Bolkan Bonnie J , Booker Ronald , Goldberg Michael L , Barbash Daniel A
Published: October 2007

Matings between D. melanogaster females and males of sibling species in the D. melanogaster complex yield hybrid males that die prior to pupal differentiation. We have reexamined a previous report suggesting that the developmental defects in these lethal hybrid males reflect a failure in cell proliferation that may be the consequence of problems in mitotic chromosome condensation. We also observed a failure in cell proliferation, but find in contrast that the frequencies of mitotic figures and of nuclei staining for the mitotic marker phosphohistone H3 in the brains of hybrid male larvae are extremely low. We also found that very few of these brain cells in male hybrids are in S phase, as determined by BrdU incorporation. These data suggest that cells in hybrid males are arrested in either the G1 or G2 phases of the cell cycle. The cells in hybrid male brains appear to be particularly sensitive to environmental stress; our results indicate that certain in vitro incubation conditions induce widespread cellular necrosis in these brains, causing an abnormal nuclear morphology noted by previous investigators. We also document that hybrid larvae develop very slowly, particularly during the second larval instar. Finally, we found that the frequency of mitotic figures in hybrid male larvae mutant for Hybrid male rescue (Hmr) is increased relative to lethal hybrid males, although not to wild-type levels, and that chromosome morphology in Hmr− hybrid males is also not completely normal.
Accelerated Rate of Gene Gain and Loss in Primates
Authors: Hahn Matthew W , Demuth Jeffery P , Han Sang-Gook
Published: October 2007

The molecular changes responsible for the evolution of modern humans have primarily been discussed in terms of individual nucleotide substitutions in regulatory or protein coding sequences. However, rates of nucleotide substitution are slowed in primates, and thus humans and chimpanzees are highly similar at the nucleotide level. We find that a third source of molecular evolution, gene gain and loss, is accelerated in primates relative to other mammals. Using a novel method that allows estimation of rate heterogeneity among lineages, we find that the rate of gene turnover in humans is more than 2.5 times faster than in other mammals and may be due to both mutational and selective forces. By reconciling the gene trees for all of the gene families included in the analysis, we are able to independently verify the numbers of inferred duplications. We also use two methods based on the genome assembly of rhesus macaque to further verify our results. Our analyses identify several gene families that have expanded or contracted more rapidly than is expected even after accounting for an overall rate acceleration in primates, including brain-related families that have more than doubled in size in humans. Many of the families showing large expansions also show evidence for positive selection on their nucleotide sequences, suggesting that selection has been important in shaping copy-number differences among mammals. These findings may help explain why humans and chimpanzees show high similarity between orthologous nucleotides yet great morphological and behavioral differences.
Major Regulatory Genes in Maize Contribute to Standing Variation in Teosinte (Zea mays ssp. parviglumis)
Authors: Weber Allison , Clark Richard M , Vaughn Laura , de Jesús Sánchez-Gonzalez José , Yu Jianming , Yandell Brian S , Bradbury Peter , Doebley John
Published: October 2007

In plants, many major regulatory genes that control plant growth and development have been identified and characterized. Despite a detailed knowledge of the function of these genes little is known about how they contribute to the natural variation for complex traits. To determine whether major regulatory genes of maize contribute to standing variation in Balsas teosinte we conducted association mapping in 584 Balsas teosinte individuals. We tested 48 markers from nine candidate regulatory genes against 13 traits for plant and inflorescence architecture. We identified significant associations using a mixed linear model that controls for multiple levels of relatedness. Ten associations involving five candidate genes were significant after correction for multiple testing, and two survive the conservative Bonferroni correction. zfl2, the maize homolog of FLORICAULA of Antirrhinum, was associated with plant height. zap1, the maize homolog of APETALA1 of Arabidopsis, was associated with inflorescence branching. Five SNPs in the maize domestication gene, teosinte branched1, were significantly associated with either plant or inflorescence architecture. Our data suggest that major regulatory genes in maize do play a role in the natural variation for complex traits in teosinte and that some of the minor variants we identified may have been targets of selection during domestication.
Selection Against Demographic Stochasticity in Age-Structured Populations
Authors: Shpak Max
Published: October 2007

It has been shown that differences in fecundity variance can influence the probability of invasion of a genotype in a population; i.e., a genotype with lower variance in offspring number can be favored in finite populations even if it has a somewhat lower mean fitness than a competitor. In this article, Gillespie's results are extended to population genetic systems with explicit age structure, where the demographic variance (variance in growth rate) calculated in the work of Engen and colleagues is used as a generalization of “variance in offspring number” to predict the interaction between deterministic and random forces driving change in allele frequency. By calculating the variance from the life-history parameters, it is shown that selection against variance in the growth rate will favor a genotypes with lower stochasticity in age-specific survival and fertility rates. A diffusion approximation for selection and drift in a population with two genotypes with different life-history matrices (and therefore different mean growth rates and demographic variances) is derived and shown to be consistent with individual-based simulations. It is also argued that for finite populations, perturbation analyses of both the mean and the variance in growth rate may be necessary to determine the sensitivity of fitness to changes in the life-history parameters.
Evolution and Horizontal Transfer of a DD37E DNA Transposon in Mosquitoes
Authors: Biedler James K , Shao Hongguang , Tu Zhijian
Published: October 2007

ITmD37E, a unique class II transposable element (TE) with an ancient origin, appears to have been involved in multiple horizontal transfers in mosquitoes as ITmD37E sequences from 10 mosquito species of five genera share high nucleotide (nt) identities. For example, ITmD37E sequences from Aedes aegypti and Anopheles gambiae, which have an estimated common ancestor of 145–200 million years ago, display 92% nt identity. The comparison of ITmD37E and host mosquito phylogenies shows a lack of congruence. The wide distribution of conserved ITmD37Es in mosquitoes and the presence of intact copies suggest that this element may have been recently active.
Exposure to Lead of Boatyard Workers in Southern Thailand
Authors: Thanapop Chamnong , Geater Alan F. , Robson Mark G. , Phakthongsuk Pitchaya , Viroonudomphol Duangkamol
Published: October 2007

Exposure to Lead of Boatyard Workers in Southern Thailand: Chamnong Thanapop, et al. Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Thailand—Lead oxide is used extensively in the construction and repair of wooden boats in Thailand, but the behaviors of boatyard workers that could place them at risk of contamination have not previously been documented. Baseline data on practices and behaviors of boatyard workers and on the level of worker and workplace contamination with lead were therefore collected. Fifty workers in two boatyards participated in this study. Lead exposure of workers was assessed by determining airborne and blood lead levels. A questionnaire was administered to collect information on work history, suspected exogenous lead sources, personal behavior and knowledge about lead. Evidence obtained by the study indicated that safety behavior and personal hygiene were poor—workers used no mask, gloves or hood, wore open sandals, smoked, drank, chewed and ate during work and did not wash their hands before drinking or eating. Some workers had lunch in the working area. The mean personal airborne lead of caulkers (36.4 µg/m3) was higher than that of carpenters (8.3 µg/m3). Forty‐eight percent of all workers and 67% of caulkers had a blood lead level (BLL) exceeding 40 µg/dl. Multiple linear regression indicated that blood lead levels of workers were significantly related to job and education level, with significant differences between boatyards. In addition, the potential for “takehome” contamination was high; none of the workers took a shower or changed their clothes prior to going home. These results indicate a problem of lead exposure of sufficient magnitude to be a public health concern.
Differential Effects of Aging, Drinking and Exercise on Serum Cholesterol Levels Dependent on the PPARA‐V227A Polymorphism
Authors: Naito Hisao , Kamijima Michihiro , Yamanoshita Osamu , Nakahara Ai , Katoh Takahiko , Tanaka Naoki , Aoyama Toshifumi , Gonzalez Frank J. , Nakajima Tamie
Published: October 2007

Differential Effects of Aging, Drinking and Exercise on Serum Cholesterol Levels Dependent on the PPARA‐V227A Polymorphism: Hisao Naito, et al. Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine—Peroxisome proliferator‐activated receptor α (PPAR α) plays a pivotal role in lipid metabolism. Our previous study reported that PPARA‐V227A was a major polymorphism in Japanese, which was associated with markedly lower serum total cholesterol (TC) levels, which were significantly affected by alcohol drinking compared to subjects with the wild‐type (PPARA‐WT) allele. However, serum lipids are also associated with aging and exercise frequency. The objective of the present study was to evaluate the relationship between PPARA‐V227A and these factors. Genetic analysis of the polymorphism was performed in 1058 Japanese men and 281 women, and the relationship with aging, drinking and exercise on serum lipids was analyzed in 989 men and 245 women after exclusion criteria had been applied. In men, drinking increased high‐density lipoprotein cholesterol (HDL‐C) levels in both PPARA‐WT and A227 carriers, but to a significantly higher degree in the latter. In women, TC and low‐density lipoprotein cholesterol (LDL‐C) levels in the A227 carriers drinking at least once a week were significantly higher than in PPARA‐WT carriers. TC and LDL‐C levels in males with PPARA‐WT increased with aging regardless of drinking habit, while LDL‐C levels in the A227 drinking carriers were significantly lower in 45yr‐old or older subjects than in 35‐ to 45‐yr‐olds. In addition, no effect of exercising was observed in the A227 carriers, while increase in the HDL‐C of the PPARA‐WT carriers was exercise frequency dependent. These results suggest that the influence of drinking, aging or exercise on TC, LDL‐C and HDL‐C levels in the A227 carriers may be different from those in the PPARA‐WT subjects.
The Association of the Reporting of Somatic Symptoms with Job Stress and Active Coping among Japanese White‐collar Workers
Authors: Nomura Kyoko , Nakao Mutsuhiro , Sato Mikiya , Ishikawa Hirono , Yano Eiji
Published: October 2007

The Association of the Reporting of Somatic Symptoms with Job Stress and Active Coping among Japanese White‐collar Workers: Kyoko Nomura, et al. Department of Hygiene and Public Health, Teikyo University School of Medicine—To assess the associations between job stress and somatic symptoms and to investigate the effect of individual coping on these associations. In July 2006, a cross‐sectional study was conducted during a periodic health check‐up of 185 Japanese male office workers (21–66 yr old) at a Japanese company. Job stress was measured by job demand, control, and strain (=job demand/control) based on the Job Content Questionnaire (JCQ). Major somatic symptoms studied were headache, dizziness, shoulder stiffness, back pain, shortness of breath, abdominal pain, general fatigue, sleep disturbance, and skin itching. Five kinds of coping were measured using the Job Stress Scale: active coping, escape, support seeking, reconciliation, and emotional suppression. Comorbidities of hypertension, diabetes, obesity, depression, and anxiety were also evaluated. The most frequently cited somatic symptom was general fatigue (66%), followed by shoulder stiffness (63%) and sleep disturbance (53%). Of the five kinds of coping, only “active coping” was significantly and negatively associated with the number of somatic symptoms. The generalized linear models showed that the number of somatic symptoms increased as job strain index (p=0.001) and job demand (p=0.001) became higher, and decreased as active coping (p=0.018) increased, after adjusting for age and comorbidities. There was no statistical interaction among active coping, the number of somatic symptoms, and the three JCQ scales. Reporting somatic symptoms may be a simple indicator of job stress, and active coping could be used to alleviate somatization induced by job stress.
Degree of Agreement between Weight Perception and Body Mass Index of Japanese Workers: MY Health Up Study
Authors: Inoue Mariko , Toyokawa Satoshi , Miyoshi Yuji , Miyano Yukie , Suzuki Toshiko , Suyama Yasuo , Inoue Kazuo , Kobayashi Yasuki
Published: October 2007

Degree of Agreement between Weight Perception and Body Mass Index of Japanese Workers: MY Health Up Study: Mariko Inoue, et al. Department of Public Health, Graduate School of Medicine, University of Tokyo—The objective of this study was to assess the degree of agreement between body mass index (BMI) and weight perception of Japanese office workers between the ages of 20 and 65. We sent 43,064 self‐administered health‐related questionnaires to all employees of a financial firm in Japan in October 2004. The questionnaire asked the respondents for their height, weight, and their weight perception. The kappa coefficient was calculated to investigate the degree of agreement between the BMI calculated using the self‐reported data and weight perception for three categories. Of the questionnaires, 34,921 (81.1%) were returned and 33,514 responses (77.8%) were used for the analysis. Based on Japanese obesity criteria, 2,202 men (31.2%) and 5,145 women (19.5%) were obese; and 179 men (2.5%) and 2,769 women (10.5%) were underweight. The kappa coefficient was 0.374 for men and 0.297 for women. The kappa coefficients for different age groups—twenties, thirties, forties, fifties, and sixties (up to 65)—were respectively as follows: 0.315, 0.355, 0.374, 0.406, and 0.425 for men; and 0.194, 0.275, 0.285, 0.334, and 0.355 for women. In conclusion, the degree of agreement between BMI and weight perception differed by age and sex. The degree of agreement was smaller among women than among men and the degree of agreement among younger women was weaker than among older women.
A Prospective Cohort Study of Perceived Noise Exposure at Work and Cerebrovascular Diseases among Male Workers in Japan
Authors: Fujino Yoshihisa , Iso Hiroyasu , Tamakoshi Akiko ,   JACC study Group
Published: October 2007

A Prospective Cohort Study of Perceived Noise Exposure at Work and Cerebrovascular Diseases among Male Workers in Japan: Yoshihisa Fujino,et al. Department of Preventive Medicine and Community Health, University of Occupational and Environmental Health, Japan—This study prospectively examined the association between perceived noise exposure at work and cerebrovascular diseases among Japanese male workers. A baseline survey was conducted between 1988 and 1990, which involved 110,792 inhabitants (age range: 40–79 yr) from 45 areas throughout Japan. Subsequent causes of death were identified from death certificates. The analysis was restricted to 14,568 men free of a cerebrovascular diseases (age range: 40–59 yr) who were in work at the time of the baseline survey. All subjects completed a self‐administered questionnaire at the baseline. This included a question regarding perceived noise exposure at work. The Cox proportional‐hazards model was used to estimate the risks of perceived noise exposure for death due to cerebrovascular diseases. The model included age, smoking, alcohol consumption, educational level, perceived mental stress, past medical history, body mass index, hours of walking, hours of exercise, shift work, and job type. During the 190,777 person‐years of follow‐up, a total of 1,064 deaths were recorded, 98 from cerebrovascular diseases, 27 deaths from subarachnoid haemorrhage, 35 deaths from intracerebral haemorrhage, and 25 deaths from cerebral infarction. Noise exposure did not increase the risk of cerebrovascular diseases, subarachnoid haemorrhage, or cerebral infarction. However, perceived noise exposure increased the risk of intracerebral haemorrhage diseases (hazard ratio (HR)=2.38, 95%CI: 1.20, 4.71,p=0.013). Furthermore, individuals with hypertension were highly susceptible to the effect of perceived noise exposure on the risk of intracerebral hemorrhage, but this association was not observed among the subjects without hypertension. Although the underlying mechanisms are not clear, hypertensive individuals with perceived noise exposure at work should be regarded as a high‐risk group for intracerebral hemorrhage.
Oxidative DNA Damage Estimated by Plasma 8‐hydroxydeoxyguanosine (8‐OHdG): Influence of 4, 4'‐methylenebis (2‐chloroaniline) Exposure and Smoking
Authors: Chen Hong‐I , Liou Saou‐Hsing , Ho Shu‐Fen , Wu Kuen‐Yuh , Sun Chien‐Wen , Chen Ming‐Fong , Cheng Li‐Chuan , Shih Tung‐Sheng , Loh Ching‐Hui
Published: October 2007

Oxidative DNA Damage Estimated by Plasma 8‐hydroxydeoxyguanosine (8‐OHdG): Influence of 4, 4'‐methylenebis (2‐chloroaniline) Exposure and Smoking: Hong‐I Chen, et al. Division of Urology, Department of Surgery, Tri‐Service General Hospital, Taiwan, R.O.C—Oxidative DNA damage may play an important role in the human carcinogenic process. Recently, we reported a case of bladder cancer among 4, 4’‐methylenebis (2‐chloroaniline) (MBOCA)‐exposed workers. By measuring the plasma level of 8‐hydroxydeoxyguanosine (8‐OHdG), we investigated the association between oxidative DNA damage and MBOCA exposure. In addition, we examined the effects of different confounders on the plasma level of 8‐OHdG. We undertook a cross‐sectional survey at four MBOCA‐producing factories in Taiwan (158 subjects). Plasma 8‐OHdG levels and urinary MBOCA concentrations were measured by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). Personal characteristics were collected by questionnaire. The workers were classified according to their job titles as exposed (n=57) or unexposed (n=101) groups as well as classified according to urinary MBOCA levels as high urinary MBOCA (>20 µg/g creatinine) (n=45) or low urinary MBOCA (n=108) groups. Neither the MBOCA‐exposed workers nor the high urinary MBOCA workers had a significant increase in the mean plasma 8‐OHdG level, even after adjustment for potential confounders. Age and gender were significantly positively correlated with plasma 8‐OHdG levels. Smokers among high urinary MBOCA workers also had significantly higher 8‐OHdG levels than non‐smokers among high urinary MBOCA workers. Our study provides evidence that smoking rather than MBOCA exposure induces elevation of plasma 8‐OHdG levels among workers exposed to MBOCA, indicating that oxidative DNA damage does not play an important role in the carcinogenic processes of MBOCA.
The Effectiveness of a Training Program on Reducing Needlestick Injuries/Sharp Object Injuries among Soon Graduate Vocational Nursing School Students in Southern Taiwan
Authors: Yang Ya‐Hui , Liou Saou‐Hsing , Chen Chiou‐Jong , Yang Chun‐Yuh , Wang Chao‐Ling , Chen Chiu‐Ying , Wu Trong‐Neng
Published: October 2007

The Effectiveness of a Training Program on Reducing Needlestick Injuries/Sharp Object Injuries among Soon Graduate Vocational Nursing School Students in Southern Taiwan: Ya‐Hui Yang, et al. Institute of Occupational Safety and Health, Kaohsiung Medical University, Taiwan—Needlestick/ sharp injuries (NSIs/SIs) are a serious threat to medical/ nursing students in hospital internships. Education for preventing NSIs/SIs is important for healthcare workers but is rarely conducted and evaluated among vocational school nursing students. We conducted an educational intervention for such students after their internship rotations before graduation. This program consisted of a lecture to the students after the internship training and a self‐study brochure for them to study before their graduation. This study used the pre‐test questionnaires completed by all students and the post‐test questionnaires completed by 107 graduates after work experience as licensed nurses to assess the effectiveness of the intervention. After educational intervention, the incidence of NSIs/SIs decreased significantly from 50.5% pre‐test to 25.2% post‐test, and the report rate increased from 37.0% to 55.6%, respectively. In conclusion, this intervention significantly reduced the incidence of NSIs/SIs and increased the report rate of such events.
Cornelius Nepos király-életrajzai?
Authors: Szabó Ferenc Krisztián
Published: October 2007

A Regesszel(XXI) kapcsolatban megjelent elemzések részben bizonytalan,
részben téves követ_0
Rehabilitative training program for end-stage renal disease patients
Authors: Apor Péter
Published: October 2007

A 4–5. (vég-)stádiumú és transzplantált vesebetegek izomereje, állóképessége, cardiovascularis kockázati tényezői, életminősége és a dialízishatásfoka is jelentősen javul a heti 3 × 30–60 perces, 45–60%-os intenzitású testmozgás során, amelyet többnyire a dialízis alatt végez a beteg. A korlátozó tényezők és ellenjavallatok figyelembevételével a vesebetegek többsége számára is kínálni kellene a rehabilitációs programokat.
The objective assessment of the quality of hospital care: dream or reality?
Authors: Belicza Éva , Takács Erika
Published: October 2007

A nemzetközi szakirodalom egyre gyakrabban foglalkozik azzal a kérdéssel, hogy a minőségi indikátorokra támaszkodó nyilvános minőségértékelésnek mi a hatása az ellátás minőségére és az érintettek döntésére vonatkozóan, illetve melyek azok a kritériumok, amelyek mentén nyilvános minőségértékelési rendszereket célszerű kialakítani. A nemzetközi szakirodalom alapján a dolgozat hat témakört mutat be: (1) az indikátorok képessége a szolgáltatók megkülönböztetésére; (2) az eredményindikátorok alkalmassága a szolgáltatók megítélésére; (3) a bajnoki tabellák képessége a szolgáltatók rangsorolására; (4) a lakosság viselkedése a szolgáltatók választása során; (5) az indikátorokra támaszkodó nyilvános minősítések hatásai; (6) ajánlások minősítési rendszerek kidolgozására. A szakirodalmi kutatások szerint elsősorban a kockázatkiegyenlítési problémák miatt az indikátorok képessége a szolgáltatók megkülönböztetésére a nyújtott ellátás minősége szempontjából kérdéses; az elért ellátási eredmények nem feltétlenül utalnak vissza az ellátási folyamatok minőségére; a több indikátorból komponált intézményi sorrendek (bajnoki tabellák) nem megbízhatóak; a lakosság a szolgáltatók kiválasztásakor elsősorban a környezet véleményét és a távolságot veszi figyelembe; és a nyilvános közlések hatására igazoltan romlik az ellátás átfogó minősége. A szolgáltatók értékelésében alkalmazott mérési eredmények közzétételét eszköznek kell tekinteni. A lakosság intézményválasztásának elősegítésére az ő preferenciáik mentén végzett betegelégedettségi vizsgálatok nyilvánossá tétele hozhatja meg a kívánt eredményt. A minőségfejlesztési célokat igazoltan segítik a szolgáltatói körben végzett közvetlen visszajelzések az indikátorok mért értékeiről, illetve pontosabb kép kapható az ellátási és szervezési folyamatok, standardok egységes felülvizsgálatára alapozott eljárások külső értékelési rendszerekbe történő beemelésével.
Current thoughts on psychosexual disorders in women
Authors: Coulson Catherine , Crowley Tessa
Published: October 2007

Key content

The importance of responsive desire in women, triggered by physical and mental arousal rather than spontaneous desire, is now acknowledged.

A review of the DSM‐IV classification of sexual dysfunction in 1999 led to retention of the categories of desire, arousal, orgasmic and pain disorder and were expanded to include physical, as well as psychological, causes. A new diagnosis of non‐coital pain disorder was also suggested.

Historically, pain syndromes are categorised as dyspareunia or vaginismus, but they often overlap.

Management of psychosexual disorders requires an understanding of psychosexual function and an ability to communicate about sexual matters.

Learning objectives

To gain an understanding of the complexities of the female sexual response and psychosexual problems.

To understand that sexual problems are common in women attending gynaecology clinics.

To be more willing to communicate with patients about sexual matters.

Ethical issues

The sensitive nature of sexual problems raises the dilemma of how to talk to women about significant events without causing further trauma.

Please cite this article as: Coulson C, Crowley T. Current thoughts on psychosexual disorders in women.The Obstetrician & Gynaecologist2007;9:217–222.
Sentinel node mapping
Authors: Acheson Nigel
Published: October 2007

Key content

Cancers involving the regional lymphatic system around the primary site have a poor prognosis.

The sentinel node is understood to be the first node to which lymphatic drainage occurs from an organ or area of skin.

The sentinel node can be identified using a blue dye or radiolabel.

If the sentinel node does not contain metastatic tumour, the risk of involved regional nodes is small.

The technique has the potential to reduce the morbidity associated with regional lymphadenectomy.

Learning objectives

To understand the sentinel node concept.

To understand the role of sentinel node biopsy in vulval, cervical and endometrial cancer.

Ethical issues

Randomised controlled trials should be performed before the technique can be introduced into routine practice.

Please cite this article as: Acheson N. Sentinel node mapping. The Obstetrician & Gynaecologist 2007;9:270–275.
Expression and role of estrogen receptor α and β in medullary thyroid carcinoma: different roles in cancer growth and apoptosis
Authors: Cho Mi Ae , Lee Mi Kyung , Nam Kee-Hyun , Chung Woung Youn , Park Cheong Soo , Lee Ju Hyeong , Noh Taewoong , Yang Woo Ick , Rhee Yumie , Lim Sung-Kil , Lee Hyun Chul , Lee Eun Jig
Published: October 2007

Medullary thyroid carcinoma (MTC) originates from parafollicular C cells. Estrogen receptor β(ERβ) expressionwas detected in normal parafollicular C cells and MTC tumor tissue, but ERα expression in MTC tumors still remains undetermined. The appearance and loss of ERα or ERβ expression has been known to play a role in the development and progression of many human cancers. We performed immunohistochemical studies of ERα, ERβ, and Ki67, a mitotic index, in 11 human MTC tissue samples. ERα was detected in 10 cases (91%), and ERβ expression was observed in 8 cases (72.7%). A majority (8/10) of ERα-positive tumors showing ERβ Ki67 expression was detected in three cases (27.3%). Neither clinical parameters nor tumor node metastasis (TNM) tumor staging was correlated with the positivity for ERs or Ki67. To investigate the biological role of each ER, we used ER-negative MTC TT cells and adenoviral vectors carrying ERα (Ad-ERα), ERβ (Ad-ERβ), estrogen response element (ERE)-Luc (Ad-ERE-Luc), and activator protein 1 (AP1)-Luc (Ad-AP1-Luc). Estrogen stimulated and anti-estrogen, ICI 182 780, suppressed ERE reporter activity in TT cells expressing ERα or ERβ, suggesting that both ERs use the same classical ERE-mediated pathway. Ad-ERα infection stimulated TT cell growth; in contrast, Ad-ERβ infection suppressed their growth. Apoptosis was detected in Ad-ERβ-infected TT cells. Estrogen and anti-estrogen suppressed AP1 activity in Ad-ERα-infected cells, whereas upon Ad-ERβ infection estrogen further stimulated AP1 activity which in turn is suppressed by anti-estrogen, suggesting that each ER acts differently through a non-ERE-mediated pathway. Our results suggest that ERα and ERβ may play different roles in MTC tumor growth and progression.
Salicylate prevents hepatic insulin resistance caused by short-term elevation of free fatty acids in vivo
Authors: Park Edward , Wong Victor , Guan Xinyu , Oprescu Andrei I , Giacca Adria
Published: October 2007

Recent evidence indicates that inflammatory pathways are causally involved in insulin resistance. In particular, Iκ Bα kinase β (IKKβ ), which can impair insulin signaling directly via serine phosphorylation of insulin receptor substrates (IRS) and/or indirectly via induction of transcription of proinflammatory mediators, has been implicated in free fatty acid (FFA)-induced insulin resistance in skeletal muscle. However, it is unclear whether liver IKKβ activation plays a causal role in hepatic insulin resistance caused by acutely elevated FFA. In the present study, we wished to test the hypothesis that sodium salicylate, which inhibits IKKβ , prevents hepatic insulin resistance caused by short-term elevation of FFA. To do this, overnight-fasted Wistar rats were subject to 7-h i.v. infusion of either saline or Intralipid plus 20 U/ml heparin (IH; triglyceride emulsion that elevates FFA levels in vivo) with or without salicylate. Hyperinsulinemic–euglycemic clamp with tracer infusion was performed to assess insulin-induced stimulation of peripheral glucose utilization and suppression of endogenous glucose production (EGP). Infusion of IH markedly decreased (P < 0.05) insulin-induced stimulation of peripheral glucose utilization and suppression of EGP, which were completely prevented by salicylate co-infusion. Furthermore, salicylate reversed IH-induced 1) decrease in Iκ Bα content; 2) increase in serine phosphorylation of IRS-1 (Ser 307) and IRS-2 (Ser 233); 3) decrease in tyrosine phosphorylation of IRS-1 and IRS-2; and 4) decrease in serine 473-phosphorylated Akt in the liver. These results demonstrate that inhibition of IKKβ prevents FFA-induced impairment of hepatic insulin signaling, thus implicating IKKβ as a causal mediator of hepatic insulin resistance caused by acutely elevated plasma FFA.
Pituitary adenylate cyclase-activating polypeptide stimulates corticotropin-releasing factor, vasopressin and interleukin-6 gene transcription in hypothalamic 4B cells
Authors: Kageyama Kazunori , Hanada Komaki , Iwasaki Yasumasa , Sakihara Satoru , Nigawara Takeshi , Kasckow John , Suda Toshihiro
Published: October 2007

Corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) are the two major regulatory peptides in the hypothalamic–pituitary–adrenal axis. CRF, produced in the hypothalamic paraventricular nucleus (PVN) in response to stress, is secreted into the pituitary portal circulation, resulting in the release of adrenocorticotropic hormone from the anterior pituitary. AVP is synthesized in the PVN and supraoptic nucleus by various stressors. Hypothalamic 4B cells coexpress CRF and AVP. In 4B cells transfected with either a CRF or an AVP promoter-luciferase construct, forskolin increased the transcriptional activity of CRF or AVP. In the present study, we tried to determine whether pituitary adenylate cyclase-activating polypeptide (PACAP) regulates both CRF and AVP genes in the hypothalamic cells, because receptors for PACAP were expressed in the hypothalamic cells. PACAP stimulated activity of both CRF and AVP promoter via protein kinase A pathway. PACAP stimulated interleukin (IL)-6 promoter activity and the levels of IL-6 mRNA and protein. IL-6 stimulated activity of both CRF and AVP promoter in a dose-dependent manner. Finally, we found that the stimulatory effects of PACAP on both activities were significantly inhibited by treatment with anti-IL-6 monoclonal antibody. These data suggest that PACAP is involved in regulating the synthesis of IL-6 mRNA and IL-6 protein, and that the increase in endogenous IL-6 also contributes to stimulate the expression of both CRF and AVP genes. Taken together, these findings indicate that PACAP stimulates the transcription of CRF, AVP, and IL-6 genes in hypothalamic 4B cells.
RESP18, a homolog of the luminal domain IA-2, is found in dense core vesicles in pancreatic islet cells and is induced by high glucose
Authors: Zhang Guofeng , Hirai Hiroki , Cai Tao , Miura Junnosuke , Yu Ping , Huang Hanxia , Schiller Martin R , Swaim William D , Leapman Richard D , Notkins Abner L
Published: October 2007

The regulated endocrine-specific protein, RESP18, first found in the rat pituitary, was thought to be regulated by dopaminergic drugs. Bioinformatics studies showed that RESP18 shares sequence homology with the luminal region of IA-2, a dense core vesicle (DCV) transmembrane protein involved in insulin secretion. The present study was initiated to examine the genomic structure and subcellular localization of RESP18 and the effect of glucose on its expression. Human RESP18 was isolated from a pancreas cDNA library and its subcellular localization was determined by immunoelectron microscopy. MIN6 cells and mouse islets were used to study the effect of glucose on RESP18 expression. Bioinformatics analysis revealed that RESP18 and IA-2 are tandemly arranged within a 45 kb region on human chromosome 2 and share common intron–exon boundaries. By confocal microscopy, RESP18 was found in α, β and δ cells in the pancreatic islets. Electron microscopy revealed that RESP18 is present in the lumen of DCVs. The expression of RESP18 in β cells is markedly increased following exposure to high glucose and also elevated in the islets of diabetic, but not non-diabetic, NOD mice. We conclude that RESP18 is a luminal protein of DCVs and its expression is regulated by exposure to glucose.
Role of glucocorticoid receptor and CCAAT/enhancer-binding protein α in the feed-forward induction of 11β-hydroxysteroid dehydrogenase type 1 expression by cortisol in human amnion fibroblasts
Authors: Yang Zhen , Guo Chunming , Zhu Ping , Li Wenjiao , Myatt Leslie , Sun Kang
Published: October 2007

The amount of cortisol available to its receptors is increased by the pre-receptor enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which converts cortisone to cortisol. We examined the molecular mechanisms of the feedback effect of cortisol on 11β-HSD1 mRNA expression in human amnion fibroblasts. Our data showed that cortisol-induced 11β-HSD1 mRNA expression dose dependently in amnion fibroblasts, which could be completely blocked both by the mRNA transcription inhibitor 5,6-dichlorobenzimidazole riboside and by the glucocorticoid receptor (GR) antagonist RU486, and partially blocked by global inhibition of CCAAT/enhancer-binding proteins (C/EBPs) with transfection of C/EBP-specific dominant-negative expression CMV500 plasmid (AC/EBP) into the cells. Likewise, the induction of the promoter activity by cortisol could also be completely blocked by RU486 and partially by AC/EBP transfection. Progressive 5′ deletion of the 11β-HSD1promoter located the region responsible for cortisol’s induction within −204 bp upstream to the transcription start site. Specific nucleotide mutations of the putative glucocorticoid responsive element or CCAAT in this promoter region attenuated the induction by cortisol. Moreover, chromatin immunoprecipitation assay and electrophoretic mobility shift assay showed that GR and C/EBPα but not C/EBPβ could bind this promoter region upon cortisol stimulation of amnion fibroblasts. In conclusion, we demonstrated that GR and C/EBPα were involved in cortisol-induced 11β-HSD1 mRNA expression via binding to 11β-HSD1 promoter in amnion fibroblasts, which may cast a feed-forward production of cortisol in the fetal membranes at the end of gestation.
Regulation of prostaglandin D synthase and prostacyclin synthase in the endometrium of cyclic, pregnant, and pseudopregnant rats and their regulation by sex steroids
Authors: Kengni Junie Hurette Chansi , St-Louis Isabelle , Parent Sophie , Leblanc Valérie , Shooner Carl , Asselin Eric
Published: October 2007

Prostaglandins (PGs) are critical regulators of a number of reproductive processes. To date, the presence and regulation of PGS in the rat endometrium have not yet been described. The objective of the present study was to investigate the expression of PGD synthase (PGDS) and prostacyclin synthase (PGIS) in the endometrium. Endometrial proteins and tissues were collected from cyclic non-pregnant, pregnant, and steroid-induced pseudopregnant rats. PGIS and PGDS were detected in the endometrium of cyclic, pregnant, and pseudopregnant rats but were not influenced by the estrous cycle. During early pregnancy, PGIS was significantly higher at day 5 and was gradually decreased from day 5.5 to 6.5. Later during pregnancy, PGIS was maximal on day 12 and gradually decreased to the end of pregnancy. PGDS expression was high during early and was maximal at the end of pregnancy. During pseudopregnancy, PGDS and PGIS were increased in a time-dependent manner and were maximal at day 5. Immunohistochemical analysis revealed that PGDS and PGIS were found in luminal as well as glandular epithelial cells and in stroma during late pregnancy. We also found a significant increase of PGD2 serum metabolite at days 21 and 22 of pregnancy. During steroid-induced pseudopregnancy, PGI2 serum metabolite was increased in a time-dependent manner and was maximal at day 7. These results suggest that PGDS and PGIS are present and could be regulated by steroids in the rat uterus during pregnancy, and that the endometrium could be a significant source of PGD2 and PGI2 at specific times during pregnancy.
Biphasic Effect of Androgens on Prostate Cancer Cells and Its Correlation With Androgen Receptor Coactivator Dopa Decarboxylase
Authors: Shao Chen , Wang Yong , Yue Hong‐Hong , Zhang Yun‐Tao , Shi Chang‐Hong , Liu Fan , Bao Ting‐Yi , Yang Zeng‐Yue , Yuan Jian‐Lin , Shao Guo‐Xing
Published: October 2007

ABSTRACT: The aim of this study was to explore the mechanism underlying the dual effect of androgen on prostate cancer cells and further explore its correlation with dopa decarboxylase (DDC), an androgen receptor (AR) coactivator and a traditional neuroendocrine differentiation (NED) marker. Cell proliferation and cycling after treatment with synthetic nonmetabolizable androgen R1881 was determined by the MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide) method and flow cytometry. Differential gene expression was analyzed by cDNA microarrays. DDC expression during the dual effect of R1881 was further explored with microarray, quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR), Western blot, and enzyme activity assays. Proliferation of LNCaP cells was inhibited by 1 nM R1881 but stimulated by 0.1 nM R1881. Compared with the untreated cells, 320 (2.26%; 170 up‐regulated, 150 down‐regulated) and 4608 (32.65%; 2046 up‐regulated, 2562 down‐regulated) genes were found to be expressed differentially in the 1 nM and 0.1 nM R1881‐treated cells, respectively. The results were partially confirmed by RT‐PCR and Western blot. The DDC gene was down‐regulated in the 1 nM R1881‐treated cells and up‐regulated in 0.1 nM R1881‐ and 30 nM hydroxyflutamide‐treated cells. The enzymatic activity of DDC in the latter 2 groups was also strengthened. Meanwhile, the NED markers CgA and synaptophysin were not affected by these AR activators. R1881 had a dose‐dependent biphasic effect on LNCaP cell proliferation. AR coactivator DDC was respectively down‐ and up‐regulated in high and low concentrations of R1881. DDC up‐regulation by exogenous AR activators is not accompanied by up‐regulation of definitive NED markers.