bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein intake regulates the vasodilatory function of the kidney and NMDA receptor expression
Authors: Slomowitz Larry A. , Gabbai Francis B. , Khang Ser J. , Satriano Joseph , Thareau Sonia , Deng Aihua , Thomson Scott C. , Blantz Roland C. , Munger Karen A.
Published: July 2004

Glycine infusion in normal rats causes an increase in renal plasma flow and glomerular filtration rate (GFR). Although the renal response to glycine infusion is well characterized, the mechanism initiating this vasodilation is unknown. We recently observed functionally active N-methyl-d-aspartate (NMDA) receptors in the kidney, located primarily in tubular structures. The mechanisms regulating activity of the NMDA receptor within the kidney are also unknown, as is its normal day-to-day functional role. Therefore, we hypothesize that dietary protein may impact the functional response to glycine infusion in both untreated rats and rats pretreated with angiotensin-converting enzyme (ACE) inhibitor and, furthermore, that renal NMDA receptors may be involved in the glycine response. Surprisingly, 2 wk of low-protein diet (8% protein vs. 21% protein in control diet) totally inhibited the glycine-induced vasodilation and GFR response. Associated with the absence of renal vasodilation, a significant reduction in proximal tubular reabsorption was observed during glycine infusion in low-protein-diet rats. In contrast to the disease models previously studied in our laboratory, administration of ACE inhibitors did not restore the glycine response in rats treated with low-protein diet. Western blots of normal- and low-protein-diet kidneys demonstrate that the newly described renal NMDA receptor is downregulated in rats fed a low-protein diet. Low-protein feeding results in loss of glycine-induced vasodilation and GFR responses associated with decreased renal NMDA receptor expression. Kidney NMDA receptor expression is conditioned by protein intake, and this receptor may play an important role in the kidney vasodilatory response to glycine infusion and protein feeding in rats.
Increased release of serotonin from rat ileum due to dexfenfluramine
Authors: Rezaie-Majd Shahrzad , Murar Jozef , Nelson Daniel P. , Kelly Rosemary F. , Hong Zhigang , Lang Irene M. , Varghese Anthony , Weir E. Kenneth
Published: July 2004

Plasma levels of serotonin are elevated in primary pulmonary hypertension even after bilateral lung transplantation, suggesting a possible etiologic role. Serotonin is released primarily from the small intestine. Anorectic agents, such as dexfenfluramine, which can cause pulmonary hypertension, are known to inhibit potassium channels in vascular smooth muscle cells. We examined the hypothesis that dexfenfluramine may stimulate release of serotonin from the ileum by inhibition of K+ channels. In an isolated loop of rat ileum perfused with a physiological salt solution, the administration of dexfenfluramine, its major metabolite d-norfenfluramine, the potassium channel blocker 4-aminopyridine (5 mM), and caffeine (30 mM) increased serotonin levels in the venous effluent. Potassium chloride (60 mM) tended to increase serotonin levels. In genetically susceptible individuals, dexfenfluramine may induce pulmonary hypertension by increasing cytosolic calcium in enterochromaffin cells of the small intestine, thus releasing serotonin and causing vasoconstriction. This work indicates that dexfenfluramine and its major metabolite d-norfenfluramine can increase serotonin release from the small intestine.
Local heating of human skin causes hyperemia without mediation by muscarinic cholinergic receptors or prostanoids
Authors: Golay Sandrine , Haeberli Christian , Delachaux Anne , Liaudet Lucas , Kucera Paul , Waeber Bernard , Feihl François
Published: July 2004

Local changes in surface temperature have a powerful influence on the perfusion of human skin. Heating increases local skin blood flow, but the mechanisms and mediators of this response (thermal hyperemia response) are incompletely elucidated. In the present study, we examined the possible dependence of the thermal hyperemia response on stimulation of muscarinic cholinergic receptors and on production of vasodilator prostanoids. In 13 male healthy subjects aged 20–30 yr, a temperature-controlled chamber was positioned on the volar face of one forearm and used to raise surface temperature from 34 to 41°C. The time course of the resulting thermal hyperemia response was recorded with a laser-Doppler imager. In one experiment, each of eight subjects received an intravenous bolus of the antimuscarinic agent glycopyrrolate (4 μg/kg) on one visit and saline on the other. The thermal hyperemia response was determined within the hour after the injections. Glycopyrrolate effectively inhibited the skin vasodilation induced by iontophoresis of acetylcholine but did not influence the thermal hyperemia response. In a second experiment, conducted in five other subjects, 1 g of the cyclooxygenase inhibitor aspirin administered orally totally abolished the vasodilation induced in the skin by anodal current but also failed to modify the thermal hyperemia response. The present study excludes the stimulation of muscarinic receptors and the production of vasodilator prostaglandins as essential and nonredundant mechanisms for the vasodilation induced by local heating in human forearm skin.
Induction of Proliferation by 15-Deoxy-Δ12,14-Prostaglandin J2 and the Precursors in Monocytic Leukemia U937
Authors: Azuma Yasutaka , Watanabe Kyoko , Date Masataka , Daito Michiharu , Ohura Kiyoshi
Published: July 2004

Peroxisome proliferator-activated receptor γ (PPARγ) is expressed in several human tumors including gastric, lung, colon, prostate and breast. However, the role of PPARγ signals in leukemia is still unclear. The aim of this study is to evaluate the ability of 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2), that is a ligand for PPARγ, on proliferation of human leukemia cell line U937. 15dPGJ2 at 5 µmol/l stimulated the proliferation. In contrast, 15dPGJ2 at concentrations of >10 µmol/l inhibited the proliferation through the induction of apoptosis. PGD2, PGJ2 and Δ12-PGJ2 (ΔPGJ2), those are precursors of 15dPGJ2, had similarly proliferative effects, whereas they showed antiproliferative effects at high concentrations. FACScan analysis revealed that PGD2 at 5 µmol/l, PGJ2 at 1 µmol/l, ΔPGJ2 at 1 µmol/l and 15dPGJ2 at 5 µmol/l, all accelerated cell cycle progression. Immunoblotting analysis revealed that PGD2 at 5 µmol/l and 15dPGJ2 at 5 µmol/l inhibited the expression of phospho-p38, phospho-MKK3/MKK6 and phospho-ATF-2, and the expression of Cdk inhibitors including p18, p27. In contrast, PGJ2 at 1 µmol/l and ΔPGJ2 at 1 µmol/l did not affect the expression of them. These results suggest that 15dPGJ2 and PGD2 may, through inactivation of the p38 MAPK pathway, inhibit the expression of Cdk inhibitors, leading to acceleration of proliferation.
Presynaptic Excitability as a Potential Target for the Treatment of the Traumatic Cerebellum
Authors: Ai Jinglu , Baker Andrew
Published: July 2004

Using an extracellular recording method, we have previously shown a hyperexcitability of the presynaptic response in fluid percussion injury (FPI) in rats. In this study, we demonstrated that treatment with cis-ACBD, a glutamate reuptake inhibitor, depressed the presynaptic potential (PSP) in naive/sham controls, while it potentiated the PSP in FPI rats. On the contrary, (RS)-APICA, a selective group II metabotropic glutamate receptor antagonist, potentiated PSP in controls, but depressed PSP in FPI rats. These results indicate that an alteration of the normal function of metabotropic glutamate receptors and glutamate reuptake system or an altered reactivity of presynaptic fibers was induced by FPI. This alteration may contribute to the reported loss of Purkinje cells after FPI. PSP may be used as a potential tool for evaluating treatments of FPI or as a potential target for the prevention of Purkinje cell death.
Mechanism of CGRP-Induced Vasodilation in the Rat Isolated Perfused Kidney
Authors: Ay Ilknur , Tuncer Meral
Published: July 2004

We investigated the intracellular mechanisms involved in calcitonin gene-related peptide (CGRP)-induced vasodilation in rat isolated perfused kidney. CGRP-1 receptor antagonist, CGRP-8-37, abolished the responses. Endothelial denudation by Triton X-100 or nitric oxide (NO) synthase inhibition by NG-nitro-L-arginine attenuated the maximum dilation by about 63 and 55%, respectively. Protein kinase A inhibitor, KT-5720, caused an about 72% inhibition in CGRP-induced maximum dilation. Soluble guanylate cyclase inhibitor, ODQ, and ATP-sensitive potassium channel blocker, glibenclamide, inhibited the CGRP-induced maximum responses by 75 and 55%, respectively. Cyclooxygenase inhibitor, indomethacin, had no effect. Our data suggest that CGRP-1 receptors, endothelium, NO synthase, protein kinase A, soluble guanylate cyclase, and ATP-sensitive potassium channels, but not the cyclooxygenase pathway, may play a role in CGRP-induced vasodilation in rat isolated perfused kidney.
The mouse “tool box” for meiotic studies
Authors: Ashley T.
Published: July 2004

Besides availability, there are numerous advantages to using mice for meiotic studies: (1) techniques exist for enriching the population of spermatocytes at particular meiotic stages; (2) spermatogenesis in mice is highly synchronized and testis sections afford a highly accurate method of staging meiotic events; (3) knock-out mice provide a rich source of meiotic mutants. Coupled with antibody localization techniques these tools, singularly and in combination, provide multiple means of temporally and physically dissecting meiosis.
Male mouse meiotic chromosome cores deficient in structural proteins SYCP3 and SYCP2 align by homology but fail to synapse and have possible impaired specificity of chromatin loop attachment
Authors: Kolas N.K. , Yuan L. , Hoog C. , Heng H.H.Q. , Marcon E. , Moens P.B.
Published: July 2004

The targeted deletion of the meiotic chromosome core component MmSYCP3 results in chromosome synaptic failure at male meiotic prophase, extended meiotic chromosomes, male sterility, oocyte aneuploidy and absence of the MmSYCP2 chromosome core component. To test the functions of SYCP2 and SYCP3 proteins in the cores, we determined the effect of their deletion on homology recognition by whole chromosome painting and the effect on chromatin loop attachment to the cores with endogenous and exogenous sequences. Because we observed that the alignment of cores is between homologs, it suggested that alignment is not a function of the chromosome core components but might be mediated by chromatin-chromatin interactions. The alignment function therefore appears to be separate from intimate synapsis function of homologous cores that is observed to be defective in the SYCP3–/– males. To examine the functions of the SYCP2 and 3 core proteins in chromatin loop attachment, we measured the loop sizes of the centromeric major satellite chromatin and the organization of an exogenous transgene in SYCP3+/+ and SYCP3–/– males. We observed that these satellite chromatin loops have a normal appearance in SYCP3–/– males, but the loop regulation of a 2-Mb exogenous λ phage insert appears to be altered. Normally the insert fails to attach to the core except by flanking endogenous sequences, but in the absence of SYCP2 and SYCP3, there appears to be multiple attachments to the core. This suggests that the selective preference for the attachment of mouse sequences to the chromosome core in the wild-type male is impaired in the SYCP3–/– male. Apparently the SYCP2 and SYCP3 proteins function in the specificity of chromatin attachment to the chromosome core.
Role of retinoid signaling in the regulation of spermatogenesis
Authors: Chung S.S.W. , Wolgemuth D.J.
Published: July 2004

While the need for vitamin A for the normal progression of male germ cell differentiation has been known for many years, the molecular mechanisms underlying this requirement are poorly understood. This review will explore the aspects of the effects on spermatogenesis of dietary deprivation of vitamin A, in particular as to how they compare to the male sterility that results from the genetic ablation of function of the retinoid receptor RARα. The effects of other genes involved with retinoid synthesis, transport, and degradation are also considered. The possible cellular mechanisms that may be affected by the lack of retinoid signaling are discussed, in particular, cell cycle regulation and cell-cell interaction, both of which are critical for normal spermatogenesis.
Male germline-specific histones in mouse and man
Authors: Churikov D. , Zalenskaya I.A. , Zalensky A.O.
Published: July 2004

In mice and humans, the production of male gametes is a result of a complex multistep process of stem cell differentiation. The final product, the mature spermatozoon, is designed for the safe delivery of a haploid copy of the paternal genetic information to the oocyte in a structural state suitable for zygote formation and embryogenesis. A remarkable structural reorganization of chromosomes in germline cells during mammalian spermatogenesis has been characterized. The most important steps are connected with the recombination events during meiosis and the final packaging of the haploid genome in the genetically inert, compacted nucleus of the sperm. Underlying the changes in chromatin organization is the appearance of testis-specific histones. Although the existence of such histones has been known for decades, their exact functions still are not established. Deciphering of the mouse and human genomes has allowed a more detailed description of the organization and regulation of the testis-specific histone genes. In addition, it has facilitated the discovery of previously unknown proteins. This review summarizes contemporary information on these germline-specific/enriched histones in both the mouse and human and outlines early achievements in the identification of their functions.
Single-cell quantitative RT-PCR analysis of Cpt1b and Cpt2 gene expression in mouse antral oocytes and in preimplantation embryos
Authors: Gentile L. , Monti M. , Sebastiano V. , Merico V. , Nicolai R. , Calvani M. , Garagna S. , Redi C.A. , Zuccotti M.
Published: July 2004

Fatty acids represent an important energy source for preimplantation embryos. Fatty acids oxidation is correlated with the embryo oxygen consumption which remains relatively constant up to the 8-cell stage, but suddenly increases between the 8-cell and morula stages. The degradation of fatty acids occurs in mitochondria and is catalyzed by several carnitine acyl transferases, including two carnitine palmitoyl transferases, CPT-I and CPT-II. We have carried out a study to determine the relative number of transcripts of Cpt1b and Cpt2 genes encoding for m-CPT-I and CPT-II enzymes, during mouse preimplantation development. Here we show that Cpt1b transcripts are first and temporally detected at the 2-cell stage and reappear at the morula and blastocyst stage. Cpt2 transcripts decrease following fertilization to undetectable levels and are present again later at the morula stage. These results show that transcription of both Cpt1b and Cpt2 is triggered at the morula stage, concomitantly with known increasing profiles of oxygen uptake and fatty acids oxidation. Based on the number of Cpt2 transcripts detected, we could discriminate the presence of two groups of embryos with high and low number of transcripts, from the zygote throughout preimplantation development. To further investigate if the establishment of these two groups of embryos occurs prior to fertilization, we have analyzed the relative number of transcripts of both genes in antral and ovulated MII oocytes. As for preimplantation embryos, MII oocytes show two groups of Cpt2 expression. Antral oocytes, classified according to their chromatin configuration in SN (surrounded nucleolus, in which the nucleolus is surrounded by a rim of Hoechst-positive chromatin) and NSN (not surrounded nucleolus, in which this rim is absent), show three groups with different numbers of Cpt2 transcripts. All NSN oocytes have a number of Cpt2 transcripts doubled compared to that of the group of MII oocytes with high expression. Instead, SN oocytes could be singled out into two groups with high and low numbers of Cpt2 transcripts, similar to those found in MII oocytes. The results of this study point out a correlation between the timing of fatty acids oxidation during preimplantation development and the expression of two genes encoding two enzymes involved in the oxidative pathway. Furthermore, although the biological meaning for the presence of two groups of oocytes/embryos with different levels of Cpt2 transcripts remains unclear, the data obtained suggest a possible correlation between the levels of Cpt2 expression and embryo developmental competence.
New mouse genetic models for human contraceptive development
Authors: Lessard C. , Pendola J.K. , Hartford S.A. , Schimenti J.C. , Handel M.A. , Eppig J.J.
Published: July 2004

Genetic strategies for the post-genomic sequence age will be designed to provide information about gene function in a myriad of physiological processes. Here an ENU mutagenesis program (http://reprogenomics.jax.org) is described that is generating a large resource of mutant mouse models of infertility; male and female mutants with defects in a wide range of reproductive processes are being recovered. Identification of the genes responsible for these defects, and the pathways in which these genes function, will advance the fields of reproduction research and medicine. Importantly, this program has potential to reveal novel human contraceptive targets.
Notch-1, c-kit and GFRα-1 are developmentally regulated markers for premeiotic germ cells
Authors: von Schönfeldt V. , Wistuba J. , Schlatt S.
Published: July 2004

Culture, transfection and immortalization of mouse germ line stem cells, germ cell transplantation and grafting of testicular tissue are milestones of recent biotechnological breakthroughs. Alone and in combination they offer new pathways to explore the cellular mechanisms responsible for pluripotency and the requirements of cells to enter the germ line. Efficient markers, isolation and culture systems as well as transfection approaches are developed to elucidate the molecular and cellular mechanisms leading to the development of male germ line cells. Here, we describe the localization pattern of c-kit, Notch-1 and GFRα-1 in postnatal, immature and adult testes. All three proteins are potentially useful markers for spermatogonial characterization and enrichment. First attempts and various future perspectives to use spermatogonial stem cells as pathway for the introduction of transgenes are discussed.
Genetic and genomic approaches to study placental development
Authors: Hemberger M. , Zechner U.
Published: July 2004

Recent technological advances in genetic manipulation and expression profiling offer excellent opportunities to elucidate the molecular mechanisms controlling developmental processes during embryogenesis. Thus, this revolution also strongly benefits studies of the molecular genetics of placental development. Here we review the findings of several expression profiling analyses in extraembryonic tissues and assess how this work can contribute to the identification of essential components governing placental development. We further discuss the relevance of these components in the context of genetic manipulation experiments. In conclusion, the intelligent combination of genetic and genomic approaches will substantially accelerate the progress in identifying the key molecular pathways of placental development.
Nuclear reprogramming in mammalian somatic cell nuclear cloning
Authors: Tamada H. , Kikyo N.
Published: July 2004

Nuclear cloning is still a developing technique used to create genetically identical animals by somatic cell nuclear transfer into unfertilized eggs. Despite an intensive effort in a number of laboratories, the success rate of obtaining viable offspring from this technique remains less than 5%. In the past few years many investigators reported the reprogramming of specific nuclear activities in cloned animals, such as genome-wide gene expression patterns, DNA methylation, genetic imprinting, histone modifications and telomere length regulation. The results highlight the tremendous difficulty the clones face to reprogram the original differentiation status of the donor nuclei. Nevertheless, nuclei prepared from terminally differentiated lymphocytes can overcome this barrier and produce apparently normal mice. Study of this striking nuclear reprogramming activity should significantly contribute to our understanding of cell differentiation in more physiological settings.
DNA methylation in mouse gametogenesis
Authors: Marchal R. , Chicheportiche A. , Dutrillaux B. , Bernardino-Sgherri J.
Published: July 2004

DNA methylation is involved in many biological processes and is particularly important for both development and germ cell differentiation. Several waves of demethylation and de novo methylation occur during both male and female germ line development. This has been found at both the gene and all genome levels, but there is no demonstrated correlation between them. During the postnatal germ line development of spermatogenesis, we found very complex and drastic DNA methylation changes that we could correlate with chromatin structure changes. Thus, detailed studies focused on localization and expression pattern of the chromatin proteins involved in both DNA methylation, histone tails modification, condensin and cohesin complex formation, should help to gain insights into the mechanisms at the origin of the deep changes occurring during this particular period.
Chromosome painting in the long-tailed field mouse provides insights into the ancestral murid karyotype
Authors: Stanyon R. , Yang F. , Morescalchi A.M. , Galleni L.
Published: July 2004

We report on the hybridization of mouse chromosomal paints to Apodemus sylvaticus, the long-tailed field mouse. The mouse paints detected 38 conserved segments in the Apodemus karyotype. Together with the species reported here there are now six species of rodents mapped with Mus musculus painting probes. A parsimony analysis indicated that the syntenies of nine M. musculus chromosomes were most likely already formed in the muroid ancestor: 3, 4, 7, 9, 14, 18, 19, X and Y. The widespread occurrence of syntenic segment associations of mouse chromosomes 1/17, 2/13, 7/19, 10/17, 11/16, 12/17 and 13/15 suggests that these associations were ancestral syntenies for muroid rodents. The muroid ancestral karyotype probably had a diploid number of about 2n = 54. It would be desirable to have a richer phylogenetic array of species before any final conclusions are drawn about the Muridae ancestral karyotype. The ancestral karyotype presented here should be considered as a working hypothesis.
Sox genes and cancer
Authors: Dong C. , Wilhelm D. , Koopman P.
Published: July 2004

Sox genes encode transcription factors belonging to the HMG (High Mobility Group) superfamily. They are conserved across species and involved in a number of developmental processes. In vitro studies have shown at least one Sox gene to be capable of inducing oncogenic transformation of fibroblast cells. In addition, overexpression and/or amplification of Sox genes are associated with a large number of tumour types in vivo. We review here the available evidence linking Sox gene expression and cancer, and show that this link is supported by extensive EST database analysis. This work provides a basis for further studies aimed at investigating the possible role of Sox genes in the oncogenic process.
Occupational Safety and Health Aspects of Voice and Speech Professions
Authors: Vilkman Erkki
Published: July 2004

A well-functioning voice is an essential tool for one third of the labour force. Vocal demands vary to a great extent between the different voice and speech professions. In professions with heavy vocal loading (e.g. school and kindergarten teachers), occupational voice disorders threatening working ability are common. Vocal loading is a combination of prolonged voice use and additional loading factors (e.g. background noise, acoustics, air quality) affecting the fundamental frequency, type and loudness of phonation or the vibratory characteristics of the vocal folds as well as the external frame of the larynx. The prevention and treatment of occupational voice disorders calls for improved occupational safety and health (OSH) arrangements for voice and speech professionals. On the basis of epidemiological and acoustic-physiological research, the presence of risk to vocal health can be substantiated. From the point of view of the physical load on the vocal apparatus, loading-related physiological changes (adaptation) may play a role in the occupational risk. Environmental factors affect vocal loading changes. In teaching professions, the working environment is shared with children, who benefit from amendments of OSH legislation concerning their teachers.
21st Century Literacy for a Diverse World
Authors: Westby Carol
Published: July 2004

Literacy demands in the 21st century require that proficient readers do more than ‘read along the lines’ or decode words and know their meaning. Proficient readers must be able to ‘read between the lines’, making relevant inferences to interpret, analyze, and synthesize information in texts; and ‘read across the lines’, applying these critical reading processes to multiple texts for purposes of problem-raising and problem-solving. This article will review literature on the cognitive and linguistic skills necessary for reading along the lines in a variety of scripts; the nature of the language and cognitive skills essential for the text comprehension necessary for reading between and across the lines, and the ways that culture and language influence text comprehension.
Different C-Reactive Protein Kinetics in Post-Operative Hip-Fractured Geriatric Patients with and without Complications
Authors: Beloosesky Yichayaou , Grinblat Joseph , Pirotsky Anatoly , Weiss Avraham , Hendel David
Published: July 2004

Background: Hip fracture is a frequent injury in the elderly, and is associated with a high incidence of functional impairment, complications and mortality. Objective: To determine kinetics of C-reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate (ESR) in hip-fractured patients over a 1-month post-operative period; to examine the relationship of these parameters to cognition, operation type, post-operational complications, functional level 1 month post-operatively and 6-month mortality. Methods and Subjects: 32 aged patients operated on for hip fracture were prospectively followed-up for 6 months. Fracture, type of operation and anesthetic risk were recorded. Cognition was evaluated by the Mini-Mental State Examination and pre-fracture functional level evaluated by the Katz Index of ADL. Follow-up included complications, mortality and functional outcome. CRP, fibrinogen and ESR were assessed during the first 10 h post-fracture; 48–60 h, and 7 and 30 days post-operatively, respectively. Results: Only CRP kinetics were found to differ in patients with complications vs. those without, as a group (p = 0.006), and in patients suffering infections, delirium and cardiovascular complication vs. patients with no complications (p = 0.06, 0.03, 0.02, respectively). Mean (±SEM) CRP 48–60 h post-operatively was 20.9 ± 2.1 and 13.1 ± 1.6 mg/dl in complicated and uncomplicated patients, respectively (p = 0.002). The mean CRP 48–60 h post-operatively was highly correlated with the CRP area under the curve, R = 0.88 (p < 0.001). A cut-off level of 15 mg/dl for CRP, 48– 60 h post-operatively, was calculated for patients with complications (sensitivity 93%, specificity 65%, p = 0.003). CRP, fibrinogen and ESR were not related to fracture or type of operation, cognition, anesthetic risk, 1-month post-operative functioning and 6-month mortality. Conclusions: CRP measurement in elderly patients operated for hip fracture may be valuable in assessing and monitoring complications.
Do White Matter Changes Have Clinical Significance in Alzheimer’s Disease?
Authors: Kono Ichiyo , Mori Satoru , Nakajima Kenji , Nakagawa Masanori , Watanabe Yoshiyuki , Kizu Osamu , Yamada Kei , Sakai Yasuichi
Published: July 2004

Background: Although white matter changes visible with MRI are generally considered to result from ischemia, it has become clear that these changes also appear in patients with Alzheimer’s disease (AD). However, their significance in AD is unknown. Objective: We evaluated the clinical significance of white matter changes in AD. Methods: Ninety-six AD patients (79.4 ± 5.92 years old) and 48 age-matched control subjects (80.0 ± 7.03 years old) participated in the study. Three neuroradiologists assessed the degree of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) using a modified Fazekas’ rating scale. We examined whether there was a difference in the severity and the histogram pattern of the white matter changes, or in vascular factors (hypertension, diabetes mellitus, and ischemic heart disease) between the two groups. We also analyzed the association between the severity of the white matter changes and the degree of dementia (MMSE score and disease duration). Results: There were no differences in the vascular factors between AD and control subjects. The degree of PVH in AD was severe compared with that in the control subjects. In histograms of the number of subjects with each degree of PVH severity, the distribution of AD patients had peaks at both the low and intermediate degrees of PVH, while most of the controls had a low degree of PVH. There was no difference in the degree or the histogram pattern of DWMH between the two groups. The severity of white matter changes was not associated with severity of dementia in AD. Conclusions: Although PVH might have several causative factors, and may have some clinical significance, the change itself does not contribute to the progression of AD.
Hospitalization for Initiation of Maintenance Hemodialysis
Authors: Agraharkar Mahendra , Martinez Mario A. , Kuo Yong-Fang , Ahuja Tejinder S.
Published: July 2004

Background: Recent data on complications of hemodialysis (HD) is lacking. With advancement in dialysis technology the incidence of complications such as dialysis disequilibrium syndrome (DDS) has decreased. Notwithstanding these improvements many patients with end-stage renal disease (ESRD) continue to be hospitalized solely for initiation of hemodialysis. This study was undertaken to assess if such admissions are justified and also to determine incidence and predictors of complications of HD during initiation. Methods: Medical records of adult patients (>18 years) initiated on maintenance hemodialysis from January 1st, 1998 through December 31st, 2000 at our institution were reviewed. The demographics of the patients, cause of renal failure, creatinine clearance, type of vascular access, comorbidities, serum chemistries, ultrafiltration (UF) rate and indications for initiating dialysis were noted. Intradialytic complications were retrieved from the dialysis flow sheets. Results: Of the 240 patients reviewed, 18.3% developed complications during initiation of dialysis, and none was severe. Hypotension and leg cramps were the most frequent complications. The patients who developed hypotension and cramps were significantly older than those with no complications, 57.7 ± 14.9 (mean ± SD) years versus 52.3 ± 14.8 years, respectively (p = 0.02). The increment of age significantly influenced the complication rate [odds ratio (OR): 1.03, 95% confidence interval (CI) 1.01–1.05 (p = 0.03)], and so did hematocrit (HCT) (OR: 1.07, 95% CI 1.01–1.13). Multivariate analysis using age and hematocrit as continuous variables revealed that the older patients with anemia had a significantly higher risk of developing HD related complications than younger patients with anemia (OR: 1.05, 95% CI 1.01–1.09 at HCT of 24%, and OR: 1.03, 95% CI 1.00–1.06 at HCT 27%). When patients were stratified by hematocrit level, older patients with hematocrit <27% had higher risk of complications and the risk increased with increasing age [complication rate (HCT <27%): age <40 = 0%, age 40–64 = 11.7%, age >65 = 25%, p < 0.016]. Conclusion: Although very few, hypotension and muscle cramps were the main complications during initiation of HD. Older patients with anemia are prone for these complications although no physician intervention was necessary. Hospitalization solely for initiation of maintenance dialysis is not necessary and the additional cost from such admissions cannot be justified.
Nonsteroidal Anti-Inflammatory Drugs for the Prevention of Alzheimer’s Disease: A Systematic Review
Authors: Szekely Christine A. , Thorne Jennifer E. , Zandi Peter P. , Ek Mats , Messias Erick , Breitner John C.S. , Goodman Steven N.
Published: July 2004

Objective: Alzheimer’s disease, the most prevalent dementia, is a prominent source of chronic illness in the elderly. Laboratory evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) might prevent the onset of Alzheimer’s disease. Since the early 1990s, numerous observational epidemiological studies have also investigated this possibility. The purpose of this meta-analysis is to summarize and evaluate available evidence regarding exposure to nonaspirin NSAIDs and risk of Alzheimer’s disease using meta-analyses of published studies. Methods: A systematic search was conducted using Medline, Biological Abstracts, and the Cochrane Library for publications from 1960 onwards. All cross-sectional, retrospective, or prospective observational studies of Alzheimer’s disease in relation to NSAID exposure were included in the analysis. At least 2 of 4 independent reviewers characterized each study by source of data and design, including method of classifying exposure and outcome, and evaluated the studies for eligibility. Discrepancies were resolved by consensus of all 4 reviewers. Results: Of 38 publications, 11 met the qualitative criteria for inclusion in the meta-analysis. For the 3 case-control and 4 cross-sectional studies, the combined risk estimate for development of Alzheimer’s disease was 0.51 (95% CI = 0.40–0.66) for NSAID exposure. In the prospective studies, the estimate was 0.74 (95% CI = 0.62–0.89) for the 4 studies reporting lifetime NSAID exposure and it was 0.42 (95% CI = 0.26–0.66) for the 3 studies reporting a duration of use of 2 or more years. Conclusions: Based on analysis of prospective and nonprospective studies, NSAID exposure was associated with decreased risk of Alzheimer’s disease. An issue that requires further exploration in future trials or observational studies is the temporal relationship between NSAID exposure and protection against Alzheimer’s disease.
Epidemiology of Multiple System Atrophy: A Prevalence and Pilot Risk Factor Study in Aquitaine, France
Authors: Chrysostome V. , Tison F. , Yekhlef F. , Sourgen C. , Baldi I. , Dartigues J.F.
Published: July 2004

We investigated the prevalence of multiple system atrophy (MSA) in Gironde, France, through a network of 120 public and private specialists and assessed the relationship between some environmental factors and MSA in a case-control study involving 50 MSA patients, 50 Parkinson’s disease (PD) patients and 50 healthy controls. The occupational exposure to pesticides was evaluated through a job-exposure matrix. On prevalence day (November 1, 1998), the crude prevalence of MSA in Gironde was 1.94/100,000 inhabitants. We found no significant relationship between occupational exposure to pesticides and MSA. PD patients were significantly less frequently ever-smokers than controls and the same tendency was observed for MSA patients. We also described the clinical features that heralded the disease among this nonselected population.
German Adaptation of the Skindex-29 Questionnaire on Quality of Life in Dermatology: Validation and Clinical Results
Authors: Augustin Matthias , Wenninger Kerstin , Amon Ulrich , Schroth Michael Joachim , Küster Wolfgang , Chren Margret , Kupfer Jörg , Gieler Uwe
Published: July 2004

Background: Health-related quality of life (HRQOL) has increasingly been recognized as an important aspect of a comprehensive clinical assessment in dermatology. Objective: The aim of the present study was to translate and validate one of the most frequently used and established skin disease-specific HRQOL questionnaires originally developed in English for the German language area: the Skindex-29. Methods: 295 in-patients with psoriasis and atopic dermatitis completed the German translation of the Skindex as well as a number of additional skin disease-specific questionnaires. Data from 2 subsamples were analysed separately to test for the robustness of results. Results: Results from principal component analyses supported the scale structure of the original Skindex. Internal consistency coefficients were high for all scales. Further analyses supported the convergent validity of the German adaptation of the Skindex-29 as well as its sensitivity to change. Conclusion: The study provides evidence for the validity and reliability of the Skindex-29.
Nephrogenic Fibrosing Dermopathy in a Renal Transplant Recipient with Tubulointerstitial Nephritis and Uveitis
Authors: Hauser Conrad , Kaya Gürkan , Chizzolini Carlo
Published: July 2004

We report a patient with nephrogenic fibrosing dermopathy. He had chronic renal failure with arthritis, uveitis and histologically severe tubulointerstitial nephritis for which he received a renal transplant from a family relative. After an episode of acute renal failure with the transplant he developed painful, erythematous, firm papules and plaques with geographic borders on the legs, anterior thorax and elbow. A skin biopsy revealed increased fibroblast and collagen fiber content of the dermis and subcutaneous septae. Mucin deposition, sparse smooth-muscle-actin-positive cells and an increased number of CD34-positive cells in the deep dermis were found. After several weeks of hemodialysis, the lesions changed from an inflammatory to a purely sclerotic phase. The fibrocyte, a recently described circulating cell type, that is deposited in scar tissue may be involved in the pathogenesis of this novel pseudosclerodermatous skin disorder.
Focal Monophasic Demyelinating Leukoencephalopathy in Advanced HIV Infection
Authors: Corral Iñigo , Quereda Carmen , García-Villanueva Mercedes , Casado José-Luis , Pérez-Elías María-Jesús , Navas Enrique , Ariza Aurelio , Moreno Santiago
Published: July 2004

A multiple sclerosis (MS)-like illness has been reported in human immunodeficiency virus (HIV)-infected patients, usually in the early stages of HIV infection. We report 3 patients with advanced HIV infection (CD4 lymphocyte count under 200/mm3) presenting with monophasic focal leukoencephalopathy, in whom biopsy demonstrated demyelinating lesions compatible with acute MS lesions. In 1 patient, recently started on highly active antiretroviral therapy, MS-like disease could represent an immune reconstitution syndrome. The lesions were reversible in 2 patients, but rapidly fatal in the third patient. These cases show that an MS-like disease may present in advanced HIV infection as focal monophasic leukoencephalopathy with either a reversible or fulminating course, mimicking progressive multifocal leukoencephalopathy.
Longitudinal Cerebral Perfusion Decrease in Mild Alzheimer’s Disease Revealed by SPECT with Statistical Parametric Mapping Method
Authors: Lee Yi-Chung , Liu Ren-Shyan , Liao Yi-Chu , Wang Pei-Ning , Lin Ker-Neng , Liu Hsiu-Chih
Published: July 2004

Fifteen patients with mild Alzheimer’s disease received baseline and follow-up technetium-99m hexamethylpropylene amine oxime SPECT examinations paired with neuropsychological assessments, including the Cognitive Ability Screening Instruments (CASI). The differences between baseline and follow-up SPECT images were analyzed by the voxel-based paired t test of the statistical parametric mapping technique. A simple regression analysis was also conducted to analyze the correlation between CASI sub-scores and both sets of SPECT images. In comparison with baseline images, cerebral perfusion at follow-up was significantly reduced in the left superior and middle temporal gyri, right middle and inferior temporal gyri, and right fusiform gyrus. A significant correlation was demonstrated between the list-generating fluency CASI sub-score and perfusion of the left fusiform gyrus. The visual construction sub-score was significantly correlated with perfusion of the right superior and medial frontal gyri.
The Tei Index Permits Evaluation of Cardiopulmonary Function during Inhaled Nitric Oxide Therapy in the Hypoxic Newborn Piglet
Authors: Sugiura Takahiro , Suzuki Satoshi , Hussein Mohamed Hamed , Kato Takenori , Okubo Yumiko , Imamine Hiroki , Sugiura Tokio , Togari Hajime
Published: July 2004

The purpose of this study was to test the effectiveness of a new Doppler index combining systolic and diastolic time intervals (the Tei index) in the prospective assessment of ventricular function and pulmonary circulation in a newborn piglet model with hypoxic pulmonary hypertension during inhaled nitric oxide (NO). Piglets were prepared for the experiments under normal air, hypoxia, and hypoxia-with-inhaled-NO conditions. Complete two-dimensional Doppler echocardiographic examinations were performed in each condition. The right-ventricle (RV) Tei index increased with hypoxia and decreased following the inhalation of NO. Furthermore, there was a direct correlation between the individual changes in the RV Tei index and individual changes in mean pulmonary arterial pressure in each condition. We conclude that the Tei index is useful for assessing cardiac function and pulmonary circulation in hypoxic pulmonary hypertension during inhaled NO. These results suggest that the Tei index provides an objective assessment of persistent pulmonary hypertension of the newborn.
Esophageal Perforation Associated with Cervical Spine Surgery: Report of Two Cases and Review of the Literature
Authors: Vrouenraets B.C. , Been H.D. , Brouwer-Mladin R. , Bruno M. , van Lanschot J.J.B.
Published: July 2004

Background/Aims: Esophageal perforation after anterior cervical spine surgery is a rare complication with various clinical presentations and treatments. Methods: Two cases of esophageal perforation after anterior cervical spine surgery are described, one occurring in the immediate postoperative period and one several years after plate stabilization of the cervical spine. Results: Primary suturing of the acute perforation and diversion of the salivary flow by means of T-tube placement after delayed presentation allowed successful healing of the esophageal defects. Conclusion: When encountering acute dysphagia after cervical spine surgery, one should think of an esophageal perforation and install immediate further diagnostics and therapy. Treatment depends on the time of detection and size of the perforation. In early stages, with vital tissues, primary suturing is the treatment of choice. If presentation is late, it seems advisable to limit the procedure to simple drainage after removal of foreign bodies.
A Case of Sotos Syndrome (Cerebral Gigantism) and Psychosis
Authors: Compton Michael T. , Celentana Marc , Price Brian , Furman Andrew C.
Published: July 2004

Sotos syndrome, or cerebral gigantism, is a syndrome of accelerated growth during early childhood, and a number of craniofacial and other physical abnormalities are commonly present. Behavioral and psychiatric manifestations of the disorder include attention deficits, aggressiveness, and social inhibition. The authors describe a case of psychosis that developed in a patient with Sotos syndrome.
Murine metastable epialleles and transgenerational epigenetic inheritance
Authors: Chong S. , Whitelaw E.
Published: July 2004

For decades it has been recognized that a number of genes in the mouse genome do not behave according to Mendelian rules. Some of these genes exhibit unique patterns of expression, including variegation, variable expressivity in the context of isogenicity and transgenerational epigenetic inheritance. They are known as metastable epialleles. A correlation between expression and epigenetic state has been observed at these alleles, and information is emerging about the temporal course of erasure and re-establishment of these epigenetic marks during mouse development. Perhaps the most intriguing aspect of this process is the stochastic nature of the re-establishment of epigenetic state. This review aims to discuss the genomic structure and function of known and suspected metastable epialleles, to gain insight into the possible molecular mechanisms involved, and to aid in the future identification of other such alleles in the mouse and man.
The Latex Allergen Hev b 5 Is an Antigen with Repetitive Murine B-Cell Epitopes
Authors: Beezhold Donald H. , Hickey Vicky L. , Sutherland Michael F. , O’Hehir Robyn E.
Published: July 2004

Background: Hev b 5 is a potent latex allergen. In this study, we characterize the linear B-cell epitopes for three monoclonal antibodies (mAbs) to Hev b 5. Methods: The mAbs included 2 IgG1 (6A10, 3G3) and 1 IgG2b (6F6) isotypes. We used SPOTscan analysis with overlapping octapeptides to identify the binding regions for the antibodies and then methionine substitution analysis to further define the critical amino acids (aa) in each epitope. Site-directed mutagenesis was used to selectively eliminate the IgG binding for each epitope and single and multiple mutations were expressed as recombinant GST fusion proteins. Antibody recognition of the mutant proteins was determined by inhibition ELISA. Results: All three mAbs recognized the same aa sequence by SPOTs analysis with slight variations, and this epitope was repeated 3 times in the Hev b 5 sequence; APETEK (63–68), PAEGEK (120–125), and PAEEEK (126–131). Sequential methionine substitution by SPOTsalogue identified K68, E122, and K131 as critical aa in each epitope to change by site-directed mutagenesis. Inhibition ELISA with the mutant proteins indicated that epitope 126–131 was the dominant epitope, but mutation of epitope 120–125 was also required to eliminate mAb reactivity to Hev b 5. The antibodies did not appear to recognize the epitope 63–68 in the recombinant fusion protein. Conclusions: We identified an immunodominant B-cell epitope in Hev b 5 that is repeated 3 times within the sequence, making Hev b 5 multivalent. Well-characterized monoclonals recognizing repeated epitopes would be a good choice for immunodetection of Hev b 5 in glove extracts where individual epitopes could get altered by the manufacturing process.