bluuebunny/crossref_metadata_2025 huggingface dataset:
The Management of Skin and Soft Tissue Infections: Outpatient Parenteral Antibiotic Therapy in the United Kingdom
Authors: Nathwani Dilip
Published: April 2003

In a study in Scotland, skin and soft tissue infections (SSTIs) accounted for 10% of hospitalizations, with mean stays of approximately 5 days, and were the second most common reason for hospital-based intravenous antibiotic therapy lasting more than 48 h. A total of 125 patients with SSTIs were recently treated using an outpatient parenteral antibiotic therapy (OPAT) service. The patients received intravenous antibiotic therapy for a mean duration of 5.32 days. The two primary agents administered were once-daily ceftriaxone and teicoplanin. Of the 125 patients, 123 (98.4%) were cured or improved; 2 worsened and required surgery. Patient satisfaction was very high. OPAT saved the inpatient facility 665 bed days. Economic benefits were realized despite use of more expensive agents. Data indicate that if the hospital stay of patients with SSTIs were reduced by only 1 day, savings would amount to £½–1 million per year. OPAT is a feasible alternative to inpatient management of SSTIs and may safely, effectively and cost-effectively reduce the number of hospital days for these infections.
Comparison of the Sensititre YeastOne Colorimetric Microdilution Panel and the NCCLS Broth Microdilution Method for Antifungal Susceptibility Testing against Candida Species
Authors: Bernal Samuel , Aller Ana Isabel , Chávez Mónica , Valverde Anastasio , Serrano Carmen , Gutiérrez M , Quindós G. , Martín Mazuelos Estrella
Published: April 2003

We evaluated the commercially prepared Sensititre YeastOne colorimetric antifungal panel to determine the susceptibility of 170 Candida spp isolates to amphotericin B, fluconazole, itraconazole, and flucytosine. The NCCLS reference microdilution method (M27-A document) was used as reference method. The YeastOne panel was performed according to the manufacturer’s instructions. For the colorimetric method, MICs were determined at 24 h of incubation. MICs for the NCCLS reference method were read at 48 h of incubation. The overall agreement within ±2 dilutions by both methods was calculated against the four antifungal agents. This agreement was 92.9, 68.2, 77.6 and 80% for amphotericin B, fluconazole, itraconazole, and flucytosine, respectively. Thirteen isolates (7.6%) showed very major discrepancies for fluconazole and 12 (7%) for itraconazole. We found that the reading of MIC with the YeastOne panel was somewhat easier than the reading of reference MIC, although the determination of endpoint was sometimes difficult, especially for azoles, because the trailing effect appeared in a high percentage of isolates.
Investigation of Various Antibiotic Combinations Using the E-Test Method in Multiresistant Pseudomonas aeruginosa Strains
Authors: Kocazeybek Bekir Sami , Arabacı Ümit , Erentürk Selim , Akdur Hülya
Published: April 2003

Background: Antibiotic combinations are frequently used in order to obtain wide-spectrum effects in the treatment of serious infections such as septicemia and endocarditis, and also to produce an in vivo effect against strains which are defined as resistant to the known inhibiting or fatal dose of one antibiotic. The synergistic effects of combinations such as aminoglycoside + beta-lactam, aminoglycoside + quinolone and quinolone + beta-lactam on Pseudomonas aeruginosa have been revealed in different studies. The multiple resistance rate of nosocomial P. aeruginosa strains isolated from intensive care units (ICUs) has been reported as high in many studies. Methods: In this study, the effects of various combinations of antibiotics (aminoglycoside + beta-lactam and aminoglycoside + quinolone) against 101 multiresistant P. aeruginosa strains which were isolated from the ICUs of three different hospitals in İstanbul were investigated using the E-test method. The combinations for which the highest synergistic effects were determined by the E-test method were also tested with the checkerboard method, i.e. in addition to the E-test method, in 19 of a total of 23 strains. Results: When the synergistic results which were obtained with the combinations of aminoglycoside + beta-lactam were compared with those of the aminoglycoside + quinolone combinations, they were determined to be higher for the two aminoglycosides gentamicin (GM) and tobramycin (TM). We determined the synergistic rates to be 23, 21, 19, 18, 16, 14, 10 and 10% for GM + ceftriaxone (TX), GM + piperacillin (PP), GM + ceftazidime (TZ), TM + PP, TM + TX, TM + TZ, GM + ciprofloxacin (CI) and TM + CI, respectively. The GM + TX combination – for which the highest synergistic effects were determined with the E-test stripes – was also determined as synergistic with the checkerboard method in 19 of a total of 23 strains (23%), and the agreement rate between the two methods was 100% (ĸ > 0.7). The highest synergistic effects against strains which were sensitive to both of the antibiotics which constitute the combinations were found for the GM + TX combination, as 50%, whereas for strains which were resistant to both of the antibiotics, this was found for the TM + PP combination, also as 50%. Conclusions: We consider that the minimal inhibitory concentration values of antibiotics are not sufficient alone in order to constitute a combination for multiresistant strains and it would be advisable to begin a treatment by applying a combination study. The E-test method has been evaluated as a good alternative for combination investigations because of its ease both of application and evaluation and also for its good agreement with the standard checkerboard method.
Protection Effects of Taurine Supplementation against Cisplatin-Induced Nephrotoxicity in Rats
Authors: Saad Sherif Y. , Al-Rikabi Ammar C.
Published: April 2003

Backgound: Taurine, which is the major intracellular free β-amino acid, is known to be an antioxidant and a membrane-stabilizing agent. This study was designed to investigate the protective role of taurine supplementation against cisplatin-induced nephrotoxicity. Methods: Male Wistar rats were divided into six groups and treated as follows: (1) saline-treated control drinking tap water, (2) saline-treated plus taurine-supplemented (1.5% taurine in the drinking water), (3) saline-treated plus taurine-depleted (3% β-alanine in the drinking water), (4) cisplatin-treated, CDDP 6 mg/kg intraperitoneally, (5) taurine-supplemented plus CDDP-treated and (6) taurine-depleted plus CDDP-treated. Rats were sacrificed 7 days after CDDP treatment, and serum as well as kidneys were isolated and analyzed. Results: CDDP-treated rats showed increased kidney weight as a percentage of total body weight, serum creatinine and BUN levels and decreased serum albumin and calcium levels. Also, CDDP treatment resulted in a depletion of kidney GSH content, a reduction in the kidney glutathione peroxidase (GSH-Px) activity and increased kidney MDA production level. Taurine supplementation attenuated CDDP-induced nephrotoxicity which was manifested by jeopardizing the elevation in serum creatinine and BUN levels and the reduction in serum albumin and calcium levels. Moreover, taurine supplementation restored kidney GSH content and GSH-Px activity and reduced platinum accumulation and MDA production levels in the kidney tissue following CDDP treatment. Histopathological examination of the kidney of CDDP-treated rats revealed tubular atrophy, tubular necrosis and desquamation of renal tubular cells. However, taurine supplementation protected against CDDP-induced histopathological changes. Conclusions: The data suggest that taurine supplementation effectively attenuates the accumulation of platinum within kidney tissue and counteracts the deleterious effect of CDDP on the renal tubular function.
Ceftriaxone versus Other Cephalosporins for Perioperative Antibiotic Prophylaxis: A Meta-Analysis of 43 Randomized Controlled Trials
Authors: Dietrich Eva Susanne , Bieser Ute , Frank Uwe , Schwarzer Guido , Daschner Franz D.
Published: April 2003

The efficacy of ceftriaxone versus other cephalosporins in the perioperative prophylaxis of surgical wound, urinary tract and respiratory tract infections was compared in a meta-analysis of randomized controlled trials published between 1986 and 1996, identified from the Medline, Embase, SIGLE, ROPU, DHSS-Data and Medikat Cologne databases. Studies were grouped by type of infection, operative specialty, wound classification, study quality and other factors, and assessed for relative risk (RR). Forty-three studies with a total of 13,482 patients met our inclusion criteria. RR for surgical wound infection (n = 13,303 patients) was 30% lower in the ceftriaxone versus control groups [98.3% confidence interval (CI): 0.55–0.89; p = 0.0002]. In urinary tract infections (n = 8,865 patients), the primary analysis of all studies showed marked superiority for ceftriaxone (RR: 0.53; 98.3% CI: 0.43–0.67) but not in studies with CDC-defined infections (RR: 0.63; 98.3% CI: 0.36–1.12). In both types of infection, ceftriaxone was superior in contaminated operations. The data showed no advantage for ceftriaxone in other operations. In respiratory tract infections (n = 9,567 patients), there was no significant difference: the RR was 0.81 (98.3% CI: 0.61–1.09; p = 0.04).
GENEHUNTER: Your ‘One-Stop Shop’ for Statistical Genetic Analysis?
Authors: Nyholt Dale R.
Published: April 2003

The past decade has brought a proliferation of statistical genetic (linkage) analysis techniques, incorporating new methodology and/or improvement of existing methodology in gene mapping, specifically targeted towards the localization of genes underlying complex disorders. Most of these techniques have been implemented in user-friendly programs and made freely available to the genetics community. Although certain packages may be more ‘popular’ than others, a common question asked by genetic researchers is ‘which program is best for me?’. To help researchers answer this question, the following software review aims to summarize the main advantages and disadvantages of the popular GENEHUNTER package.
Faster Haplotype Frequency Estimation Using Unrelated Subjects
Authors: Zhao Jing Hua , Sham Pak Chung
Published: April 2003

Linkage disequilibrium (LD) between tightly linked loci provides fine mapping information of disease-predisposing allelic variants. The most common method of LD analysis involves unrelated cases and controls. We have previously proposed model-free and permutation tests for diseases with unknown mode of inheritance that can be applied to several highly polymorphic loci. However, performing such analyses remained computer intensive. In this report we propose a speed-up of both the gene-counting procedure and the permutation procedure. We demonstrate the improved method with an analysis of schizophrenia and human leucocyte antigen markers, and an analysis of alcoholism and mitochondrial aldehyde dehydrogenase markers. Our implementation also allows the rapid calculation of permutation-based LD measures and related statistics.
The Linkage Information Content Value of Polymorphism Genetic Markers in Model-Free Linkage Analysis
Authors: Guo Xiuqing , Olson Jane M. , Elston Robert C. , Niu Tianhua
Published: April 2003

Guo and Elston [Hum Hered 1999;49:112–118] developed a linkage information content (LIC) value to measure the informativeness of a marker for identity-by-descent (IBD) sharing status of relative pairs. LIC values were derived for five types of relative pairs: full sib, half sib, grandparent-grandchild, first cousin and avuncular. In this paper, we give corrected LIC values for full sib, grandparent-grandchild, first cousin and avuncular pairs, and indicate the availability of a computer program to calculate them.
Hypothesis Testing for Data from Different Family Study Designs
Authors: Wilson Susan R.
Published: April 2003

A test statistic that is valid for data collected according to a particular type of family study design is not necessarily valid when applied to data obtained from a different type of family study design. When this can occur, a different test that usually is valid is developed for each type of family study design. However, investigators might find that their data come from two (or more) different family study designs, each requiring a different test, yet they want an overall conclusion, essentially a valid hypothesis test that is as powerful as possible. When the underlying genetic model is unknown, it is not clear how to proceed, as several alternative approaches might appear feasible. By using as an example the development of a test of association for data concerning affected singletons and their parents and affected sib pairs and their parents, it is shown that it may not be possible to develop a universally optimal approach without knowledge of the underlying genetic model.
Economic Evaluation of Donepezil Treatment for Alzheimer’s Disease in Japan
Authors: Ikeda Shunya , Yamada Yukari , Ikegami Naoki
Published: April 2003

To demonstrate the economic impact of donepezil treatment for patients with mild to moderate Alzheimer’s disease (AD) in Japanese clinical settings, we conducted a cost-utility analysis using the Markov model. This analysis was made from a payer’s perspective, and the cost was estimated based on the fee schedule of the Japanese national health insurance and the long-term care insurance. The results of the clinical trial of donepezil on AD in Japan were used to estimate the drug efficacy. Under the base-case analysis with a 2-year time horizon, donepezil treatment for patients with mild to moderate AD was considered to be an economically dominant strategy compared to conventional therapy.
Age- and Dementia-Associated Impairments in Divided Attention: Psychological Constructs, Animal Models, and Underlying Neuronal Mechanisms
Authors: Sarter M. , Turchi J.
Published: April 2003

Following a brief description of the psychological construct ‘divided attention’, impairments in divided attention and related executive functions are discussed as the major variable in the development and manifestation of age- and dementia-associated cognitive impairments. Neuropsychological and functional imaging studies in humans have indicated that dorsolateral and ventrolateral prefrontal, cingulate, parietal and premotor cortical areas are involved in the mediation of dual task performance. Furthermore, reduced activity in these areas has been suggested to mediate age- and dementia-associated impairments in divided attention. Experimental studies in animals have provided strong support for the hypothesis that cholinergic projections terminating in all cortical areas and layers crucially mediate the performance in tasks that tax processing capacity and/or the allocation of processing resources to competing demands. This specification of the ‘cholinergic hypothesis’ is evaluated in light of recent critical accounts of the role of this system in the development of age- and dementia- related cognitive disorders. The converging animal experimental and human neuropathological, as well as neuropsychological, evidence indicates that decreases in the integrity of cortical cholinergic inputs represent a necessary, possibly even sufficient, neuronal process mediating the impairments in divided attention and the resulting, broad decline in cognitive functions.
The Disablement Process: A Conceptual Framework for Dementia-Associated Disability
Authors: Barberger-Gateau P. , Fabrigoule C. , Amieva H. , Helmer C. , Dartigues J.F.
Published: April 2003

Most of the social and economic burden of dementia is attributable to its consequences in terms of disability. In this review, we describe the concepts defined in the disablement process model of Verbrugge and Jette [Soc Sci Med 1994;38:1–14] and show how they apply to dementia. The main pathway leads from pathology to impairments, functional limitations and disability. Pathologies (any cause of dementia) are expressed by impairments in specific cognitive processes. Functional limitations are limitations in generic cognitive tasks such as remembering a list of words or orientating oneself in time and space. They are responsible for disability in activities of daily living. Predisposing risk factors as well as introduced intraindividual and extraindividual factors speed up or slow down the main pathway. We show how the model can help in understanding the functional consequences of dementia, for better assessment and management of demented subjects.
Frontal Impairment in Subcortical Ischemic Vascular Dementia in Comparison to Alzheimer’s Disease
Authors: Cannatà A.P. , Alberoni M. , Franceschi M. , Mariani C.
Published: April 2003

We compared the performance of patients with Alzheimer’s disease to that of patients with subcortical vascular dementia (s-IVD) in a set of tasks assessing categorization abilities, sustained and selective attention, and set-shifting and set-maintaining skills. Only the measures of naming and categorization abilities on the Test of Classification and Recall of Pictures (TCRP) proved useful in differentiating AD from s-IVD patients. s-IVD patients showed worse performance than AD on the TCRP categorization measures, while both AD and s-IVD patients were equally impaired in other tasks assessing executive functions (EF). With respect to the naming task, s-IVD patients made significantly more perseverative and unrelated errors than AD patients. Moreover, in the s-IVD group, we found a strong correlation between categorization ability and an attentional test score (Attentional Matrices), while no such correlation emerged in the AD group. These results suggest a dissociated impairment of EF in the 2 dementia groups. In our view, the lack of inhibition and the inability to manipulate complex information are responsible for a greater executive dysfunction in s-IVD patients in comparison with AD patients. The capacity to build up strategies appears more preserved in AD patients, whose impaired performance in executive tasks seems to be related to an impairment of attentional shifting and working memory.
Decreased CSF-β-Amyloid 42 in Alzheimer’s Disease and Amyotrophic Lateral Sclerosis May Reflect Mismetabolism of β-Amyloid Induced by Disparate Mechanisms
Authors: Sjögren Magnus , Davidsson Pia , Wallin Anders , Granérus Ann-Kathrine , Grundström Eva , Askmark Håkan , Vanmechelen Eugeen , Blennow Kaj
Published: April 2003

Both tau and β-amyloid 42 (Aβ42) have been implicated in Alzheimer’s disease (AD) and tau alone in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). These proteins can be measured in the cerebrospinal fluid (CSF); differences from normal CSF levels may reflect pathophysiological mechanisms. Using ELISAs, we investigated the levels of total CSF-tau (here referred to as tau), phosphorylated CSF-tau (phosphotau), and Aβ42 in patients with AD (n = 19), FTD (n = 14), ALS (n = 11) and Parkinson’s disease (PD; n = 15) and in age-matched controls (n = 17). Both CSF-tau and CSF-phosphotau were increased in AD compared with FTD (p < 0.001), ALS (p < 0.001), PD (p < 0.001) and controls (p < 0.001). CSF-Aβ42 was markedly decreased in AD and ALS (both p < 0.001) and slightly decreased in FTD (p < 0.01) and PD (p < 0.05) compared with controls. Using CSF-phosphotau may improve the differentiation of AD from FTD and ALS in clinical praxis. Furthermore, decreased CSF-Aβ42 levels may be common in neurodegenerative disorders possibly reflecting changes in the metabolism of β-amyloid or axonal degeneration.
Cognitive Deficits and Polymorphism of Apolipoprotein E in Alzheimer’s Disease
Authors: Łuczywek Elżbieta , Nowicka Anna , Pfeffer Anna , Czyżewski Krzysztof , Styczyńska Maria , Łałowski Maciej , Barcikowska Maria
Published: April 2003

The aim of this study was to test the relationship between apolipoprotein E (ApoE) genotypes and patterns of cognitive deficits in Alzheimer’s disease (AD). All subjects were diagnosed as probable AD patients on the basis of the DSM-IV and NINCDS-ADRDA criteria. Each subject was examined for (1) ApoE genotype, (2) general level of mental activity (Global Deterioration Scale and Mini-Mental State Examination) and (3) cognitive functions by means of a battery of neuropsychological tests. On the basis of ApoE genotype, patients were subdivided into two groups: the first group consisted of patients with at least one Ε4 allele (Ε4+ group), while the second one consisted of patients without the Ε4 allele (Ε4– group). Our results showed that several cognitive processes depended on the ApoE genotype. In early stages of AD, patients from the Ε4+ group had greater deficits in delayed recall of new information. On the other hand, working memory appeared to be more impaired in the Ε4– group of patients. Independent of the genotype, both groups showed similar impairment of learning ability without, however, deficits in remote memory.
Increased Serum Levels of CD95 in Alzheimer’s Disease
Authors: Richartz E. , Noda S. , Schott K. , Günthner A. , Lewczuk P. , Bartels M.
Published: April 2003

There is growing evidence for a role of apoptosis in Alzheimer’s disease (AD). Recent findings suggest an increased susceptibility of lymphocytes to apoptosis in AD. To prove the hypothesis of systemic alterations in the apoptotic balance in AD, serum and cerebrospinal fluid levels of soluble CD95, which is known to mediate apoptosis, were measured. In the serum, AD patients exhibited significantly higher levels of CD95 than the controls (p = 0.017), suggesting an involvement of peripheral markers in AD.
Growth Factor Control of CNS Myelination
Authors: Park Song-Kyu , Solomon David , Vartanian Timothy
Published: April 2003

The molecular signals required for initiating myelination and maintenance of the myelin internode are not known. Several growth factor families have been implicated in promoting oligodendrocyte survival or differentiation and may have consequences on formation of myelin. We developed a reliable assay for detecting ensheathment of neurites by oligodendrocytes in spinal cord explants. This system was used to assay the effect of selected growth factors on myelin internode formation. We examined the influence on myelination of the polypeptide growth factors neuregulin (NRG), platelet-derived growth factor (PDGF), leukemia inhibitory factor (LIF), and the thyroid hormone T3. We found that NRG, PDGF, and T3 treatments enhanced myelination while LIF treatment inhibited it. We furthermore found that the most potent combination of factors to enhance myelination was NRG and T3. Our results demonstrate that the role of growth factors on CNS myelination can be reliably studied in a controlled in vitro environment and that the impact of individual or combinations of growth factors on myelination cannot be predicted by their known effects on oligodendrocyte survival, proliferation, or differentiation.
Neuregulin: An Oligodendrocyte Growth Factor Absent in Active Multiple Sclerosis Lesions
Authors: Viehover Andrea , Miller Robert H. , Park Song-Kyu , Fischbach Gerald , Vartanian Timothy
Published: April 2003

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) which results in demyelination and axonal injury. Conventional therapy for MS is immune suppression in the absence of agents that promote neural and glial survival or remyelination. Neuregulins are a family of ligands that exert trophic effects on both neurons and glia. Using mice bearing a null mutation in the neuregulin gene, here we demonstrate that neuregulins are necessary for the normal development of oligodendrocytes. In addition, neuregulins are produced in the normal human CNS by astrocytes as well as neurons. Astrocyte-derived neuregulin is functionally active in bioassays and exists in secreted and membrane-associated β-isoforms. In active and chronic active MS lesions, however, the expression of astrocyte neuregulin is dramatically reduced. The absence of neuregulin in active MS lesions may contribute to the paucity of remyelination in MS.
Identification of Genes in the Oligodendrocyte Lineage through the Analysis of Conditionally Immortalized Cell Lines
Authors: Campagnoni Celia W. , Landry Charles F. , Pribyl Thomas M. , Schonmann Vilma , Kampf Kathy , Handley Vance W. , Watson Joseph B. , Bongarzone Ernesto R. , Campagnoni Anthony T.
Published: April 2003

The mouse oligodendrocyte cell lines, N19 and N20.1, were used as sources of potential stage-specific RNA in order to construct a subtraction library enriched in cDNAs expressed early in the oligodendrocyte (OL) lineage. From this library, 23 clones were examined and three were examined in most detail. The mRNAs of the three library clones were preferentially expressed in the N19 (progenitor) compared to the N20.1 (immature) OL line. One of these corresponded to the intermediate filament protein cytokeratin K19, which has not been reported to be expressed in OLs previously. Another was identified as the mouse homolog of T-cadherin, previously reported not to be present in OLs. Antisera raised against a T-cadherin peptide indicated the protein colocalized with the OL lineage markers A2B5, A007, and 01 in mouse primary glial cultures. However, small round cells resembling OL precursors labeled intensely with T-cadherin, but were negative for the other markers, suggesting that this gene might be expressed earlier in the lineage. In early postnatal brain, in addition to the expected neuronal tracts, the T-cadherin antibody labeled small bipolar cells, ∼8–10 µm in diameter, in white matter tracts. These cells had the morphology of OLs or their precursors and were identified within the cerebellar white matter and the corpus callosum, regions rich in OLs. The third clone, 3g5, was homologous to the P8 clone isolated from rat pancreas. It encoded an 80-amino-acid polypeptide with a protein kinase C domain suggesting a possible role in signal transduction. Antisera to this peptide also colocalized 3g5 with cells expressing A2B5, A007, and 01 in culture and in cells within white matter tracts which had the same morphology as those labeled by T-cadherin in these regions. In addition to these, β10 thymosin and mevalonate kinase clones were also isolated from the screen.
The Expression of Thymidine Phosphorylase Suppresses Spontaneous Apoptosis of Cancer Cells in Esophageal Squamous Cell Carcinoma
Authors: Ikeguchi Masahide , Sakatani Takashi , Ueta Tsuyoshi , Fukuda Kenji , Yamaguchi Ken-ichi , Tsujitani Shun-ichi , Kaibara Nobuaki
Published: April 2003

Objective: Thymidine phosphorylase (TP) is an enzyme which converts thymidine to thymine. TP is expressed in a variety of human carcinomas and is known to be a potent angiogenic factor. A recent in vitro study indicated that TP is involved in the intracellular apoptotic signal transduction pathway. The aim of this study was to investigate the correlations between the expression of TP, microvessel density (MVD) and the occurrence of spontaneous apoptosis in esophageal squamous cell carcinoma (ESCC). Methods: The expression of TP, intratumoral MVDs and percentages of apoptotic cancer cells, expressed by the apoptotic index (AI), of 155 tumors from 155 patients with ESCC were analyzed by immunohistochemistry and compared. Results: Positive TP expression in cancer and stromal cells was detected in 89 (57.4%) and 104 (67.1%) cases, respectively. The mean MVD and mean AI of the 155 tumors were 288/mm2 (range: 36–668/mm2) and 2.1% (range: 0–20.4%). The mean MVD of 104 tumors with TP-positive stromal cells (336/mm2) was higher than that of 51 tumors with TP-negative stromal cells (188/mm2, p < 0.001). However, the mean MVD of 89 tumors with TP-positive cancer cells (293/mm2) did not differ from that of 66 tumors with TP-negative cancer cells (280/mm2, p = 0.509). On the other hand, the mean AI of 89 tumors with TP-positive cancer cells (1.2%) was lower than that of 66 tumors with TP-negative cancer cells (3.4%, p < 0.001). However, the mean AI of 104 tumors with TP-positive stromal cells (1.9%) did not differ from that of 51 tumors with TP-negative stromal cells (2.6%, p = 0.058). No significant correlation between the MVDs and the AIs was observed (ρ = –0.067, p = 0.409). Conclusion: In ESCC, TP may play an important role in tumor progression by increasing microvessels and suppressing apoptosis of cancer cells.
Differential Effects of Sex Steroids on T and B Cells: Modulation of Cell Cycle Phase Distribution, Apoptosis and bcl-2 Protein Levels
Authors: McMurray Robert W. , Suwannaroj Siraphop , Ndebele Kenneth , Jenkins John K.
Published: April 2003

Sex steroids have dramatic and differential effects on classic endocrine organ proliferation and apoptosis. In this investigation we sought to delineate similar effects of sex steroids on proliferation, cell cycle phase and apoptosis in lymphocyte cell lines as models for T and B cells. Estrogen and testosterone inhibited T cell line proliferation, induced accumulation of cells in S/G2M phases of the cell cycle, and increased apoptosis in a concentration- and time-dependent manner. There was a more modest effect of estrogen and testosterone on cell cycling and apoptosis in B lymphocyte cell lines, suggesting that estrogen and testosterone are inhibitory to T but not B cell lines. In comparison, progesterone induced cytostasis and modestly increased apoptosis in both T and B cell lines. Estrogen and testosterone were not antagonistic or synergistic to each other in their effects on cell cycle phase distribution, and only minimally synergistic for apoptosis. In contrast, progesterone antagonized cell cycle and apoptotic effects of estrogen in T cells. Estrogen-induced cell cycle and apoptotic effects in T cell lines were associated with suppression of bcl-2 protein levels, which were unaffected in Raji B cells. Progesterone also antagonized the estrogen-induced changes in T cell bcl-2 protein levels. These results suggest that there may be significant and differential sex steroid effects on T and B lymphocytes that may be important to sexual dichotomies in immune and autoimmune responses.
Expression of TCL1 in Hematologic Disorders
Authors: Roos J. , Hennig I. , Schwaller J. , Zbären J. , Dummer R. , Burg G. , Tobler A. , Virgilio L. , Croce C.M. , Fey M.F. , Borisch B.
Published: April 2003

Objective:TCL1, MTCP1 and TCL1b are three members of a new family of oncogenes that are expressed in T cell leukemias of ataxia telangiectasia patients (T-PLL, T-CLL). TCL1 is located at 14q32.1 and activated by juxtaposition to the α/δ-locus at 14q11 or β-locus at 7q35 of the T cell receptor during the reciprocal translocations t(14;14)(q11;q32), t(7;14)(q35;q32), or inversion inv(14)(q11;q32). TCL1 encodes a predominantly cytoplasmic protein of 114 aa (14 kD) of unknown function. Recent studies suggest that TCL1 promotes cell survival rather than stimulating cell proliferation, as previously proposed. Methods: In an attempt to clarify the contexts in which TCL1 is expressed, we investigated TCL1 expression in 114 lymphoma and leukemia patients by Northern blot, RT-PCR and immunohistochemistry. Results:TCL1 expression is restricted to lymphoid cells, and is found in neoplastic (T and B cell neoplasms, and Hodgkin’s disease) and nonneoplastic proliferations (reactive lesions). Out of 114 cases, 18 neoplasms of myeloid and 4 cases of epithelial origin were TCL1-negative. In lesions of the lymphoid system, both low- and high-grade lymphomas were found to express TCL1. Conclusions: We propose that TCL1 expression especially in high-grade B cell non-Hodgkin’s lymphomas might interfere with B cell differentiation and promote the transition from low- to high-grade lymphoma.
Genetic Analysis of the Human Oncoprotein MDM2 in Benign and Malignant Tumors of the Salivary Gland
Authors: Schlott Thilo , Nagel Holger , Laskawi Rainer , Eiffert Helmut , Droese Manfred
Published: April 2003

Introduction: Genetic alterations of oncogene MDM2 promote malignant transformation of several human tumors. In tumors of the salivary gland, however, the genetic status of MDM2 has not been evaluated so far. Methods and Results: Benign and malignant tumors of the salivary gland (6 pleomorphic adenomas, 3 Warthin’s tumors, 1 adenocarcinoma, 1 basal cell adenocarcinoma, 1 mucoepidermoid carcinoma, 3 acinic cell carcinomas, 2 adenoid cystic carcinoma, 1 squamous cell carcinoma) were analyzed by fluorescence-based PCR techniques and immunochemistry for MDM2 gene amplification, MDM2 gene expression, MDM2 gene mutation, MDM2 RNA splicing and MDM2 accumulation. Data show that all samples contained nonamplified MDM2 genes with nonmutant zinc finger regions. However, in two benign and two malignant samples, novel MDM2 mRNA splicing variant types 1 and 2 were detected. Furthermore, three malignant tumors revealed significant nuclear MDM2 accumulation. Correlation between levels of MDM2 mRNA and MDM2 protein could not be detected in the specimens. Conclusion: The present study suggests that MDM2 gene mutation and gene amplification do not contribute to MDM2 accumulation detected in malignant tumors of the salivary gland. However, the role of novel MDM2 splicing variants in MDM2 expression and malignant transformation must be elucidated further.
Expression of Minichromosome Maintenance 2 (MCM2), Ki-67, and Cell-Cycle-Related Molecules, and Apoptosis in the Normal-Dysplasia-Carcinoma Sequence of the Oral Mucosa
Authors: Kodani Isamu , Shomori Kohei , Osaki Mitsuhiko , Kuratate Itaru , Ryoke Kazuo , Ito Hisao
Published: April 2003

Objective: We examined cell cycle and cell death biomarker trends with the normal-dysplasia-carcinoma sequence of the oral epithelia analyzing the pathological significance of a new biomarker, minichromosome maintenance 2 (MCM2). Methods: This study analyzed 12 patients with normal oral epithelia, 69 with dysplasia, and 35 with squamous cell carcinoma (SCC); in 13 patients, SCCs were preceded by dysplasia. The sections were immunostained for MCM2, Ki-67, P53, P27Kip1 and P21CIP1/WAF1, and conducted by TUNEL methods. Western blot analysis of MCM2 was performed in the 4 human cultured oral SCCs, all of which showed the expression. Results: Significantly higher labeling indices (LI; %) of MCM2, Ki-67, and P53, as well as lower LI of TUNEL indices (TI; %), P27, and P21 were noted in the SCCs than in the dysplasias. The 13 dysplasias developed SCC with significantly higher LI of MCM2 and P53, and lower LI of P21 than the other dysplasias (each p < 0.05). The LI of MCM2, P21 and the TI were not correlated with P53 expression. Conclusions: Oral dysplasia was characterized by lower cell proliferation and a higher frequency of cell death compared to SCCs. The higher LI of MCM2 and P53 and the lower LI of P21 might predict malignant transformation of oral dysplasia. MCM2 is regulated via a P53-independent pathway, and a useful biomarker of proliferating cells.
Genomic organization and chromosomal mapping of the basic helix-loop-helix factor OUT (Tcf23/TCF23)
Authors: Tachibana M. , Narumi O. , Muguruma K. , Yamamoto I. , Shinkai Y. , Yokota Y.
Published: April 2003

The genomic organization of Tcf23, the gene coding for mouse OUT, a basic helix-loop-helix transcription factor, was determined and its chromosome location was assigned to the A3 region of chromosome 5. By in silico searching, we further found the human counterpart of the mouse OUT gene (TCF23) in the draft human genome sequence and assigned it to 2p24→p23.
Conserved synteny and gene order difference between human chromosome 12 and pig chromosome 5
Authors: Goureau A. , Garrigues A. , Tosser-Klopp G. , Lahbib-Mansais Y. , Chardon P. , Yerle M.
Published: April 2003

A comparative map of human chromosome 12 (HSA 12) and pig chromosome 5 (SSC 5) was constructed using ten pig expressed sequence tags (ESTs). These ESTs were isolated from primary granulosa cell cultures by differential display (EST b10b), or from a granulosa cDNA library (VIIIE1, DRIM, N*9, RIIID2 and RVIC1) or from a small intestine cDNA library (ATPSB, ITGB7, MYH9, and STAT2). Also used were two Traced Orthologous Amplified Sequence Tags (TOASTs) (LALBA, TRA1), one microsatellite-associated gene (IGF1) and finally five human YACs selected for their cytogenetic position, with a view to increasing the number of informative markers for the comparison. Large-insert clones were obtained by screening a pig bacterial artificial chromosome (BAC) library with specific primers for each EST and TOAST and for IGF1. These BACs were used as probes for fluorescent in situ hybridisation (FISH) both on porcine and human metaphases. In addition, the human YACs were FISH mapped on pig chromosomes. This allowed us to refine and, in some cases, to correct the previous mapping obtained with a somatic cell hybrid panel. While these data confirm chromosome painting results showing that the distal part of SSC 5p arm is conserved on HSA 22, while the rest of the chromosome corresponds to HSA 12, they also demonstrate gene-order differences between human and pig. In addition, it was also possible to determine the position of the synteny breakpoint.
Chromosomal localization of SLC12A5/Slc12a5, the human and mouse genes for the neuron-specific K+-Cl– cotransporter (KCC2) defines a new region of conserved homology
Authors: Sallinen R. , Tornberg J. , Putkiranta M. , Horelli-Kuitunen N. , Airaksinen M.S. , Wessman M.
Published: April 2003

K+-Cl– cotransporters (KCCs) constitute a branch of the cation-chloride cotransporter (CCC) family. To date, four KCC isoforms (KCC1-KCC4) have been identified and they all mediate obligatorily coupled, electroneutral transmembrane movement of K+ and Cl– ions. KCC2 (gene symbol SLC12A5) is expressed exclusively in neurons within the central nervous system and abnormalities in its expression have been proposed to play a role in pathological conditions such as epilepsy and neuronal trauma. Here we have determined chromosome location of both the human and the mouse genes encoding KCC2, which may assist in future efforts to determine the contribution of KCC2 to inherited human disorders. We assigned human SLC12A5 to 20q12→q13.1 and its murine homolog, Slc12a5, to 5G2–G3 by fluorescence in situ hybridization (FISH). These mapping data are contradictory to the previously reported human-mouse conserved synteny relationships disrupting an exceptionally well-conserved homology segment between human Chr 20 and mouse Chr 2. We hence suggest the first region of conserved homology between human Chr 20 and mouse Chr 5.
Expression pattern and further characterization of human MAGED2 and identification of rodent orthologues
Authors: Langnaese K. , Kloos D.U. , Wehnert M. , Seidel B. , Wieacker P.
Published: April 2003

In a search for genes involved in X-linked mental retardation we have analyzed the expression pattern and genomic structure of human MAGED2. This gene is a member of a new defined MAGE-D cluster in Xp11.2, a hot spot for X-linked mental retardation. Rat and mouse orthologues have been isolated. In contrast to the genes of the MAGE-A, MAGE- B and MAGE-C clusters, MAGED2 is expressed ubiquitously. High expression was detected in specific brain regions and in the interstitium of testes. Five SNPs in the coding region of human MAGED2 were characterized and their allele frequencies determined in a German and Turkish population.
Dilated Intercellular Spaces as Markers of Reflux Disease: Histology, Semiquantitative Score and Morphometry upon Light Microscopy
Authors: Villanacci V. , Grigolato P.G. , Cestari R. , Missale G. , Cengia G. , Klersy C. , Rindi G.
Published: April 2003

Background and Aims: A recent electron microscopy study suggested that dilated intercellular spaces (DIS) are specific for acid reflux-damaged esophageal epithelium. Electron microscopy is, however, expensive and difficult to apply to routine biopsies. The aims of this study are to establish a method for assessing DIS on light microscopy of esophageal biopsies and to estimate its association with current clinicopathological parameters of esophagitis. Materials and Methods: 21 patients with reflux symptoms were investigated. Light microscopy biopsies were assessed for DIS size by a semiquantitative method and computer-assisted, static morphometry. A DIS score accounting for DIS size and distribution was assigned to each patient and its association with 30 clinicopathological variables investigated by univariate and multivariate logistic regression. Results: Both the semiquantitative method and static morphometry identified 4 different classes of DIS size. The DIS score was significantly and independently associated with the esophageal symptoms score, the histological score of esophagitis and the relevant morphometry data. Conclusions: DIS may be efficiently assessed during light microscopy of routine esophageal biopsies. Since correlation with both the histology and the symptoms of esophagitis, the DIS score may be considered a novel parameter of esophagitis and is suggested for the routine evaluation of esophageal biopsies in patients with reflux disease.
Detection of Human Papillomavirus DNA and p53 Gene Mutations in Esophageal Cancer Samples and Adjacent Normal Mucosa
Authors: Astori Giuseppe , Merluzzi Sonia , Arzese Alessandra , Brosolo Piero , de Pretis Giovanni , Maieron Roberto , Pipan Corrado , Botta Giuseppe A.
Published: April 2003

Background/Aim: There is evidence of a possible etiological role of human papillomaviruses (HPVs) in the development of esophageal tumors. Loss of function of the wild-type p53 tumor suppressor gene product by binding to E6 oncoproteins of high-risk HPVs is considered an important event in tumor development. The aim of this study was to verify the prevalence of HPV infection and p53 mutation in esophageal tumor tissue samples and in the adjacent normal mucosa in patients from a high-risk area in Italy. Methods: DNA from 33 biopsy specimens (17 tumor sample biopsies and 16 samples of adjacent normal mucosa) was screened for HPV DNA using two polymerase chain reaction based procedures. Restriction fragment length polymorphism analysis was used for typing. Screening of p53 mutations was performed with polymerase chain reaction-single strand conformation polymorphism analysis and DNA sequencing. Results: Overall, 8 of 17 patients presented HPV DNA; HPV 16 was detected in 4 of 8 samples. Samples from tumors and adjacent mucosa were positive for mucosal HPVs in 7 of 17 and 4 of 16 cases, respectively. In 1 case, HPV DNA was detected in the normal mucosa only. None of the samples contained HPVs of the epidermodysplasia verruciformis or cutaneous groups. Mutations of p53 were detected in two HPV DNA negative samples. In both cases, the mutation was present in the tumor only. Conclusions: Our results are in favor of the involvement of both aberrant p53 expression and HPV infection in the development of esophageal tumors. The high HPV infection rate in patients from a high-risk region suggests that subjects harboring HPVs (in particular HPV 16) in the esophagus should be considered at risk of esophageal malignancies.
Sensory and Biomechanical Responses to Distension of the Normal Human Rectum and Sigmoid Colon
Authors: Petersen Poul , Gao Chunwen , Rössel Petra , Qvist Peter , Arendt-Nielsen Lars , Gregersen Hans , Mohr Drewes Asbjørn
Published: April 2003

Background: Visceral pain is a major clinical problem. The aim of the present study was to compare the pain and biomechanical responses to standardized distension of the human colon. Methods: The relation between pain intensity and pressure, cross-sectional area (CSA) and tension-strain relations of the rectum and sigmoid colon were studied in 11 normal subjects following standardized distension using impedance planimetry. The bag was inflated stepwise with pressures up to 6 kPa. The subjects, who were blinded for the distension procedure, rated their pain intensity using an aggregate visual analogue score (VAS) combining the intensity of the feeling of air, urge to defecate and pain. Results: The distensions produced an initial rapid increase in CSA followed by a phase of slow increase until a steady state CSA was reached after 0.5–1 min. Several phasic contractions (observed as short-term decreases in the CSA) were recorded in the rectum from the end of the rapid phase to the end of distension at pressures from 1 to 5 kPa. The CSA in the rectum and sigmoid colon was 3,706 ± 426 mm2 and 2,305 ± 426 mm2 at the maximum bag pressure of 6 kPa (F = 52.4, p < 0.001). The tension-strain relation did not differ between the normal rectum and sigmoid colon. The VAS score for every modality (air, defecation and pain) revealed an increase in intensity as a function of pressure. The VAS score in the rectum and the sigmoid colon as a function of tension and strain did not show any differences. Conclusions: The biomechanical properties in the sigmoid colon and rectum were alike. For a given wall tension and circumferential strain the sensibility seems equal in the rectum and the sigmoid colon. The observed difference in perception between the two segments was related to the greater CSA in the rectum.
Less Damaging Effect of Whisky in Rat Stomachs in Comparison with Pure Ethanol
Authors: Iino Taeko , Nakahara Koichi , Miki Wataru , Kiso Yoshinobu , Ogawa Yoshihiro , Kato Shinichi , Takeuchi Koji
Published: April 2003

Background/Aim: Ellagic acid (EA), one of the polyphenols that are abundantly contained in whisky as a nonalcoholic component, has antioxidant and anti-inflammatory activities. In the present study, we compared the action of whisky and pure ethanol on the rat gastric mucosa, and examined the role of EA in the less-damaging effect of whisky in the stomach. Methods: Under urethane anesthesia, a rat stomach was mounted in an ex vivo chamber, perfused with saline, and the transmucosal potential difference (PD) was measured before and after exposure to whisky (Yamazaki, Suntory) and ethanol (43%). In a separate study, the animals were given whisky or ethanol (1 ml, 43%) p.o. under unanesthetized conditions, killed 1 h later, and the gastric mucosa was examined for hemorrhagic lesions. Results: Both whisky and ethanol caused a PD reduction, resulting in damage in the stomach, but these responses were less marked in the case of whisky. Although the reduced PD recovered gradually after removal of ethanol, this process was significantly expedited by co-application of EA (80 µg/ml), the recovery rate being much the same as that observed after exposure to whisky. The less-damaging effect of whisky was confirmed in unanesthetized rats after p.o. administration of these agents. In addition, EA (1–30 mg/kg), administered p.o. together with absolute ethanol (99.9%), reduced the severity of gastric lesions induced by ethanol, in a dose-dependent manner, and the effect at 30 mg/kg was equivalent to that obtained by the whisky component containing several low- and high-molecular-weight polyphenols. EA had a scavenging action against both oxygen and hydroxyl radicals in vitro, the effect being equivalent to that of catechol or α-tocopherol. Conclusion: These results suggest that whisky is less irritating to the gastric mucosa, as compared with pure ethanol, and this property of whisky may be explained by EA, one of polyphenols contained in whisky, and its radical scavenging action.