bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a High-Affinity Folate Receptor in Normal and Malignant Human Testicular Tissue
Authors: Holm Jan , Hansen Steen Ingemann , Høier-Madsen Mimi , Christensen Thomas Broe , Nichols Carl W.
Published: March 2003

We have characterized the folate receptor in normal and malignant tissue from male gonads. Radioligand binding displayed characteristics typical of other folate receptors. Those included a high-affinity type of binding (K = 1010 M−1), apparent positive cooperativity changing into non-cooperativity at low receptor concentrations, a tendency to increased binding affinity with decreasing receptor concentrations, a slow dissociation at pH 7.4 becoming rapid at pH 3.5 and inhibition by folates, in particular oxidized forms. The gel filtration profile of Triton X-100 solubilized tissue contained a 25 and 100 kDa peak of radioligand-receptor. The latter peak could represent receptor equipped with a hydrophobic membrane anchor that inserts into Triton X-100 micelles. The concentration of radiolabelled receptor ranged from 0.41 nmol/g protein to 1.68 nmol/g protein in specimens of normal testicular tissue from patients with prostatic carcinomas and from 1.54 nmol/g protein to 3.82 nmol/g protein in testicular tissue from young individuals. Compared to normal testicular tissue the concentration of receptor in seminoma tissue was low (0.38–1.27 nmol/g protein) but showed a higher degree of immunoreactivity in the presence of antibodies against human milk folate binding protein as evidenced by ELISA and immunohistochemistry data. Hence a folate receptor isoform homologous to human milk folate binding protein is apparently expressed in seminomas where the total expression of receptor, however, seems to be lower than in normal testicles.
Tumor Necrosis Factor-Induced Cytotoxicity is Not Related to Rates of Mitochondrial Morphological Abnormalities or Autophagy-Changes that can be Mediated by TNFR-I or TNFR-II
Authors: Prins Johannes B. , Ledgerwood Elizabeth C. , Ameloot Paul , Vandenabeele Peter , Faraco Paulo R. , Bright Nicholas A. , O'Rahilly Stephen , Bradley John R.
Published: March 2003

Tumor necrosis factor (TNF) may cause apoptosis or necrosis and induces mitochondrial changes that have been proposed to be central to cytotoxicity. We report similar patterns of TNF-induced mitochondrial morphological alterations and autophagy in cell types with differing sensitivity to TNF-induced cytotoxicity. Specific ligation of TNFR-I or TNFR-II induces different rates of apoptosis and mitochondrial morphological change, but similar rates of autophagy. These changes do not invariably lead to cell death, and survival or progression to apoptosis or necrosis following TNF exposure may depend in part on the extent of mitochondrial damage and/or the autophagic capacity of the cell.
Theoretical and Methodological Problems of a 10-Year Follow-Up Program Evaluation Study
Authors: Heller Kurt A. , Reimann Ralph
Published: March 2003

Summary In this paper, conceptual and methodological problems of school program evaluation are discussed. The data were collected in conjunction with a 10 year cross-sectional/longitudinal investigation with partial inclusion of control groups. The experiences and conclusions resulting from this long-term study are revealing not only from the vantage point of the scientific evaluation of new scholastic models, but are also valuable for program evaluation studies in general, particularly in the field of gifted education.
An examination of the effects of early and late entry on career attainment
Authors: Hurley Amy E. , Wally Stefan , Segrest Sharon L. , Scandura Terri , Sonnenfeld Jeffrey A.
Published: March 2003

Literature on tournament mobility in internal labor markets (ILMs) is reviewed revealing a paucity of studies examining the promotion patterns of late entrants into internal promotion systems. An investigation of 502 managers in a large corporation indicated that late entry into the ILM organization was significantly and positively related to career attainment, supporting the “clean slate effect”. In addition, experience in the corporate office was positively related to managerial career attainment, while being female was negatively related to career attainment. In contrast to the tournament model theory, the number of years to reach middle management was positively related to career success. While no effect for race was found, this may be due to the relatively low representation of minorities in the firm studied. Moderating effects of late entry on gender, race or corporate experience were also not found.
Men and women engineers in a large industrial organization: interpretation of career progression based on subjective‐career experience
Authors: Ismail Maimunah
Published: March 2003

This paper explores the interpretation of career progression of a group of men and women engineers in a large industrial organization in Malaysia. Data were gathered through in‐depth interviews with 20 engineers about their subjective‐career experience. They were senior engineers selected from four operating units of the organization. The career‐history data indicate that the interpretation of career progression of these engineers is grouped into four themes, namely, the importance of technical and managerial career ladders, engineering career from the perspective of gender, influence of structural change on career, and the importance of personal and organizational factors as well as opportunities affecting career progression.
Recruiting for diversity
Authors: Freeman Cheryl
Published: March 2003

This paper describes some of the findings of an ongoing research study sponsored by a major UK graduate employer wishing to increase the number of job applications that it receives from women. The findings suggest that males and females may hold different perceptions of particular organisations and that this factor may be as significant as different (career) needs or desires in determining their different job application intentions. The paper reviews some of the related points from the organisational choice and work values literature, before going on to describe the research and its findings in more detail. The implications for organisations are discussed, with a particular focus on the role of personal interaction between (current) employees and potential recruits. The application of concepts from the organisational image and identity literatures is used to explore whether making changes to an organisation’s recruitment image, in order to attract more diverse recruits, first requires changing existing employees’ view of the organisation.
Gender asymmetries and the manager stereotype among management students
Authors: Fernandes Emília , Cabral‐Cardoso Carlos
Published: March 2003

In spite of the progress made in the last decades, women still face difficulties in being accepted and recognised as managers. The manager’s role has been perceived as masculine, and the gender stereotypes are therefore, a barrier to women’s access to management. With the aim to explore the relationship between gender stereotypes and management characteristics and discuss its implications for the discrimination of women in management a study was conducted among Portuguese undergraduate management students. The findings indicate that students of both sexes tend to perceive the “manager” category as closer to the masculine stereotype than to the feminine stereotype. Additionally, for male students the “man manager” and “manager” are more similar to each other than the “woman manager” and “manager” categories. However, the image of “woman manager” appears not to distance itself considerably from the “manager” stereotype as a result of her masculinisation. This paper discusses the implications of this asymmetric gender social representation that ultimately hinders the acceptance of women as a social group in the management context.
Suppression Subtractive Hybridization Identifies Distinctive Expression Markers for Coronary and Internal Mammary Arteries
Authors: Qin Minghui , Zeng Zhaohui , Zheng Jie , Shah Prediman K. , Schwartz Stephen M. , Adams Lawrence D. , Sharifi Behrooz G.
Published: March 2003

Objective—We sought to identify differentially expressed genes in the athero-prone coronary artery and athero-resistant internal mammary arteries.

Methods and Results—Using suppressive subtraction hybridization, we generated reciprocal cDNA collections of representative mRNAs specific to porcine coronary arteries versus porcine mammary arteries. We screened 1000 suppressive subtraction hybridization cDNA clones by dot blot array and sequenced 600 of those showing the most marked expression differences. Northern blot, in situ hybridization, and immunostaining confirmed the differential gene expression patterns identified by the dot blot arrays. Genes associated with mammary arteries included claudin-10 and h-cadherin, which are genes associated with tight junctions and intermediate junctions. In contrast, genes associated with proatherosclerotic processes, such as lipid retention and metabolism, inflammation, and cell growth, were preferentially expressed in coronary arteries.

Conclusions—Normal coronary arteries have gene expression program that is significantly different than internal mammary arteries. These differences may partly explain the resistance of coronary arteries and internal mammary arteries to atherosclerosis.
Influence of Interferon-γ on the Extent and Phenotype of Diet-Induced Atherosclerosis in the LDLR-Deficient Mouse
Authors: Buono Chiara , Come Carolyn E. , Stavrakis George , Maguire Graham F. , Connelly Philip W. , Lichtman Andrew H.
Published: March 2003

Objective—

The aim of this study was to investigate the influence of interferon-γ (IFN-γ) on atherosclerosis in low density lipoprotein receptor (LDLR)–null mice.

Methods and Results—

We cross-bred IFN-γ–deficient mice with LDLR-null mice and analyzed lipoprotein profiles and atherosclerosis in the compound mutant progeny after 8 and 20 weeks on a cholesterol-enriched diet. IFN-γ deficiency did not affect serum cholesterol levels or lipoprotein profiles, but it did affect the extent and phenotype of atherosclerosis. Atherosclerotic lesions in IFN-γ–deficient mice were reduced by 75% in the aortic arch and by 46% in the descending aorta compared with control mice after 8 weeks on the diet. After 20 weeks, arch lesions were reduced by 43%, and descending aorta lesions were reduced by 65% in IFN-γ–deficient mice compared with controls. At 8 weeks, percent lesional macrophage and smooth muscle content was significantly less in the IFN-γ–deficient mice, but not at 20 weeks. Although there were fewer class II major histocompatibility complex–positive cells in the lesions of IFN-γ–deficient animals compared with controls, class II major histocompatibility complex expression on endothelial cells overlying lesions persisted in the absence of IFN-γ.

Conclusions—

These data provide direct evidence that IFN-γ influences atherosclerosis development and phenotype in the LDLR-deficient mouse, independent of changes in blood lipoprotein profiles.
Metal concentrations in tissues of the Black Sea fish Mugil auratus from Sinop-Icliman, Turkey
Authors: Filazi Ayhan , Baskaya Ruhtan , Kum Cavit , Hismiogullari Sahver Ege
Published: March 2003

Levels of five heavy metals [copper (Cu), lead (Pb), cadmium (Cd), chromium (Cr) and nickel (Ni)] were evaluated in liver and muscle tissues of fish (Mugil auratus) collected from the Black Sea at Sinop-Icliman, Turkey. Sampling and analysis methods are described. Variations of heavy metal concentrations with seasons are discussed. Cr and Ni concentrations were below the limits of detection (<0.05 and 0.1 ug/g dry weight) in all tissues and seasons. Cu, Pb and Cd were detected within these limits, as mg/kg dry weight, in liver tissue: 0.49-1.30, 0.60-1.21 and 0.15-0.50, and in muscle tissue: 0.30-1.00, 0.57-1.12 and 0.10-0.40, respectively. Cu, Pb and Cd concentrations in these tissues were elevated and the highest heavy metal concentrations were found in the liver. While Cu, Pb and Cd concentrations were highest in fish tissues collected in August 2000, the lowest concentrations of these metals were observed in fish tissues collected in May 2000. Pb had the highest level observed in fish tissues. According to the Turkish Food Codex Regulation's residue limits, the cadmium level determined in fish tissues was high (0.1 mg/g) and the lead level, especially in liver tissue, was high in August (1 mg/ g), while other metals (Cu, Cr and Ni) were within the maximum residue limits.
The role of oxidative stress on the effect of 1,4,7,10,13,16-hexathiacyclooctadecane on copper and zinc toxicity in HepG2 cells
Authors: Smet P W , Elskens M , Bolle F , Dierickx P J
Published: March 2003

Experiments have shown that 1,4,7,10,13,16-hexathiacy clooctadecane (L3) increased the Cu2 toxicity on HepG2 cells, whereas the combination Zn2 /L3 was less toxic relative to the metal control. In all cases, glutathione (GSH) levels were decreased and vitamins C and E supplementation partially counteracted the increased toxicity in the Cu2 /L3-treated cells. The previously observed effects of this hexathiamacrocyclic ligand (L3) on the Cu2 and Zn2 toxicity were further investigated by first depleting the intracellular GSH levels by means of L-buthionine S,R-sulphoximine. Combined treatment with Cu2 /L3 resulted in complete cell death, whereas for Zn2 /L3 no severe effects were observed. Direct measurement of reactive oxygen species (ROS) revealed that Cu2 induced a high degree of oxidative stress on the cells. This was not the case for Zn2. The results proved a previously proposed mechanism in which GSH is used to conjugate the metal–ligand complex, but as a result of this, GSH is no longer available for inactivation of ROS. Also, both the intracellular copper and zinc content were determined for each experiment by means of inductively coupled plasma–atomic emission spectroscopy. According to these data, zinc is depleted in Cu2 /L3-treated cells, which could have consequences on superoxide dismutase and as a result of this on the amount of oxidative stress.
Failure of resting echocardiography and cardiac catheterization to identify pulmonary hypertension in two patients with type I Gaucher disease
Authors: Sirrs S. , Irving J. , McCauley G. , Gin K. , Munt B. , Pastores G. , Mistry P.
Published: March 2003

Pulmonary hypertension (PHT) is a complication of Gaucher disease. Screening with echocardiography is recommended for Gaucher patients. Two patients naive to enzyme replacement therapy are presented in whom resting echocardiography revealed no evidence of PHT. One of the patients also had normal pulmonary artery pressures at cardiac catheterization. The diagnosis of PHT was made with open lung biopsy in one patient and dobutamine echocardiography in the other. In both cases, diagnosis of PHT altered patient management. Resting echocardiographic assessment may fail to identify PHT in patients with Gaucher disease.
A Quantitative Trait Locus Influencing Free Plasma Protein S Levels on Human Chromosome 1q
Authors: Almasy Laura , Soria José Manuel , Souto Juan Carlos , Coll Imma , Bacq Delphine , Faure Alexandra , Mateo José , Borrell Montserrat , Muñoz Xavier , Sala Nuria , Stone William H. , Lathrop Mark , Fontcuberta Jordi , Blangero John
Published: March 2003

Objective—Protein S (PS) is a component of the protein C anticoagulant system. PS deficiency is associated with myocardial infarction and venous thromboembolism, two highly prevalent causes of death in industrialized nations. As part of the Genetic Analysis of Idiopathic Thrombophilia (GAIT) project, we conducted a genome-wide linkage screen to localize genes influencing variation in free PS (fPS) plasma levels.

Methods and Results—fPS levels were measured in 397 individuals in 21 Spanish families. A total of 363 highly informative microsatellite markers were genotyped to provide a 10-cM genetic map, and variance component linkage methods were used. A region on chromosome 1q32, flanked by markers D1S425 and D1S213, showed strong evidence of linkage with fPS levels (LOD score, 4.07; nominalP=7.5×10−6; genome-wideP=0.0024). This region contains two positional candidate genes, the complement component 4-binding protein α and β chains, which encode the principal binding protein for PS. Suggestive evidence for linkage was also observed on chromosomes 11p and 19p.

Conclusions—These results represent one of the first genomic screens for quantitative variation in a component of the hemostatic pathway and provide strong evidence for a locus on chromosome 1q influencing fPS levels.
Construction and initial validation of the Self‐Worth Protection Scale
Authors: Thompson Ted , Dinnel Dale L.
Published: March 2003

Background: The self‐worth theory of achievement motivation holds that in certain circumstances students stand to gain by deliberately withdrawing effort. When failure occurs despite effort, students are likely to conclude that failure resulted from lack of ability. Thus, withdrawing effort offers a defence against conclusions of low ability, thereby protecting self‐worth.

Aim: We undertook to assess the psychometric properties of the Self‐Worth Protection Scale (SWPS).

Sample: Data were obtained from 243 participants (Study 1) and 411 participants (Study 2) enrolled in undergraduate psychology courses at a university in the United States.

Method: We administered a number of scales, including the SWPS and scales assessing a fear of negative evaluation, academic self‐esteem, uncertain global self‐evaluations, self‐handicapping, and causal uncertainty.

Results: Exploratory factor analysis indicated a three‐factor solution (ability doubts, the importance of ability as a criterion of self‐worth, and an avoidance orientation) utilising 33 of the original 44 items. A confirmatory factor analysis indicated that this three‐factor solution was a poor fit of the data. After modifying the model, a confirmatory factor analysis indicated that a three‐factor solution with 26 of the original items and a higher order factor of self‐worth protection was an adequate fit of the data. Reliability measures were acceptable for the three subscales and total score. The total score of the SWPS was positively correlated with theoretically related constructs, demonstrating construct validity.

Conclusions: The SWPS appears to be a psychometrically sound scale to assist in identifying individuals who manifest self‐worth protection in achievement situations.
Direct luminescence chronology of the Epipaleolithic Kebaran site of Nahal Hadera V, Israel
Authors: Godfrey‐Smith D.I. , Vaughan K.B. , Gopher A. , Barkai R.
Published: March 2003

We report direct luminescence ages for the culture‐bearing sediments of the Kebaran site of Nahal Hadera V (NHV) in the coastal plain of Israel. Although the site contains, in addition to rich lithic deposits, plentiful mammalian bone, it has proved to be undatable using radiocarbon dating, in spite of the fact that the cultural context places the time of occupation well within the range of radiocarbon dating. In contrast, luminescence dating of the site sediments proved successful. Luminescence ages were determined using the single aliquot additive‐dose (SAA) method, applied to sand‐sized quartz extracts to determine past equivalent doses (De). Dose rates (R) were calculated using thick source alpha counting for the uranium (U) and thorium (Th) concentrations and x‐ray fluorescence analysis for the potassium (K20) concentration. Of the five samples collected at the site, four represent cultural and subcultural deposits and the fifth represents the geological substrate for the archaeological deposit, a quartz‐rich, carbonate‐cemented dune sand known as aeolianite or kurkar. The luminescence age of the kurkar is 42.7 ± 6.3 ka. Human occupation of the site occurred between 21.3 ka and 14.0 ka ago, during the Last Glacial Maximum. © 2003 Wiley Periodicals, Inc.
Recent progress in the development of coumarin derivatives as potent anti‐HIV agents
Authors: Yu Donglei , Suzuki Madoka , Xie Lan , Morris‐Natschke Susan L. , Lee Kuo‐Hsiung
Published: March 2003

Numerous plant‐derived compounds have been evaluated for inhibitory effects against HIV replication, and some coumarins have been found to inhibit different stages in the HIV replication cycle. This review article describes recent progress in the discovery, structure modification, and structure–activity relationship studies of potent anti‐HIV coumarin derivatives. A dicamphanoyl‐khellactone (DCK) analog, which was discovered and developed in our laboratory, and calanolide A are currently in preclinical studies and clinical trials, respectively. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 3, 322‐345, 2003
Assessing the impact of environmental management systems on corporate and environmental performance
Authors: Melnyk Steven A , Sroufe Robert P , Calantone Roger
Published: March 2003

There has been an increase in interest towards corporate activities aimed at reducing or eliminating the waste created during the production, use and/or disposal of the firm’s products. Prior research has focused on the need for such activities, while current research tries to identify those components that encourage or discourage such activities. As a result of the introduction of ISO 14001, attention has turned to corporate environmental management systems (EMS). The underlying assumption is that such a system is critical to a firm’s ability to reduce waste and pollution while simultaneously improving overall performance. This study evaluates this assumption. Drawing on data provided by a survey of North American managers, their attitudes toward EMS and ISO 14001, this study assesses the relative effects of having a formal but uncertified EMS compared to having a formal, certified system. The results strongly demonstrate that firms in possession of a formal EMS perceive impacts well beyond pollution abatement and see a critical positive impact on many dimensions of operations performance. The results also show that firms having gone through EMS certification experience a greater impact on performance than do firms that have not certified their EMS. Additionally, experience with these systems over time has a greater impact on the selection and use of environmental options. These results demonstrate the need for further investigation into EMS, the environmental options a firm chooses, and the direct and indirect relationships between these systems and performance.
Factors Influencing Men's Interest in Gene Testing for Prostate Cancer Susceptibility
Authors: Culler Duane D. , Silberg Judy , Vanner‐Nicely Lauren , Ware Joy L. , Jackson‐Cook Colleen , Bodurtha Joann
Published: March 2003

Interest in genetic testing for inherited cancer susceptibility is high in the general population. Women at risk for BRCA1 and BRCA2 mutations represent the best‐studied population undergoing genetic testing for cancer susceptibility. However, it is unclear whether factors influencing interest in genetic testing in women are directly applicable to men. We designed a study to examine factors associated with men's interest in genetic testing to identify prostate cancer susceptibility. Our sample consisted of 267 men present in waiting rooms of a urology clinic in an urban area. We examined whether the concept of “monitoring” could be used to predict the interest of men in a genetic test for prostate cancer susceptibility. Our results indicated that “monitoring” trait was positively associated with interest in genetic testing in these men, but principally for patients rather than nonpatients. Moreover we found that monitoring was associated with over estimation of risk in those men with prostate cancer. Other factors found to influence interest in genetic testing included recommendation by a doctor, family history of prostate cancer, and cost. This study indicated that interest in genetic testing and estimation of risk is influenced by a complex interaction between both psychological factors (monitoring) and nonbehavioral factors (such as patient status, cost, and doctor recommendation).
Quantum Logic and Quantum Theory in a Game-Theoretic Perspective
Authors: Pietarinen Ahti
Published: March 2003

Extensive games of imperfect information, together with the associated semantic machinery, can be brought to bear on logical aspects of quantum-theoretic phenomena. Among other things, this kinship implies that propositional logic of informational independence is useful in understanding such quantum theoretic issues as non-locality and EPR-type paradoxes, and that quantum logic exhibits the overall game-theoretical notion of uncertainty.
The Histidine Decarboxylase (HDC) Gene of Tetrahymena Pyriformis is Similar to the Mammalian One. A Study of HDC Expression
Authors: Hegyesi Hargita , Szalai Cs. , Falus A. , Csaba G.
Published: March 2003

RNA was isolated from Tetrahymena pyriformis GL and using human histidine decarboxylase (HDC) gene primers, the RT-PCR product was sequenced. A fraction containing 207 base pairs was compared to the published sequences of prokaryotic and mammalian (rat, mouse and human) HDC cDNA (exons). The HDC-cDNA fraction of Tetrahymena was similar to the mammalian cDNA-s and it was completely different from the prokaryotic HDC-gene. The results indicate the presence of a mammalian-like HDC-gene already in a unicellular eukaryote organism and demonstrates also that the divergence of the prokaryotic–eukaryotic common gene took place already at this low evolutionary level.
Effect of political imprisonment and trauma history on recent Tibetan refugees in India
Authors: Crescenzi Antonella , Ketzer Eva , van Ommeren Mark , Phuntsok Kalsang , Komproe Ivan , de Jong Joop T. V. M.
Published: March 2003

We sought to examine the impact of political imprisonment on anxiety depression, and somatic symptoms reported by newly arrived Tibetan refugees in Dharamsala, India. We used the Hopkins Symptom Checklist‐25 to compare 76 previously imprisoned with 74 never imprisoned recent Tibetan refugees. Previously imprisoned refugees reported more traumatic events, especially torture and deprivation. Previously imprisoned refugees reported more anxiety than nonimprisoned refugees, but the groups were similarly high in terms of depression and number ot somatic complaints. According to assessment with the Harvard Trauma Questionnaire, 20% of the tortured and imprisoned refugees met criteria for posttraumatic stress disorder.
The Effects of pH and Intraliposomal Buffer Strength on the Rate of Liposome Content Release and Intracellular Drug Delivery
Authors: Lee Robert J. , Wang Susan , Turk Mary Jo , Low Philip S.
Published: March 2003

Targeted liposomal drug formulations may enter cells by receptor-mediated endocytosis and then traffick by membrane flow into acidic intracellular compartments. In order to understand the impact of these intracellular pH changes on liposomal drug unloading, the effect of pH on the release from folate-targeted liposomes of three model compounds with distinct pH dependencies was examined. 5(6)-carboxyfluorescein, which titrates from its anionic to uncharged form following internalization by KB cells, displays strong endocytosis-dependent release, since only its uncharged (endosomal) form is membrane permeable. Endocytosis-triggered unloading of drugs of this sort is enhanced by encapsulating the drug in a weak buffer at neutral pH, so that acidification of the intraliposomal compartment following cellular uptake can occur rapidly. Sulforhodamine B, in contrast, retains both anionic and cationic charges at endosomal pH (∼pH 5), and consequently, escapes the endosomes only very slowly. Doxorubicin, which is commonly loaded into liposomes in its membrane-impermeable (cationic) form using an acidic buffer, still displays endocytosis-triggered unloading, since sufficient uncharged doxorubicin remains at endosomal pHs to allow rapid re-equilibration of the drug according to the new proton gradient across the membrane. In this case, when the extraliposomal [H+] increases 250-fold from 4 × 10−8 M (pH 7.4, outside the cell) to 10−5 M (pH 5, inside the endosome), the ratio of doxorubicin inside to outside the liposome must decrease by a factor of 250. Therefore, the collapse of the transliposomal pH gradient indirectly drives an efflux of the drug molecule from the liposome. Since a change in intraliposomal pH is not required to unload drugs of this type, the intraliposomal compartment can be buffered strongly at acidic pH to prevent premature release of the drug outside the cell. In summary, pH triggered release of liposome-encapsulated drugs can be achieved both with drugs that increase as well as decrease their membrane permeabilities upon acidification, as long as the intraliposomal buffer strength and pH is rationally selected.
A secondary respiratory chain defect in a patient with Fanconi–Bickel syndrome
Authors: Odièvre M. H. , Lombès A. , Dessemme P. , Santer R. , Brivet M. , Chevallier B. , Lagardère B. , Odièvre M.
Published: March 2003

A North African boy, the son of consanguineous parents, presented at 8 years of age with hypophosphataemic rickets due to De Toni–Debré–Fanconi syndrome. Hepatomegaly and abnormalities of carbohydrate metabolism were suggestive of Fanconi–Bickel syndrome. This was confirmed by the detection of a mutation within GLUT2, the gene encoding the liver‐type facilitative glucose transporter. The study of the respiratory chain revealed a deficiency of complexes I, III and IV in muscle. Mechanisms responsible for an impairment of mitochondrial function, which we interpret as a secondary phenomenon, are discussed.
One Step Isolation of Bovine Asialoglycoprotein Receptor and Its Characterization by Sequence Analysis and MALDI Mass Spectrometry
Authors: Seimetz Diane , Frei Eva , Schnölzer Martina , Kempf Tore , Wiessler Manfred
Published: March 2003

The asialoglycoprotein receptor (ASGP-R), which is responsible for the uptake of partially deglycosylated serum glycoproteins was isolated from bovine liver. The receptor was purified in one step from solubilized plasma membranes by affinity chromatography on 6-(β-D-lactosyl)-n-hexylamine coupled to N-hydroxysuccinimide activated Sepharose with a coupling degree of 7.6 μmol/ml gel. The preparation yielded two distinct polypeptides with apparent molecular weights of 48 and 43 kDa as determined by sodium dodecyl sulfatepolyacrylamide gel electrophoresis. A polyclonal antibody raised against the human ASGP-R recognized the bovine 43 kDa protein in Western blot analysis. The 48 and 43 kDa polypeptides were digested by trypsin and the digests were subsequently analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Sequence analysis of four tryptic fragments, two each of the 48 kDa and of the 43 kDa polypeptides revealed that these were highly homologous to ASGP-R subunits from man, mouse and rat.
Elevated plasma phenylalanine concentrations may adversely affect bone status of phenylketonuric mice
Authors: Yannicelli S. , Medeiros D. M.
Published: March 2003

Children with phenylketonuric (PKU) are at risk for fractures. This study used a PKU murine model (PAHenu‐2) to evaluate effects of moderate dietary protein restriction and elevated plasma phenylalanine concentration impact upon bone status. Fifty‐four male weanling PKU and control mice were assigned to either an elemental phenylalanine (Phe)‐restricted diet (treated) or Phe‐unrestricted diet (untreated) with low or normal protein levels for 56 days. Untreated mice and control mice received equal amounts of dietary Phe; treated mice consumed prescribed dietary Phe to maintain plasma Phe concentrations between 120 and 480 µmol/L. Plasma Phe, osteocalcin, and urine deoxypyridinoline (DPD)/creatinine were analysed at baseline and at days 28 and 56. Femur strength, bone mineral density (BMD) and bone mineral content (BMC) were analysed at day 56. Moderate protein restriction did not significantly affect bone status. Mean plasma Phe concentrations were significantly greater in untreated vs treated and control mice (p<0.0001). Total body weight was significantly less in untreated vs control mice (p<0.01). Mean femur weight was reduced in untreated mice vs both treated and control mice (p<0.03). Untreated mice had smaller mean femur length than control mice (p<0.002). Femur strength was greater in treated mice compared to control mice (p<0.01) but not compared to untreated mice. No significant difference among groups was found in BMD and BMC. At day 56 there was a statistical trend (p<0.056) towards higher urine DPD/creatinine excretion in untreated mice than in treated mice. Plasma Phe concentration was positively correlated with urine DPD/creatinine. These data suggested that hyperphenylalaninaemia may adversely affect bone status in PKU mice.
Patterns of Substance Use in Early Through Late Adolescence
Authors: Zapert Kinga , Snow David L. , Tebes Jacob Kraemer
Published: March 2003

This study examined patterns of substance use throughout adolescence. A cluster analytic approach was used to identify subgroups of adolescents on the basis of their levels of substance use from early through late adolescence (Grades 6 through 11). Six distinct clusters of substance users emerged—2 groups representing relatively stable patterns of substance use from early through late adolescence (i.e., nonusers and alcohol experimenters), and 4 groups of users showing escalating patterns of substance use (i.e., low escalators, early starters, late starters, and high escalators). The study provides a comprehensive view of adolescent substance use by examining the progression of use from early to late adolescence, demonstrates the usefulness of studying patterns of use across multiple substances, and underscores the importance of building classification schemes based on repeated measurements of substance use to reflect changes over time. Implications of the findings for future research and for identifying high‐risk subgroups of adolescents for purposes of intervention based on timing and pattern of escalation are discussed.
Verotoxin/Globotriaosyl Ceramide Recognition: Angiopathy, Angiogenesis and Antineoplasia
Authors: Lingwood C. A.
Published: March 2003

Verotoxin (VT) is involved in the etiology of both hemorrhagic colitis and the hemolytic uremic syndrome which are microvasculopathies of the colon and pediatric renal glomerulus respectively. Thus, VT can be considered a vasotoxin. Cell sensitivity in vitro varies according to the receptor glycolipid (globotriaosyl ceramide-Gb3) expression and also to intracellular trafficking of the receptor/toxin complex, such that in highly sensitive cells, the toxin is targeted to the endoplasmic reticulum and nuclear envelope. Such cells include tumor cells which have become drug resistant. Thus Gb3 is upregulated in certain tumors and when such tumor cells become drug resistant, their sensitivity to verotoxin increases. This may be due to a direct role of the MDR1 drug efflux pump in glycolipid biosynthesis. In addition to the tumor tissue, the toxin receptor may also be expressed in the tumor neovasculature suggesting that activated endothelial cells may be verotoxin sensitive. Thus VT may have both a direct and indirect antineoplastic potential. VT has proved highly effective in a xenograft cancer model and the possible therapeutic use of VT is discussed.
The Children Depression Inventory as Predictor of Social and Scholastic Competence
Authors: Aluja Anton , Blanch Angel
Published: March 2003

Summary This work analyzes the relationship between the different CDI factors, nonsocialized personality traits as measured by the Psychoticism and Antisocial Behavior EPQ scales, academic achievement, and general intelligence. Participants in this study were 678 8th-grade Basic General Education students (secondary), of whom 315 were boys and 363 girls, with an average mean age of 13 years. The exploratory and confirmatory factor analyses of the CDI performed yielded four orthogonal factors. The third factor (CDI-III; Incompetence/Maladjustment) was integrated by items related to social and academic maladjusted behavior. The CDI was negatively correlated with academic achievement, although this correlation disappeared when performing partial correlations controlling for CDI-III. A regression analysis further corroborated that CDI-III was the only CDI factor related to low academic achievement. The results also show that the CDI-III and Introversion for boys, and the CDI-III and Neuroticism for girls, were the most predictive variables of low academic achievement.
Gm–Csf Expands Dendritic Cells and Their Progenitors in Mouse Liver
Authors: Pillarisetty Venu G. , Miller George , Shah Alaap B. , DeMatteo Ronald P.
Published: March 2003

Dendritic cells (DCs) are rare but ubiquitous antigen–presenting cells situated in lymphoid and nonlymphoid organs throughout the body. The study of DCs located in the liver has been restricted by their relative scarcity and the difficulty of their isolation. Because granulocyte–macrophage colony-stimulating factor (GM–CSF) is a critical growth factor for DCs in
vitro, we postulated that it would expand hepatic DCs in vivo. We found that adenoviral–mediated GM–CSF overexpression in normal mice increased the number of liver DCs 400–fold to more than 100 million cells. GM–CSF-recruited DCs were CD11c+DEC205- and had high expression of major histocompatibility complex (MHC) class II, CD54, and CD80 but low CD40 and CD86 staining. Further maturation occurred after overnight culture. In addition to CD11c+DEC205- DCs, a population of CD11c-DEC205low/- cells resembling DC progenitors described previously in normal mice was expanded as serum GM–CSF levels increased. GM–CSF-recruited CD11c+DEC205- DCs and CD11c-DEC205low/- cells had different functional capabilities. CD11c+DEC205- DCs captured far more protein antigen in vivo, produced higher amounts of interleukin (IL)–6 and tumor necrosis factor (TNF)–α, and induced greater allogeneic and antigen–specific T–cell stimulation. A proportion of CD11c-DEC205low/- cells differentiated into CD11c+ cells and gained T–cell stimulatory ability when cultured in the presence of GM–CSF. In conclusion, our findings show that GM–CSF can profoundly influence recruitment and development of DCs in murine liver.
Hepatic Cytochrome P450 2E1 Activity in Nondiabetic Patients With Nonalcoholic Steatohepatitis
Authors: Chalasani Naga , Gorski Christopher J. , Asghar Maleeha S. , Asghar Ali , Foresman Brian , Hall Stephen D. , Crabb David W.
Published: March 2003

Cytochrome P450 2E1 (CYP2E1) plays an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH) in animal models, but its role in the pathogenesis of human NASH is unclear. Therefore, we measured hepatic CYP2E1 activity and its correlates in a cohort of nondiabetic patients with NASH (NDN) and controls to explore its role in the pathogenesis of human NASH. Hepatic CYP2E1 activity was assessed using the oral clearance (CLPO) of chlorzoxazone (CHZ) in 20 NDN and 17 age, gender, and body mass index (BMI)–matched controls. The relationship between hepatic CYP2E1 activity and demographic and anthropometric variables; fasting levels of insulin, glucose, lipids, and β–OH butyrate; insulin resistance; and nocturnal hypoxemia was assessed. Furthermore, expression of CYP2E1 in the peripheral lymphocytes was assessed using reverse transcription–polymerase chain reaction (RT–PCR). The CLPO of CHZ was significantly (P = .03) greater in NDN (41 ± 12 L/h) compared with controls (33 ± 16 L/h). Lymphocyte CYP2E1 messenger RNA was significantly higher in NDN compared with controls (11.5 × 103 ± 10 × 103 vs. 2.6 × 103 ± 1.2 × 103 molecules/μg total RNA, respectively, P < .001). On univariate analysis, BMI, respiratory quotient, high–density lipoprotein, triglycerides, insulin, insulin resistance, hypoxemia, and β–OH butyrate significantly correlated with hepatic CYP2E1 activity. However, on stepwise regression analysis, only nocturnal hypoxemia (r = 0.50, P = .009) and β–OH butyrate (r = 0.37, P = .04) were independent predictors of hepatic CYP2E1 activity. In conclusion, hepatic CYP2E1 activity and lymphocyte CYP2E1 expression are enhanced in NDN. The significant correlations noted between CYP2E1 and hypoxemia and β–OH butyrate suggest that these factors play a role in increased CYP2E1 activity that is seen in patients with NASH.
Prediction of Treatment Outcome in Patients With Chronic Hepatitis C: Significance of Baseline Parameters and Viral Dynamics During Therapy
Authors: Berg Thomas , Sarrazin Christoph , Herrmann Eva , Hinrichsen Holger , Gerlach Tilman , Zachoval Reinhart , Wiedenmann Bertram , Hopf Uwe , Zeuzem Stefan
Published: March 2003

In patients with chronic hepatitis C virus (HCV) infection scheduled for a 48–week treatment period, premature discontinuation of treatment was previously recommended if HCV–RNA levels remained detectable at week 24 of therapy. Considering the number of side effects and treatment costs, measurement of initial viral decline during therapy may identify virologic nonresponse earlier than 24 weeks. We retrospectively analyzed 260 European patients treated with standard or pegylated interferon alfa (IFN–α) and ribavirin for 24 to 48 weeks. Early prediction of virologic response by HCV–RNA decline at weeks 4 and 12 (Versant Quantitative [branched DNA (bDNA) 3.0]; Bayer Diagnostics, Emeryville, CA; and Qualitative [transcription–mediated amplification (TMA)] HCV RNA assay; Bayer Diagnostics) as well as clinical, biochemical, virologic, and histologic baseline parameters were analyzed by logistic regression and receiver operating characteristic (ROC) curves. A viral load at treatment week 4 above 450,000 IU/mL and at week 12 above 30,000 IU/mL was 100% predictive for virologic nonresponse in all patients. From multivariate logistic regression analysis of all patients, independent predictors for sustained virologic response were: genotypes 2 and 3 (P < .0001), a low baseline gamma–glutamyltransferase (GGT) level (P < .0001), a high baseline alanine aminotransferase level (P = .002), and a low baseline viral load (P = .04). None of the latter 3 factors were predictive for sustained virologic response when analysis was restricted to the subgroup of genotypes 2- and 3-infected patients. In conclusion, virologic nonresponse can be predicted early at week 12 of treatment independent from the applied therapeutic regimen based on a cutoff level for HCV RNA of 30,000 IU/mL. This algorithm recognizes 53.7% of nonresponders previously identified at week 24 of treatment.
Work‐life policy: does it do exactly what it says on the tin?
Authors: Wise Sarah , Bond Sue
Published: March 2003

Policies which help employees balance their work and non‐work priorities have become increasingly popular among UK employers in recent years. Along with a legislative imperative for family leave‐related policies, employers are being encouraged to introduce work‐life policies and make them more inclusive in order to enhance their business performance. This paper looks at how four financial services organisations have approached the work‐life balance agenda and examines the fit between the organisational intentions for work‐life policy and actual outcomes for both organisations and employees. Culture played a large part in determining the experience of policies but so did resources. What managers were being asked to achieve in the business was often incompatible with formal work‐life policies. Despite the rhetoric, work‐life balance was still viewed as a tool for, and was used by female parents, limiting its potential to achieve the promoted business benefits.
Organochlorine and organophosphorus pesticide residues in breast milk from Bhopal, Madhya Pradesh, India
Authors: Sanghi Rashmi , Pillai M KK , Jayalekshmi T R , Nair A
Published: March 2003

HCH isomers, endosulfan, malathion, chlorpyrifos, and methyl-parathion were monitored in human milk samples from Bhopal, Madhya Pradesh. The endosulfan concentrations were highest and exceeded the S-HCH, chlorpyrifos, and malathion concentrations by 3.5-, 1.5-, and 8.4-fold, respectively. Through breast milk, infants consumed 8.6 times more endosulfan and 4.1 times more malathion than the average daily intake levels recommended by the World Health Organization. A correlation analysis (r values) between mothers' age and the content of the chemicals accumulated in breast milk indicated a substantial degree of correlation for malathion (r–0.5). The other chemicals showed low to negligible correlation with donor age.
Ochratoxin a and human chronic nephropathy in Tunisia: is the situation endemic?
Authors: Abid Salwa , Hassen Wafa , Achour Abdellatif , Skhiri Habib , Maaroufi Khira , Ellouz Farielle , Creppy Edmond , Bacha Hassen
Published: March 2003

Ochratoxin A (OTA) is a nephrotoxic mycotoxin that is being increasingly considered as the main causal agent of Balkan endemic nephropathy (BEN), a fatal kidney disease associated with the end stage of urothelial tumours. However, despite the considerable amount of data, it is still controversial whether OTA plays a causative or only a subordinate role in the induction of this human nephropathy. Tunisia for years had to confront a very similar human nephropathy, which is tentatively called chronic interstitial nephropathy of unknown cause. This study tends firstly to consolidate the suspected link between this Tunisian chronic interstitial nephropathy (CIN) of unknown cause and the presence of OTA in the blood and food of such patients, and second to enlighten the endemic character of this particular nephropathy. Therefore, in four consecutive inquiries, performed within the period 1991-2000, blood and food OTA contaminations were assayed and compared for 954 nephropathy patients and 205 healthy subjects from the Tunisian general population. This survey was also designed to show that, although the whole population is likely to be exposed to OTA, specific people living in conditions showing similarities with the Balkans do have a kidney disease apparently linked to ochratoxin in food. The results showed that the highest incidences were found in patients with CIN of unknown cause. Indeed, the percentages of OTA-positive samples ranged from 93% to 100%, whereas it was only from 62% to 82% in healthy subjects. Mean OTA concentrations were also higher in patients with CIN of unknown cause than in controls (44.4±-19 mg/L to 55.6±-19 mg/L as opposed to 1.22±-1.2 mg/L to 3.35±-2.32 mg/L, respectively). This study emphasizes further the implication of OTA on this particular human nephropathy and underlines the probable causative role of OTA in the onset of this disease. It is important to note that the highest levels of food OTA contamination were found in the group presenting with CIN of unknown cause, indicating that, similar to the case in the Balkans, people are exposed to OTA essentially by their food.