bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of stably transfected fusion protein GFP‐estrogen receptor‐α in MCF‐7 human breast cancer cells
Authors: Zhao Helen , Hart Laura L. , Keller Ulrike , Holth Laurel T. , Davie James R.
Published: October 2002

Tagging hormone receptors with the green fluorescent protein (GFP) has increased our knowledge of ligand dependent sub‐cellular trafficking of hormone receptors. However, the effect of the tagged hormone receptor expression on the corresponding wild type hormone receptor and endogenous gene expression has not been investigated. In this study, we constructed a MCF‐7 cell line stably expressing GFP‐tagged human estrogen receptor‐α (ER) under control of the tetracycline‐on system to determine the effect of GFP‐ER expression on cell proliferation and expression of endogenous ER and hormone‐responsive genes. Further, the inducible system was applied to determine the ligand dependent turnover rates of GFP‐ER protein and mRNA. Our results demonstrate that GFP‐ER expression did not affect cell cycling. Independent of ligand, GFP‐ER markedly reduced the level of endogenous ER mRNA and protein, suggesting that ER negatively autoregulates its expression. Cisplatin cross‐linking studies showed that GFP‐ER is associated with nuclear DNA in situ, suggesting that GFP‐ER is partially replacing ER at estrogen response elements. Furthermore, GFP‐ER expression did not affect the estradiol induced temporal expression of hormone responsive genes c‐myc and pS2. J. Cell. Biochem. 86: 365–375, 2002. © 2002 Wiley‐Liss, Inc.
A novel mechanism for the regulation of osteoblast differentiation: Transcription of periostin, a member of the fasciclin I family, is regulated by the bHLH transcription factor, twist
Authors: Oshima Akira , Tanabe Hideyuki , Yan Tao , Lowe Gina N. , Glackin Carlotta A. , Kudo Akira
Published: October 2002

Periostin is a secreted protein that is highly expressed in early osteoblastic cells in vitro and in periosteum and periodontal ligament tissues in vivo. It is known that periostin supports cellular adhesion and spreading in vitro. Although, the mechanisms of transcriptional regulation of periostin are poorly understood, gene‐profiling data have revealed that overexpression of Twist, a basic helix‐loop‐helix (bHLH) transcription factor, resulted in increased periostin expression as validated by Northern blot and reverse transcription‐polymerase chain reaction (RT‐PCR) analyses. Twist is an important transcription factor for cell type determination and differentiation and has been shown to play an important regulatory role in early osteogenesis. In situ hybridization of mouse calvarial bones indicated that periostin and Twist mRNA are co‐localized at the osteogenic fronts of calvarial bones. To characterize the 5′ flanking region of the periostin gene, primer extension was carried out to identify the transcription start site, and DNA sequence analysis confirmed the presence of a ‘Twist‐box’ response element. The results of electrophoretic mobility shift assay (EMSA) using nuclear extracts of MC3T3‐E1 cells revealed that Twist bound to the Twist‐box sequence on the periostin promoter. In vivo footprinting experiments using ligation‐mediated PCR (LM‐PCR) indicated that the Twist‐box sequence was protected in undifferentiated MC3T3‐E1 preosteoblasts but not in differentiated MC3T3‐E1 osteoblasts. To determine whether Twist actually regulates the periostin expression, 293T cells were transiently co‐transfected with the periostin promoter construct and the human Twist expression vector. Reporter analysis indicated that the periostin promoter activities were enhanced by overexpression of Twist. These data suggest that Twist can bind to the periostin promoter in undifferentiated preosteoblasts and up‐regulate periostin expression, consistent with the up‐regulation of periostin expression by Twist as observed in the gene‐profiling data. J. Cell. Biochem. 86: 792–804, 2002. © 2002 Wiley‐Liss, Inc.
Gravitational smoothing as a global optimization strategy
Authors: Whitfield T. W. , Straub John E.
Published: October 2002

An optimization scheme for atomic cluster structures, based on exaggerating the importance of the gravitational force, is introduced. Results are presented for calculations on Lennard‐Jones clusters of 13, 38, and 55 atoms, and the 13‐atom Morse cluster. © 2002 Wiley Periodicals, Inc. J Comput Chem 11: 1100–1103, 2002
Stable conformations of 12‐crown‐O3N and its Li+ complex in aqueous solution
Authors: Hori Kenzi , Dou Nobumitsu , Okano Katsuhiko , Ohgami Ai , Tsukube Hiroshi
Published: October 2002

Stable conformations of 12‐crown‐O3N and its Li complexes in aqueous solution were investigated. To calculate the free energy differences of conformers of 12‐crown‐O3N and its Li+ complex, our procedure was to make use of two programs, CONFLEX and BOSS. The former generates conformers, and the latter calculates the differences in free energy of solvation between two conformers in aqueous solution. It was confirmed that the present procedure is applicable in solving the question of what is the most stable conformation of 12‐crown‐O3N in aqueous solution. Results of the calculations suggest that the order of stability for conformers in a vacuum is different from that in aqueous solution. It was also confirmed that the coordination geometry of solvent waters to Li+ changes depending on the distance between the cation and the crown ring. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1226–1235, 2002
Prediction of aqueous solubility of drugs and pesticides with COSMO‐RS
Authors: Klamt Andreas , Eckert Frank , Hornig Martin , Beck Michael E. , Bürger Thorsten
Published: October 2002

The COSMO‐RS method, originally developed for the prediction of liquid–liquid and liquid–vapor equilibrium constants based on quantum chemical calculations, has been extended to solid compounds by addition of a heuristic expression for the Gibbs free energy of fusion. By this addition, COSMO‐RS is now capable of a priori prediction of aqueous solubilities of a wide range of typical neutral drug and pesticide compounds. Only three parameters in the heuristic expression have been fitted on a data set of 150 drug‐like compounds. On these data an rms deviation of 0.66 log‐units was achieved. Later, the model was tested on a set of 107 pesticides, which have been critically selected based on two experimental data sources and by a crosscheck with an independent HQSAR model. On this data set an rms of 0.61 log‐units was achieved, without any adjustments to the structurally extremely diverse pesticides. This result verifies the ability of this extended COSMO‐RS to predict aqueous solubilities of drugs and pesticides of almost arbitrary structural classes. The new method is COSMO‐RSol. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 275–281, 2002
Childhood antecedents of adult sense of belonging
Authors: Hagerty Bonnie M. , Williams Reg Arthur , Oe Hiroaki
Published: October 2002

Sense of belonging has been proposed to be a basic human need, and deficits in sense of belonging have been linked to problems in social and psychological functioning. Yet, there is little evidence about what early life experiences contribute to sense of belonging. The purpose of this study was to examine potential childhood antecedents of adult sense of belonging. The sample consisted of 362 community college students ranging in age from 18 to 72 years, with a mean age of 26 years. Measures included the Sense of Belonging Instrument, the Parental Bonding Instrument, and the Childhood Adversity and Adolescent Deviance Instrument. Multiple regression analysis was used to correlate childhood antecedents with adult sense of belonging. The final reduced model included 12 variables, which accounted for 25% of the variance in sense of belonging. Significant positive antecedents with a relationship with sense of belonging were perceived caring by both mother and father while growing up, participation in high school athletic activity, and parental divorce. Significant negative variables with a relationship with sense of belonging included perceived overprotection of father, high school pregnancy, family financial problems while growing up, incest, and homosexuality. Knowledge of these factors should influence interventions with families regarding child‐rearing and parenting practices, mediating the effects of crises during childhood such as divorce and teen pregnancy, and the interpersonal growth needs of teenagers. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 793‐801, 2002.
CTGF/Hcs24, a hypertrophic chondrocyte‐specific gene product, stimulates proliferation and differentiation, but not hypertrophy of cultured articular chondrocytes
Authors: Nishida Takashi , Kubota Satoshi , Nakanishi Tohru , Kuboki Takuo , Yosimichi Gen , Kondo Seiji , Takigawa Masaharu
Published: October 2002

We previously reported that connective tissue growth factor/hypertrophic chondrocyte‐specific gene product 24 (CTGF/Hcs24) stimulated the proliferation and differentiation of rabbit growth cartilage (RGC) cells in vitro. In this study, we investigated the effects of CTGF/Hcs24 on the proliferation and differentiation of rabbit articular cartilage (RAC) cells in vitro. RAC cells transduced by recombinant adenoviruses generating mRNA for CTGF/Hcs24 synthesized more proteoglycan than the control cells. Also, treatment of RAC cells with recombinant CTGF/Hcs24 (rCTGF/Hcs24) increased DNA and proteoglycan syntheses in a dose‐dependent manner. Northern blot analysis revealed that the rCTGF/Hcs24 stimulated the gene expression of type II collagen and aggrecan core protein, which are markers of chondrocyte maturation, in both RGC and RAC cells. However, the gene expression of type X collagen, a marker of hypertrophic chondrocytes, was stimulated by rCTGF/Hcs24 only in RGC cells, but not in RAC cells. Oppositely, gene expression of tenascin‐C, a marker of articular chondrocytes, was stimulated by rCTGF/Hcs24 in RAC cells, but not in RGC cells. Moreover, rCTGF/Hcs24 effectively increased both alkaline phosphatase (ALPase) activity and matrix calcification of RGC cells, but not of RAC cells. These results indicate that CTGF/Hcs24 promotes the proliferation and differentiation of articular chondrocytes, but does not promote their hypertrophy or calcification. Taken together, the data show that CTGF/Hcs24 is a direct growth and differentiation factor for articular cartilage, and suggest that it may be useful for the repair of articular cartilage. © 2002 Wiley‐Liss, Inc.
Interview with the retinoblastoma family members: Do they help each other?
Authors: Tonini Tiziana , Hillson Christina , Claudio Pier Paolo
Published: October 2002

The ultimate destiny of a cell to undergo division, differentiation, survival, and death results from an intricate balance between multiple regulators including oncogenes, tumor suppressor genes, and cell cycle associated proteins. Deregulation of the cell cycle machinery switches the phenotype from a normal cell to a cancerous cell. Fundamental alterations of tumor suppressor genes may result in an unregulated cell cycle with the accumulation of mutations and eventual neoplastic transformation. As such, one may define cancer as a genetic disease of the cell cycle. In this review, we will emphasize our current understanding of how the cell cycle machinery maintains cellular homeostasis by studying the consequences of its deregulation. © 2002 Wiley‐Liss, Inc.
Primary human articular chondrocytes, dedifferentiated chondrocytes, and synoviocytes exhibit differential responsiveness to interleukin‐4: Correlation with the expression pattern of the common receptor gamma chain
Authors: Guicheux Jérôme , Palmer Gaby , Relic Biserka , Mezin Françoise , Caverzasio Joseph , Apostolides Pierre , Gauchat Jean‐François , Gabay Cem , Guerne Pierre‐André
Published: October 2002

Interleukin (IL)‐4, which exhibits potent anti‐inflammatory activities, is of potential therapeutic value in destructive arthropathies. To further define the response of human joint cells to IL‐4, we analyzed the ability of this cytokine to modulate the effects of IL‐1β and growth factors. Freshly isolated chondrocytes, dedifferentiated chondrocytes, and synoviocytes were treated with IL‐4 before determination of nitric oxide (NO) and collagenase production in response to IL‐1β, or before proliferation assays in presence of IL‐1β, platelet‐derived growth factor (PDGF), or transforming growth factor (TGF)‐β. IL‐4 downregulated IL‐1β induced NO production in dedifferentiated chondrocytes and inhibited IL‐1β induced collagenase release, as well as IL‐1β and growth factor induced proliferation in dedifferentiated chondrocytes and synoviocytes. In contrast, IL‐4 had no effect in freshly isolated primary chondrocytes and in cartilage explants. The lack of response to IL‐4 in primary chondrocytes was associated with impaired signal transduction, as indicated by markedly decreased IL‐4 dependent tyrosine phosphorylation of signal transducer and activator of transcription (STAT)‐6. It also correlated with differences in the expression pattern of IL‐4 receptor (IL‐4R) subunits during chondrocyte dedifferentiation. Indeed, whereas the IL‐4Rα and IL‐13Rα′ subunits were expressed in all cell types, expression of the common receptor gamma chain was restricted to freshly isolated chondrocytes. In conclusion, IL‐4 downregulated IL‐1β‐induced catabolic events and cell proliferation in dedifferentiated chondrocytes and synoviocytes, but had no effects in freshly isolated chondrocytes. The difference in IL‐4 responsiveness between primary and dedifferentiated chondrocytes correlated with changes in proximal signaling events and in the expression pattern of IL‐4R subunits during cell dedifferentiation. © 2002 Wiley‐Liss, Inc.
Role of the phagocytes on embryos: Some morphological aspects
Authors: Da Silva José Roberto Machado Cunha
Published: October 2002

Phagocytosis in embryos was studied by Elie Metchnikoff more than a century ago and is a pillar of the Phagocytic Theory. Throughout the last three decades phagocytosis in embryos has been studied from different perspectives, which this review describes and analyzes. The following branches were identified: 1) the search for the origin and first identification of well‐known adult phagocytes in embryos, including their role after induced injuries; 2) the search for the occurrence of phagocytosis in embryos and its role during their physiological development; and 3) the search for phagocytosis in embryos, as a tool to study identity and self‐recognition. It is possible to verify that different cell types are able to undertake phagocytosis, under a variety of different stimuli, and that the nature of what is phagocytosed also varies widely. Although the overwhelming majority of species described among metazoarians are invertebrates, most published articles in this field relate to mammals (particularly mice and humans) and birds (particularly chicks). In order to enrich this field of knowledge, research using a wider variety of vertebrate and invertebrate species should be undertaken. Furthermore, the present knowledge of phagocytosis in embryos needs a revised paradigm capable of embracing all the above‐mentioned research trends under a single, more general, biological theory. In this sense, Metchnikoff's Phagocytic Theory, which is based on a broad biological paradigm and is thus capable of dealing with all research trends mentioned herein, should be revisited in order to contribute to this edification. Microsc. Res. Tech. 57:498–506, 2002. © 2002 Wiley‐Liss, Inc.
Immune response by host after allogeneic chondrocyte transplant to the cartilage
Authors: Moskalewski Stanisław , Hyc Anna , Osiecka‐Iwan Anna
Published: October 2002

Chondrocytes constitutively express class I and, in some species, class II major histocompatibility complex (MHC). It is also possible that they possess specific differentiation antigen(s). Furthermore, lymphocytic cells, corresponding to NK cells, display spontaneous cytotoxic activity against chondrocytes. Studies on articular cartilage repair by transplants of allogeneic chondrocytes were mainly done on non‐inbred animals, such as rabbits and hens. Surprisingly, only in single instances these transplants were rejected. In inbred rats, allogeneic chondrocytes transplanted into full‐thickness defects in articular cartilage immediately after isolation evoked systemic immunological reaction and produced cartilage was rejected. Combined immunosuppression with cyclosporin A and cladribine did not prevent rejection of such transplants. Mechanical separation of transplants from bone marrow prevented sensitization of recipients and rejection of the produced cartilage. Successful allogeneic chondrocyte transplants in rabbits and hens could be tentatively explained by a certain degree of inbreeding among experimental animals, by the use of chondrocytes cultivated before grafting in artificial scaffolds and thus protected by matrix produced in vitro, and also by creation of a temporary mechanical barrier between transplant and bone marrow by tissues damaged during preparation of the defect. Microsc. Res. Tech. 58:3–13, 2002. © 2002 Wiley‐Liss, Inc.
Increasing membrane contrast by means of imidazole‐osmium post‐fixation as exemplified by skeletal muscle fiber
Authors: Voigt Tilman , Dauber Wolfgang , Bensemann‐Ryvkin Irina , Härtel Xenia
Published: October 2002

Until now, the interpretation of findings derived from investigations on membrane structures (T tubules, sarcoplasmic reticulum, the Golgi apparatus) in thick sections of mammalian muscle tissue has been limited in TEM due to the lack of sharp resolution of the membrane contours. This article shows how the imidazol‐osmium post‐fixation of tissue blocks can be used to achieve well‐contrasted, sharply defined membrane contours. Therefore, unstained sections from imidazol‐osmium post‐fixed tissue can be examined immediately. But protein structures (e.g., ribosomes) remain uncontrasted with this technique. If needed, it is possible to visualize the protein structures by conventional section staining with uranyl acetate and lead citrate. This method is suitable for both ultrathin and thick sections (>150 nm). Microsc. Res. Tech. 58:121–124, 2002. © 2002 Wiley‐Liss, Inc.
Branchial chloride cells in sea bass (Dicentrarchus labrax) adapted to fresh water, seawater, and doubly concentrated seawater
Authors: VARSAMOS STAMATIS , DIAZ JEAN PIERRE , CHARMANTIER GUY , FLIK GERT , BLASCO CLAUDINE , CONNES ROBERT
Published: October 2002

Branchial chloride cells (CC) were studied in sea bass (Dicentrarchus labrax) maintained in seawater (SW: 35‰) or gradually adapted to and subsequently maintained in fresh water (0.2‰) or doubly concentrated seawater (DSW: 70‰). Changes were observed in the location, number, and structure of CCs, that were discriminated by light, scanning, and transmission electron microscopy, as well as by immunofluorescence on the basis of their high Na+/K+‐ATPase antigen content. The number of CCs increased in both fresh water and doubly concentrated seawater compared to control fish maintained in SW. In both experimental conditions, these cells were found on the gill filament (as in control fish) and even on the lamellae, especially in hypersaline conditions. Structural changes concerned the shapes and sizes of CCs and their apical outcrops and particularly the structures of their functional complexes (mitochondria, tubular system, and endoplasmic reticulum), which developed significantly in DSW adapted fish. The changes in the expression of the Na+/K+‐ATPase were evaluated by assessing the enzyme's density at the ultrastructural level following immunogold labeling. This parameter was significantly higher in doubly concentrated seawater. The adaptative significance of the quantitative and morphofunctional changes in branchial chloride cells is discussed in relation to the original osmoregulatory strategy of this marine euryhaline teleost. © 2002 Wiley‐Liss, Inc.
DNA transfection of macaque and murine respiratory tissue is greatly enhanced by use of a nuclease inhibitor
Authors: Glasspool‐Malone Jill , Steenland Peter R. , McDonald Ruth J. , Sanchez Rigoberto A. , Watts Tammara L. , Zabner Joseph , Malone Robert W.
Published: October 2002

Background

Nuclease activity present within respiratory tissues contributes to the rapid clearance of injected DNA and therefore may reduce the transfection activity of directly injected transgenes. Most gene transfer technologies transduce or transfect murine tissues more efficiently than corresponding primate tissues. Therefore, it is prudent to assess the utility of novel gene transfer strategies in both rodent and primate models before proceeding with further development.

Methods

This study analyzed the effects of ATA (a nuclease inhibitor) on the direct transfection of macaque and murine lung tissue; compared the levels of DNase activity in murine, primate, and human lung fluids; and tested the inhibitory activity of ATA on the DNase activity present in these samples. Fluorescent microspheres were used to detect areas of transfection in lung.

Results

Intratracheal administration of a nuclease inhibitor (ATA) with naked DNA (0.5 µg ATA/g body weight) enhanced direct transfection efficacy in macaque lung by over 86‐fold and by over 54‐fold in mouse lung. Hematoxylin and eosin staining showed no apparent tissue toxicity. Moreover, macaque, human, and mouse lung fluids were found to possess similar levels of DNase activity and this activity was inhibited by similar concentrations of ATA. The authors also successfully pioneered the use of carboxylate‐modified microsphere tracers to identify areas of transfection and/or treatment.

Conclusion

This work provides evidence that using direct nuclease inhibitors will enhance lung transfection and that nuclease activity is present in all lung fluids tested, which can be inhibited by the use of direct DNase inhibitors. Copyright © 2002 John Wiley & Sons, Ltd.
Reproducibility of total cerebral blood flow measurements using phase contrast magnetic resonance imaging
Authors: Spilt Aart , Box Frieke M.A. , van der Geest Rob J. , Reiber Johan H.C. , Kunz Patrik , Kamper Adriaan M. , Blauw Gerard J. , van Buchem Mark A.
Published: October 2002

Purpose

To evaluate reproducibility of total cerebral blood flow (CBF) measurements with phase contrast magnetic resonance imaging (pcMRI).

Materials and Methods

We repeated total CBF measurements in 15 healthy volunteers with and without cardiac triggering, and with and without repositioning. In eight volunteers measurements were performed at two different occasions. In addition, measurement of flow in a phantom was performed to validate MR measurements.

Results

A difference of 40.4 ml/minute was found between CBF measurements performed with and without triggering (P < 0.05). For repeated triggered measurements, the coefficient of variation (CV) was 7.1%, and for nontriggered measurements 10.3%. For repeated measurements with repositioning, the CV was 7.1% with and 11.2% without triggering. Repeated measurements at different occasions showed a CV of 8.8%. Comparing measured with real flow in the phantom, the triggered differed 4.9% and the nontriggered 8.3%.

Conclusion

The findings of this study demonstrate that pcMRI is a reliable method to measure total CBF in terms of both accuracy and reproducibility. J. Magn. Reson. Imaging 2002;16:1–5. © 2002 Wiley‐Liss, Inc.
In vivo measurement of the apparent diffusion coefficient in normal and malignant prostatic tissues using echo‐planar imaging
Authors: Issa Bashar
Published: October 2002

Purpose

To measure for the first time the apparent diffusion coefficient (ADC) values in anatomical regions of the prostate for normal and patient groups, and to investigate its use as a differentiating parameter between healthy and malignant tissue within the patient group.

Materials and Methods

Single‐shot diffusion‐weighted echo‐planar imaging (DW‐EPI) was used to measure the ADC in the prostate in normal (N = 7) and patient (N = 19) groups. The spin‐echo images comprised 96 × 96 pixels (field of view of 16 cm, TR/TE = 4000/120 msec) with six b‐factor values ranging from 64 to 786 seconds/mm2.

Results

The ADC values averaged over all patients in non‐cancerous and malignant peripheral zone (PZ) tissues were 1.82 ± 0.53 × 10−3 (mean ± SD) and 1.38 ± 0.52 × 10−3 mm2/second, respectively (P = 0.00045, N = 17, paired t‐test). The ADC values were found to be higher in the non‐cancerous PZ (1.88 ± 0.48 × 10−3) than in healthy or benign prostatic hyperplasia central gland (BPH‐CG) region (1.62 ± 0.41 × 10−3). For the normal group, the mean values were 1.91 ± 0.46 × 10−3 and 1.63 ± 0.30 × 10−3 mm2/second for the PZ and CG, respectively (P = 0.011, N = 7). Significant overlap exists between individual values among all tissue types. Furthermore, ADC values for the same tissue type showed no statistically significant difference between the two subject groups.

Conclusion

ADC is quantified in the prostate using DW‐EPI. Values are lower in cancerous than in healthy PZ in patients, and in BPH‐CG than PZ in volunteers. J. Magn. Reson. Imaging 2002;16:196–200. © 2002 Wiley‐Liss, Inc.
Cardiac MRI: Recent progress and continued challenges
Authors: Earls James P. , Ho Vincent B. , Foo Thomas K. , Castillo Ernesto , Flamm Scott D.
Published: October 2002

Cardiac MRI continues to develop and advance. MRI accurately depicts cardiac structure, function, perfusion, and myocardial viability with an overall capacity unmatched by any other single imaging modality. MRI is an accepted and widely utilized tool for cardiovascular research. Its clinical use has been limited, but is increasing because of its proven clinical efficacy, the proliferation of cardiac‐capable MRI systems, and the development of improved pulse sequences. The following article reviews the landmark developments in this field, with an emphasis on recent progress in the evaluation of ischemic or acquired heart disease. J. Magn. Reson. Imaging 2002;16:111–127. Published 2002 Wiley‐Liss, Inc.
Transforming growth factor‐β enhances human T‐cell leukemia virus type I infection
Authors: Moriuchi Masako , Moriuchi Hiroyuki
Published: October 2002

Human T‐cell leukemia virus type I (HTLV‐I), the causative agent of adult T‐cell leukemia/lymphoma, is transmitted vertically by breast milk and sexually by semen. The transforming growth factor‐β (TGF‐β), a pleiotropic cytokine that is abundant in breast milk and semen, facilitates replication of HTLV‐I in lymphocytes derived from asymptomatic HTLV‐I carriers and transmission to cord blood lymphocytes in vitro. Transient expression assays revealed that TGF‐β can transactivate HTLV‐I long terminal repeat promoter. These results suggest that TGF‐β may play a role in replication and transmission of HTLV‐I. J. Med. Virol. 67:427–430, 2002. © 2002 Wiley‐Liss, Inc.
Hepatitis B in Italy: Where we are ten years after the introduction of mass vaccination
Authors: Mele Alfonso , Stroffolini Tommaso , Zanetti Alessandro R.
Published: October 2002

In Italy, a program of vaccination against hepatitis B targeted at the immunisation of persons at high risk began in 1983. In 1991, vaccination became mandatory for all newborns and adolescents. Since then, the vaccine has been given to more than 10 million children, with an outstanding record of safety and efficacy. The coverage rate is globally around 94%, with differences between the Northern and Southern regions, with the latter having the lower acceptance rate. According to the National Surveillance System (SEIEVA), the incidence of acute hepatitis B per 105 inhabitants declined from 5.4 in 1990 to 2 in 2000. The reduction was even greater among 15–24‐year‐old individuals, where the incidence rate per 105 decreased from 17.3 to 2 in the same period. In parallel with the decline of hepatitis B, hepatitis delta has also declined significantly. Catch‐up immunisation of unvaccinated adolescents, as well as an effort to improve the vaccination coverage rate in high‐risk groups, are required to ameliorate the efficacy of the vaccination campaign. Routine administration of booster doses of vaccine is not considered necessary to sustain immunity in immunocompetent persons. J. Med. Virol. 67:440–443, 2002. © 2002 Wiley‐Liss, Inc.
Factors associated with viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after liver transplantation
Authors: Chan Henry Lik‐Yuen , Chui Albert Ka‐Keung , Lau Wan‐Yee , Chan Francis Ka‐Leung , Wong May‐Ling , Tse Chi‐Hang , Rao Araga Ramesha Nitin , Wong John , Sung Joseph Jao‐Yiu
Published: October 2002

This study aimed to investigate the factors associated with viral breakthrough among liver transplant recipients who receive lamivudine monoprophylaxis. Consecutive patients receiving liver transplantation for HBV‐related liver disease from June 1999 to October 2000 were studied. All patients received lamivudine 100 mg daily pre‐ and post‐transplant. Serum samples were collected before lamivudine treatment, before liver transplantation, and then every 3–6 months after liver transplantation. Lamivudine‐resistant mutations at the YMDD motif of HBV P gene were detected by direct sequencing and HBV DNA was quantified by real‐time polymerase chain reaction (PCR). Ten patients, 7 males and 3 females, aged 50.5 ± 7.9 years, were studied. Three patients had fulminant hepatitis and 7 patients had end‐stage cirrhosis before liver transplantation. Lamivudine was started at 4.5 (range 0–40) weeks before liver transplantation. The median post‐transplant follow‐up was 16 (range 12–23) months. Four patients developed YMDD mutations 10.5 (0–16) months after transplantation with relapse of viraemia (median 1,294, range 51–3,135 MEq/ml). All patients who developed YMDD mutants had end‐stage liver cirrhosis, and HBV DNA were detectable on the day of liver transplantation (median 0.62, range 0.086–1.63 MEq/ml). On the contrary, all 3 patients transplanted for fulminant hepatitis did not have YMDD mutation. Among the 3 end‐stage cirrhotic patients who had negative HBV DNA before liver transplantation, none developed YMDD mutation. In conclusion, patients transplanted for fulminant hepatitis B and cirrhotic patients in whom HBV DNA could be rendered PCR negative before liver transplantation are unlikely to develop YMDD mutation on lamivudine monoprophylaxis. J. Med. Virol. 68:182–187, 2002. © 2002 Wiley‐Liss, Inc.
Human herpesvirus 6 and multiple sclerosis: A study of t cell cross‐reactivity to viral and myelin basic protein antigens
Authors: Cirone Mara , Cuomo Laura , Zompetta Claudia , Ruggieri Stefano , Frati Luigi , Faggioni Alberto , Ragona Giuseppe
Published: October 2002

Several reports have suggested an association of human herpesvirus 6 (HHV‐6) with multiple sclerosis. Autoreactive T lymphocytes directed against myelin components seem to contribute to the pathogenesis of the disease. It has been suggested that molecular mimicry between viral and self‐antigens might be one of the mechanisms that determine the onset of several autoimmune diseases. Following this hypothesis, the purpose of the present study was to evaluate if HHV‐6 could play a role in activating T cells capable of cross‐reaction with an important myelin component, the myelin basic protein. T cell lines were established from 22 multiple sclerosis patients and from 16 healthy controls, and their capability to react to both virus and myelin basic protein antigens was compared. The analysis of T cell cross‐reactivity in patients and controls did not show significant differences in the HHV‐6 ability to activate myelin basic protein‐reactive T cells. Similarly, the evaluation of the humoral immune response to HHV‐6 in patients and controls did not mirror any abnormality in the HHV‐6 status in multiple sclerosis patients. Therefore, although the findings of activity in vitro of T cell lines with dual specificity are consistent with the hypothesis of molecular mimicry, the lack of differences in cross‐reactivity between patients and controls do not support molecular mimicry as an important mechanism in the physiopathology of this disease. J. Med. Virol. 68: 268–272, 2002. © 2002 Wiley‐Liss, Inc.
Neurological complications of acute and persistent Epstein‐Barr virus infection in paediatric patients
Authors: Häusler Martin , Ramaekers Vincent Thomas , Doenges Martin , Schweizer Klaus , Ritter Klaus , Schaade Lars
Published: October 2002

Neurological complications of Epstein‐Barr virus (EBV) have been reported almost exclusively in the course of acute primary infections. The role of EBV in paediatric neurological disease was investigated prospectively over a 2‐year period, searching for acute primary, chronic, and reactivated EBV infections. Active EBV infections were diagnosed in 10/48 patients, including two with acute primary EBV infections (cranial neuritis and cerebellitis), one with chronic active infection (T/NK cell lymphoma with cranial neuritis), and seven with reactivated infections. Among these seven patients, three showed “Alice in Wonderland” syndrome, one facial nerve palsy, one progressive macrocephaly, and two prolonged encephalitic illness. The prognosis was good except for the patient with lethal T/NK cell lymphoma and the two girls with encephalitic illness. Despite steroid treatment, these girls suffered prolonged cognitive impairment and epileptic seizures. Both developed left‐sided hippocampal atrophy, and one of them hippocampal sclerosis. Like primary infections, reactivated EBV infections cause neurological complications in a considerable number of paediatric patients, lead to serious long‐term complications, and may contribute to the pathogenesis of hippocampal lesions. J. Med. Virol. 68: 253–263, 2002. © 2002 Wiley‐Liss, Inc.
Monocyte recruitment and myelin removal are delayed following spinal cord injury in mice with CCR2 chemokine receptor deletion
Authors: Ma Manhong , Wei Tao , Boring Landin , Charo Israel F. , Ransohoff Richard M. , Jakeman Lyn B.
Published: October 2002

The inflammatory response initiated after spinal cord injury (SCI) is characterized by the accumulation of macrophages at the impact site. Monocyte chemoattractant protein‐1 (MCP‐1) is a strong candidate for mediating chemotaxis of monocytes to the injured nervous system. To help in defining the role of MCP‐1 in inflammation after SCI, we evaluated the time course of macrophage accumulation for 2 weeks following a midthoracic spinal cord contusion injury in mice lacking CCR2, a principal receptor for MCP‐1. Mice with a deletion of CCR2 resulted in significantly reduced Mac‐1 immunoreactivity restricted to the lesion epicenter at 7 days postinjury. The regions devoid of Mac‐1 immunoreactivity corresponded to areas of reduced myelin degradation at this time. By 14 days postinjury, however, there were no differences in Mac‐1 staining between CCR2 (+/+) and CCR2 (–/–) mice. Analyses of mRNA levels by RNase protection assay (RPA) revealed increases in MCP‐1 as well as MCP‐3 and MIP‐2 mRNA at 1 day postinjury compared with 7 day postinjury. There were no differences in chemokine expression between CCR2‐deficient mice and wild‐type littermate controls. The CCR2‐deficient mice also exhibited reduced expression of mRNA for chemokine receptors CCR1 and CCR5. Together, these results indicate that chemokines acting through CCR2 contribute to the early recruitment of monocytes to the lesion epicenter following SCI. © 2002 Wiley‐Liss, Inc.
S‐adenosyl‐methionine‐induced apoptosis in PC12 cells
Authors: Zhao Wan‐Qian , Williams Zakia , Shepherd Kennie R. , Reuben Jayne S. , Lee Eun‐Sook , Darling‐Reed Selina , Lamango Nazarius , Soliman Karam F.A. , Charlton Clivel G.
Published: October 2002

Our previous studies showed that S‐adenosyl‐methionine (SAM) induced Parkinson's disease‐like changes in rat. It caused death to dopamine neurons in the substantia nigra, which appeared shrunken and fragmented, indicative of apoptosis‐like changes (Charlton and Crowell [1995] Mol. Chem. Neuropathol. 26:269–284; Charlton [1997] Life Sci. 61:495–502). In this study, we investigated whether SAM causes apoptosis in both undifferentiated PC12 (PC12) cells and nerve growth factor (NGF)‐differentiated PC12 (D‐PC12) cells. S‐adenosyl‐homocysteine (SAH), the nonmethyl analog of SAM, was also tested. SAM and SAH (1.0 nM to 10.0 μM) caused lactate dehydrogenase (LDH) release from the PC12 cells and D‐PC12 cells; cells with morphological changes and fluorescent DNA fragmentation staining were detected among both PC12 cell and D‐PC12 cell. Compared with the PC12 cell, the D‐PC12 cell, a postmitotic cell, was more sensitive to the toxic effects of SAM or SAH and presented much greater LDH release, suggesting a lethal effect; surprisingly, the amounts of apoptotic cells did not differ significantly between the two kinds of cells. In medium deprived of exogenous methionine, a decline in LDH release was observed in PC12 and D‐PC12 cells. Also, lower levels of intracellular SAM and SAH were observed in the methionine‐deleted media, which were reversed by the addition of either SAM or SAH. An antivitamin B12 monoclonal antibody was added to methionine‐depleted medium, resulting in deficiency of both endogenous and exogenous methionine, which caused further decreases in LDH release and reduction in the levels of intracellular SAM and SAH. The preliminary data showed different sensitivities to SAM or SAH between PC12 cell and D‐PC12 cells, which suggests that PC12 cell may be more stable as a metabolic model. Apoptosis of PC12 cells was also assessed by PARP cleavage detection, Western blot analysis of Bax and Bcl‐2 proteins, and DNA laddering on agarose gel electrophoresis. The proapoptoic protein Bax was dominantly expressed, whereas Bcl‐2 was slightly down‐regulated by SAM. SAH weakly induced the expression of Bax and slightly decreased Bcl‐2 levels. The effects of SAM and its analog, SAH, were demonstrated conclusively to induce apoptosis in PC12 cells. © 2002 Wiley‐Liss, Inc.
Relative power and influence strategy: the effects of agent/target organizational power on superiors' choices of influence strategies
Authors: Somech Anit , Drach‐Zahavy Anat
Published: October 2002

The present study examined superiors' tendency to utilize different top–down influence strategies according to their evaluation of their own power relative to that of their subordinates. Four hundred and fifty‐five subordinates (schoolteachers) from different schools described the extent to which their superiors used each item of the influence strategy questionnaire to influence them, while their immediate superiors evaluated superior's power and subordinate's power. Overall, superiors tended to use soft and rational strategy more often than hard strategy. However, regarding the parameter of relative power, the results indicated that the agent's power, as well as the target's power, affected the superior's choice of particular influence strategy. The results suggest that power should be discussed in relative rather than absolute terms. Copyright © 2001 John Wiley & Sons, Ltd.
Attitudinal organizational commitment and job performance: a meta‐analysis
Authors: Riketta Michael
Published: October 2002

A meta‐analysis was conducted to estimate the true correlation between attitudinal organizational commitment and job performance and to identify moderators of this correlation. One‐hundred and eleven samples from 93 published studies were included. The corrected mean correlation was 0.20. The correlation was at least marginally significantly stronger for: (a) extra‐role performance as opposed to in‐role performance; (b) white‐collar workers as opposed to blue‐collar workers; and (c) performance assessed by self ratings as opposed to supervisor ratings or objective indicators. Four other assumed moderators (commitment measure: Affective Commitment Scale versus Organizational Commitment Questionnaire, job level, age, and tenure) did not have at least marginally significant effects. Copyright © 2002 John Wiley & Sons, Ltd.
Age effects on the predictors of technical workers' commitment and willingness to turnover
Authors: Finegold David , Mohrman Susan , Spreitzer Gretchen M.
Published: October 2002

Building commitment and preventing costly turnover of technical employees are key challenges facing organizations today. We examine whether the elements of the employment relationship that predict commitment and willingness to change companies vary significantly with age. Using a sample of over 3000 technical professionals from six large companies, we find that in comparison to those under 30, satisfaction with job security is more strongly related to the commitment of more senior workers (ages 31–45 and those over age 45) and to their desire to remain with their companies. In contrast, satisfaction with work–life balance is more strongly related to commitment of those under age 30 than those over 30. Also, for the under‐30s, satisfaction with opportunities to develop technical skills and pay linked to individual performance has a stronger negative relationship with willingness to change companies than for those over 45. While statistically significant, the size of the age effects is small, suggesting popular and managerial attention devoted to differences among age groups may be overblown. Copyright © 2002 John Wiley & Sons, Ltd.
Stress‐related aftermaths to workplace politics: the relationships among politics, job distress, and aggressive behavior in organizations
Authors: Vigoda Eran
Published: October 2002

In light of the growing theoretical and practical interest on organizational politics, especially its probable impact on work outcomes, two stress‐related aftermaths of influence and politics in organizations were examined. On the basis of a model by Ferris, Russ, and Fandt (1989b) the idea was pursued that workplace politics may have a long‐range impact on employees' job distress and aggressive behavior in and around organizations. Three samples (n1 = 155, n2 = 184, n3 = 201) were used to examine direct and indirect/mediating relationships among the research variables. Participants were Israeli employees from the private, public, and third sectors. Findings showed that: (1) job distress was an immediate response to organizational politics across the three types of organization, and (2) job distress proved a possible mediator between organizational politics and aggressive behavior as enacted by the employees themselves. Several theoretical and practical implications of the findings that may extend our knowledge on various stress‐related aftermaths of organizational politics are noted. Copyright © 2002 John Wiley & Sons, Ltd.
Meteorological conditions associated with sea surges in Venice: a 40 year climatology
Authors: Trigo Isabel F. , Davies Trevor D.
Published: October 2002

The frequency of sea surges in Venice has increased during the 20th century, and the trend has been particularly pronounced in the last four decades. However, the time series of independent surge events (i.e. events separated by at least 1 week) has remained nearly stationary during that period. This suggests that, although the sea level rise (due to global warming and human activity in the region) is leading to more multiple events, the frequency of meteorological conditions that trigger independent events seems to be nearly balancing the effects of sea level change.

Such meteorological conditions are identified by compositing sea level pressure (SLP) and 995 hPa wind during and before independent sea surge events in Venice. The composite analysis shows that these correspond to storms orographically induced over the western Mediterranean basin, when an Atlantic synoptic system is perturbed by the Pyrenees and/or the Alps. It is, however, the persistence, intensity and relative position of such storms to the Adriatic Sea that contribute to the optimum conditions for the occurrence of floodings in its northern embayment.

It is shown that the synoptic picture is translated into persistent low SLP over the Venice region, negative north–south SLP gradient over the Adriatic, and south‐southeasterly to southeasterly wind over the central and northern parts of the sea. During the 40 year period under analysis, the persistence and intensity of the most adverse scenarios for the occurrence of sea surges in Venice have been generally decreasing; significant trends have been found in the tails of the distributions of Venice SLP, SLP north–south gradient, and of surface wind over the northern Adriatic. It is the balance between these trends and the continuing sea level rise that may account for the near‐stationarity of independent sea surge events during the last four decades. Copyright © 2002 Royal Meteorological Society
Raman spectra enhancement with a fuzzy logic approach
Authors: Soneira M. J. , Perez‐Pueyo R. , Ruiz‐Moreno S.
Published: October 2002

A filter based on the fuzzy logic technique to enhance the signal‐to‐noise ratio of Raman spectra is presented. The reasoning for generating a fuzzy filter is explained and its performance is evaluated on Raman spectra contaminated with cosmic ray events and shot noise. The filter suppresses noise and simultaneously preserves information without requiring a priori knowledge on the accurate shape of the Raman band and on the statistics of the noise that masks the information signal. Copyright © 2002 John Wiley & Sons, Ltd.
The concept of workplace marketing: a management development model for corporate and enterprise sectors
Authors: Mumby‐Croft Roger , Williams Juliet
Published: October 2002

This article addresses the following issues:

The role of organizational culture in creating business success.

The importance of internal marketing in relation to creating a sustainable business environment.

The importance of applied research to the development of effective business models.

Management development education as an investment in success not as a cost factor hindering profitability.

Rigorous interventions make a positive difference to company performance.

Copyright © 2002 John Wiley & Sons, Ltd.
Thioredoxin: a photosynthetic regulatory protein finds application in food improvement
Authors: Buchanan Bob B
Published: October 2002

Experiments initiated in the early 1960s on fermentative bacteria led to the discovery of ferredoxin‐dependent α‐ketocarboxylation reactions that were later found to be key to a new cycle for the assimilation of carbon dioxide in photosynthetic bacteria (the reductive carboxylic acid cycle). The latter finding set the stage for the discovery of a regulatory system, the ferredoxin/thioredoxin system, functional in photosynthesis in chloroplasts (and oxygen‐evolving photosynthetic prokaryotes). The chloroplast research, in turn, led to the finding of a system regulating seed germination. Each of these regulatory systems depends on thioredoxin, a ubiquitous 12 kDa protein with a catalytically active disulphide group that reduces specific disulphide sites of target enzymes or proteins. The seed work has begun to open doors to new technologies, also based on thioredoxin, that have broad application, including use in the improvement of major foods. This paper traces the history of this research and shows the current status of its application to food products.

© 2001 Society of Chemical Industry