bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite element prediction of endosteal and periosteal bone remodelling in the turkey ulna: Effect of remodelling signal and dead-zone definition
Authors: Taylor W R , Warner M D , Clift S E
Published: November 2003

Bone remodelling is the adaptation of bone mass in response to localized changes in loading conditions. The nature of the mechanical signal governing remodelling, however, remains the subject of continued investigation. The aims of this study were to use an iterative finite element (FE) bone remodelling technique to explore the effect of different remodelling signals in the prediction of bone remodelling behaviour. A finite element model of the turkey ulna, following that of Brown et al., was analysed using the ABAQUS package. The model was validated against the static predictions of the Brown et al. study. A bone remodelling technique, based on swelling algorithms given by Taylor and Clift, was then applied to predict the dramatic change in loading conditions imposed. The resulting changes in FE mid-shaft bone geometry were compared with the remodelling observed experimentally and showed good agreement. The tensile principal stress was found to be the best remodelling signal under the imposed conditions. Localized sensitivities in the remodelling patterns were found, however, and the definition of the dead zone was modified as a result. Remodelling with the new dead-zone definition showed that both the tensile principal stress and the tensile principal strain produced the remodelling patterns that agreed most closely with experiment.
Nanoindentation properties of compression-moulded ultra-high molecular weight polyethylene
Authors: Ho S P , Riester L , Drews M , Boland T , LaBerge M
Published: November 2003

This paper investigates the elastic modulus and hardness of untreated and treated compression-moulded ultra-high molecular weight polyethylene (UHMWPE) tibial inserts of a total knee replacement (TKR) prosthesis. Investigations were carried out at a nanoscale using a Nanoindenter™ at penetration depths of 100, 250 and 500 nm. The nanomechanical properties of surface and subsurface layers of the compression-moulded tibial inserts were studied using the untreated UHMWPE. The nanomechanical properties of intermediate and core layers of the compression-moulded tibial insert were studied using the cryoultrasectioned and etched UHMWPE treated samples. The cryoultrasectioning temperature (-150°C) of the samples was below the glass transition temperature, Tg(-122± 2°C), of UHMWPE. The measurement of the mechanical response of crystalline regions within the nanostructure of UHMWPE was accomplished by removing the amorphous regions using a time-varying permanganic-etching technique. The percentage crystallinity of UHMWPE was measured using differential scanning calorimetry (DSC) and the Tg of UHMWPE was determined by dynamic mechanical analysis (DMA). Atomic force microscopy (AFM) was used to assess the effect of surface preparation on the samples average surface roughness, Ra.

In this study, it was demonstrated that the untreated UHMWPE samples had a significantly lower ( p<0.0001) elastic modulus and hardness relative to treated UHMWPE cryoultrasectioned and etched samples at all penetration depths. No significant difference ( p > 0.05) in elastic modulus and hardness between the cryoultrasectioned and etched samples was observed. These results suggest that the surface nanomechanical response of an UHMWPE insert in a total joint replacement (TJR) prosthesis is significantly lower compared with the bulk of the material. Additionally, it was concluded that the nanomechanical response of material with higher percentage crystallinity (67 per cent) was predominantly determined by the crystalline regions within the semi-crystalline UHMWPE nanostructure.
Taguchi's technique: An effective method for improving X-ray medical radiographic screen performance
Authors: Vlachogiannis J G
Published: November 2003

Taguchi's technique is a helpful tool to achieve experimental optimization of a large number of decision variables with a small number of off-line experiments. The technique appears to be an ideal tool for improving the performance of X-ray medical radiographic screens under a noise source. Currently there are very many guides available for improving the efficiency of X-ray medical radiographic screens. These guides can be refined using a second-stage parameter optimization, based on Taguchi's technique, selecting the optimum levels of controllable X-ray radiographic screen factors. A real example of the proposed technique is presented giving certain performance criteria. The present research proposes the reinforcement of X-ray radiography by Taguchi's technique as a novel hardware mechanism.
A Quadrupole Ion Trap and Fourier Transform Ion Cyclotron Resonance Concerted Study of the Kinetics of an Ion/Molecule Association Reaction: A Chemometric Approach
Authors: Gal Jean-François , Maria Pierre-Charles , Operti Lorenza , Rabezzana Roberto , Vaglio Gian Angelo
Published: November 2003

The effects of different experimental parameters on rate constant measurements performed by mass spectrometry were investigated with a two-level fractional factorial design. This chemometric technique allows a study of the effects of selected factors and of their interactions on the response of an experiment by performing a limited number of analyses. The selected factors were: sample pressure, energy of the ionising electrons, reaction time and ionisation time. In this work, two mass spectrometric techniques were compared: Fourier transform ion cyclotron resonance (FT-ICR) and quadrupole ion trap (QIT) mass spectrometries. Experimental results were obtained from a study of a reaction system consisting of the condensation between triethylphosphite and its fragment ion (CH3CH2O)2P+. Apparent bimolecular rate constants are clearly larger when determined by QIT than by FT-ICR, because of collisional stabilisation of the adduct ion by helium buffer gas introduced in the QIT spectrometer. However, the QIT rate constant extrapolated to zero helium pressure is almost identical to the FT-ICR value; this supports the conclusion regarding the buffer gas effect. Minor effects evidenced by the chemometric method were attributed to the sample pressure and to the reaction time.
Characterisation of the Intact Rainbow Trout Vitellogenin Protein and Analysis of its Derived Tryptic and Cyanogen Bromide Peptides by Matrix-Assisted Laser Desorption/Ionisation Time-of-Flight-Mass Spectrometry and Electrospray Ionisation Quadrupole/Time-of-Flight Mass Spectrometry
Authors: Banoub Joseph , Thibault Pierre , Mansour Atef , Cohen Alejandro , Heeley David H. , Jackman Donna
Published: November 2003

Vitellogenin (VTG) is a protein produced by the liver of oviparous animals. It is being used as a biomarker for exposure to endocrine disruptors in many species. Rainbow trout Vtg has recently been sequenced by the conventional cDNA nucleotide approach. We focused on protein characterization of the intact protein and its derived tryptic and cyanogen bromide peptides by matrix-assisted laser desorption/ionisation and electrospray ionisation mass spectrometry. The molecular mass of the intact protein was found to be 183127 Da. A large number of unidentified peptide ions encourage further structural analysis to propose possible sequence variants and post-translational modifications.
Electron Ionization and Atmospheric Pressure Photochemical Ionization in Gas Chromatography-Mass Spectrometry Analysis of Amino Acids
Authors: Revelsky Igor A. , Yashin Yuri S. , Sobolevsky Tim G. , Revelsky Alexander I. , Miller Barbara , Oriedo Vincent
Published: November 2003

The mass spectra of tert-butyldimethylsilyl (TBDMS) derivatives of 17 amino acids were obtained using electron ionization (EI) and atmospheric pressure photochemical ionization (APPhCI) mass spectrometry. The APPhCI mass spectra for all of the derivatives except arginine were shown to consist of only molecular [M]+. and quasimolecular [MH]+ ions whereas, in the case o EI, the compounds in question underwent a drastic fragmentation. The application of APPhCI to gas chromatography-mass spectrometry enables a reliable identification of the TBDMS derivatives of amino acids in a mixture, even if its components are only partially resolved, due to the unique molecular masses for each compound. Comparison of the respective positive-ion chemical ionization (PICI) mass spectra available in the literature with APPhCI spectra has shown that, in the case of PICI, unlike APPhCI, noticeable fragmentation occurs.
Response Styles in Marketing Research: A Cross-National Investigation
Authors: Baumgartner Hans , Steenkamp Jan-Benedict E.M.
Published: November 2003

Response styles are a source of contamination in questionnaire ratings, and therefore they threaten the validity of conclusions drawn from marketing research data. In this article, the authors examine five forms of stylistic responding (acquiescence and disacquiescence response styles, extreme response style/response range, midpoint responding, and noncontingent responding) and discuss their biasing effects on scale scores and correlations between scales. Using data from large, representative samples of consumers from 11 countries of the European Union, the authors find systematic effects of response styles on scale scores as a function of two scale characteristics (the proportion of reverse-scored items and the extent of deviation of the scale mean from the midpoint of the response scale) and show that correlations between scales can be biased upward or downward depending on the correlation between the response style components. In combination with the apparent lack of concern with response styles evidenced in a secondary analysis of commonly used marketing scales, these findings suggest that marketing researchers should pay greater attention to the phenomenon of stylistic responding when constructing and using measurement instruments.
Index Construction with Formative Indicators: An Alternative to Scale Development
Authors: Diamantopoulos Adamantios , Winklhofer Heidi M.
Published: November 2003

Although the methodological literature is replete with advice regarding the development and validation of multi-item scales based on reflective measures, the issue of index construction using formative measures has received little attention. The authors seek to address this gap by (1) examining the nature of formative indicators, (2) discussing ways in which the quality of formative measures can be assessed, and (3) illustrating the proposed procedures with empirical data. The aim is to enhance researchers' understanding of formative measures and assist them in their index construction efforts.
Fibrinolytic activity in multiple myeloma
Authors: Yağcı Münci , Sucak Gülsan Türköz , Haznedar Rauf
Published: November 2003

The incidence of thromboembolic events is high as a result of disease, disease‐related complications, and therapy in multiple myeloma (MM). In patients with hematologic tumors, impaired fibrinolysis may be present and may contribute to the development of thrombotic complications. Therefore, we designed a study to investigate fibrinolytic activity in MM. We compared plasma levels of interleukin (IL)‐6, C‐reactive protein (CRP), IL‐1β, IL‐11, tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor‐1 (PAI‐1) activity, and global fibrinolytic capacity (GFC) in patients with MM (n = 66) and in control subjects (n = 18). The prevalence of venous thromboembolism was 4.5%, with a median follow‐up period of 7 months in our myeloma group. Results are given as mean (median, range). Plasma levels of IL‐6 (8.27 ± 0.74 [9.65, 0.90–13.32] pg/mL versus 2.64 ± 0.66 [1.80, 0.10–11.86] pg/mL, P < 0.001), CRP (45.57 ± 9.92 [21.00, 1.34–330.00] mg/L versus 1.96 ± 0.50 [1.05, 0.19–8.03] mg/L, P < 0.001), PAI‐1 (7.40 ± 0.67 [5.57, 2.40–31.80] IU/mL versus 4.73 ± 0.65 [3.60, 2.32–11.00] IU/mL, P < 0.01), GFC score (1.90 ± 0.02 [2, 1–3] versus 2.50 ± 0.14 [3, 1–3], P < 0.001) were increased compared with controls. In patients with MM, the level of IL‐6 was positively correlated with CRP (r = 0.66, P < 0.001), IL‐1β (r = 0.29, P < 0.05), and PAI‐1 (r = 0.35, P < 0.01) and negatively correlated with GFC (r = −0.37, P < 0.01). CRP level was positively correlated with plasma PAI‐1 level (r = 0.40, P < 0.01) and negatively correlated with GFC (r = −0.44, P < 0.001). A significant negative correlation between PAI‐1 level and GFC (r = −0.75, P < 0.001) was also detected. IL‐1β levels were negatively correlated with tPA level (r = −0.26, P < 0.05). These results suggest that patients with myeloma have a decreased fibrinolytic activity mainly because of increased PAI‐1 activity. In MM, increased PAI‐1 activity seems to be related with elevated IL‐6 level. MM should be considered as a hypercoagulable state as a result of both increased procoagulant activity and decreased fibrinolytic activity. Achieving a plateau by means of conventional chemotherapies does not improve the decreased fibrinolytic activity. Am. J. Hematol. 74:231–237, 2003. © 2003 Wiley‐Liss, Inc.
Cancer among women textile workers in Shanghai, China: Overall incidence patterns, 1989–1998
Authors: Wernli Karen J. , Ray Roberta M. , Gao Dao Li , Thomas David B. , Checkoway Harvey
Published: November 2003

Background

Cancer incidence in women textile workers has not been adequately studied. The aim of this study was to examine site‐specific cancer incidence patterns in a cohort of 267,400 women textile workers in Shanghai, China.

Methods

Women employed by the Shanghai Textile Industry Bureau (STIB) were followed for cancer incidence from 1989 to 1998. Age‐adjusted standardized incidence ratios (SIRs) and 95% confidence intervals (CI) were computed based on Shanghai Cancer Registry (SCR) rates.

Results

There was a decrease in cancer incidence for the cohort compared with urban Shanghai women (SIR = 0.91, 95% CI = 0.89–0.93). There were small increased risks of other endocrine tumors (SIR = 1.31, 95% CI = 1.02–1.65). There were decreased risks for esophageal (SIR = 0.54, 95% CI = 0.44–0.66), stomach (SIR = 0.79, 95% CI = 0.73–0.85), rectal (SIR = 0.88, 95% CI = 0.78–0.98), lung (SIR = 0.80, 95% CI = 0.74–0.86), cervical (SIR = 0.37, 95% CI = 0.28–0.50), ovarian (SIR = 0.85, 95% CI = 0.75–0.96), and bladder cancers (SIR = 0.63, 95% CI = 0.46–0.85).

Conclusions

Women employed in the textile industry had a lower than expected cancer experience compared with urban Shanghai women. Further research on this cohort will examine associations between site‐specific cancers and occupational exposures to dusts and chemicals. Am. J. Ind. Med. 44:595–599, 2003. © 2003 Wiley‐Liss, Inc.
Exposure assessment in epidemiology: Does gender matter?
Authors: Kennedy Susan M. , Koehoorn Mieke
Published: November 2003

Background

The pathway from potential hazards in the work environment to the measurement or estimation of personal exposure for epidemiologic studies comprises many steps, each of which can be influenced by factors that may or may not differ by gender. This article explores this pathway to address the question, “Should the potential for gender differences be taken into account in the activity of exposure assessment for epidemiologic studies?”

Methods

Evidence from previously published studies and data from the investigators' own research were examined to explore whether or not several theoretical sources of gender ‘bias’ in exposure assessment have been found in actual studies. Sources of bias examined included: differences in job tasks despite same job titles; differences in delivered exposure due to differences in protective equipment, body size, or other relationships to exposure sources; and differences in estimated exposure arising from study methods or design.

Results and Conclusions

Evidence was found for gender differences (and thus potential bias) from all these sources, at least in some studies. We conclude that the answer to the question posed, “Does gender matter, in exposure assessment for epidemiology?” is a qualified ‘yes,’ but that the magnitude and direction of the potential bias cannot be predicted, a priori. Am. J. Ind. Med. 44:576–583, 2003. © 2003 Wiley‐Liss, Inc.
Cancer incidence among laboratory workers in biomedical research and routine laboratories in Israel: Part I—the cohort study
Authors: Shaham Judith , Gurvich Rachel , Kneshet Yael
Published: November 2003

Background

Laboratory work is associated with exposure to a mixture of carcinogens.

Methods

The cohort is comprised of 4,300 laboratory workers. Cancer incidence was followed from 1960 to 1997.

Results

A total of 230 cases were included in the cohort. The overall cancer standardized incidence ratio (SIR) was 1.04 (0.91–1.18). When a 20‐year latency was introduced, SIR was increased significantly: 1.35 (1.13–1.61). Among routine workers and researchers, SIR was elevated significantly for the total population and for women, when a 20‐year latency was introduced. SIR was also elevated significantly in research, routine, bacteriology and virology, and isotope laboratories. With respect to specific sites, significantly increased SIR was observed in breast, ovary, and thyroid cancer among women; and prostate cancer, leukemia, and melanoma among men.

Conclusions

We suggest that work in research and biomedical laboratories might involve an increased risk of certain types of cancer. Am. J. Ind. Med. 44:600–610, 2003. © 2003 Wiley‐Liss, Inc.
Kinesin motors as molecular machines
Authors: Endow Sharyn A.
Published: November 2003

Molecular motor proteins, fueled by energy from ATP hydrolysis, move along actin filaments or microtubules, performing work in the cell. The kinesin microtubule motors transport vesicles or organelles, assemble bipolar spindles or depolymerize microtubules, functioning in basic cellular processes. The mechanism by which motor proteins convert energy from ATP hydrolysis into work is likely to differ in basic ways from man‐made machines. Several mechanical elements of the kinesin motors have now been tentatively identified, permitting researchers to begin to decipher the mechanism of motor function. The force‐producing conformational changes of the motor and the means by which they are amplified are probably different for the plus‐ and minus‐end kinesin motors. BioEssays 25:1212–1219, 2003. © 2003 Wiley Periodicals, Inc.
Investigating protein–protein interfaces in bacterial transcription complexes: a fragmentation approach
Authors: Burrows Patricia C.
Published: November 2003

Transcription initiation by σ54–RNA polymerase (RNAP) relies explicitly on a transient interaction with a complex molecular machine belonging to the AAA+ (ATPases associated with various cellular activities) superfamily. Members of the AAA+ superfamily convert chemical energy derived from NTP hydrolysis to a mechanical force used to remodel their target substrate. Recently Bordes and colleagues,1 using a protein fragmentation approach, identified a unique sequence within σ54‐dependent transcriptional activators that constitutes a σ54‐binding interface. This interface is not static, but subject to nucleotide‐dependent movement which may represent a common mechanism for controlling output that has been adopted by other AAA+ proteins. BioEssays 25:1150–1153, 2003. © 2003 Wiley Periodicals, Inc.
Stereospecificity of flobufen metabolism in guinea pigs in vitro and in vivo: Phase I of biotransformation
Authors: Kral Radim , Skalova Lenka , Szotakova Barbora , Babu Yogeeta N. , Wsol Vladimir
Published: November 2003

Flobufen (F) is an original nonsteroidal antiinflammatory drug that exists in two enantiomeric forms. Its biotransformation was investigated in male guinea pigs because of the similarities shown in a preliminary F metabolic study between guinea pig and man. Stereospecificity of the respective enzymes was studied in vitro, using microsomes and cytosol, and in vivo, in urine and feces. Rac‐F, R‐F, and S‐F served as substrates. The amount of 4‐dihydroflobufen stereoisomers (DHF) and other metabolites (M‐17203 and UM‐2) was determined by chiral HPLC using an R,R‐ULMO column. It was observed that F reductases were distributed differently in microsomes and cytosol. The microsomal fraction showed higher activity and different stereospecificity in rac‐F, R‐F, and S‐F reduction compared to cytosol. (2R;4S)‐DHF was the principle metabolite in microsomes and (2S;4S)‐DHF was the principle metabolite in cytosol. In vivo experiments revealed the excretion of a main metabolite UM‐2 in addition to other metabolites M‐17203 and DHF stereoisomers. UM‐2 was predominantly excreted after S‐F administration. Stereoselectivity of DHF stereoisomers excretion was different in urine and in feces. The absence of UM‐2 and M‐17203 in microsomes and cytosol and their presence in urine and feces showed that both could arise in some other extrahepatic tissue or cell compartment or that their formation depends on liver cell integrity. Chirality 16:1–9, 2004. © 2003 Wiley‐Liss, Inc.
Novel chiral sulfur‐containing ferrocenyl ligands for palladium‐catalyzed asymmetric allylic substitution
Authors: Nakamura Shuichi , Fukuzumi Takeo , Toru Takeshi
Published: November 2003

New chiral ferrocenyl ligands having chiral sulfinyl and phosphinyl groups were prepared. The palladium‐catalyzed allylic substitution reaction using these chiral ligands showed good enantioselectivity. The mechanism for the asymmetric reaction is proposed on the basis of the stereochemical outcome. Chirality 16:10–12, 2004. © 2003 Wiley‐Liss, Inc.
Enantioresolution of fluorinated diphenylmethanols and determination of their absolute configurations by X‐Ray crystallographic and 1H NMR anisotropy methods
Authors: Naito Junpei , Kosaka Masashi , Sugito Takeo , Watanabe Masataka , Harada Nobuyuki , Pirkle William H.
Published: November 2003

Various fluorinated diphenylmethanols were enantioresolved by the methods of chiral camphorsultam‐dichlorophthalic acid (CSDP acid) and/or 2‐methoxy‐2‐(1‐naphthyl)propionic acid (MαNP acid) yielding enantiopure alcohols. Their absolute configurations were unambiguously determined by X‐ray crystallography of CSDP esters and/or by the 1H NMR anisotropy method of MαNP esters for the first time. Chirality 16:22–35, 2004. © 2003 Wiley‐Liss, Inc.
Separation of cefoperazone enantiomers using β‐cyclodextrin as chiral additive by capillary zone electrophoresis
Authors: Wang Rong , Jia Zheng‐Ping , Fan Jun‐Jie , Hu Xiao‐Li , Li Yong‐Min , Chen Li‐Ren , Xie Jing‐Wen , Zhang Qiang
Published: November 2003

A capillary electrophoresis method was developed to separate the enantiomers of cefoperazone. Different cyclodextrins, including α‐cyclodextrin (α‐CD), β‐cyclodextrin (β‐CD), γ‐cyclodextrin (γ‐CD), 2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD), and methyl‐β‐cyclodextrin (Me‐β‐CD), were tested as chiral additives in the running buffer. The effect of various parameters on enantioseparation such as concentration of NaH2PO4, buffer pH, and CD concentration was also studied. The cefoperazone enantiomers were baseline separated under conditions of 0.04 mmol/L β‐CD, 75 mmol/L NaH2PO4 buffer at pH 4.0. A fused silica capillary (40 cm effective length × 75 μm ID) was used. The applied voltage and capillary temperature were 20 kV and 25°C, respectively. Under these conditions, linear calibration curves were obtained in the 5–500 μg/ml range using UV detection at 280 nm. The limit of detection for both isomers was 0.1 μg/ml. The method was used for the analysis of different pharmaceutical preparations (dose) and biological samples containing cefoperazone. Chirality 16:45–49, 2004. © 2003 Wiley‐Liss, Inc.
Concentration of a potent calcium oxalate monohydrate crystal growth inhibitor in the urine of normal persons and kidney stone patients by ELISA‐based assay system employing monoclonal antibodies
Authors: Moghadam Mehdi F. , Tandon C. , Aggarwal S. , Singla S.K. , Singh S.K. , Sharma S.K. , Varshney G.C. , Jethi R.K.
Published: November 2003

Standardized calcium oxalate monohydrate (COM) crystal growth assay system was employed to study the ability of various test samples to influence growth rates of COM crystals. The inhibitory activity (IA) of various samples was expressed in terms of inhibitory units. Urine samples obtained from normal persons and kidney stone patients were found to have IA of 3.18 ± 0.62 and 1.02 ± 0.08, respectively. A potent inhibitor having molecular weight between 14.2 and 16.2 kDa was found to be primarily responsible for the differences observed in the urinary IAs between normal persons and kidney stone patients. The potent inhibitor was found to be tightly associated with a chromophore resembling Urobilirubin. An ELISA based assay system, using monoclonal antibodies against the above most potent inhibitor confirmed the difference observed in the urinary IA between the normal persons and kidney stone patients. This assay system has the potential to be routinely used to screen human beings for potential stone formers. © 2003 Wiley‐Liss, Inc.
Molecular imaging of proteolytic activity in cancer
Authors: McIntyre J. Oliver , Matrisian Lynn M.
Published: November 2003

The early detection of both primary tumors and metastatic disease continue to be significant challenges in the diagnosis and staging of cancer. The growing recognition of the role of proteinases and proteolytic cascades in both the growth and metastasis of tumors has led to the development not only of therapeutic strategies using proteinase inhibitors, but also of methods to detect and image tumors in vivo via tumor‐associated proteolytic activities. These imaging strategies derive from the enhanced sensitivity afforded by amplification that can be obtained by enzymatic processing to increase the efficacy of imaging “contrast agents” coupled with the inherent substrate specificity and selectivity of proteinases. This review describes key proteinases important in cancer progression, the strategies that have been devised to detect and image proteolytic activity in vivo, and the potential for this kind of functional imaging to serve as a marker for targeted therapy. The intent is to draw attention to the developing methods of molecular imaging to facilitate not only cancer diagnosis, but also for devising strategies for individualized targeted therapy and non‐invasive monitoring of therapeutic efficacy. © 2003 Wiley‐Liss, Inc.
Thymic epithelial cells in age‐dependent involution
Authors: Brelińska Renata
Published: November 2003

Aging involves morphological and functional alterations within the microenvironment of the thymus where heterogenous populations of thymic epithelial cells (TEC) play the main roles. The studies performed to date on thymic involution signalize a disturbed interaction between individual thymic compartments that disrupt thymocyte‐TEC interactions and, as a sequele, disturb differentiation of both TEC and thymocytes. The process of aging affects the various subsets of TEC at different periods of life. Changes in different subsets of TEC are documented on the basis of their phenotypical characteristics, involving morphological analysis and immunocytochemistry. The character and kinetics of changes in TEC are typical for individual subsets and probably sex‐dependent. In the course of life, the involutionary changes, expressed by disorganised thymic structure and function, are accompanied by changes in medullary TEC, manifested by alterations in the differentiation process of the cells. In parallel, at the same stage of individual life, the aging process induces increased proliferative and secretory activity of subseptal TEC, which seem to functionally replace medullary TEC. Structural and phenotypic modifications of TEC are locally controlled by complex sets of different factors and seem to represent a morphological adaptation of the gland to the process of aging. Microsc. Res. Tech. 62:488–500, 2003. © 2003 Wiley‐Liss, Inc.
Age‐related changes in the function of T cells
Authors: Aspinall Richard
Published: November 2003

At the start of the last century in the United Kingdom, only 24% of the 587,830 deaths registered were of individuals over 65, but by the end of the century these figures had changed markedly. Of the 558,052 deaths in 1997, 84% were in the population over 65. This “right shift” in the survival curve is projected to continue. The UK Government Actuary's Department forecast that by 2020, 11.75 million people (19% of the population) will be over 65 rising to 15.1 million people (25% of the population) by 2040. Older members of society show infections of the urinary tract, respiratory tract, skin, soft tissue or intra‐abdominal region, infectious endocarditis, bacterial meningitis, tuberculosis, and herpes zoster, at a higher incidence than among younger adults. Moreover, mortality rates for these diseases are often 2–3 times higher among elderly patients than younger individuals with the same disease. The higher morbidity and mortality from these infections, plus the increased prevalence of specific cancers and certain autoimmune diseases point to an immune system deteriorating with age. At the core of the immune system are the T cells and this review analyses possible causes for the changes in T cell function that may account for the deterioration of the immune system. Any intervention to reverse the decline in the immune system must have a rational basis built on a hypothesis‐driven inquiry, and one such intervention process is presented here. Microsc. Res. Tech. 62:508–513, 2003. © 2003 Wiley‐Liss, Inc.
Predictive value of early HCV RNA quantitation for sustained response in nonresponders receiving daily interferon and ribavirin therapy
Authors: Trimoulet Pascale , de Lédinghen Victor , Foucher Juliette , Castéra Laurent , Fleury Hervé , Couzigou Patrice
Published: November 2003

The prognostic value of early hepatitis C virus (HCV)‐RNA load was evaluated among nonresponder patients to previous interferon (IFN) therapy treated with daily IFN and ribavirin. One hundred‐six nonresponders (83 men), mean age 44.8 ± 11 years, were treated with IFN‐α2b 3 MU/day for 24 weeks, followed by 3 MU × 3/week for 24 weeks plus ribavirin 1–1.2 g/day for 48 weeks. HCV RNA was quantified by Versant HCV RNA 3.0 assay (Bayer). The predictive values of the baseline and the change in viral load at week 1, 4, and 12 for sustained virological responses were analyzed using receiver operating characteristic (ROC) curves, as well as predictive values of >2 log10 drop from baseline by weeks 1, 4, and 12 in combination with undetectable HCV RNA for sustained virological response. Thirty‐two patients (30.2%) were sustained virological responders. The highest area under the curve was obtained at week 4. The unquantifiable HCV RNA level, in combination with at least a 2 log10 drop in viral load by week 4 and week 12, had a negative predictive value of 96% and 97%, respectively. Nonresponse can be predicted as early as week 4 or week 12 in nonresponders treated with daily IFN and ribavirin. J. Med. Virol. 72:46–51, 2004. © 2004 Wiley‐Liss, Inc.
Time course of hepatitis A viremia and viral load in the blood of human hepatitis A patients
Authors: Normann Andrea , Jung Christian , Vallbracht Angelika , Flehmig Bertram
Published: November 2003

The hepatitis A virus (HAV) is the most common etiological cause of acute hepatitis infections in humans in industrialized countries. Investigations into the viral load during HAV viremia, however, are rare. Therefore, correlation studies between viral load, biochemical, and specific serological markers have been undertaken. The group of sera comprised a series of multiple consecutive blood samples drawn from 11 patients at different times after onset of the disease. During the period up to 70 days after the onset of icterus, the individual range was at 1×103 to 3×104 HAV genome equivalents/ml. From day 75 until 120 after onset of the disease, the levels traced were at 103. In one case, it was possible to trace 1.25×104 genome equivalents/ml up to 180 days after onset of icterus and in two cases even up to 408 and 490 days viral load levels of 5×103 and 4×104 were detected, respectively. The same sera were used to measure IgM class antibodies to hepatitis A virus and the total anti‐HAV. The results demonstrate that a direct correlation to peak levels of viral load exists with peak serum transaminase levels, but neither with peak anti‐HAV IgM levels nor with total anti‐HAV. Decreasing amounts of anti‐HAV IgM tend to occur with decreasing amounts of HAV genome equivalents; and, vice versa, increasing amounts of total anti‐HAV are accompanied by decreasing amounts of HAV genome equivalents. The longest duration of viremia was found in patients infected with HAV genotype IA. J. Med. Virol. 72:10–16, 2004. © 2004 Wiley‐Liss, Inc.
Prevalence and characterization of astroviruses in Argentinean children with acute gastroenteritis
Authors: Espul Carlos , Martínez Norma , Noel Jacqueline S. , Cuello Hector , Abrile Cristina , Grucci Sandra , Glass Roger , Berke Tamas , Matson David O.
Published: November 2003

Among viral agents causing gastroenteritis, human astroviruses (HAstVs) take second or third place, after rotaviruses and caliciviruses, as the most frequent cause of illness. The aims of this study were to determine the prevalence of HAstV infection and to characterize the circulating HAstV strains in children with diarrhea under 3 years of age treated between 1995 and 1998 at out‐ or in‐patient facilities of the children's hospital in Mendoza, Argentina. Reverse transcription‐polymerase chain reaction (RT‐PCR) and enzyme immunoassay (EIA) were used to detect HAstVs in stool specimens. Positive specimens were tested further by EIA and/or sequenced to type detected HAstV strains. HAstVs were detected in 40 (3.7%) of 1,070 samples that were rotavirus and calicivirus‐negative: 14 (3.5%) of 402 from outpatients and 26 (3.9%) of 668 from inpatients. HAstV infection tended to be more severe in children during their first year of life: 18 (4.7%) of 383 HAstV‐positive children 0–11 months old were hospitalized versus 8 (2.8%) of 285 children 1 year of age or older (P = 0.29). Type 1 (HAstV‐1) was the most common type (41%), followed by HAstV‐4 (25%), HAstV‐2 (13%), HAstV‐3 (13%), and HAstV‐5 (8%). In this first epidemiological study of HAstV infection in this region, we confirmed HAstV to be a cause of severe gastroenteritis in children, more often among children younger than 12 months of age. HastV‐4 caused 25% of HastV infections in Mendoza, although it has been detected commonly elsewhere. Distinct genetic lineages were apparent but their epidemiological significance remains to be demonstrated. J. Med. Virol. 72:75–82, 2004. © 2004 Wiley‐Liss, Inc.
Stress‐induced subclinical reactivation of varicella zoster virus in astronauts
Authors: Mehta Satish K. , Cohrs Randall J. , Forghani Bagher , Zerbe Gary , Gilden Donald H. , Pierson Duane L.
Published: November 2003

Varicella zoster virus (VZV) becomes latent in human ganglia after primary infection. VZV reactivation occurs primarily in elderly individuals, organ transplant recipients, and patients with cancer and AIDS, correlating with a specific decline in cell‐mediated immunity to the virus. VZV can also reactivate after surgical stress. The unexpected occurrence of thoracic zoster 2 days before space flight in a 47‐year‐old healthy astronaut from a pool of 81 physically fit astronauts prompted our search for VZV reactivation during times of stress to determine whether VZV can also reactivate after non‐surgical stress. We examined total DNA extracted from 312 saliva samples of eight astronauts before, during, and after space flight for VZV DNA by polymerase chain reaction: 112 samples were obtained 234–265 days before flight, 84 samples on days 2 through 13 of space flight, and 116 samples on days 1 through 15 after flight. Before space flight, only one of the 112 saliva samples from a single astronaut was positive for VZV DNA. In contrast, during and after space flight, 61 of 200 (30%) saliva samples were positive in all eight astronauts. No VZV DNA was detected in any of 88 saliva samples from 10 healthy control subjects. These results indicate that VZV can reactivate subclinically in healthy individuals after non‐surgical stress. J. Med. Virol. 72:174–179, 2004. © 2004 Wiley‐Liss, Inc.
Differential regulation of polysialyltransferase expression during hippocampus development: Implications for neuronal survival
Authors: Brocco Marcela , Pollevick Guido D. , Frasch Alberto C.C.
Published: November 2003

Polysialyltransferases ST8SiaII/STX and ST8SiaIV/PST add polysialic acid (PSA) to the neural cell adhesion molecule (NCAM). Surface‐located PSA is involved in cell–cell interactions participating in structural and functional plasticity of neuronal circuits. This study was undertaken to investigate the polysialyltransferase regulation pattern during hippocampal development. Polysialyltransferase expression levels analyzed by real‐time RT‐PCR indicated that ST8SiaII/STX mRNA is markedly down‐regulated in vivo, decreasing abruptly at about the first week of postnatal development. ST8SiaII/STX mRNA is also down‐regulated in hippocampal cells in culture, accompanying the morphological differentiation of neuronal interconnectivity. In contrast, ST8SiaIV/PST levels remain comparatively low during hippocampus ontogeny. Immunolabeling of primary hippocampal culture assays demonstrated that PSA expression parallels ST8SiaII/STX mRNA levels. In comparison, polysialyltransferase mRNA levels are not regulated in neuroblastoma cells during their proliferation. Sequence analysis of the 3′‐untranslated region of ST8SiaII/STX cDNA indicated putative regulatory motifs. This information and the observed changes in mRNA half‐life during development suggest that ST8SiaII/STX might be also regulated at the posttranscriptional level. To understand the reasons for the tight control of ST8SiaII/STX expression during development, we overexpressed the enzyme in hippocampal primary cultures by transfection. Overexpression of ST8SiaII/STX wild type as well as of a mutant lacking enzymatic activity affected neuronal viability, leading to cell death. However, this phenomenon was abolished by a double mutation in the ST8SiaII/STX that prevents formation of its three‐dimentional structure. Interestingly, the overexpressed polysialyltransferase accumulates not only in the perinuclear region but also in the plasma membrane. Thus, overexpression of an ST8SiaII/STX that conserves its structure leads to abnormal accumulation of the protein, probably on the neuronal surface, affecting cell viability. This result explains the importance of an accurate regulation of polysialyltransferase expression during development. © 2003 Wiley‐Liss, Inc.
Hepatocyte growth factor stimulates cell motility in cultures of the striatal progenitor cells ST14A
Authors: Cacci E. , Salani M. , Anastasi S. , Perroteau I. , Poiana G. , Biagioni S. , Augusti‐Tocco G.
Published: November 2003

Hepatocyte growth factor/scatter factor (HGF/SF) is a growth factor with pleiotropic effects on different cell types. It acts as a mitogen and motility factor for many epithelial cells. HGF/SF and its receptor Met are present in the developing and adult mammalian brain and control neuritogenesis of sympathetic and sensory neurons. We report that the striatal progenitor ST14A cells express the Met receptor, which is activated after binding with HGF/SF. The interaction between Met and HGF/SF triggers a signaling cascade that leads to increased levels of c‐Jun, c‐Fos, and Egr‐1 proteins, in agreement with data reported on the signaling events evoked by HGF in other cellular types. We also studied the effects of the exposure of ST14A cells to HGF/SF. By time‐lapse photography, we observed that a 24‐hr treatment with 50 ng/ml HGF/SF induced modification in cell morphology, with a decrease in cell‐cell interactions and increase of cell motility. In contrast, no effect on cell proliferation was observed. To investigate which intracellular pathway is primarily involved we used PD98059 and LY294002, two specific inhibitors of mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MAP‐kinase/ERK‐kinase) and phosphoinositide 3‐OH kinase (PI3‐K), respectively. Cell motility in HGF/SF treated cultures was inhibited by LY294002 but not by PD98059, suggesting that PI3‐K plays a key role in mediating the HGF/SF‐induced dissociation of ST14A cells. Previous evidence of HGF stimulation of motility in nervous system has been obtained on postmitotic neurons, which have already acquired their specificity. Data reported here of a motogenic response of ST14A cell line, which displays properties of neuronal progenitors, seem of interest because they suggest that HGF could play a role in very early steps of neurogenesis. © 2003 Wiley‐Liss, Inc.
Expression of gangliosides in an immortalized neural progenitor/stem cell line
Authors: Suetake Keiji , Liour Sean S. , Tencomnao Tewin , Yu Robert K.
Published: November 2003

Glycosphingolipids (GSLs) are known to play important roles in cellular growth and differentiation in the nervous system. The change in expression of gangliosides is correlated with crucial developmental events and is evolutionarily conserved among many vertebrate species. The emergence of neural progenitors represents a crucial step in neural development, but little is known about the exact composition and subcellular localization of gangliosides in neural progenitor cells. The C17.2 cell line was derived after v‐myc transformation of neural progenitor cells isolated from neonatal mouse cerebellar cortex. The developmental potential of C17.2 cells is similar to that of endogenous neural progenitor/stem cells in that they are multipotential and capable of differentiating into all neural cell types. We characterized the GSL composition of C17.2 cells and found the presence of only a‐series gangliosides. Subcellular localization studies revealed that GM1 and GD1a are localized mainly on the plasma membrane and partly in the cytoplasm, both as punctate clusters. Reverse transcription‐polymerase chain reaction revealed the absence of ST‐II transcripts in C17 cells, which most likely accounts for the lack of expression of b‐ and c‐series complex gangliosides in this cell line. These data suggest that the divergence in ganglioside expression in C17.2 cells is regulated at the transcriptional level. © 2003 Wiley‐Liss, Inc.
Precipitation changes and variability in Turkey linked to the North Atlantic oscillation during the period 1930–2000
Authors: Türkeş Murat , Erlat Ecmel
Published: November 2003

Relationships between the variability of the North Atlantic oscillation (NAO) indices and the normalized precipitation at 78 stations in Turkey, and the influences of the extreme NAO index (NAOI) episodes and the year‐to‐year and longer time‐scale variations in the NAO on the precipitation conditions were investigated. The results of the study have led to the following main conclusions and evaluations for Turkey:

(i) There is a negative relationship between interannual variability of the Turkish precipitation series and the NAO indices. Negative relationships that are particularly strong in winter and partly in autumn are detected to be weaker in spring and almost non‐existent in summer. Correlation coefficients are significant at 61 stations in winter, whereas they are significant at 23 and eight stations in autumn and spring respectively. (ii) Composite precipitation means corresponding to the extreme NAOI phases mostly exhibit an apparent opposite anomaly pattern, except in summer, between the negative and positive NAOI phases. (iii) Annual, winter, spring, autumn and partly the summer composite precipitation means are mostly characterized by wetter than the long‐term average conditions during the negative NAOI phase, whereas the positive NAOI responses mostly exhibit drier than the long‐term average conditions annually and in all seasons except summer. (iv) Spatially coherent and statistically significant changes in the precipitation amounts during the extreme NAOI phases are more apparent in the west and mid Turkey. (v) Low‐frequency fluctuations in the circulation over the Atlantic have been closely linked to the coherent large‐scale precipitation anomalies that have persisted, particularly in winter, over Turkey since the early 1960s. (vi) There is a great resemblance between the spatial distribution and magnitude of the negative correlation coefficients and the spatial distribution patterns and severity of the wet (dry) conditions with negative (positive) NAOI phase, annually and in the winter and autumn seasons. (vii) The coherent regions characterized with significant correlation coefficients coincide perfectly with the coherent regions characterized by the extreme NAOI signals. These clear associations increase our confidence with the results. Copyright © 2003 Royal Meteorological Society
Better prediction of sub‐cellular localization by combining evolutionary and structural information
Authors: Nair Rajesh , Rost Burkhard
Published: November 2003

The native sub‐cellular compartment of a protein is one aspect of its function. Thus, predicting localization is an important step toward predicting function. Short zip code‐like sequence fragments regulate some of the shuttling between compartments. Cataloguing and predicting such motifs is the most accurate means of determining localization in silico. However, only few motifs are currently known, and not all the trafficking appears regulated in this way. The amino acid composition of a protein correlates with its localization. All general prediction methods employed this observation. Here, we explored the evolutionary information contained in multiple alignments and aspects of protein structure to predict localization in absence of homology and targeting motifs. Our final system combined statistical rules and a variety of neural networks to achieve an overall four‐state accuracy above 65%, a significant improvement over systems using only composition. The system was at its best for extra‐cellular and nuclear proteins; it was significantly less accurate than TargetP for mitochondrial proteins. Interestingly, all methods that were developed on SWISS‐PROT sequences failed grossly when fed with sequences from proteins of known structures taken from PDB. We therefore developed two separate systems: one for proteins of known structure and one for proteins of unknown structure. Finally, we applied the PDB‐based system along with homology‐based inferences and automatic text analysis to annotate all eukaryotic proteins in the PDB (http://cubic.bioc.columbia.edu/db/LOC3D). We imagine that this pilot method—certainly in combination with similar tools—may be valuable target selection in structural genomics. Proteins 2003;53:000–000. © 2003 Wiley‐Liss, Inc.