bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive factors and the risk of renal cell cancer among women
Authors: Chow Wong‐Ho , McLaughlin Joseph K. , Mandel Jack S. , Blot William J. , Niwa Shelley , Fraumeni Joseph F.
Published: September 2008

In etiologic studies of renal cell carcinoma the role of reproductive variables and the use of exogenous hormones have not been well examined. In a population‐based case‐control study including 165 female cases and 227 controls, we assessed the risk of renal cell cancer associated with reproductive factors and use of oral contraceptives and menopausal hormones. Odds ratios were computed using logistic regression analyses. Risk was positively associated with number of births and inversely associated with age at first birth, with the largest increases in risk (more than 2‐fold) among women with 5 or more births after age 25. After adjustment for age, smoking status, body mass index and age at first birth, women with 5 or more births had a 2‐fold risk (OR = 2.2, 95% CI = 1.2‐4.0) relative to those with 1 or 2 births. Age at first birth, however, was no longer a risk factor when the number of births was adjusted for. The association with parity was considerably stronger among women with a history of hypertension or above‐median body mass index than among those without these conditions. In addition, risk was reduced among long‐term oral contraceptive users but elevated among women who had had a hysterectomy or used menopausal hormones. Our findings suggest that reproductive factors, particularly the number of births, may play an etiologic role in renal cell cancer among women and deserve further study. © 1995 Wiley‐Liss, Inc.
Cancer in patients with ulcerative colitis
Authors: Mellemkjaer Lene , Olsen Jsorgen H. , Frisch Morten , Johansen Christoffer , Gridley Gloria , McLaughlin Joseph K.
Published: September 2008

A cohort of 5,546 ulcerative colitis patients was identified from the Danish Hospital Discharge Register for 1977–1989. Patients not included in the cohort comprised those with proctitis, those treated in outpatient clinics and those for whom follow‐up was less than 1 year. The cohort was linked to the Danish Cancer Registry in order to assess the risks for colorectal and other cancers. The linkage revealed a significant increase in the number of colorectal cancers over that in the general population (RR = 1.8; n = 42; 95% CI = 1.3–2.4) with consistent relative risks during early and late follow‐up. The relative risk was considerably higher among younger (20–39 years: RR = 22; n = 8; 95% CI = 9.7–44) than older patients (≥60 years: RR = 1.3; n = 25; 95% CI = 0.8–1.9), but the risk difference between patients and the general population was approximately constant across all ages. In addition, we observed a significant increase in the relative risk of hepatobiliary cancers (RR = 2.3; n = 9; 95% = 1.0–4.3) and a slight but significant increase in the relative risk of non‐melanoma skin cancer (RR = 1.4; n = 37; 95% CI = 1.0–1.9). In summary, our population‐based study confirms the increased risk of colorectal cancer among patients with ulcerative colitis and provides new leads suggesting that hepatobiliary cancer and non‐melanoma skin cancer should be considered as possible sites for future patient monitoring. © 1995 Wiley‐Liss, Inc.
Prostate cancer risk in U.S. blacks and whites with a family history of cancer
Authors: Hayes Richard B. , Liff Jonathan M , Pottern Linda M. , Greenberg Raymond S. , Schoenberg Janet B. , Schwartz Ann G. , Swanson G. Marie , Silverman Debra T. , Brown Linda Morris , Hoover Robert N. , Fralmeni Joseph F.
Published: September 2008

Prostate cancer occurs more frequently in U.S. blacks than whites. A population‐based case‐control study which investigated the association with family history of cancer was carried out among 981 men (479 black, 502 white) with pathologically confirmed prostate cancer, diagnosed between August 1, 1986, and April 30, 1989, and 1,315 controls (594 black, 721 white). Study subjects, aged 40–79, resided in Atlanta, Detroit, and 10 counties in New Jersey, geographic areas covered by population‐based cancer registries. Prostate cancer risk was significantly elevated among those who reported a history of prostate cancer in first‐degree relatives (O.R. = 3.2; 95% C.I.: 2.0–5.0), with blacks and whites having similarly elevated risks. These risks were unchanged by statistical adjustment for job‐related socio‐economic status, education, income, and marital status. Overall, the ORs associated with history of prostate cancer in fathers and brothers were 2.5 (95% C.I.: 1.5–4.2) and 5.3 (95% C.I.: 2.3–12.5), respectively. Risks associated with a family history of prostate cancer were consistently elevated among younger and older subjects. Only small non‐significant excesses of prostate cancer risk were associated with a family history of breast, colorectal, or other cancers. While familial occurrence is a key risk factor for prostate cancer and likely to be genetically based, the similar familial risks among blacks and whites suggest that the ethnic disparity in incidence is influenced by environmental factors. © 1995 Wiley‐Liss, Inc.
Genetic characterization of the human papillomavirus (HPV) 18 E2 gene in clinical specimens suggests the presence of a subtype with decreased oncogenic potential
Authors: Hecht Julia L. , Kadish Anna S. , Jiang Gang , Burk Robert D.
Published: September 2008

HPV 18 is associated with 2 divergent phenotypes: (i) aggressive cervical cancer and a preponderance of cancer relative to cervical intra‐epithelial neoplasia (CIN) and (ii) benign warty lesions of the cervix. The E2 gene of HPV 18 encodes a regulatory protein that represses viral oncogene transcription and is involved in viral replication. Variation within the E2 gene of HPV 18 and its correlation with the morphologic grade of associated lesions were analyzed in a sample of 20 HPV 18‐positive cervical specimens representing a spectrum of pathology from low‐grade CIN to cervical cancer. An amplifiable HPV 18 E2 gene was present in 3 of 5 cancers, indicating that E2 disruption was not required for cancer development. Single‐strand conformation polymorphism and PCR analyses revealed a high degree of polymorphism throughout the E2 gene. Direct DNA sequencing of both strands of a 154‐bp fragment revealed a variability of 5.8%. Six intra‐epithelial lesions contained alterations in common that account for 3.9% of the variation and appear to constitute a subtype. Within the 154‐bp region, 2 of 3 cervical cancers and 0 of 12 intra‐epithelial lesions were identical to the published HPV 18 sequence. DNA sequence analysis of a region extending into the E5 open reading frame revealed deletions in the E2/E5 intragenic region that were present in 50% of the members of the subtype. Our data demonstrate significant sequence variation within the E2 gene and suggest the presence of an HPV 18 subtype with decreased oncogenic potential. © 1995 Wiley‐Liss, Inc.
DNA ploidy and clonal selection in ras + myc – Induced mouse prostate cancer
Authors: Greene D. R. , Taylor S. R. , Aihara M. , Yoshida K. , Egawa S. , Park S. H. , Timme T. L. , Yang G. , Scardino P. T. , Thompson T. C.
Published: September 2008

An important goal in prostate cancer research is to define specific molecular and cellular alterations that are associated with malignant progression. The mouse prostate reconstitution model is a relevant and useful system as it allows the study of early events in cancer progression under conditions where oncogene‐initiated cells are surrounded by normal tissue. Using this model, activated ras and myc oncogenes are introduced into urogenital sinus cells via the recombinant retrovirus Zipras/myc 9. After 4 weeks' growth as subcapsular renal grafts, poorly differentiated carcinomas are produced in C57BL/6 mice. In this study we examined the temporal relationships between morphological alterations, growth, DNA ploidy status and clonal selection as determined by Southern blotting in ras + myc‐initiated carcinomas. Nuclear image analysis demonstrated that the emergence of a cycling DNA tetraploid cell population strongly correlated with growth and histologic progression. These tightly linked events culminated in the outgrowth of mono‐ or oligoclonal cancer. © 1995 Wiley‐Liss, Inc.
Apoptosis in colorectal tumour cells: Induction by the short chain fatty acids butyrate, propionate and acetate and by the bile salt deoxycholate
Authors: Hague Angela , Elder Douglas J. E. , Hicks Diane J. , Paraskeva Christos
Published: September 2008

The short chain fatty acids acetate, propionate and butyrate are produced when dietary fibre is fermented by the colonic bacteria. We have previously shown that sodium butyrate induces apoptosis in 3 colorectal tumour cell lines. We have extended our study to 3 adenoma and 4 carcinoma cell lines and investigated whether propionate and acetate also induce apoptosis. All 3 short chain fatty acids induced apoptosis at physiological concentrations, but of the 3, butyrate was the most effective. Since these fatty acids are produced as a result of bacterial fermentation of dietary fibre, this may in part explain the correlation between a high‐fibre diet and low colorectal cancer incidence. Sodium butyrate induced apoptosis in all 7 of the cell lines studied; however, 2 of the 4 carcinoma cell lines (PC/JW/F1 and S/KS/F1) were more resistant to butyrate‐induced apoptosis than the 3 adenoma cell lines, suggesting that at least some carcinomas may evolve mechanisms to protect the cells from the induction of apoptosis. The bile acid deoxycholic acid has previously been reported as a possible tumour promoter in the large intestine and its levels are reduced by dietary fibre. Concentrations of between 10 nM and 0.1 mM had no effect on either the proliferation or apoptosis of colonic tumour cells in vitro. However, a significant induction of apoptosis was obtained at a concentration of 0.5 mM. These results may have significance for the aetiology of colorectal cancer. © 1995 Wiley‐Liss, Inc.
The effect of platelets on invasiveness and protease production of human mammary tumor cells
Authors: Belloc Catherine , Lu He , Soria Claudine , Fridman Rafael , Legrand Yves , Menashi Suzanne
Published: September 2008

Interaction of tumor cells with platelets facilitates metastasis of tumor cells. It has been proposed that platelets protect tumor cells against the host's immune defense and enhance tumor‐cell extravasation. In the present work we show that platelets increase the invasiveness of 3 mammalian cell lines (MCF‐7, ZR‐51 and MDA‐MB231) through extracellular matrix, and propose this as an additional mechanism by which platelets facilitate metastasis. Since gelatinase and urokinase have both been implicated in degradation of the extracellular matrix and cell migration, and therefore in tumor invasion, we have also analyzed whether the interaction of platelets with tumor cells can modify the secretion of these proteases by tumor cells. MDA‐MB231, which was the most invasive cell line among the 3 tested and was the most potent in inducing platelet aggregation, secreted the highest level of urokinase and was the only one in which gelatinase was detected. While platelets had no significant effect on the urokinase activity expressed by these cells, they induced in MDA‐MB231 an important increase in the secretion of gelatinase, which can be reproduced by both platelet membrane and platelet releasate of activated platelets. This increase in gelatinase could be responsible, at least in part, for the increased invasiveness of these cells, since added TIMP‐1 significantly reduced the number of cells which traversed matrigel. © 1995 Wiley‐Liss, Inc.
Six‐week postpartum maternal depressive symptoms and 4‐month mother–infant self‐ and interactive contingency
Authors: Beebe Beatrice , Jaffe Joseph , Buck Karen , Chen Henian , Cohen Patricia , Feldstein Stanley , Andrews Howard
Published: September 2008

Associations of 6‐week maternal depressive symptoms [Center for Epidemiological Studies Depression Scale (CES‐D)] with 4‐month mother–infant self‐ and interactive contingency patterns during face‐to‐face play were investigated in 132 dyads. Self‐ and interactive contingency (auto‐ and lagged cross‐correlation, respectively) were assessed by multilevel time‐series analysis. Infant and mother gaze, facial and vocal affect, touch, and spatial orientation behaviors were coded second‐by‐second from split‐screen videotape, and a multimodal measure of facial–visual “engagement” was constructed, generating nine modality pairings. With higher CES‐D, the self‐contingency of both partners was lowered in most modalities. With higher CES‐D, interactive contingency values were both heightened (in some modalities) and lowered (in others), varying by partner. These results are consistent with an optimal midrange model. With higher CES‐D, interactive contingency showed the following patterns: (a) Mothers and their infants had a reciprocal orientational sensitivity; (b) mothers and infants manifested a reciprocal intermodal discordance in attention versus affect coordination, lowering gaze coordination, but heightening affective coordination; (c) infants heightened, but mothers lowered, touch coordination with partner touch—an “infant approach–mother withdraw” touch pattern. Nonlinear analyses indicated that altered self‐ and interactive contingency were similar at both the low (“denial”) as well as the high (“endorsement”) poles of depressive symptoms, in half the findings. These complex, multimodal findings define different aspects of communication disturbance, with relevance for therapeutic intervention.
Prospectus of growing barley and mustard with saline groundwater irrigation in fine‐ and coarse‐textured soils of Cholistan desert
Authors: Kahlown Muhammad Akram , Akram Muhammad , Soomro Zamir Ahmed , Kemper W. D.
Published: September 2008

The groundwater in Pakistani sandy deserts is generally highly saline and not suitable for drinking. However, it can be utilized for growing beneficial salt‐tolerant plants. To explore the potential of desert land for farm production two crops of barley and mustard were cultivated on coarse‐ and fine‐textured soils with saline water irrigations in the Cholistan desert. The salinity (electrical conductivity, EC) of irrigation water was 6.2 dS m−1. The barley and mustard crops were irrigated five and four times, respectively, including pre‐sowing irrigation. At the end of crop maturity, as a result of saline water irrigation the soil infiltration was reduced by an average of 7.0%. The EC and exchangeable sodium percentage (ESP) of the experimental plots were increased by 2.2 dS m−1 and 9.0, respectively. The average yield of barley and mustard was 264 and 177 kg ha−1 respectively. It was concluded that production of barley and mustard crops could be increased further by better levelling the plots, reducing level differences to less than 10 cm. The saline water should be used carefully to irrigate fine‐textured soils to keep the salinity within the safe limit to avoid permanent failure of crop growth and yield. Copyright © 2008 John Wiley & Sons, Ltd.
Butyl benzyl phthalate: effects on immune responses to ovalbumin in mice
Authors: Dearman Rebecca Jane , Betts Catherine Jean , Beresford Lorna , Bailey Laura , Caddick Helen Theresa , Kimber Ian
Published: September 2008

During recent decades the prevalence of IgE‐mediated (atopic) allergic diseases in Western Europe and the USA has been increasing dramatically. It has been suggested that one possible cause is the presence in the environment of chemicals that may act as adjuvants, enhancing immune and allergic responses. Certain commonly used phthalate plasticizers such as butyl benzyl phthalate (BBP) have been implicated in this way. In the current experiments, the impact of BBP, applied by a physiologically relevant exposure route, on the vigour of immune responses induced in BALB/c strain mice has been examined. Mice were immunized via subcutaneous injection with the reference allergen ovalbumin (OVA) and received concurrent topical treatment with doses of BBP that induced significant changes in liver weight. The generation of specific anti‐OVA IgE and IgG1 antibodies was measured by passive cutaneous anaphylaxis and by enzyme‐linked immunosorbant assays, respectively. Topical administration of BBP was without impact on anti‐OVA IgE antibody responses, regardless of whether BBP was applied locally or distant to the site of OVA immunization. However, same‐site treatment with high‐dose BBP (100 mg) did result in a modest elevation in anti‐OVA IgG1 antibody production, a subclass of antibody used as a surrogate marker of IgE responses. Taken together with human exposure data, these results suggest that the doses of phthalate encountered in the home environment are unlikely to be a major factor contributing to the increased incidence of asthma and allergy in the developed world. Copyright © 2008 John Wiley & Sons, Ltd.
mrtl—A translation/localization regulatory protein encoded within the human c‐myc locus and distributed throughout the endoplasmic and nucleoplasmic reticular network
Authors: Choi Hyoungsoo , Jackson Nateka L. , Shaw Denise R. , Emanuel Peter D. , Liu Y. Lucy , Tousson Albert , Meng Zheng , Blume Scott W.
Published: September 2008

mrtl (myc‐related translation/localization regulatory factor) is a previously uncharacterized protein synthesized from the first open reading frame contained within the human c‐myc P0 transcript, ∼800 nucleotides upstream of the Myc coding sequence. The mrtl protein, 114 amino acids in length, is projected to contain an N‐terminal transmembrane domain and a highly charged C‐terminal interaction domain with homology to numerous RNA‐binding proteins. Using monoclonal antibodies raised against the hydrophilic C‐terminal domain, endogenous mrtl was visualized in human breast tumor cell lines and primary mammary epithelial cells at the nuclear envelope and contiguous endoplasmic/nucleoplasmic reticulum. mrtl colocalizes and coimmunoprecipitates with translation initiation factor eIF2α and the 40S ribosomal protein RACK1, and appears capable of binding specifically to the c‐myc RNA. Inducible ectopic overexpression of wild‐type mrtl interferes with the function of endogenous mrtl, which results in loss of Myc from the nucleus. Furthermore, treatment of cells with a peptide derived from the C‐terminal domain displaces endogenous mrtl and causes a dramatic reduction in total cellular Myc protein levels. Together with our previous work demonstrating complete loss of tumorigenicity in association with ectopic expression of the c‐myc P0 5′‐UTR (containing the mrtl coding sequence), these results suggest that mrtl may serve an important function in regulating Myc translation and localization to the nucleus, perhaps ultimately contributing to the role of the c‐myc locus in oncogenesis. J. Cell. Biochem. 105: 1092–1108, 2008. © 2008 Wiley‐Liss, Inc.
2‐methoxyestradiol‐induced cell death in osteosarcoma cells is preceded by cell cycle arrest
Authors: Maran Avudaiappan , Shogren Kristen L. , Benedikt Michaela , Sarkar Gobinda , Turner Russell T. , Yaszemski Michael J.
Published: September 2008

The article to which this erratum refers was published in J. Cell. Biochem. 104: 1937–1945, 2008. © 2008 Wiley‐Liss, Inc.
Conformational transitions of cyclic D,L‐peptides
Authors: Okamoto Hajime , Yamada Tetsuo , Kihara Shuichiro , Takechi Kazumasa , Takagi Hiroyuki , Takeda Kyozaburo
Published: September 2008

Conformational transitions of cyclic D,L‐hexapeptides have been studied by first‐principles calculations. Geometry optimizations for 20 types of homoresidue cyclic D,L‐hexapeptide revealed that the cyclic peptides have two types of energetically stable backbone (extended (E) and bound (B) types); and for each type, the amino acid side chains have two orientations (equatorial and axial). Among the four types of isomer [E‐type equatorial (Eeq), B‐type equatorial (Beq), E‐type axial (Eax), and B‐type axial (Bax)], Bax is the energetically most preferred by most of the 20 encoded amino acid residues, whereas Eax is the least preferred. A search for transition states indicated that six types of conformational transition are possible between the isomers of the cyclic peptide, i.e., the backbone–backbone conversions (Eeq‐Beq and Eax‐Bax transitions), the side chain–side chain conversions (Eeq‐Eax and Beq‐Bax transitions), and the simultaneous conversions of the backbone and the side‐chain orientation (Eeq‐Bax and Eax‐Beq transitions). All the six transitions proceed with the breaking of the high molecular symmetry (S6) and go through the triangular (C3) intermediate structure with either equatorial or axial side‐chain orientation. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Molecular dynamics with restrictions derived from optical spectra
Authors: Kaminský Jakub , ŠEbek Jiří , Bouř Petr
Published: September 2008

The information about molecular structure coded in the optical spectra must often be deciphered by complicated computational procedures. A combination of spectral modeling with the molecular dynamic simulations makes the process simpler, by implicit accounting for the inhomogeneous band broadening and Boltzmann averaging of many conformations. Ideally, geometries of studied systems can be deduced by a direct confrontation of such modeling with the experiment. In this work, the comparison is enhanced by restrictions to molecular dynamics propagations based on the Raman and Raman optical activity spectra. The methodology is introduced and tested on model systems comprising idealized H2O2, H2O3 molecules, and the alanine zwitterion. An additional gradient term based on the spectral overlap smoothed by Fourier transformation is constructed and added to the molecular energy during the molecular dynamics run. For systems with one prevalent conformation the method did allow to enrich the Boltzmann ensemble by a spectroscopically favored structure. For systems with multiconformational equilibria families preferential conformations can be selected. An alternative algorithm based on the comparison of the averaged spectra with the reference enabling iterative updates of the conformer probabilities provided even more distinct distributions in shorter times. It also accounts for multiconformer equilibria and provided realistic spectra and conformer distribution for the alanine. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Morphological alterations of radicular dentine pretreated with different irrigating solutions and irradiated with 980‐nm diode laser
Authors: Alfredo Edson , Souza‐Gabriel Aline E. , Silva Silvio Rocha C. , Sousa‐Neto Manoel D. , Brugnera‐Junior Aldo , Silva‐Sousa Yara T.C.
Published: September 2008

Background: The topographical features of intraradicular dentine pretreated with sodium hypochlorite (NaOCl) or ethylenediamine tetraacetic acid (EDTA) followed by diode laser irradiation have not yet been determined. Purpose: To evaluate the alterations of dentine irradiated with 980‐nm diode laser at different parameters after the surface treatment with NaOCl and EDTA. Study design: Roots of 60 canines were biomechanically prepared and irrigated with NaOCl or EDTA. Groups were divided according to the laser parameters: 1.5 W/CW; 1.5 W/100 Hz; 3.0 W/CW; 3.0 W/100 Hz and no irradiation (control). The roots were splited longitudinally and analyzed by scanning electron microscopy (SEM) in a quali‐quatitative way. The scores were submitted to two‐way Kruskal–Wallis and Dunn's tests. Results: The statistical analysis demonstrated that the specimens treated only with NaOCl or EDTA (control groups) were statistically different (P < 0.05) from the laser‐irradiated specimens, regardless of the parameter setting. The specimens treated with NaOCl showed a laser‐modified surface with smear layer, fissures, and no visible tubules. Those treated with EDTA and irradiated by laser presented absence of smear layer, tubules partially exposed and melting areas. Conclusions: The tested parameters of 980‐nm diode laser promoted similar alterations on dentine morphology, dependent to the type of surface pretreatment. Microsc. Res. Tech., 2009. © 2008 Wiley‐Liss, Inc.
Involvement of glycosaminoglycans in vesicular stomatitis virus G glycoprotein pseudotyped lentiviral vector‐mediated gene transfer into airway epithelial cells
Authors: Copreni Elena , Castellani Stefano , Palmieri Lucia , Penzo Marianna , Conese Massimo
Published: September 2008

Background

The involvement of surface molecules in HIV‐1‐derived lentivirus (LV)‐mediated transduction of airway epithelial cells has not been studied so far. The present study aimed to evaluate the role of glycosaminoglycans (GAGs) in gene transfer mediated by a third generation vesicular stomatitis virus G glycoprotein (VSV‐G) pseudotyped LV vector in an in vitro model of polarized airway epithelial cells.

Methods

Human bronchial (16HBE‐S1) and tracheal (CFT1‐C2) epithelial cells were grown either on plastic or on filters and transduced with the LV vector polypurine tract (PPT)‐green fluoresecent protein (GFP). Zonula Occludens (ZO)‐1, a marker of tight junction, and GAG localization were assessed by cytofluorimetry and confocal microscopy. Soluble GAGs and removal of cell surface GAGs were used to affect LV‐mediated transduction.

Results

Extensive optimization of experimental parameters (presence of polybrene during the infection, the incubation time in the presence of LV particles, period of time intercurring between infection and gene expression analysis) was carried out in plastic‐adherent cells. Polybrene resulted to be cytotoxic and was not further used. In CFT1‐C2 polarized cells, EGTA treatment determined a 20% decrease in transepithelial resistance, a diminished ZO‐1 localization at the tight junction location and a 31% increase in GFP positive cells. Heparane sulfate was distributed evenly on the cell surface. Heparin and soluble chondroitin sulfate A and B inhibited LV‐mediated transduction in a dose‐dependent fashion. These results were confirmed upon enzymatic removal of GAGs from the cell surface.

Conclusions

Taken together, these results show that GAGs are involved in VSV‐G LV transduction of airway epithelial cells. Copyright © 2008 John Wiley & Sons, Ltd.
Synthesis of a radioiodinated thymidine phosphorylase inhibitor and its preliminary evaluation as a potential SPECT tracer for angiogenic enzyme expression
Authors: Takahashi Masayuki , Seki Koh‐ichi , Nishijima Ken‐ichi , Zhao Songji , Kuge Yuji , Tamaki Nagara , Ohkura Kazue
Published: September 2008

The expression of thymidine phosphorylase (TP) is strongly associated with angiogenesis in tumors and activation of antitumor agents. We designed a novel 5‐125I‐labeled 6‐(2‐iminoimidazolidinyl)methyluracil hydrochloride ([125I]5I6IMU‐HCl) to develop an effective radiotracer for in vivo assessment of TP expression in tumors and prognosis of cancer chemotherapy. Radiotracer synthesis was achieved by radioiodination of the precursor, 6‐(2‐iminoimidazolidinyl)methyluracil at the C‐5 position with NCS/radioiodide. After purification by HPLC, [125I]5I6IMU‐HCl was obtained in high radiochemical yield with satisfactory specific activity. The radiotracer showed high inhibitory potency for the target enzyme and good stability in vivo. Copyright © 2008 John Wiley & Sons, Ltd.
Absence of transmission of potentially xenotic viruses in a prospective pig to primate islet xenotransplantation study
Authors: Garkavenko Olga , Dieckhoff Britta , Wynyard Shaun , Denner Joachim , Elliott Robert B. , Tan Paul L. , Croxson Margaret C.
Published: September 2008

Shortage of human donor organs for transplantation has prompted usage of animals as an alternative donor source. Pigs are the most acceptable candidate animals but issues of xenozoonoses remain. Despite careful monitoring of designated pathogen free pigs there is still a risk that their tissues may carry infectious agents. Thus xenotransplantation requires extensive pre‐clinical study on safety of the graft especially for those viruses that are either potentially oncogenic and/or immunosuppressive, or can establish persistent infection. A prospective pig‐to‐primate islet xenotransplantation study was performed which includes monitoring for potentially xenotic viruses namely porcine endogenous retrovirus (PERV), porcine cytomegalovirus (PCMV), porcine lymphotropic herpesvirus (PLHV), and porcine circovirus (PCV) using both molecular diagnostic—PCR and RT‐PCR and serology methods. There was no evidence of pig virus transmission into primate recipients. This preclinical study underlines the information concerning viral safety of islet cell xenograft in pig‐to‐primate xenotransplantation. J. Med. Virol. 80:2046–2052, 2008. © 2008 Wiley‐Liss, Inc.
Phylogenetic and molecular analysis of HTLV‐1 isolates from a medium sized town in Northern of Brazil: Tracing a common origin of the virus from the most endemic city in the country
Authors: Magalhães Themístocles , Mota‐Miranda Aline Cristina , Alcantara Luiz Carlos Junior , Olavarria Viviana , Galvão‐Castro Bernardo , Rios‐Grassi Maria Fernanda
Published: September 2008

Salvador‐Bahia has the highest prevalence of HTLV‐1 infection in Brazil; about 2% of the population is infected. In this city, the prevalence of HTLV in pregnant women is 1%. There is no data of the HTLV‐1 prevalence in others cities of the Bahia's Recôncavo, where the population has similar social and demography characteristics to those from Salvador. Our aim was to evaluate the seroprevalence of HTLV in pregnant women in Cruz das Almas‐Bahia, a medium‐sized city from the Bahia's Recôncavo. All individuals were tested for HTLV (ELISA) and the positive samples were confirmed by Western Blot. Phylogenetic analyses of the total LTR region were performed in all positive samples. We tested 408 samples (45.4% of the estimate pregnant women population) between June 1st and October 31, 2005. The prevalence of HTLV‐1 infection was 0.98%. In addition, all isolated virus were grouped in the subtype HTLV‐1a, in the Latin American group. Our results suggest that the introduction of HTLV‐1 occurred after the slave trade into Salvador. In addition, HTLV‐1‐infection should be screened during the pregnancy in women originating from HTLV‐1 endemic areas. J. Med. Virol. 80:2040–2045, 2008. © 2008 Wiley‐Liss, Inc.
Whole genomic characterization of a human rotavirus strain B219 belonging to a novel group of the genus rotavirus
Authors: Nagashima Shigeo , Kobayashi Nobumichi , Ishino Masaho , Alam Mohammed Mahbub , Ahmed Muzahed Uddin , Paul Shyamal Kumar , Ganesh Balasubramanian , Chawla‐Sarkar Mamta , Krishnan Triveni , Naik Trailokya Nath , Wang Yuan‐Hong
Published: September 2008

Novel rotavirus strains B219 and ADRV‐N derived from adult diarrheal cases in Bangladesh and China, respectively, are considered to belong to a novel rotavirus group (species) distinct from groups A, B, and C, by genetic analysis of five viral genes encoding VP6, VP7, NSP1, NSP2, and NSP3. In this study, the nucleotide sequences of the remaining six B219 gene segments encoding VP1, VP2, VP3, VP4, NSP4, and NSP5 were determined. The nucleotide sequences of the group B human rotavirus VP1 and VP3 genes were also determined in order to compare the whole genome of B219 with those of group A, B, and C rotavirus genomes. The nucleotide and deduced amino acid sequences of all B219 gene segments showed considerable identity to the ADRV‐N (strain J19) sequences (87.7–94.3% and 88.7–98.7%, respectively). In contrast, sequence identity to groups A–C rotavirus genes was less than 61%. However, functionally important domains and structural characteristics in VP1‐VP4, NSP4, and NSP5, which are conserved in group A, B, or C rotaviruses, were also found in the deduced amino acid sequences of the B219 proteins. Hence, the basic structures of all B219 viral proteins are considered to be similar to those of the known rotavirus groups. J. Med. Virol. 80:2023–2033, 2008. © 2008 Wiley‐Liss, Inc.
Tissue persistence of parvovirus B19 genotypes in asymptomatic persons
Authors: Corcioli Fabiana , Zakrzewska Krystyna , Rinieri Alessio , Fanci Rosa , Innocenti Massimo , Civinini Roberto , De Giorgi Vincenzo , Di Lollo Simonetta , Azzi Alberta
Published: September 2008

Parvovirus B19 (B19V) can persist in immunocompetent symptomatic and non‐symptomatic individuals, as demonstrated by the finding of viral DNA in different tissues, in absence of viremia and of anti‐B19V IgM. The spread and the nature of this phenomenon have not been clearly determined. In order to investigate the frequency of persistence and the tissue distribution of the three genotypes of B19V, the viral load of the persistent virus and its expression in the affected tissues, 139 tissue samples and 102 sera from 139 asymptomatic individuals have been analyzed by consensus PCRs and genotype specific PCRs for B19V detection and genotyping. Viral load was measured by real time PCR and viral mRNAs were detected by RT‐PCR. Altogether, 51% individuals carried B19V DNA, more frequently in solid tissues (65%) than in bone marrow (20%). Genotype 1 was found in 28% tissue samples, genotype 2 in 68% and genotype 3 in 3% only. Viral load ranged from less then 10 copies to 7 × 104 copies per 106 cells, with the exception of two samples of myocardium with about 106 copies per 106 cells. mRNA of capsid proteins was present in two bone marrow samples only. In conclusion, in asymptomatic individuals B19V persistence is more common in solid tissues than in bone marrow, and genotype 2 persists more frequently than genotype 1. The results suggest that the virus persists without replicating, at sub‐immunogenic levels. J. Med. Virol. 80:2005–2011, 2008. © 2008 Wiley‐Liss, Inc.
Enteric viruses in pediatric diarrhea in Saudi Arabia
Authors: Tayeb Hamsa T. , Dela Cruz Damian M. , Al‐Qahtani Ahmed , Al‐Ahdal Mohammed N. , Carter Michael J.
Published: September 2008

Between September 1st, 2002 and August 31st, 2003, a panel of 1,000 stool samples was collected from patients presenting with diarrhea in the three major urban centers of Saudi Arabia; Riyadh, Mecca, and Jeddah. Each sample was tested for rotavirus, and astrovirus by ELISA, G and P type was determined for all rotaviruses. Adenoviruses were sought by hexon‐specific PCR and identified by RFLP. A subset of 253 samples was also tested for norovirus by ELISA. Data were analyzed for seasonality of infection, patient nationality and likelihood of hospitalization. Although the overall incidence of rotavirus identification in acute diarrheal stool continued to decline, this was still the virus identified most commonly (6%). Norovirus accounted for 3.5%, astrovirus, 1.9% and adenovirus, 1.4%. Type G9 rotavirus was found to be present (and already common) in 2003, predating its first reported identification in the country in 2004. Most of the virus infections (and most of the G9 detections) occurred in April, the month following the occurrence of the Hajj in the study year. Although most viruses were spread equally in the population, rotaviruses were significantly more common in non‐Saudis than in Saudi citizens. Overall the data are consistent with an increase in all virus infections following al Hajj and the potential introduction of novel strains (such as the G9 rotaviruses) by pilgrims. Hospitalization was significantly associated only with norovirus infections. J. Med. Virol. 80:1919–1929, 2008. © 2008 Wiley‐Liss, Inc.
HTLV‐1 infection in blood donors from the Western Brazilian Amazon region: Seroprevalence and molecular study of viral isolates
Authors: Mota‐Miranda Aline Cristina , Araújo Sérgio Pereira , Dias Juarez Pereira , Colin Denise Duizit , Kashima Simone , Covas Dimas Tadeu , Tavares‐Neto José , Galvão‐Castro Bernardo , Alcantara Luiz Carlos Junior
Published: September 2008

To determine the seroprevalence of HTLV‐1 in Brazil, and to review the virus molecular epidemiology in this Amazon population (Rio Branco‐Acre), 219 blood donors were screened for HTLV‐1. Only one case of infection (0.46% seroprevalence) was detected during July 2004 screening at the Acre Hospital Foundation (FUNDACRE). Neighbor‐joining and Maximum Likelihood phylogenetic analyses of two (n = 2) complete LTR region sequences were performed with the PAUP* software. Since the HTLV‐1 envelope surface (gp46) and transmembrane (gp21) glycoproteins are important for virus fitness, three envelope glycoproteins sequences (n = 3) were analyzed using the Prosite tool to determinate potential protein sites. Phylogenetic analysis demonstrated that the new isolate described in this study, and the unpublished LTR strain described in a previous report belong to the Transcontinental subgroup of the Cosmopolitan subtype, inside the Latin American cluster. A similar result was obtained when submitting, to the Automated Genotyping System, three LTR partial sequences from a previous study of the seroprevalence of HTLV‐1 in the same Amazon population. In all analyzed env sequences, the potential protein site was found: two PKC phosphorylation sites at amino acid (aa) positions 310–312 and 342–344, one CK2 phosphorylation site at 194–197aa, three N‐glycosylation sites at 222–225aa, 244–247aa and 272–275aa, and a single N‐myristylation site at 327–338aa. In conclusion, potential protein sites described in HTLV‐1 gp46 and gp21 confirm the presence of conserved sites in the HTLV‐1 envelope proteins, likewise phylogenetic analysis suggests a possible recent introduction of the virus into North Brazil. J. Med. Virol. 80:1966–1971, 2008. © 2008 Wiley‐Liss, Inc.
GBV‐C coinfection is negatively correlated to Fas expression and Fas‐mediated apoptosis in HIV‐1 infected patients
Authors: Moenkemeyer Maren , Schmidt Reinhold E. , Wedemeyer Heiner , Tillmann Hans L. , Heiken Hans
Published: September 2008

Persistent coinfection with the apathogenic GB virus C (GBV‐C) is associated with slower disease progression of human immunodeficiency virus (HIV)‐1 infection. Aim of this study was to investigate whether Fas plays a role in this beneficial effect. Fas expression and susceptibility to Fas‐mediated apoptosis (FMA) was analyzed in peripheral blood mononuclear cells (PBMCs) of HIV‐1 patients coinfected and non‐coinfected with GBV‐C. Fas expression and function was evaluated in 42 GBV‐C coinfected and 101 non‐coinfected HIV‐1 patients. Thirteen healthy and 11 Hepatitis C virus (HCV)‐monoinfected individuals were analyzed as controls. Cell surface Fas expression was determined by flow cytometric analysis. Apoptosis was evaluated by staining with Annexin V and Viaprobe followed by multiparameter flow cytometry analysis. In untreated HIV‐1 patients GBV‐C coinfection was associated with significantly lower percentage of Fas expressing cells as compared to GBV‐C non‐coinfected individuals. Expression of Fas was directly correlated with sensitivity to Fas‐mediated apoptosis. Sensitivity to FMA was unchanged in GBV‐C coinfected patients. PBMCs of patients receiving highly active antiretroviral therapy (HAART) did not show such a difference. Untreated HIV‐1 patients with GBV‐C coinfection have reduced cell surface Fas expression. Lower FMA of T‐cells might contribute to prolonged survival of GBV‐C coinfected HIV‐1 patients. J. Med. Virol. 80:1933–1940, 2008. © 2008 Wiley‐Liss, Inc.
Molecular characterization of VP6‐encoding gene of group A human rotavirus samples from central west region of Brazil
Authors: Tavares Talissa de Moraes , de Brito Wilia Marta Elsner Diederichsen , Fiaccadori Fabíola Souza , Parente Juliana Alves , da Costa Paulo Sérgio Sucasas , Giugliano Loreny Gimenes , Andreasi Márcia Sueli Assis , Soares Célia Maria Almeida , Cardoso Divina das Dôres de Paula
Published: September 2008

Group A rotaviruses are the main cause of acute gastroenteritis in children worldwide. The intermediate capsid protein VP6 encoded by segment 6 of the dsRNA genome is the major structural component of the virus and it is highly antigenic and immunogenic. VP6 is responsible for group and subgroup (SG) specificities, allowing classification of group A rotavirus into SG I, SG II, SG I + II, and SG non‐I‐non‐II. VP6‐encoding gene of 154 group A human rotavirus samples of different G and P genotypes recovered from children in three cities of Central West region of Brazil was amplified by reverse transcription‐polymerase chain reaction followed by sequencing and phylogenetic analysis. Two distinct genetic groups could be recognized: VP6 genogroups I and II. Sequences analysis also revealed that all samples identified as VP6 genogroup I were associated with NSP4 genotype A, whereas samples identified as VP6 genogroup II were associated with NSP4 genotype B. This is the first study in Central West region regarding genetic variability of the VP6 gene. Further molecular surveillance of rotavirus strains is needed to understand better the occurrence of VP6 gene diversity in Brazil and the significance of VP6 for the control and prevention of rotavirus gastroenteritis. J. Med. Virol. 80:2034–2039, 2008. © 2008 Wiley‐Liss, Inc.
Emergence of the GII4/2006b variant and recombinant noroviruses in China
Authors: Jin Miao , Xie Hua‐ping , Duan Zhao‐jun , Liu Na , Zhang Qing , Wu Bing‐shan , Li Hui‐ying , Cheng Wei‐xia , Yang Su‐hua , Yu Jie‐mei , Xu Zi‐qian , Cui Shu‐xian , Zhu Lin , Tan Ming , Jiang Xi , Fang Zhao‐yin
Published: September 2008

Noroviruses are an important cause of acute gastroenteritis. Increasing data showed that the GII‐4 strains are predominant worldwide and new GII‐4 variants emerge every 1–2 years causing major epidemics. Surveillance of gastroenteritis in hospitalized children under 5 years of age in China is described. Among 1,110 specimens, 114 (10.3%) were positive for noroviruses, which was higher than adenoviruses (7.6%), astroviruses (3.5%), and sapoviruses (0.9%) and only lower than group A rotaviruses (40.6%). Thirty‐eight of the 114 positive norovirus cases were co‐infected with other enteric viruses. Five norovirus genotypes (GI‐2, GI‐4, GII‐3, GII‐4, and GII‐14) were detected, with GII‐4/2006b the most predominant type (64.9%). The reported recombinant of GII‐3 capsid and GII‐4 polymerase described previously was also detected frequently and a recombinant of GII‐14 capsid and GII‐6 polymerase was found for the first time. This study suggests that continual surveillance focusing on strain variation and dynamic change is important for understanding the epidemiology and development of a strategy for disease control and prevention. J. Med. Virol. 80:1997–2004, 2008. © 2008 Wiley‐Liss, Inc.
Natural polymorphisms in HIV‐1 protease: Impact on effectiveness of a first‐line lopinavir‐containing antiretroviral therapy regimen
Authors: Champenois Karen , Deuffic‐Burban Sylvie , Cotte Laurent , André Patrice , Choisy Philippe , Ajana Faiza , Bocket Laurence , Yazdanpanah Yazdan
Published: September 2008

Mutations on HIV protease lead to resistance to protease inhibitors. However, resistance development may be different according to primary, secondary or polymorphic mutations. The present study was designed to assess the impact of natural protease mutations on the effectiveness of a first‐line antiretroviral therapy (ART), and secondarily, their effect on the initial viral load (VL). The study was conducted in 175 HIV‐1‐infected patients, who initiated a first‐line lopinavir/r‐containing ART regimen and who had an available genotype resistance testing before initiating therapy. We assessed the association between mutations (prevalence ≥10%) and the initial VL. We assessed the association between mutations and ART effectiveness using two surrogate markers: the slope of VL decrease at 1 month and the time to VL undetectability. For the 175 patients, the initial median VL was 4.94 log10 copies/ml [interquartile range: 4.44–5.47] and the initial median CD4 lymphocyte count, 219/µl [129–296]. Eighteen mutations had a prevalence ≥10%. At 1 month, the median VL decrease was 2.35 log10 copies/ml [1.76–2.82]. The median time to VL undetectability was 128 days [91–196]. No mutation was associated significantly with the initial VL, the slope of VL decrease at 1 month or the time to VL undetectability. This study of antiretroviral‐naive patients showed that protease polymorphisms had no impact on the effectiveness of a lopinavir/r‐containing ART regimen. However, polymorphisms may affect ART effectiveness differently in other populations, such as ART‐experienced patients and/or patients treated with protease inhibitors other than the one used here. J. Med. Virol. 80:1871–1879, 2008. © 2008 Wiley‐Liss, Inc.
Lack of cross‐immune reactivity against influenza H5N1 from seasonal influenza vaccine in humans
Authors: Tang Julian W. , Ngai Karry L.K. , Chan Paul K.S.
Published: September 2008

In a small pilot study, sera from 10 healthy human volunteers were taken pre‐vaccine, then 1, 3, and 6 months post‐seasonal influenza immunization (using the 2005/2006 Northern hemisphere vaccine: A/New Caledonia/20/99(H1N1)‐like, A/California/7/2004(H3N2)‐like, and B/Shanghai/361/2002‐like strains). Eight out of 10 subjects demonstrated satisfactory HAI titers (≥40) after seasonal influenza vaccination between 1 and 6 months post‐vaccine. These sera were then tested for inhibitory activity against A/HK/483/97 and A/Thailand/1(KAN‐1)/04 H5N1 influenza viruses using standard hemagglutination inhibition and microneutralization assays. In contrast to several other studies in both humans and animals on the cross‐immunity between different influenza A viruses, antibodies produced to the influenza A(H1N1) component of the seasonal influenza vaccine showed no cross‐reactivity to these avian influenza A(H5N1) viruses. Possible reasons for this contrasting result are discussed. J. Med. Virol. 80:1992–1996, 2008. © 2008 Wiley‐Liss, Inc.
Molecular characterization of influenza viruses circulating in Northern Italy during two seasons (2005/2006 and 2006/2007) of low influenza activity
Authors: Pariani Elena , Amendola Antonella , Zappa Alessandra , Bianchi Silvia , Colzani Daniela , Anselmi Giovanni , Zanetti Alessandro , Tanzi Elisabetta
Published: September 2008

The influenza activity and circulation of influenza viruses in Lombardy (the most populous Italian region) were observed during two consecutive seasons (2005/2006 and 2006/2007) characterized by low influenza activity by the Italian Influenza Surveillance Network. The molecular characteristics of circulating viruses were analyzed to evaluate the introduction of new variants and emergence of vaccine‐escape viruses. In both seasons, the epidemic in Lombardy was sustained almost exclusively by influenza A viruses, accounting for 80.5% and 93.6% of total detections, respectively, and the co‐circulation of A/H3 viruses belonging to distinct phylogenetic groups was observed. The A/H1N1 viruses isolated during the 2005/2006 season were closely related to A/New Caledonia/20/99, while the hemagglutinin (HA) sequences of the A/H1N1 viruses from the 2006/2007 season exhibited a greater diversity. These viruses were A/Solomon Islands/3/2006‐like and showed several variants. All B isolates were similar to B/Malaysia/2506/2004 belonging to the B/Victoria/2/87‐lineage. Influenza B virus was the dominant virus in Europe in the 2005/2006 season and accounted for the 20% of total detections in Lombardy. Overall, the viruses studied presented heterogeneity in their HA sequences suggesting the circulation of a miscellaneous set of variants during the two seasons notwithstanding the medium‐low activity of influenza. The importance of virological surveillance of influenza viruses is recognized widely and the molecular characterization of the viruses, especially in vaccinated subjects, is of particular importance to evaluate the introduction and circulation of new variants. J. Med. Virol. 80:1984–1991, 2008. © 2008 Wiley‐Liss, Inc.