bluuebunny/crossref_metadata_2025 huggingface dataset:
Life expectancy of people living with HIV/AIDS and associated socioeconomic factors in Kenya
Authors: Adari Johnson Samuel , Moghadam Mashaallah Rahnama , Starnes Charles N.
Published: January 2007

There is a strong correlation between the life expectancy of the people living with HIV/AIDS and socioeconomic factors such as poverty, female literacy rate, government spending on health care, external grants, geographical location and HIV prevalence rate. The findings of this study indicate that poverty at household and/or regional levels reduces life expectancy of the people living with HIV/AIDS. HIV‐infected urban residents have a longer life span than their rural counterparts. Greater resource endowment improves the chances of extending the lives of the infected people. As expected, an increase in female literacy rate initially reduces HIV/AIDS‐related deaths. This could be a result of better skills and knowledge acquired by women who care for the sick. However, as female literacy rate increases, the mortality rate also increases as education changes the role of women in the society from homecare providers to labour force participants. Copyright © 2007 John Wiley & Sons, Ltd.
Detection of Δ9‐tetrahydrocannabinolic acid A in human urine and blood serum by LC‐MS/MS
Authors: Jung Julia , Kempf Juergen , Mahler Hellmut , Weinmann Wolfgang
Published: January 2007

Δ9‐Tetrahydrocannabinolic acid A (Δ9‐THCA‐A) is the precursor of Δ9‐tetrahydrocannabinol (Δ9‐THC) in hemp plants. During smoking, the non‐psychoactive Δ9‐THCA‐A is converted to Δ9‐THC, the main psychoactive component of marihuana and hashish. Although the decarboxylation of Δ9‐THCA‐A to Δ9‐THC was assumed to be complete—which means that no Δ9‐THCA‐A should be detectable in urine and blood serum of cannabis consumers—we found Δ9‐THCA‐A in the urine and blood serum samples collected from police controls of drivers suspected for driving under the influence of drugs (DUID). For LC‐MS/MS analysis, urine and blood serum samples were prepared by solid‐phase extraction. Analysis was performed with a phenylhexyl column using gradient elution with acetonitrile. For detection of Δ9‐THCA‐A, the mass spectrometer (MS) (SCIEX API 365 triple‐quadrupole MS with TurboIonSpray source) was operated in the multiple reaction monitoring (MRM) mode using the following transitions: m/z357 → 313, m/z357 → 245 and m/z357 → 191. Δ9‐THCA‐A could be detected in the urine and blood serum samples of several cannabis consumers in concentrations of up to 10.8 ng/ml in urine and 14.8 ng/ml in serum. The concentration of Δ9‐THCA‐A was below the Δ9‐THC concentration in most serum samples, resulting in molar ratios of Δ9‐THCA‐A/Δ9‐THC of approximately 5.0–18.6%. Only in one case, where a short elapsed time between the last intake and blood sampling is assumed, the molar ratio was 18.6% in the serum. This indicates differences in elimination kinetics, which need to be investigated in detail. Copyright © 2007 John Wiley & Sons, Ltd.
Perioperative outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy for non‐appendiceal peritoneal carcinomatosis from a prospective database
Authors: Yan Tristan D. , Zappa Luis , Edwards Gary , Alderman Robert , Marquardt Christina E. , Sugarbaker Paul H.
Published: January 2007

Background

Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has expanded its application in the management of peritoneal carcinomatosis from gastrointestinal and ovarian malignancies. An accurate assessment of perioperative outcomes is crucial for integration of this combined procedure into clinical practice.

Methods

A prospective study of 80 patients undergoing the combined treatment for non‐appendiceal peritoneal carcinomatosis was conducted. Forty‐seven adverse events by eight organ‐systems were rated from Grade I to IV with increasing severity.

Results

One patient (1.3%) died postoperatively. Postoperative adverse events affected genitourinary system (38%), hematological system (31%), gastrointestinal system (25%), infection (20%), intravenous catheters status (15%), pulmonary system (14%), cardiovascular system (11%) and neurological system (4%). Thirty‐six patients (45%) experienced 49 Grade III adverse events. Six patients (8%) experienced eight Grade IV adverse events. More than four peritonectomy procedures (P = 0.010), and length of hospital stay of more than 21 days (P = 0.007) were strongly associated with Grade III and/or Grade IV morbidity.

Conclusion

The morbidity and mortality rates after the combined treatment for non‐appendiceal peritoneal carcinomatosis were within the acceptable range of surgical treatments for other gastrointestinal cancers. A standardized prospective database is required for an accurate assessment of perioperative outcomes. J. Surg. Oncol. 2007;96:102–112. © 2007 Wiley‐Liss, Inc.
Estimation of soil salinity in semi‐arid land using a geostatistical model
Authors: Navarro‐Pedreño J. , Jordan M. M. , Meléndez‐Pastor I. , Gómez I. , Juan P. , Mateu J.
Published: January 2007

Soil salinity is one of the great problems in arid and semi‐arid environments. The estimation and prediction of spatial soil salinity may be considered as a stochastic process, observed at irregular locations in space. Environmental variables usually show spatial dependence among observations which is an important drawback to traditional statistical methods. Geostatistical techniques that analyse and describe the spatial dependence and quantify the scale and intensity of the spatial variation, provides spatial information for local estimation of soil salinity. In this paper we propose a Gaussian Spatial Linear Mixed Model (GSLMM), which involves a non‐parametric term, accounting for a deterministic trend given by exogenous variables, and a parametric component defining the purely spatial random variation, possibly due to latent spatial processes. We focus here on the analysis of the relationship between soil electrical conductivity as a parameter related directly to soil salinity as well as sodium content (sodicity) to identify spatial variations in these parameters. This kind of methodology is demonstrated as a useful tool for environmental land management. Copyright © 2007 John Wiley & Sons, Ltd.
Epigenetic reprogramming of liver cells in tamoxifen‐induced rat hepatocarcinogenesis
Authors: Tryndyak Volodymyr P. , Kovalchuk Olga , Muskhelishvili Levan , Montgomery Beverly , Rodriguez‐Juarez Rocio , Melnyk Stepan , Ross Sharon A. , Beland Frederick A. , Pogribny Igor P.
Published: January 2007

Tamoxifen, a nonsteroidal anti‐estrogen, is a potent genotoxic hepatocarcinogen in rats, with both tumor initiating and promoting properties. Recently it has been demonstrated that genotoxic carcinogens, in addition to exerting genotoxic effects, often cause epigenetic alterations and these induced epigenetic changes may play important mechanistic role in carcinogenesis. In the present study, we investigated the role of tamoxifen‐induced epigenetic changes in hepatocarcinogenic process. The results of the study showed that exposure of female F344 rats to tamoxifen resulted in progressive loss of CpG methylation in regulatory sequences of long interspersed nucleotide elements (LINE‐1) and prominent increase in expression of LINE‐1 elements and c‐myc proto‐oncogene. The accumulation of tamoxifen‐induced DNA lesions was accompanied by the decreased level of Rad51, Ku70, and DNA polymerase β (Polβ) proteins that play a crucial role in maintenance of genomic stability. Furthermore, feeding rats with tamoxifen‐containing diet led to increased regenerative cell proliferation, as indicated by the increased level of Ki‐67 and proliferating cell nuclear antigen (PCNA) proteins. These data indicate that exposure of animals to genotoxic hepatocarcinogen tamoxifen led to early phenotypical alterations in livers characterized by emergence of epigenetically reprogrammed cells with a specific cancer‐related epigenetic phenotype prior to tumor formation. © 2006 Wiley‐Liss, Inc.
HnRNP E2 is downregulated in human oral cancer cells and the overexpression of hnRNP E2 induces apoptosis
Authors: Roychoudhury Paromita , Paul Ranjan Rashmi , Chowdhury Rajdeep , Chaudhuri Keya
Published: January 2007

Human hnRNP genes have been reported to be involved in human malignancies and several hnRNPs are promising biomarkers of lung, head and neck, colon, breast, and pancreatic cancers. The present study investigated the clinicopathologic and biological significance of hnRNP E2 gene expression in oral cancer. Human hnRNP E2 was significantly downregulated in oral cancer tissues compared to normal one (P < 0.0001) as determined by quantitative real‐time reverse transcription PCR. The expression of hnRNP E2 is correlated with histology, being lower in moderate and poorly differentiated squamous cell carcinoma (SCC) compared to well‐differentiated SCC. Transient transfection of hnRNP E2 in cancerous cell lines resulted in reduced cell viability and increased apoptotic nuclei. Compared to control transfectants, cells with higher expression showed an increase in the number of apoptotic cells by annexin‐PI staining and an increase in caspase activity. The present study thus implicates downregulation of hnRNP E2 as a novel mechanism to enhance the resistance of cancer cells to apoptosis. © 2006 Wiley‐Liss, Inc.
Colorectal carcinoma development in inducible nitric oxide synthase‐deficient mice with dextran sulfate sodium‐induced ulcerative colitis
Authors: Seril Darren N. , Liao Jie , Yang Guang‐Yu
Published: January 2007

The overproduction of reactive oxygen and nitrogen species (RONS) may play an important role in ulcerative colitis (UC)‐associated carcinogenesis. In order to study the role of nitric oxide (NO) in UC‐associated colorectal carcinogenesis, the development of colorectal carcinoma was studied using the DSS‐induced and iron‐enhanced model of chronic UC in inducible nitric oxide synthase (iNOS)‐deficient mice. Female wild‐type C57BL/6 (iNOS+/+) and iNOS−/− mice were administered 1% DSS (w/v) through the drinking fluid for 15 DSS cycles and fed twofold iron‐enriched diet. Colorectal inflammation and mucosal ulceration of moderate severity were observed in both iNOS+/+ and iNOS−/− mice. Similar tumor incidence and multiplicity in the colon were observed that 15 out of 23 (65.2%) iNOS+/+ mice developed colorectal tumors with a tumor multiplicity of 1.47 ± 0.17 (mean ± SE) after 15 DSS cycles, and 13 out of 19 (68.4%) iNOS−/− mice developed colorectal tumors with a tumor multiplicity of 2.08 ± 0.21. Histopathologically, the tumors were confirmed to be well‐differentiated adenocarcinomas. Nitrotyrosine, an indicator of peroxynitrite‐caused protein modification, was detectable by immunohistochemistry in inflammatory cells and epithelial cells of the colon in iNOS+/+ and iNOS−/− mice, and no difference in staining intensity was observed between the two groups. Immunostaining for endothelial NOS (eNOS) was observed in lamina propria macrophages and colonic blood vessels, and eNOS protein levels were increased in the inflamed colon. These results show that there is no difference in UC‐associated cancer development in iNOS+/+ and iNOS−/− mice, and suggest that in the absence of iNOS, other factors, such as eNOS, may play a role in nitrosative stress and UC‐associated carcinogenesis in this model system. © 2006 Wiley‐Liss, Inc.
Association between Aurora‐A kinase polymorphisms and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population
Authors: Chen Jinyun , Sen Subrata , Amos Christopher I. , Wei Chongjuan , Jones J. Shawn , Lynch Patrick , Frazier Marsha L.
Published: January 2007

Aurora‐A kinase is considered a potential cancer susceptibility gene that encodes a centrosome‐associated, cell cycle‐regulated serine/threonine kinase. We studied two single nucleotide polymorphisms (SNP) in the coding region of Aurora‐A, 91T‐to‐A (F31I) and 169G‐to‐A (V57I). We studied the influence of these two polymorphisms on age of onset of hereditary nonpolyposis colorectal cancer (HNPCC). Genotyping of the Aurora‐A polymorphisms was carried out on 125 Caucasian with mismatch repair (MMR) gene mutations with real‐time pyrophosphate DNA sequencing. For the 91T‐to‐A polymorphism, we found that patients with HNPCC who were homozygous for the wild‐type allele developed colorectal cancer (CRC) 7 years earlier than patients who were homozygous or heterozygous for the mutant allele. The169G‐to‐A polymorphism did not have a significant influence on risk for HNPCC. However, when we did haplotype analysis for these two polymorphisms, the 91A‐169G haplotype was associated with protection from HNPCC at an earlier age. © 2006 Wiley‐Liss, Inc.
Association of the EGFR intron 1 CA repeat length with lung cancer risk
Authors: Zhang Weiping , Weissfeld Joel L. , Romkes Marjorie , Land Stephanie R. , Grandis Jennifer R. , Siegfried Jill M.
Published: January 2007

Epidermal growth factor receptor (EGFR) plays an important role in the development and progression of lung cancer. A previous report noted that an increased number of polymorphic CA repeats in the first intron of the EGFR gene results in decreased transcriptional activity. To estimate the association of the length of polymorphic CA repeats in intron 1 of the EGFR gene with lung cancer, a case‐control study of 176 lung cancer patients and 161 controls was conducted in Caucasians. This case‐control study is based on two existing prospective cohorts: the Early Detection Research Network (EDRN) and the Lung Cancer Specialized Program of Research Excellence (SPORE) at the University of Pittsburgh. The frequencies of the SL (one allele>16 repeats), and SS (both allele ≤16 repeats) genotypes were statistically higher among the cases than in the controls (OR: 1.94 and 3.04, 95% CI: 1.16–3.23 and 1.53–6.04, P‐value: 0.01 and 0.001, respectively). When the length of EGFR‐CA repeat was analyzed by the sum of the number of repeats in two alleles, the frequency of the shorter repeats (sum ≤36) was 79.6% versus 63.4%, respectively, and the frequency of the longer repeats (sum >36) was 20.5% versus 36.7%, for lung cancer cases versus controls. The lower sum of EGFR‐CA repeats associated with the risk of lung cancer; the estimated odds ratio was 2.25 with 95% confidence interval: 1.38–3.66 (P = 0.001). Associations involving EGFR‐CA repeat genotype and EGFR‐CA repeat sum remained significant when adjusted for age, gender, and tobacco exposure. Our study, which is preliminary, demonstrates for the first time that shorter EGFR‐CA repeats associate with lung cancer risk. The number of EGFR‐CA repeats identifies a possible susceptible population to lung cancer. © 2007 Wiley‐Liss, Inc.
MMP‐7 (matrilysin) expression in human brain tumors
Authors: Rome Claire , Arsaut Josette , Taris Caroline , Couillaud Franck , Loiseau Hugues
Published: January 2007

Matrix metalloproteinases (MMP) which degrades protein components of the extra‐cellular matrix and basement membrane seems to be largely involved in cancer invasiveness. MMP proteolitic activity essentially comes from stromal cells but matrilysin (MMP‐7) is produced by the tumor itself. Thus, MMP‐7 is investigated to address the particular invasive behavior of human glioma. Both MMP‐7 mRNA and protein were clearly identified in human glioma. MMP‐7 mRNA expression was highly variable within our glioma population. When analyzing MMP‐7 mRNA expression in different primary brain tumors, we found highly variable levels of expression not related to their invasive behavior. In successive biopsies obtained in the same patients with glioblastoma, MMP‐7 mRNA was quantified and appeared variable, but intra‐individual variations were lower than inter‐individual differences. With a xenograft model of U87 human tumors in RAG2/γc immune‐deficient mice, the strict tumor origin of MMP‐7 was shown. Additionally, MMP‐7 expression by U87 cells which is low in culture was stimulated by these cells while forming tumors and the level of expression was higher when the tumor cells were implanted within the brain. These data provide some consistent information about cross‐talk occurring between the tumor and the surrounding stroma to regulate MMP‐7 expression. © 2007 Wiley‐Liss, Inc.
Estrogen‐dependent expression of the tissue kallikrein gene (Klk1) in the mouse uterus and its implications for endometrial tissue growth
Authors: Rajapakse Sanath , Yamano Noriko , Ogiwara Katsueki , Hirata Kensaku , Takahashi Sumio , Takahashi Takayuki
Published: January 2007

Tissue kallikrein mK1 is a serine protease involved in the generation of bioactive kinins for normal cardiac and arterial function in the mouse. In the present study, the tissue kallikrein gene Klk1, which codes for mK1, was shown to be one of the most prevalent of the Klk gene species in the uteri of adult mice, and its mRNA level was significantly higher at estrus than at diestrus. Klk1 mRNA expression was enhanced in the uteri of ovariectomized mice receiving estradiol‐17β treatment. Both endometrial epithelial and stromal cells isolated from the mice exhibited Klk1 expression at detectable levels when cultured in the presence of estradiol‐17β. mK1 was characterized using the recombinant active enzyme. mK1 had trypsin‐like activity with a strong preference for Arg over Lys in the P1 position, and its activity was inhibited by typical serine protease inhibitors. Casein, gelatin, fibronectin, collagen type IV, and high‐molecular‐weight kininogen were degraded by mK1. The single‐chain tissue‐type plasminogen activator was converted to the two‐chain form by mK1. In addition, mK1 degraded insulin‐like growth factor binding protein‐3. The present data suggest that mK1 may be implicated in the growth of uterine endometrial tissues during the proliferative phase. Mol. Reprod. Dev. 74: 1053–1063, 2007. © 2007 Wiley‐Liss, Inc.
Temporal expression of transcripts related to embryo quality in bovine embryos cultured from the two‐cell to blastocyst stage in vitro or in vivo
Authors: Corcoran Deirdre , Rizos Dimitrios , Fair Trudee , Evans Alex C.O. , Lonergan Patrick
Published: January 2007

The post‐fertilization embryo culture environment can have a dramatic effect on the pattern of gene expression in the embryo and it is widely acknowledged that bovine embryos derived from in vitro culture are of inferior quality to those derived in vivo. The objective of this study was to examine temporal variation in the mRNA abundance of several transcription and translation factors known to differ between blastocysts produced following culture in vitro and in vivo. Embryos were recovered from two in vitro culture systems SOF1 or SOF2 at five developmental stages: 2‐ to 4‐cell, 8‐cell, 16‐cell, morula, and blastocyst. In vivo embryos were produced from superovulated and artificially inseminated heifers and recovered at approximately 40 hr or 3, 4, 5, and 7 days postinsemination. Blastocysts were also produced following in vitro maturation, in vitro fertilization and culture in the ewe oviduct. Analysis of relative transcript abundance for FOXO3A, EEF1G, HMG2, and REA was performed using quantitative real‐time PCR. Irrespective of culture environment each transcript followed, approximately the same general pattern of expression where relative abundance decreased dramatically from the 2‐ to 4‐cell stage to 8‐cell stage and increased from the morula to blastocyst stage (P < 0.05). Transcripts for GNBL2 were not observed between the 2‐ and 16‐cell stage of development. Relatively high expression at the 2‐ to 4‐cell indicated that these transcripts are most likely of maternal origin produced in the oocyte during growth and final maturation. A culture‐induced change in mRNA abundance of transcription and translation factors was evident in embryos that were produced not only between in vivo and in vitro culture environments but also between different in vitro culture systems. Mol. Reprod. Dev. 74: 972–977, 2007. © 2007 Wiley‐Liss, Inc.
A gene trap mutation of a murine homolog of the Drosophila stem cell factor Pumilio results in smaller testes but does not affect litter size or fertility
Authors: Xu Eugene Yujun , Chang Rhoda , Salmon Nicholas A. , Reijo Pera Renee A.
Published: January 2007

Members of the Pumilio (also called PUF) gene family belong to a class of highly conserved developmental regulators that are present in both flies and humans. Much is known about the function of Pumilio genes in invertebrate development, in particular their role as stem cell factors required for maintenance and/or self‐renewal of germline stem cells in Drosophila and Caenorhabditis elegans. It remains unknown whether Pumilio genes are also required for development in mammals; however, several lines of evidence suggest similar functions based on extensive sequence homology, similar RNA‐binding properties to their invertebrate counterparts and well‐documented interactions with germ cell factors required for fertility. Here we report characterization of a gene trap mutation that disrupts the mouse Pumilio‐2 (Pum2) gene. Our data confirm that Pumilio‐2 is expressed most abundantly in germ cells with the highest expression in undifferentiated gonocytes and spermatogonia. Furthermore, the mutation in Pum2 results in significantly smaller testes although the mutants are otherwise viable and fertile. In addition, we observed no stronger reproductive defects on a genetic background homozygous for a Pum2 null mutation and heterozygous for a Dazl mutation than Pum2 mutant alone. Thus, as in C. elegans where single members of the Pumilio gene family are dispensable for reproductive development and viability, this individual member of the Pumilio gene family in mice is also not essential for reproduction or viability. Mol. Reprod. Dev. 74: 912–921, 2007. © 2007 Wiley‐Liss, Inc.
PP2Cδ (Ppm1d, WIP1), an endogenous inhibitor of p38 MAPK, is regulated along With Trp53 and Cdkn2a following p38 MAPK inhibition during mouse preimplantation development
Authors: Hickson Jenny A. , Fong Barry , Watson Patricia H. , Watson Andrew J.
Published: January 2007

Preimplantation embryos utilize mitogen‐activated protein kinase signaling (MAPK) pathways to relay signals from the external environment to prepare appropriate responses and adaptations to a changing milieu. It is therefore important to investigate how MAPK pathways are regulated during preimplantation development. This study was conducted to investigate whether PP2Cδ (Ppm1d, WIP1) is expressed during mouse preimplantation development and to determine the influences of p38 MAPK inhibition on expression of Trp53 (p53), Ppm1d, (WIP1), and Cdkn2a (p16) during mouse preimplantation development. Our results indicate that Trp53, Ppm1d, and Cdkn2a mRNAs and TRP53 and PP2Cδ proteins are expressed throughout mouse preimplantation development. Treatment of 2‐cell embryos with SB220025 (potent inhibitor of p38 MAPK α/β/MAPK 14/11) significantly increased Trp53, Ppm1d and Cdkn2a and Mapk14 mRNA levels at 12 and 24 hr. Treatment of 8‐cell embryos with SB220025 for 12 hr increased Trp53, Ppm1d, and Cdkn2a mRNA levels, but not Mapk14 mRNA levels. Treatment of 8‐cell embryos for 24 hr increased Trp53, and Ppm1d mRNA levels, but decreased Cdkn2a and Mapk14 mRNA levels. Therefore, blockade of p38 MAPK activity is associated with embryo stage specific influences on Trp53, Ppm1d, Cdkn2a, and Mapk14 expression during mouse preimplantation development. These results define downstream targets of p38 MAPK during preimplantation development and indicate that the p38 MAPK pathway regulates Trp53, Ppm1d, and Cdkn2a expression. This study increases our understanding of the mechanisms controlling preimplantation development and of the interactions between preimplantation embryos and their culture environments. Mol. Reprod. Dev. 74: 821–834, 2007. © 2007 Wiley‐Liss, Inc.
Morphologic and histologic comparisons between in vivo and nuclear transfer derived porcine embryos
Authors: Martin L. , Besch‐Williford C. , Lai L. , Cheong H.‐T. , Im G.‐S. , Park K.‐W. , Murphy C. , Hao Y. , Ellersieck M.R. , Keisler D.H. , Schatten H. , Green J.A. , Prather R.S.
Published: January 2007

Nuclear transfer (NT) is an inefficient but invaluable tool of the biotechnology industry. This study looked at abnormalities associated with peri‐implantation NT porcine embryos. Four experimental groups were examined: nonpregnant animals, in vivo pregnant animals, NT recipients, and manipulation control embryos (MC). Embryos (Day 10, 12, or 14) were evaluated for embryonic disc diameter, gross morphology, nucleoli density, and mitotic figure index. Day 12 (P ≤ 0.03) and Day 14 (P ≤ 0.01) NT embryos had increased numbers of nucleoli, and Day 14 NT embryos had an increased (P ≤ 0.03) mitotic index compared to in vivo and MC embryos. In vivo produced Day 14 embryos had increased (P ≤ 0.01) disk diameters when compared to other embryos except for MC Day 14, which also showed increases (P ≤ 0.01) in disk diameter except when compared to in vivo produced Day 12 and Day 14 embryos. In vivo produced Day 12 had greater (P ≤ 0.03) disk diameters when compared to NT and MC embryos except for MC Day 14, and in vivo produced Day 14 embryos, which had a significantly increased (P ≤ 0.01) disk diameter. In vivo produced Day 14 embryos were morphologically more advanced (P ≤ 0.01) than Day 14 NT and MC counterparts. NT embryos develop at a slower rate than their in vivo produced counterparts. The increase in nucleoli and mitotic index of NT embryos suggest the cell cycle may be affected or the NT embryos are employing other means to compensate for slow development. The techniques used during NT also appear to compromise embryo development. Mol. Reprod. Dev. 74: 952–960, 2007. © 2007 Wiley‐Liss, Inc.
Assessment of the reliability of central and peripheral fatigue after sustained maximal voluntary contraction of the quadriceps muscle
Authors: Place Nicolas , Maffiuletti Nicola A. , Martin Alain , Lepers Romuald
Published: January 2007

The aim of the present study was to further confirm the validity of measurements for characterizing neuromuscular alterations by establishing their reliability both before and after fatigue. Thirteen men (28 ± 5 years) volunteered to participate in two separate identical sessions requiring the performance of a sustained maximal voluntary contraction (MVC) with the quadriceps muscle for 2 min. MVC and transcutaneous electrical stimulations were used before and immediately after the fatiguing contraction to investigate the reliability of MVC torque, central activation, and peripheral variables (M‐wave properties, peak twitch, peak doublet) within and between sessions. Based on previous and present results, we advise the use of (1) voluntary activation level with potentiated doublet as a reference to describe central fatigue, (2) electromyographic activity of vastus lateralis muscle as a surrogate for quadriceps for both voluntary and evoked contraction, and (3) potentiated peak doublet amplitude to investigate contractile fatigue. These findings can be useful in the choice of the parameters describing central and peripheral fatigue of the quadriceps muscle in future studies. Muscle Nerve, 2007
Effects of intramuscular needle position on motor unit action potential metrics
Authors: Brownell Alexander A. , Bromberg Mark B.
Published: January 2007

It is unclear whether there are clinically significant differences in amplitude, duration, and numbers of turns and phases if an electromyographic (EMG) study is performed near to, or far from, the end‐plate zone. The effects of temporal dispersion of arriving muscle‐fiber action potentials on quantitative motor unit action potential (MUAP) metrics were assessed in simulated and biologic muscles. Two muscle simulation models were studied with electrode recording positions near the motor end‐plate zone and 50–75 mm away. When the electrode was moved away from the end‐plate zone, averages of 20 MUAPs significantly decreased in amplitude and area, and increased in numbers of turns and phases, but there was no significant change in duration. In biologic muscles (both normal and pathologic), similar changes in average metrics were observed, but to lesser degrees; few were statistically significant. Zones of innervation in biologic muscles are broadly distributed and, during routine electrode studies, distances between random electrode placements and end‐plate zones are therefore relatively short, leading to clinically insignificant changes in quantitative MUAP metrics with distance from the end‐plate zone. Thus, electrode position within a muscle is unlikely to affect clinical MUAP interpretation. Muscle Nerve, 2007
Polyglucosan body disease myopathy: An unusual presentation
Authors: Vucic Steve , Pamphlett Roger , Wills Edward J. , Yiannikas Con
Published: January 2007

Polyglucosan body disease (PBD) is a slowly progressive adult‐onset glycogen storage disorder that typically affects upper and lower neurons. Myopathy, as a complication of PBD has been reported rarely and clinically manifests as chronic limb‐girdle muscle weakness. We report an unusual case of PBD myopathy presenting as an asymmetric motor syndrome that clinically overlapped with amyotrophic lateral sclerosis, further expanding the phenotype of this disorder. Muscle Nerve, 2007
Intraepidermal nerve fiber density as a marker of early diabetic neuropathy
Authors: Umapathi T. , Tan Wan Loo , Loke Seng Cheong , Soon Puay Cheow , Tavintharan S. , Chan Yiong Huak
Published: January 2007

The purpose of the study was to reliably identify an early stage of diabetic polyneuropathy (DPN) by measuring injury to epidermal nerve fibers. We compared intraepidermal nerve fiber density (IENFD) at the ankle and thigh of 29 diabetic subjects who had no clinical or electrophysiological evidence of small‐ or large‐fiber neuropathy to that of 84 healthy controls. The mean ankle IENFD of diabetic subjects was 9.1 ± 5.0 mm and that of controls, 13.0 ± 4.8 mm (P < 0.001). The thigh IENFD did not differ significantly. The IENFD ratio (thigh IENFD divided by ankle IENFD) was 2.39 ± 1.30 in diabetic subjects and 1.77 ± 0.58 in controls (P < 0.001), indicating a length‐dependent reduction of IENFD in diabetics. Ankle IENFD remained significantly lower and the IENFD ratio higher in diabetic subjects after adjusting for age. Two subjects had parasympathetic dysfunction, two had retinopathy, and two early nephropathy. Age, height, weight, duration of diabetes, and average HbA1c did not influence IENFD among diabetic subjects. We used receiver operating characteristic (ROC) curves to describe and compare the utility of various threshold values of ankle IENFD and IENFD ratio for the diagnosis of early DPN. The sensitivity and specificity of diagnosing DPN using ankle IENFD of less than 10 mm were 72.4% and 76.2%, respectively. Thus, asymptomatic diabetics have a measurable, length‐dependent reduction of distal epidermal nerves. Analogous to microalbuminuria in diabetic nephropathy, reliable identification and quantitation of nascent diabetic neuropathy may have potential therapeutic implications. Muscle Nerve, 2007
Kallikrein 4 is a potential mediator of cellular interactions between cancer cells and osteoblasts in metastatic prostate cancer
Authors: Gao Jin , Collard Rachael L. , Bui Loan , Herington Adrian C. , Nicol David L. , Clements Judith A.
Published: January 2007

BACKGROUND

Prostate cancer (PCa) and bone cell interactions are critical in the metastatic phase. Kallikrein 4 (KLK4/hK4) is expressed in both PCa and mineralized tissues. We determined if KLK4/hK4 expression was associated with, and influenced by, the bone environment of metastatic PCa.

METHODS

Immunohistochemistry, in vitro co‐culture, cell migration, and attachment assays.

RESULTS

hK4 was localized to tumor cells and osteoblasts in bone metastases. KLK4/hK4 increased in LNCaP and PC3 cells co‐cultured with SaOs2 cells; SaOs2 KLK4/hK4 was unchanged. Co‐culture did not affect cell proliferation but altered alkaline phosphatase activity/mRNA levels in SaOs2 cells. KLK4‐transfected PC3 cells had increased migration towards SaOs2 conditioned medium and greater attachment to the bone‐matrix proteins, collagens I and IV.

CONCLUSIONS

hK4 expression and interaction with both tumor cells and osteoblasts suggests a role for hK4 in PCa bone metastasis. Whether this observation is unique to bone metastasis or reflects a role for hK4 in PCa metastasis generally is yet to be established. Prostate 67: 348–360, 2007. © 2007 Wiley‐Liss, Inc.
Dendritic cells program non‐immunogenic prostate‐specific T cell responses beginning at early stages of prostate tumorigenesis
Authors: Mihalyo Marianne A. , Hagymasi Adam T. , Slaiby Aaron M. , Nevius Erin E. , Adler Adam J.
Published: January 2007

BACKGROUND

Prostate cancer promotes the development of T cell tolerance towards prostatic antigens, potentially limiting the efficacy of prostate cancer vaccines targeting these antigens. Here, we sought to determine the stage of disease progression when T cell tolerance develops, as well as the role of steady state dendritic cells (DC) and CD4+CD25+ T regulatory cells (Tregs) in programming tolerance.

METHODS

The response of naïve HA‐specific CD4+ T cells were analyzed following adoptive transfer into Pro‐HA × TRAMP transgenic mice harboring variably‐staged HA‐expressing prostate tumors on two genetic backgrounds that display different patterns and kinetics of tumorigenesis. The role of DC and Tregs in programming HA‐specific CD4 cell responses were assessed via depletion.

RESULTS

HA‐specific CD4 cells underwent non‐immunogenic responses at all stages of tumorigenesis in both genetic backgrounds. These responses were completely dependent on DC, but not appreciably influenced by Tregs.

CONCLUSIONS

These results suggest that tolerogenicity is an early and general property of prostate tumors. Prostate 67: 536–546, 2007. © 2007 Wiley‐Liss, Inc.
Interaction geometry involving planar groups in protein–protein interfaces
Authors: Saha Rudra Prasad , Bhattacharyya Rajasri , Chakrabarti Pinak
Published: January 2007

The geometry of interactions of planar residues is nonrandom in protein tertiary structures and gives rise to conventional, as well as nonconventional (XH···π, XH···O, where X = C, N, or O) hydrogen bonds. Whether a similar geometry is maintained when the interaction is across the protein–protein interface is addressed here. The relative geometries of interactions involving planar residues, and the percentage of contacts giving rise to different types of hydrogen bonds are quite similar in protein structures and the biological interfaces formed by protein chains in homodimers and protein–protein heterocomplexes—thus pointing to the similarity of chemical interactions that occurs during protein folding and binding. However, the percentage is considerably smaller in the nonspecific and nonphysiological interfaces that are formed in crystal lattices of monomeric proteins. The CH···O interaction linking the aromatic and the peptide groups is quite common in protein structures as well as the three types of interfaces. However, as the interfaces formed by crystal contacts are depleted in aromatic residues, the weaker hydrogen bond interactions would contribute less toward their stability. Proteins 2007; © 2007 Wiley‐Liss, Inc.
Opuntia ficus indica (L.) Mill. mucilages show cytoprotective effect on gastric mucosa in rat
Authors: Galati E. M. , Monforte M. T. , Miceli N. , Mondello M. R. , Taviano M. F. , Galluzzo M. , Tripodo M. M.
Published: January 2007

Opuntia ficus indica cladodes possess a protective action against ethanol‐induced ulcer in the rat. The major components of cladodes are carbohydrate polymers, mainly mucilages and pectin. To clarify the cytoprotective effects of cladodes on experimental ethanol‐induced ulcer in rat, mucilages and pectin were extracted and were administered instead of cladodes. The above mentioned effects induced by cladodes may be attributed to mucilages, and not significantly to pectin. Copyright © 2007 John Wiley & Sons, Ltd.
Linked surveys of health services utilization
Authors: Sirken Monroe G. , Shimizu Iris M.
Published: January 2007

The linked population/establishment survey (LS) of health services utilization is a two‐phase sample survey that links the sample designs of the population sample survey (PS) and the health‐care provider establishment sample survey (ES) of health services utilization. In Phase I, household respondents in the PS identify their health‐care providers during a specified calendar period. In Phase II, health‐care providers identified in Phase I report the variables of interest for all or a sample of their transactions with all households during the same calendar period.

The LS has been proposed as a potential design alternative to the PS whenever the health‐care transactions of interest are hard to find or enumerate in household surveys and as a potential design alternative to the ES whenever it is infeasible or expensive to construct or maintain complete sampling provider frames that list all health‐care providers with good measures of provider size. Suppose that the non‐sampling errors are ignorable, how do the LS, PS and ES sampling errors compare? This paper addresses that question by summarizing and extending recent research findings that compare expressions of the sampling variance of (1) the LS and PS of equivalent household sample size and (2) the LS and the ES of equivalent expected health‐care provider and transaction sample sizes.

The paper identifies the parameters contributing to the precision differences and assesses the conditions that favour the LS or one or the other surveys. Published in 2007 by John Wiley & Sons, Ltd.
Using hierarchical models to attribute sources of variation in consumer assessments of health care
Authors: Zaslavsky Alan M.
Published: January 2007

The Consumer Assessments of Healthcare Providers and Systems (CAHPS®) Medicare Advantage (MA‐CAHPS) survey has provided extensive and uniform data for 8 years on the quality of Medicare health plans in the United States. The complex structure of the data makes hierarchical modelling an appropriate analytic tool. After describing the CAHPS survey and the analytic methods used in standard reports, we review research using two multilevel modelling strategies, each addressing a different aspect of the structure of the CAHPS data. The first fits a 2‐level Fay–Herriott‐type model to data aggregated by plan to estimate plan‐level correlations among summary scores on different items. By forming separate measures for healthier and sicker members of each plan, we were able to determine which items measured distinct dimensions of quality depending on health status. The second analysis evaluated the relative contributions of geography and organizational units to the various quality measures, and the amount of variation over time in each. Geographical variation predominated for aspects of member experiences that are not typically under the direct control of plans, and the geographical effects were very stable over time. Each of the two analyses can be regarded as a simplification for particular objectives of a larger underlying model. Further methodological development is needed to better characterize variation in quality. Copyright © 2007 John Wiley & Sons, Ltd.
HIV viral dynamic models with dropouts and missing covariates
Authors: Wu Lang
Published: January 2007

In recent years HIV viral dynamic models have received great attention in AIDS studies. Often, subjects in these studies may drop out for various reasons such as drug intolerance or drug resistance, and covariates may also contain missing data. Statistical analyses ignoring informative dropouts and missing covariates may lead to misleading results. We consider appropriate methods for HIV viral dynamic models with informative dropouts and missing covariates and evaluate these methodsviasimulations. A real data set is analysed, and the results show that the initial viral decay rate, which may reflect the efficacy of the anti‐HIV treatment, may be over‐estimated if dropout patients are ignored. We also find that the current or immediate previous viral load values may be most predictive for patients' dropout. These results may be important for HIV/AIDS studies. Copyright © 2007 John Wiley & Sons, Ltd.
What is the role of constructivist teachers within faculty communication networks?
Authors: Judson Eugene , Lawson Anton E.
Published: January 2007

Using the biology faculty of one high school (n = 9) and the mathematics faculty of another (n = 16), this study tested the hypothesis that constructivist teachers play an active role within teacher communication networks (the constructivist‐teacher hypothesis). This hypothesis contrasts with the view that constructivist teachers operate alone and largely severed from communications among colleagues. Two types of representations of communication patterns among faculty members (i.e., sociographs) were created and analyzed for each faculty. One type of sociograph plotted communications concerning content/pedagogical issues while the other type plotted social/informal communications. Trained raters assessed constructivist‐teaching practices using the Reformed Teaching Observation Protocol (RTOP). Positive relationships were found between constructivist‐teaching practices and the frequency and significance of communications within both faculties—more so for content/pedagogical issues than for social/informal communications. Importantly, peers sought out constructivist teachers more often than they did traditional teachers, presumably seeking advice regarding teaching practice. Results support the constructivist‐teacher hypothesis and indicate that constructivist teachers are not isolated from their peers. Instead, they appear to play an active role, particularly when colleagues are discussing issues related to content and pedagogy. © 2007 Wiley Periodicals, Inc. J Res Sci Teach 44: 490–505, 2007
The development and application of affective assessment in an upper‐level cell biology course
Authors: Kitchen Elizabeth , Reeve Suzanne , Bell John D. , Sudweeks Richard R. , Bradshaw William S.
Published: January 2007

This study exemplifies how faculty members can develop instruments to assess affective responses of students to the specific features of the courses they teach. Means for assessing three types of affective responses are demonstrated: (a) student attitudes towards courses with differing instructional objectives and methodologies, (b) student self‐efficacy (confidence) in completing tasks common to practicing experts, and (c) interests in subject‐specific topics and associated intellectual skills. The iterative processes used in refining the instruments and performing the statistical analyses of their effectiveness are detailed. An analysis of data obtained using these instruments is also included. Positive attitudes towards courses emphasizing analytical thinking increased significantly over the course of a 14‐week semester, as did the measures of self‐efficacy. Despite the rigorous analytical nature of the course experience, the initial strong interest in cell biology topics and higher order thinking skills remained unchanged. There were no significant differences based on gender in any of the affective measures. We discuss the apparent dichotomy, revealed in these assessments, between students' idealistic, academic attitudes towards the course's effectiveness and their opinions of its effects on them personally. We conclude by reporting how insights garnered both from these formal assessments and from anecdotal communications have prompted experimental modifications in the design and conduct of the course. © 2007 Wiley Periodicals, Inc. J Res Sci Teach 44: 1057–1087, 2007
Verifying a signature architecture: a comparative case study
Authors: Basin David , Kuruma Hironobu , Miyazaki Kunihiko , Takaragi Kazuo , Wolff Burkhart
Published: January 2007

We report on a case study in applying different formal methods to model and verify an architecture for administrating digital signatures. The architecture comprises several concurrently executing systems that authenticate users and generate and store digital signatures by passing security relevant data through a tightly controlled interface. The architecture is interesting from a formal-methods perspective as it involves complex operations on data as well as process coordination and hence is a candidate for both data-oriented and process-oriented formal methods.

We have built and verified two models of the signature architecture using two representative formal methods. In the first, we specify a data model of the architecture in Z that we extend to a trace model and interactively verify by theorem proving. In the second, we model the architecture as a system of communicating processes that we verify by finite-state model checking. We provide a detailed comparison of these two different approaches to formalization (infinite state with rich data types versus finite state) and verification (theorem proving versus model checking). Contrary to common belief, our case study suggests that Z is well suited for temporal reasoning about process models with complex operations on data. Moreover, our comparison highlights the advantages of proving theorems about such models and provides evidence that, in the hands of an experienced user, theorem proving may be neither substantially more time-consuming nor more complex than model checking.
Evaluation of the effectiveness of the national vitamin A supplementation programme among school children in Sri Lanka
Authors: Madatuwa Thennakoon M. J. C. , Mahawithanage Sanath T. C. , Chandrika Udumalagala G. , Jansz Errol R. , Wickremasinghe Ananda R.
Published: January 2007

The Ministry of Health in Sri Lanka commenced a vitamin A supplementation programme of school children with a megadose of 105 μmol (100 000 IU) vitamin A in school years 1, 4 and 7 (approximately 5-, 9- and 12-year-olds, respectively) in 2001. We evaluated the vitamin A supplementation programme of school children in a rural area of Sri Lanka. A cross-sectional study was conducted among children supplemented with an oral megadose of vitamin A (105 μmol; n 452) and children not supplemented (controls; n 294) in Grades 1–5. Children were clinically examined and a sample of blood was taken for serum vitamin A concentration estimation by HPLC. Socio-demographic information was obtained from children or mothers. Supplemented children had a higher proportion of males and stunted children, were younger and lived under poorer conditions as compared to controls. There was no difference in the prevalences of eye signs and symptoms of vitamin A deficiency in the two groups. Supplemented children had higher serum vitamin A concentrations than controls (1·4 (sd 0·49) μmol/l v. 1·2 (sd 0·52) μmol/l). The serum vitamin A concentrations were 1·6 (sd 0·45), 1·4 (sd 0·50), 1·3 (sd 0·44) and 1·1 (sd 0·43) μmol/l in children supplemented within 1, 1–6, 7–12 and 13–18 months of supplementation, respectively. Vitamin A concentrations were significantly greater than controls if supplementation was carried out within 6 months after adjustment. The oral megadose of 105 μmol vitamin A maintained serum vitamin A concentrations for 6 months in school children.