Estimates of HIV prevalence and incidence in Canada, 2005.
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Canada↗
Biomedical subjects
P Yan
Publications and source records attributed to P Yan.
Generalized linear latent variable models for repeated measures of spatially correlated multivariate data.
Observations of multiple-response variables across space and over time occur often in environmental and ecological studies. Compared to purely spatial models for a single response variable in the exponential family of distributions, fewer statistical tools are available for multiple-response variables that are not necessarily Gaussian. An exception is a common-factor model developed for multivariate spatial data by Wang and Wall (2003, Biostatistics 4, 569-582). The purpose of this article is to extend this multivariate space-only model and develop a flexible class of generalized linear latent variable models for multivariate spatial-temporal data. For statistical inference, maximum likelihood estimates and their standard deviations are obtained using a Monte Carlo EM algorithm. We also use a novel way to automatically adjust the Monte Carlo sample size, which facilitates the convergence of the Monte Carlo EM algorithm. The methodology is illustrated by an ecological study of red pine trees in response to bark beetle challenges in a forest stand of Wisconsin.
Algorithms↗
Foetal intrauterine growth restrictions with Helicobacter pylori infection.
BACKGROUND: Helicobacter pylori infection has been associated with growth restriction in young children. AIM: To determine whether there is an association between H. pylori infection and intrauterine growth restriction. METHODS: Four hundred and forty-eight consecutive pregnant women (aged 15-44 years), attending for routine examinations in the third trimester, were enrolled. Clinical, demographic and previous obstetric data, as well as smoking history, were collected. At delivery, the weight, height, gender and status of the neonate were recorded; intrauterine growth restriction was defined if the birth weight was below the 10th percentile according to the gestational age for infants born in Australia. RESULTS: Eighty-nine (20%) women were seropositive for H. pylori. The prevalence of H. pylori was significantly lower in Caucasians (17%) vs. non-Caucasians (42%, P < 0.0001). There were 34 (7.5%) cases of intrauterine growth restriction (7% Caucasians, 16% Asians, 12% Aborigines and 0% Pacific Islanders). Intrauterine growth restriction was more common in H. pylori-seropositive women than in H. pylori-seronegative women [13.5% vs. 6%; odds ratio (OR) = 2.41; 95% confidence interval (CI), 1.14-5.08; P = 0.018]. A multiple logistic regression model revealed that smoking (OR = 3.55; 95% CI, 1.62-7.79; P = 0.002), maternal height (OR = 0.48; 95% CI, 0.28-0.80; P = 0.005) and H. pylori seropositivity (OR = 2.59; 95% CI, 1.12-5.95; P = 0.025) were all independent risk factors for intrauterine growth restriction. CONCLUSIONS: H. pylori infection in pregnant women may affect foetal intrauterine growth.
Adolescent↗
Tumor necrosis factor receptor deletion reduces nuclear factor-kappaB activation, cellular inhibitor of apoptosis protein 2 expression, and functional recovery after traumatic spinal cord injury.
Tumor necrosis factor-alpha (TNF-alpha) expression has been documented extensively in animal models of traumatic spinal cord injury (SCI). However, the pathophysiological significance of TNF-alpha expression in the injured cord remains to be delineated. The TNF receptor (TNFR)-nuclear factor-kappaB (NF-kappaB) signal transduction pathway is important for maintaining cell viability. NF-kappaB exerts anti-apoptotic effects via an endogenous caspase inhibitory system mediated by cellular inhibitor of apoptosis protein 2 (c-IAP2). NF-kappaB transactivates c-IAP2 to inhibit caspase-3 activation. Progressive cell death, including morphological and biochemical features suggestive of apoptosis, has been noted after SCI. We explored the effects of TNFR1 or TNFR2 deletion on the apoptotic events downstream of NF-kappaB in relation to SCI pathology and functional recovery. Nuclear proteins from the injured cords of the TNFR1(-/-) mice had a reduced NF-kappaB binding activity compared with the wild-type controls. This decrease in NF-kappaB activation was accompanied by a reduction in c-IAP2 expression and an increase in the active form of caspase-3 protein. After SCI the TNFR1(-/-) mice had greater numbers of apoptotic cells, a larger lesion size, and worse functional recovery than wild-type mice. TNFR2-deficient mice had a similar, although not as pronounced, consequence as the TNFR1(-/-) mice. These findings support the argument that the TNFR-NF-kappaB pathway is beneficial for limiting apoptotic cell death after SCI and that a defective TNFR-NF-kappaB pathway results in a poorer neurological outcome. A worse functional outcome in TNFR(-/-) mice suggests that an endogenous apoptosis inhibitory mechanism mediated by TNFR activation, NF-kappaB, and c-IAP2 may be of pathophysiological importance.
Animals↗
Glucocorticoid receptor-mediated suppression of activator protein-1 activation and matrix metalloproteinase expression after spinal cord injury.
Post-traumatic inflammatory reaction may contribute to progressive tissue damage after spinal cord injury (SCI). Two key transcription factors, nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1), are activated in inflammation. An increase in NF-kappaB binding activity has been shown in the injured spinal cord. We report activation of AP-1 after SCI. Electrophoretic mobility shift assay showed that AP-1 binding activity increased after SCI, starting at 1 hr, peaking at 8 hr, and declining to basal levels by 7 d. Methylprednisolone (MP) is the only therapeutic agent approved by the Food and Drug Administration for treating patients with acute traumatic SCI. MP reduced post-traumatic AP-1 activation. RU486, a glucocorticoid receptor (GR) antagonist, reversed MP inhibition of AP-1 activation. Immunostaining showed an increase in the expression of the Fos-B and c-Jun components of AP-1 in the injured cord. A c-fos antisense oligodeoxynucleotide (ODN) inhibited AP-1, but not NF-kappaB, activation after SCI. AP-1 and NF-kappaB can transactivate genes encoding matrix metalloproteinase-1 (MMP-1) and MMP-9. Western blotting and immunostaining show increased expression of MMP-1 and MMP-9 in the injured cord. MP inhibited MMP-1 and MMP-9 expression after SCI. RU486 reversed this MP effect. The c-fos antisense ODN, however, failed to suppress MMP-1 or MMP-9 expression. These findings demonstrate that MP may suppress post-traumatic inflammatory reaction by inhibiting both the AP-1 and NF-kappaB transcription cascades via a GR mechanism. Expression of inflammatory genes such as MMP-1 and MMP-9 that are transactivated jointly by AP-1 and NF-kappaB may not be suppressed by inhibiting only AP-1 activity.
Animals↗
Expression of telomerase genes correlates with telomerase activity in human colorectal carcinogenesis.
The human telomerase enzyme is composed of two essential components, hTR, which acts as a template for reverse transcription, and hTERT, which is the putative catalytic subunit for the enzyme. Recent studies have demonstrated a good correlation between hTERT expression and telomerase activation, whereas RT-PCR results seemed to reveal that hTR is ubiquitously expressed in all cells. These observations left unclear the role of hTR, and to a lesser extent hTERT, in the regulation of telomerase activation. In the present study, the correlation of telomerase activity and the expression of these genes was examined in a total of 70 colorectal tissues (25 adenocarcinomas, 30 adenomas, and 15 samples of normal colorectal mucosa). Total RNA for RT-PCR analysis and cell extracts for TRAP assay were obtained from consecutive sections and histological control was simultaneously performed. To avoid false-positive results, due to the fact that hTR cDNA and genomic hTR DNA are identical (the gene has no introns), extensive DNase digestion was performed before cDNA synthesis. RT-PCR analysis revealed that hTERT mRNA was expressed in all cancers and in 13 of 14 telomerase-positive adenomas, but never in telomerase-negative colorectal tissues. hTR transcripts were observed in all telomerase-positive samples but also in three telomerase-negative samples, two adenomas, and one normal colonic mucosa. It is concluded that hTERT and hTR expression is strongly correlated with telomerase activity. hTR transcripts, however, also occur in some telomerase-negative tissues and these results are in keeping with the concept that hTERT expression is a major regulator of telomerase activity.
Adenocarcinoma↗
Detection of malignant effusions: comparison of a telomerase assay and cytologic examination.
Telomerase is inactive in most somatic cells, but has been found to be reactivated in a majority of cancers. Our principal goal was to test whether the presence of telomerase activity concurred with positive cytology, and was thus of potential use in detecting cancer cells in effusions. The telomeric repeat amplification protocol (TRAP) assay and cytological examination were performed in a blinded fashion on 91 unselected effusions, for which laboratory processing was done according to standard procedures. In our series, 30% (27/91) of samples were found to be malignant by cytology. Of these, 19 (70%) were also positive in the TRAP assay. Of the 8 telomerase-negative cytology-positive samples, RNA integrity was generally poor, indicating suboptimal sample conservation for molecular analysis. Negative cytology in the presence of telomerase activity was observed in 17 effusions. Of these, 11 were from patients with advanced cancer, and thus a diagnosis of malignant effusion should be suspected. The TRAP assay for telomerase activity holds promise in the analysis of effusions, but its routine use as an adjunct to cytology awaits further confirmation of its positive predictive value.
Adolescent↗
DNA methylation and ovarian cancer. I. Analysis of CpG island hypermethylation in human ovarian cancer using differential methylation hybridization.
OBJECTIVE: The aim of this study was to examine CpG island methylation patterns in ovarian cancer and determine whether epigenetic information can be related to clinical data of patients. CpG island (CpGI) hypermethylation is commonly associated with cancer progression, but little is currently known about the role of methylation in ovarian cancer. METHODS: Differential methylation hybridization (DMH) analysis at 742 loci was performed to determine methylation signatures for 20 primary epithelial ovarian carcinomas (Stages II, III, and IV adenocarcinomas, serous papillary), 6 ovarian cancer cell lines, and normal ovarian surface epithelial cells. RESULTS: Between 23 and 108 methylated CpGIs were seen in the ovarian carcinomas. Fewer (P < 0.05) methylated CpGIs were observed in the ovarian cancer cell lines; however, a number of CpGIs were commonly hypermethylated in both the cell lines and the tumor samples. A methylation signature, consisting of frequently (P < 0.05) methylated CpGIs, was determined for the samples. The observed pattern of methylation in ovarian cancers included several (11) CpGI tags that were previously reported to be hypermethylated in human breast cancer. CONCLUSIONS: Epigenetic signatures in ovarian cancer were determined using DMH. This proof-of-concept study lays the foundation for genome-wide screening of methylation to examine epigenotype-phenotype relationships in ovarian cancer.
Adult↗
iNOS and nitrotyrosine expression after spinal cord injury.
Secondary tissue damage after spinal cord injury (SCI) may be due to inflammatory mediators. After SCI, the nuclear factor-kappaB (NF-kappaB) transcription factor can activate many pro-inflammatory genes, one of which is inducible nitric oxide synthase (iNOS). iNOS catalyzes the synthesis of nitric oxide (NO), a key inflammatory mediator, which in turn reacts with superoxide to generate peroxynitrite. Peroxynitrite is a strong oxidant that can damage cellular enzymes, membranes, and subcellular organelles through the nitration of tyrosine residues on proteins. The presence of nitrotyrosine (NT) is an indirect chemical indicator of toxic NO and peroxynitrite-induced cellular damage. Using a New York University (NYU) impactor to induce SCI in adult rats, we examined the temporal and cellular expression of iNOS and NT. We observed a progressive increase in iNOS expression in the injured cord starting at day 1 with maximal expression occurring at day 7, as determined by Western blot analysis. iNOS expression corresponded temporally to an increase in iNOS enzyme activity after SCI. In parallel with the progressive increase in iNOS activity, NT expression also increased with time after SCI. The iNOS and NT immunoreactivity was localized in neurons, astrocytes, endothelial cells and ependymal cells at the epicenter and adjacent to the region of spinal cord impact and injury. Results from the present study suggest that increased iNOS and peroxynitrite anion, as reflected by the progressive accumulation of NT in the injured impacted spinal cord, may contribute to the secondary injury process after SCI.
Animals↗
Cellular localization of tumor necrosis factor-alpha following acute spinal cord injury in adult rats.
Posttraumatic inflammatory reaction may contribute to secondary injury after traumatic spinal cord injury (SCI). Expression of tumor necrosis factor-alpha (TNF-alpha), a key inflammatory mediator, has been demonstrated in the injured cord. However, the specific cell types that are responsible for TNF-alpha expression after SCI remain to be identified. In the present study, cellular sources of TNF-alpha were examined in rats that received a spinal cord impact injury at the 9th thoracic (T9) level. Here we demonstrate that, within hours after SCI, increased TNF-alpha immunoreactivity was localized in neurons, glial cells (including astrocytes, oligodendrocytes, and microglia), and endothelial cells in areas of the spinal cord adjacent to the lesion site. Myelin breakdown was noted in oligodendrocytes that are immunopositive for TNF-alpha. In sham-operated controls, a low level of TNF-alpha immunoreactivity was detected. In antigen-absorption experiments, no TNF-alpha immunoreactivity was detected, indicating the specificity of TNF-alpha immunocytochemistry in the present study. Results suggest that various cell types, including neurons, glial cells, and vascular endothelial cells, contribute to TNF-alpha production in the injured cord.
Acute Disease↗
Oxidative stress in the fetal lamb brain following intermittent umbilical cord occlusion: a path analysis.
OBJECTIVE: To evaluate the relative contribution of cord occlusion length intervals between occlusions and experimental duration on oxidative stress in the fetal lamb brain. DESIGN: Acute, partially exteriorised fetal lambs with intermittent total cord occlusion. SETTING: The Vivarium of Westmead Hospital, University of Sydney, Australia and The Chinese University of Hong Kong. MAIN OUTCOME MEASURES: Arterio-venous differences in the concentration of organic hydroperoxides, measured in paired samples of carotid arterial and jugular venous blood, as an index of oxidative stress in the brain. METHODS: Thirty-two fetal lambs were exposed to graded hypoxia, induced by intermittent total umbilical cord compression of 30 seconds, 60 seconds and 90 seconds duration, occurring every minute for a total of 27 occlusions over 81 minutes. Three sham experiments were also performed. In addition to organic hydroperoxides, carotid arterial blood samples were also assayed in 15 animals (two sham) for oxygen saturation, pH, hypoxanthine, xanthine and urate concentrations. A causal model for oxidative stress was defined: occlusions leading to hypoxia with a rise in hypoxanthine; reperfusion during intervals between occlusions leading to the accelerated production of xanthine and uric acid and the generation of oxygen free radicals, which in turn, are responsible for the rise in lipid peroxidation. Path analysis was performed to assess the strength of the relationships between these variables and the cord occlusion length, the interval between occlusions and the duration of the experiment. RESULTS: Sham experiments showed no change in organic hydroperoxide production. Following 30-second umbilical cord occlusions a sixfold drop in mean organic hydroperoxides was observed between carotid arterial and jugular venous levels. In contrast, following occlusions of 60 seconds duration (or longer) a median 20-fold increase in organic hydroperoxide production was observed. Path analysis revealed a strong indirect pathway from occlusion length --> hypoxanthine --> urate and weak positive pathways from oxygen saturation --> urate and from interval between occlusions --> urate. After accounting for these pathways reflecting oxidative stress, a strong direct path remained from time from first occlusion --> organic hydroperoxide production. CONCLUSIONS: Peroxidation of lipids in the brain occurs under conditions of severe hypoxia and reperfusion associated with intermittent umbilical cord occlusions of 60 seconds or longer. The path analysis supported the causal model as originally defined, with the exception that the indirect pathway via pH was found to be trivial.
Animals↗
Promoter methylation analysis on microdissected paraffin-embedded tissues using bisulfite treatment and PCR-SSCP.
Methylation-sensitive single-strand conformation analysis (MS-SSCA) is a new method of screening for DNA methylation changes. The combination of bisulfite modification and PCR results in the conversion of unmethylated cytosines to thymines, whereas methylated cytosines remain unchanged. This sequence conversion can lead to methylation-dependent alterations of single-strand conformation, which can be detected by SSCA. An analysis of mixtures of methylated and unmethylated DNA at known ratios revealed that the relative intensities of the corresponding bands following MS-SSCA were maintained. MS-SSCA was applied for methylation analysis of human p16 promoter region using genomic DNA obtained from either frozen, fixed, or microdissected fixed tissue sections. MS-SSCA is a rapid, specific, and semiquantitative approach that allows the detection of methylation of the p16 gene promoter. In reconstruction experiments, the method permits the detection of 10% or less of cells harboring a methylated p16 promoter. We have been successful in analyzing by MS-SSCA almost all (96%) tumor samples microdissected from archival paraffin-embedded fixed tissue sections and obtaining reproducible results. In addition, when microdissection was performed, the clonality of this genetic alteration could be identified.
DNA↗
Wilms' tumor: a paradigm for the new genetics.
Carcinogenesis can be triggered by a diverse range of molecular lesions, a variety of which can be illustrated by Wilm's tumor (WT), a pediatric kidney cancer. Molecular defects observed in WTs include several independent targets and mechanisms best exemplified by changes on the short arm of chromosome 11. This article will review the molecular pathology of WT and emphasize the broader ramifications for cancer genetics. Consideration will be given to carcinogenic pathways, novel cellular molecules, and technologies that will assist in the rapid interpretation and assimilation of DNA sequence data arising from the sequencing of the human genome.
Genes, Wilms Tumor↗
[Dust deposition and its measurement by 137Cs in the Gonghe Basin, Qinghai Province, China].
Through the dust observation at three sites in the Gonghe Basin, Qinghai Province, China and 137Cs analysis of dust samples, the 137Cs technique is firstly used to study the dust deposition by storm. The rate of dust deposition and its monthly distribution were determined and the dust source traced by 137Cs. It is apparent that the 137Cs model for accumulation rate must be modified because of the 137Cs redistribution from dust gain. These tentative results may be have some significant implications for further dust storm research.
Cesium Radioisotopes↗
Pseudo-cerebrospinal fluid rhinorrhea following traumatic cerebrospinal fluid rhinorrhea surgery: a case report.
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Adult↗
[Evaluation the pathological diagnostic values of koilocyte in condyloma acuminatum].
OBJECTIVE: To evaluate the histological diagnostic values of koilocyte in histopathologic diagnosis of condyloma acuminatum. METHODS: Koilocyte was served as diagnostic criteria to scan 2 063 biopsies and compared the results with "goldan standard" of histopathologic diagnosis of condyloma acuminatum. RESULTS: Using koilocyte as diagnostic standard to diagnose condyloma acuminatum, the sensitivity and specificity were 77.93% and 95.26%, with positive predictive value 97.25%, negative predictive value 66.70%, positive likelihood rate 81.81, negative likelihood rate 23.17, under diagnostic rate 22.07%, misdiagnostic rate 4.74%. CONCLUSION: The koilocyte was proved to be one of classical histopathological morphologic features of human papillomavirus infection and other virus infection which served one of the most important histopathological markers for diagnosis of condyloma acuminatum, but not the only one.
Biopsy↗
Glucocorticoid receptor expression in the spinal cord after traumatic injury in adult rats.
Methylprednisolone (MP), a glucocorticoid, is the only effective therapeutic agent used in the clinical treatment of acute spinal cord injury (SCI). MP given within 8 hr after SCI significantly improves neurological function. Although the glucocorticoid receptor (GR) is suggested to mediate MP actions, limited knowledge is available on its expression and possible function after SCI. Presently, the expression of GR was studied in a weight-drop SCI model in adult rats. Immunohistochemistry and Western blot analysis revealed an increase in GR protein expression as early as 15 min after injury. GR expression sharply increased at 4 hr (22-fold), peaked at 8 hr (56-fold), rapidly declined at 1 d, and returned to the baseline level at and after 3 d. During its peak expression, GR was localized in neural somata and dendrites but not in axons and their terminals. GR immunoreactivity was also found in oligodendrocytes and astrocytes. Interestingly, other cell types, such as endothelial cells, were GR-negative. An increase in the binding activity of nuclear proteins to the glucocorticoid responsive element was also observed after SCI, demonstrating a functional element of GR activation. Finally, colocalization of GR and tumor necrosis factor alpha (TNF-alpha), an inflammatory cytokine, was observed in neurons and glial cells, consistent with MP regulation of TNF-alpha in this model. Thus, the transient expression of high levels of GR after SCI may provide new insights into the anti-inflammatory action of MP.
Animals↗
Telomerase activity and human telomerase reverse transcriptase mRNA expression in soft tissue tumors: correlation with grade, histology, and proliferative activity.
Telomerase activity (TA) is detected in most human cancers but, with few exceptions, not in normal somatic cells. Little is known about TA in soft tissue tumors. We have examined a series of benign and malignant soft tissue tumors for TA using the telomerase repeat amplification protocol assay. Analysis of the expression of the human telomerase reverse transcriptase was also carried out using RT-PCR. TA was undetectable in benign lesions (15 of 15) and low-grade sarcomas (6 of 6) and was detectable in 50% (19 of 38) of intermediate-/high-grade sarcomas. Although the presence of TA in soft tissue tumors is synonymous with malignancy, it is neither a reliable method in making the distinction between reactive/benign and malignant (especially low-grade) lesions nor a reliable marker of tumor aggressiveness. Leiomyosarcomas and storiform/pleomorphic malignant fibrous histiocytomas rarely showed TA, irrespective of their grade. A strong correlation between human telomerase reverse transcriptase mRNA expression and TA was observed, supporting the close relationship between both parameters. No significant relationship was observed between proliferative activity (as assessed by MIB-1 immunolabeling) and TA. We verified that the absence of telomerase expression was not due to the presence of telomerase inhibitors and therefore alternative mechanism(s) for cell immortalization, yet to be determined, seem to be involved in the development and/or maintenance of some soft tissue sarcomas.
Gene Expression Regulation, Neoplastic↗