Knowledge representation model for systems-level analysis of signal transduction networks

A Petri-net based model for knowledge representation has been developed to describe as explicitly and formally as possible the molecular mechanisms of cell signaling and their pathological implications. A conceptual framework has been established for reconstructing and analyzing signal transduction networks on the basis of the formal representation. Such a conceptual framework renders it possible to qualitatively understand the cell signaling behavior at systems-level. The mechanisms of the complex signaling network are explored by applying the established framework to the signal transduction induced by potent proinflammatory cytokines, IL-1beta and TNF-alpha The corresponding expert-knowledge network is constructed to evaluate its mechanisms in detail. This strategy should be useful in drug target discovery and its validation.     

A systemic view of higher education and professional psychology: implications of the Combined-Integrated model of doctoral training

This article was developed in response to the proceedings of the Consensus Conference on Combined and Integrated Doctoral Training in Psychology held at James Madison University in Harrisonburg, VA, May 2 to 4, 2003. The authors approach the recommendations of the conference from the perspective of their experiences in higher education administration at the national, regional, and state levels. The authors conclude that the Consensus Conference represents an exemplar of best practice in program planning. They suggest that a major reconceptualization of higher education is under way that emphasizes broad collaboration among various professional groups as a means of providing appropriate mental health and health care services. Consequently, professional psychology will need to reconceptualize its role in the broader context of other professions within the university setting. Recommendations for the education of psychologists and the development of future training programs are provided. Suggestions for implementation of various recommendations flowing from the Consensus Conference are delineated.     

BK polyomavirus interstitial nephritis in a renal allograft recipient

Human polyomavirus (PV) interstitial nephritis has recently been recognized as a cause of severe renal allograft dysfunction. It occurs in immunosuppressed patients after reactivation of the latent virus PV type BK (BK virus) in the renal epithelium. BK disease is defined as a morphologically manifest renal infection with cytopathic signs accompanied by varying degrees of interstitial inflammatory cell infiltrates and functional impairment. It is also identified by the presence of cells containing viral inclusion bodies (decoy cells) in the urine. The authors report a case of BK PV interstitial nephritis in a 36-year-old renal allograft recipient. Under light microscopy the chief diagnostic indicator was detection of intranuclear viral inclusions, which were found exclusively in tubular epithelial cells. Cells with viral changes were often enlarged with nuclear atypia and chromatin basophilia. Widespread interstitial plasma cell infiltrates associated with tubulitis were present. Intranuclear paracrystalline arrays of virus particles 35-38 nm in diameter were present as characteristic ultrastructural indicators. Urine samples revealed decoy cells with ground-glass-type intranuclear inclusions positive for BK virus by electron microcopy.     

Molecular epidemiological and clinical aspects of hepatitis D virus in a unique triple hepatitis viruses (B,C, D) endemic community in Taiwan

The molecular epidemiological and clinical aspects of hepatitis D virus (HDV) in a unique HBV, HCV, and HDV triple virus endemic community in southern Taiwan were investigated. A total of 2,909 residents aged 45 or older were screened for hepatitis B surface antigen (HBsAg), anti-HCV antibody, and anti-HDV antibody (specifically for HBsAg-positive carriers). Factors that might be associated with HDV infection, viral nucleic acid detection, and genotyping of HBV, HCV, and HDV were investigated. The prevalence of HBsAg and anti-HCV were 12.6% (366/2,909) and 41.6% (1,227/2,909), respectively. For HBsAg carriers, 15.3% (56/366) were positive for anti-HDV assay. Living in a higher endemic district of HCV infection (odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.7-6.3), male gender (OR = 1.9; 95% CI = 1.1-3.6) and co-infection with HCV (OR = 1.8; 95% CI = 1.0-3.3) were significantly independent factors associated with HDV infection. The detection rate of HDV RNA among anti-HDV-positive patients was only 12.7% (7/55). The mean HBV titer of triple infection group was significantly lower than in the HBV/HDV co-infection group (2.23 vs 3.05 in log(10), copies/ml, P = 0.046). HCV RNA detection among the triple infection group showed 47.4% (9/19) viremia rate and viral loads of 579,121 IU/ml in median (16,803-1,551,190 IU/ml). The prevalent genotype of HBV was type B (23/25); HCV was 1b (7/9) and HDV was IIa/IIb (4/4). Only the presence of HCV RNA predicted the presence of elevated ALT significantly (OR = 25.0; 95% CI = 3.39-184.6). In conclusion, the geographical aggregation of HDV infection paralleled that of HCV infection in this community. HCV suppressed the replication of HBV among triple vital infection patients. HBV and HDV lapsed into a remission or nonreplicative phase in most cases, and HCV acted as a dominant factor in triple viral-infected individuals. Only the presence of HCV RNA was associated with elevated ALT values, but not HBV or HDV.     

Depressed type 1 cytokine synthesis by superantigen-activated CD4+ T cells of women with human papillomavirus-related high-grade squamous intraepithelial lesions

Carcinoma of the cervix is causally related to infection with the human papillomavirus (HPV), and T cells play a pivotal role in the immune response of the host to rid itself of HPV infection. Therefore, we assessed the T-cell function of women with HPV-related cervical neoplasia against a superantigen, Staphylococcus enterotoxin B (SEB). Each woman provided a cervical brush specimen for HPV DNA testing and Papanicolaou (Pap) smears for the staging of cervical lesions. They also provided a blood specimen for determination of the ability of CD4(+) T and CD8(+) T cells to synthesize Th1 (interleukin-2 [IL-2], gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and Th2 (IL-10) cytokines in response to activation with SEB. Compared with control subjects with self-attested negative Pap smears, women with high-grade squamous intraepithelial lesions (HSIL) had significantly lower percentages of activated CD4(+) T cells that produced IL-2 (P = 0.045), IFN-gamma (P = 0.040), and TNF-alpha (P = 0.015) and a significantly lower percentage of activated CD8(+) T cells that produced IL-2 (P < 0.01). These data indicate that women with HPV-related cervical HSIL show a decrease in Th1 cytokine production by activated CD4(+) T cells and suggested that compromised T-helper functions may negatively impact the function of cytotoxic CD8(+) T cells.     

Primary giant cell malignant fibrous histiocytoma of the kidney with staghorn calculi

Malignant fibrous histiocytomas (MFH) as primary renal tumours are rare, with less than 50 cases described in the literature. We report a case of primary renal MFH of giant cell type in a 56-year-old man, who presented with bilateral dull flank pain, intermittent gross haematuria and body weight loss (6 kg in 3 months). Intravenous urography, computerized tomography (CT) and magnetic resonance image (MRI) showed right ureteral stones with mild hydronephrosis, and a solid mass at the lower pole of the left kidney associated with staghorn calculi, as well as tumour thrombi in the left renal vein and inferior vena cava. Left radical nephrectomy and evacuation of tumour thrombi from the left renal vein and inferior vena cava were performed. Histopathologic examination revealed malignant fibrous histiocytoma (MFH) of giant cell type. To the best of our knowledge, this is the first report of primary renal MFH associated with staghorn calculi.     

Clinical Evaluation of Compression Ratios using JPEG2000 on Computed Radiography Chest Images

The efficient compression of radiographic images is of importance for improved storage and network utilization in support of picture archiving and communication systems (PACS) applications. The DICOM Working Group 4 adopted JPEG2000 as an additional compression standard in Supplement 61 over the existing JPEG. The wavelet-based JPEG2000 can achieve higher compression ratios with less distortion than the Discrete Cosine Transform (DCT)-based JPEG algorithm. However, the degradation of JPEG2000-compressed computed radiography (CR) chest images has not been tested comprehensively clinically. The authors evaluated the diagnostic quality of JPEG2000-compressed CR chest images with compression ratios from 5:1 to 200:1. An ROC (receiver operating characteristic analysis) and t test were performed to ascertain clinical performance using the JPEG2000-compressed images. The authors found that compression ratios as high as 20:1 can be utilized without affecting lesion detectability. Significant differences between the original and the compressed CR images were not recognized up to compression ratio of 50:1 within a confidence level of 99%.     

Wear of retrieved UHMWPE hip liners

After the gamma-irradiation sterilization, the most widely used orthopaedic grade polymer bearing liner material for the total joint replacement, ultra-high molecular weight polyethylene (UHMWPE), degrades through the progressive in vivo oxidation. The oxidative degradation makes UHMWPE brittle and leads to reduction of its mechanical properties. In this study, the effect of the in vivo post-irradiation ageing time on the wear of UHMWPE was investigated. Twelve retrieved polyethylene hip liners implanted for 3-16 years and then stored in the air for 1.5-8 years were used. Two types of the pin-on-disk wear testing were conducted. The uni-directional repeat pass rotating and the linear reciprocating wear testing were done with stainless steel disks against stationary polyethylene pins under 4MPa at 1Hz with bovine serum lubrication. Wear of the retrieved polyethylene hip liners does not have significant correlation with the in vivo or total ageing time. The linear reciprocal sliding motion generated a more pronounced wear than the uni-directional repeat pass sliding motion. This indicates that the kinematic motion significantly affects the wear of aged UHMWPE, having a brittle, white band region.     

Cytokine responses in mice infected with<Emphasis Type="Italic"> Clonorchis sinensis</Emphasis>

FVB and BALB/c mice show different morbidity, development of Clonorchis sinensis, and pathological changes following C. sinensis infection. FVB mice are susceptible and BALB/c mice are relatively more resistant to C. sinensis infection. To investigate the relationship between cytokine reaction and susceptibility to C. sinensis infection in FVB and BALB/c mice, we described both the patterns and kinetics of Th1 cytokines and Th2 cytokines in spleen cell culture. Interleukin (IL)-4 and IL-10 cytokine production in the culture supernatants of the concanavalin-A-stimulated spleen cells increased at 2–3 weeks post-infection in both strains. IL-5 production increased between 2 and 5 weeks post-infection in both strains, and reached a peak level at 2 weeks post-infection in BALB/c mice and 4 weeks post-infection in FVB mice. In contrast, gamma interferon (IFN-) production decreased between 2 and 4 weeks in both strains. IL-2 production increased slightly in BALB/c mice following infection, but was unchanged in FVB mice. IL-4 production over preinfection levels was significantly higher in FVB mice, whereas IFN-, IL-2, and IL-10 production were significantly higher in BALB/c mice. The levels of serum immunoglobulin E (IgE) and blood eosinophils in both mouse strains significantly increased between 3 and 6 weeks postinfection. Serum IgE levels were significantly higher in FVB mice than in BALB/c mice. The results of this study suggest that susceptibility to C. sinensis infection is associated with Th2 cytokine production, especially IL-4 which is predominant in relatively susceptible FVB mice.