Surgical pearl: the first dorsal web of the hand as a graft donor site for the defects on the hand and digits.
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Biomedical subjects
Publications and source records attributed to C S Wu.
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Latent membrane protein 1 (LMP-1) is the only Epstein-Barr virus (EBV)-encoded oncogenic protein that has been detected in nasopharyngeal carcinoma (NPC), a cancer that is closely associated with EBV. Previous in-vitro studies have demonstrated that LMP-1 can upregulate epidermal growth factor receptor (EGFR) in epithelial cells. It was not established whether this cellular effect exists in NPC. To assess the association between LMP-1 and EGFR in NPC tissues, 60 NPC specimens were examined by immunohistochemistry using anti-LMP-1 antibody (CS 1-4) and anti-EGFR antibodies (EGFR 1, EGFR 1005). The results revealed that 41 (68.3%) specimens were immunopositive for LMP-1 and 44 (73.3%) specimens over-expressed EGFR. Morphologically, the expressions of LMP-1 and EGFR were homogeneously distributed in the tumor nests. In addition, the correlation between LMP-1 and EGFR was statistically significant (P<0.001, chi2 test, d.f. = 1). To elucidate further the correlation between LMP-1 and EGFR in vivo and in situ, an indirect dual immunofluorescence assay was conducted, using secondary antibodies conjugated with fluorescein isothiocyanate (FITC) or indocarbocyanine (Cy3). The results disclosed an intimate co-expression of LMP-1 and EGFR. In summary, the data indicate that over-expression of EGFR is a common phenomenon in NPC, and that EGFR is co-expressed with LMP-1 in NPC. Thus, EBV may play a role in the tumorigenesis of NPC through the effects of LMP-1 and EGFR.
We describe a rare case of splenic arteriovenous fistula and venous aneurysm which developed after splenectomy in a 40-year-old woman who presented with epigastralgia, watery diarrhoea, repeated haematemesis and melaena caused by hyperkinetic status of the portal system and bleeding of oesophageal varices. It was diagnosed by computed tomography and angiography, and obliterated with giant Gianturco steel coils.
A kinetic model involving the distributed fractions of acidogens and methanogens is proposed. To determine the fluxes and biochemical reaction rates of the substrate sucrose and its intermediates, volatile fatty acids (VFAs) in bulk liquid and within the biofilm, a kinetic model was developed by combining the solid-phase model with the liquid-phase model. The predicted substrate removal efficiencies of the conventional and tapered fluidized-bed bioreactors (CFB, TFBs) are in good agreement with the experimental results. The biofilm thickness in TFBs are thicker than that in CFB, resulting in performance enhancement with TFBs. The simulated results obtained from the kinetic model show that methanogenesis is the rate-limiting step of degradation of the simple organic compound (sucrose), and the chemical oxygen demand (COD) concentration in the effluent is mainly contributed by the intermediates VFAs. The distributed fractions of acidogens and methanogens determined experimentally are 0.4 and 0.6, respectively.
We report a case of emphysematous cholecystitis with the sonographic appearance of an "effervescent gallbladder"--a large amount of gas bubbles rising like bubbles in a glass of champagne from the dependent part of the gallbladder and floating to the nondependent part. The etiology of this finding was acute obstruction of the distal common bile duct by a stone and purulent cholangitis. Short-term follow-up sonography is important to confirm the diagnosis of cholecystitis.
The immune function of peripheral mononuclear cells (MNC) in patients with endemic arsenic-induced Bowen's disease (BD) was investigated. Many cytokines and immune-related factors were determined in the present study. Interleukin-1beta and TNF-alpha production was used as an indicator of monocyte/macrophage function. II-2 and sIL-2R production was used as an indicator of lymphocyte activation. The release of sCD4 and sCD8 was used as an indicator of activation of respective T-cell subpopulations. Production of IFN-gamma and IL-2 reflected the cellular effector function of helper T-cells type 1. In vivo cell-mediated immunity was also assessed by estimation of the percentage of T-cells in peripheral blood MNC and the nonspecific delayed-type hypersensitivity (DTH) response to 2,4-dinitrochlorobenzene (DNCB). Both assays revealed depressed cell-mediated immunity in BD. Compared with healthy controls, spontaneous and PHA-induced IFN-gamma and TNF-alpha production was significantly decreased in BD whereas spontaneous release of IL-2, sCD4 and sCD8 was significantly increased. Although PHA stimulation increased IL-2 release, the expression of IL-2R alpha and beta chains and the release of sIL-2R were not proportionately increased in BD. In addition, IL-2-mediated [3H]-thymidine incorporation by MNC in patients with BD was significantly decreased. These findings suggest that the defective cell-mediated immune function in BD is due to impairment of membrane IL-2R expression in lymphocytes after stimulation.
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A pelvic support consisting of a forward sloping wedge of foam has been tested as an addition to conventional office seating for VDT work. In experiment 1 a questionnaire investigation was carried out on the impressions of 10 male and 10 female subjects who sat using pelvic supports. A general result from the questionnaire was that the waist and pelvis were felt to be stable and the evaluation was more positive with the support than without. In experiment 2, pelvis and chest inclinations were measured during sitting with and without the pelvic support. Over a long work period, significant differences were not observed. In both cases, subjects were able to move freely and there were no significant changes in posture. In experiment 3, pelvis and chest inclinations were measured in conditions of no pelvic support and with supports of 10, 20 and 30 degrees. The experiment demonstrated that a support angle of 10 degrees was stable and comfortable. In this research, it was found that the change of inclination of the pelvis can be measured continuously using an angle of inclination sensor. Imposing a forward slope of 4 to 10 degrees on the seat pan surface using the pelvic support had a positive effect, while angles of 20 and 30 degrees had a negative effect.
The study aimed to evaluate the efficacy of famotidine, an H2 receptor blocker, and misoprostol, a prostaglandin E analogue, in the treatment of non-steroidal anti-inflammatory drug-induced (NSAID) gastropathy in arthritic patients. A total of 128 patients receiving piroxicam, sulindac, indomethacin, naproxen, tolmetin and aspirin were enrolled in the study. Gastroscopic examination was performed at the beginning and after eight weeks of randomised famotidine or misoprostol treatment. A standard scoring method for gastroscopic finding was applied. Forty-four patients with scores 1-3 were classified as group A; while the other 84 with score 4 (ulcer) were placed in group B. In group A, 26 received famotidine and 18 misoprostol. In group B, 36 received famotidine and 48 misoprostol. Biopsy specimens taken from the rim of the ulcer with adjacent normal mucosa were coded and tested for Helicobacter pylori. In group A, all but two patients taking famotidine recovered from NSAID gastropathy, and there was no statistical significance between the two drugs. In group B, all but four patients receiving famotidine improved and there was no statistical significance between the two subgroups for complete healing rate. The prevalence of H. pylori was 36.9%, lower than that in the general population. It was concluded that famotidine and misoprostol have similar efficacy in the treatment of NSAID gastropathy.
PURPOSE: The retinoblastoma protein (pRB) is a key regulator of the G1 cell cycle checkpoint and has been implicated as having a role in G1 arrest and apoptosis induced by radiation damage. In this report we examine the association between pRB expression and radiation response in patients treated between 1960 and 1983 with preoperative radiotherapy (50 Gy in 25 fractions) followed 4-6 weeks later by radical cystectomy. The correlation of pRB to patient outcome and how this relationship is complimentary to that seen with p53 staining status is also described. METHODS AND MATERIALS: Immunohistochemical staining of pRB and p53 in paraffin-embedded tumor sections using WL-1 anti-RB and DO1 anti-p53 antibodies was considered adequate in 98 and 97 pretreatment tumor samples, respectively. There were 46 patients with clinical Stage T2, 28 with Stage T3a, and 24 with Stage T3b disease. The median age was 62 years and follow-up for those living was 85 months. RESULTS: Staining for pRB was negative in 30% of the cases. Correlations were observed between pRB negativity and high pretreatment apoptosis level (p = 0.06), locally advanced clinical stage (p = 0.01), increased clinical-to-pathologic downstaging (p = 0.014), and more pathologic complete responses (Path-CRs; p = 0.019). Several other factors were tested and were not associated with pRB status, including p53 expression. RB status was the only pretreatment prognostic factor in the univariate analyses that correlated with downstaging and was independently associated with Path-CR using multivariate logistic regression. Despite these significant relationships, no correlations with patient outcome were observed when the entire cohort was analyzed. Restriction of the analyses to Stage T3b patients, however, revealed that pRB negativity predicted for enhanced distant metastasis freedom (p = 0.006, log rank) and overall survival (p = 0.02). The overexpression of p53 also correlated with distant metastasis freedom and overall survival in Stage T3b patients. Patient outcome was best when RB negative and p53 negative staining were seen. CONCLUSION: Our results indicate that loss of RB function as measured by immunohistochemical staining is the strongest correlate of radiation response thus far recognized. Loss of RB expression also predicted for poor outcome in Stage T3b patients, which appeared to compliment the finding of normal p53 expression. While normal RB protein expression is usually associated with better patient outcome, other series have not examined patients treated with radiotherapy. The absence of pRB may be a useful marker for selecting patients for bladder preservation with radiotherapy, particularly when wild-type p53 is present.
Cancer cells are able to overproduce lactic acid aerobically, whereas normal cells undergo anaerobic glycolysis only when deprived of oxygen. Tumor aerobic glycolysis was recognized about seven decades ago; however, its molecular basis has remained elusive. The lactate dehydrogenase-A gene (LDH-A), whose product participates in normal anaerobic glycolysis and is frequently increased in human cancers, was identified as a c-Myc-responsive gene. Stably transfected Rat1a fibroblasts that overexpress LDH-A alone or those transformed by c-Myc overproduce lactic acid. LDH-A overexpression is required for c-Myc-mediated transformation because lowering its level through antisense LDH-A expression reduces soft agar clonogenicity of c-Myc-transformed Rat1a fibroblasts, c-Myc-transformed human lymphoblastoid cells, and Burkitt lymphoma cells. Although antisense expression of LDH-A did not affect the growth of c-Myc-transformed fibroblasts adherent to culture dishes under normoxic conditions, the growth of these adherent cells in hypoxia was reduced. These observations suggest that an increased LDH-A level is required for the growth of a transformed spheroid cell mass, which has a hypoxic internal microenvironment. Our studies have linked c-Myc to the induction of LDH-A, whose expression increases lactate production and is necessary for c-Myc-mediated transformation.
Androgen ablation is frequently used in conjunction with radiotherapy in the treatment of high-risk prostate cancer. Androgen ablation-induced cell kinetic changes could result in sub-additive (increased quiescence) or supra-additive (reduction in repopulation) interactions with radiotherapy. The cell kinetic changes were studied in R3327-G Dunning rat prostate tumors grown in vivo using double thymidine analogue labeling and flow cytometry, the terminal deoxynucleotidyl transferase-mediated nick end labeling assay for apoptosis, and measurements of tumor cell numbers. Tumors grown in intact and castrate male rats were continuously labeled for various periods of time with chlorodeoxyuridine and pulse-labeled with iododeoxyuridine 8 h before tumor removal. Androgen ablation resulted in a maximal reduction in labeling index (10 to 1.6%) and an increase in potential doubling time (Tpot; 6-42 days) within 3 days, which was related to a reduction in growth fraction (65% to <10%). In contrast, the length of S-phase was minimally altered (19 to 23 h). The response to androgen ablation involved little apoptosis and no necrosis, and Tpot was approximately the same as the tumor volume doubling time. Hence, the increase in Tpot was mainly the result of a shift to quiescence, and this shift occurred with minimal cell loss. Because quiescence is usually associated with radioresistance, these cell kinetic changes suggest that a sub-additive interaction may occur for some prostate cancers when androgen ablation and irradiation are given together.
BACKGROUND: The prognostic significance of primary tumor DNA-ploidy and S-phase fraction (SPF) was evaluated in patients treated with androgen ablation for regionally localized node-positive prostate cancer. METHODS: All patients were diagnosed with lymph node involvement by pelvic lymphadenectomy between 1984 and 1992 and were treated only with androgen ablation. Median follow-up was 45 months. Adequate material for DNA/nuclear protein flow cytometric analysis was available in 33 patients. RESULTS: The tumors were classified as diploid in 11, near-diploid in 4, tetraploid in 10, and aneuploid in 8 cases. Grouping the patients by nonaneuploidy (diploid and near-diploid and tetraploid) and aneuploidy revealed actuarial 4-year disease progression rates of 14 and 48% (log-rank, P = 0.04), and overall survival rates of 100 and 61% (P = 0.008); however, biochemical progression (rising prostate-specific antigen profile) rates were similar at around 70%. In contrast, SPF was not significantly related to any of the endpoints tested. Several other potential prognostic factors were examined and none correlated significantly with disease progression or survival. CONCLUSIONS: The biochemical progression rates for patients with nonaneuploid and aneuploid tumors were comparable and high, while the disease progression rates were higher and survival rates lower for those with aneuploid tumors. These data indicate that the lead time from biochemical to disease progression and death was shorter with aneuploidy. That these relationships were observed in such a small patient population attest to the strength of DNA-ploidy as a prognostic factor in this cohort.
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The uncommon allele (TNF2) of a polymorphism in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene has been reported to be increased in Caucasian systemic lupus erythematosus (SLE) patients (associated with HLA-DR3). To investigate whether TNF2 contributes towards susceptibility to Chinese SLE patients (not associated with HLA-DR3), 100 patients with SLE and 107 controls were studied. The frequency of TNF2 allele in controls was 0.140. There was a strong association between TNF2 allele and HLA-DR3 (P < 10(-8)) in controls. The frequency of TNF2 allele in SLE patients was 0.15. There was no difference in frequencies of TNF2 allele between patients and controls. This finding strongly suggests that TNF2 does not play a direct role in the susceptibility of SLE.
The purpose of this study was to clarify the relationship between the cellular and humoral immune components in the pathogenesis of vitiligo vulgaris. By using cytokines as indicators of peripheral mononuclear cell (MNC) function, we compared the effects of phytohemagglutinin (PHA) and purified IgG on MNCs derived from patients suffering from active vitiligo with those from normal controls. The results revealed (i) a significant increase in spontaneous production of IL-6 and IL-8 in patients; (ii) PHA, purified IgG from patients (IgG-anti-MC), or IgG from normal controls (N-IgG) induced a significant increase in IL-6 but diminished GM-CSF, TNF-alpha, and IFN-gamma release in patients; and (iii) IgG-anti-MC brought about a significantly higher stimulatory effect on IL-1beta and IFN-gamma production than N-IgG in normal controls. Immunologically, IL-6 can enhance melanocyte ICAM-1 expression, which may increase leukocyte-melanocyte attachment and cause melanocyte damage in vitiligo. A decrease in GM-CSF (an intrinsic growth factor for melanocyte) production may retard recovery from vitiligo by checking the proliferation of surviving melanocytes. A significant decrease in TNF-alpha and IFN-gamma production may partially explain the reduced inflammatory reaction in vitiliginous lesions. That IgG-anti-MC stimulates an increase in IL-1beta and IFN-gamma production in controls suggests that IgG-anti-MC may play a role in melanocyte destruction mediated by monocytes.