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Biomedical subjects

J C Luo

Publications and source records attributed to J C Luo.

At least 37 records · Page 2Linked to original sources

Plasma p53 protein and anti-p53 antibody expression in vinyl chloride monomer workers in Taiwan.

Vinyl chloride (VC) workers are known to be at risk for development of angiosarcoma of the liver (ASL), a rare tumor. Previously, a study of p53 gene mutations in tumors of VC-exposed workers found that 50% of liver angiosarcomas contained such mutations. Mutant p53 oncoprotein and anti-p53 antibodies can also be found in the sera of ASL patients and VC-exposed workers without cancer. Workers in Taiwan have also been exposed to VC, and some have contracted liver tumors. In this study, we used enzyme-linked immunosorbent assays to detect mutant p53 protein and anti-p53 antibodies in the plasma of VC-exposed workers in Taiwan. Thirty-three of 251 (13.2%) VC-workers tested positive for the p53 overexpression (10% with positive mutant p53 protein and 3.6% with positive anti-p53) in their plasma, but only 2 of 36 controls (5.6%) tested positive (2.8% with positive mutant p53 protein and 2.8% with positive anti-p53). There was a significant association between cumulative VC exposure concentration and positive p53 expression (P = 0.032) among VC workers after we adjusted for age, hepatitis, drinking, and smoking status. In summary, P53 overexpression (mutant p53 protein or anti-p53 antibody) can be found in the plasma of VC workers in Taiwan, and a significant dose-response relationship exists between plasma p53 overexpression and VC cumulative exposure concentration.

Adult↗

Clinical significance of portal lymphoid aggregates/follicles in Chinese patients with chronic hepatitis C.

OBJECTIVE: Portal lymphoid aggregates/follicles (lymphoid A/F) is a characteristically histological finding in patients with chronic hepatitis C. We assessed the prevalence of lymphoid A/F in Chinese patients with chronic hepatitis C and evaluated the correlation of this phenomenon with clinical, biochemical, immunological, virological, and other histological features of these patients. METHODS: Eighty-nine Chinese patients with chronic hepatitis C were enrolled and portal lymphoid A/F was evaluated in liver biopsy. Clinical, biochemical, immunological, histological, and virological data, including serum HCV RNA titer and HCV genotype and the response to interferon therapy, were compared between patients with and without portal lymphoid A/F. RESULTS: Twenty-nine (33%) of 89 patients with chronic hepatitis C had portal lymphoid A/F. Patients with lymphoid A/F had a significantly higher frequency of HCV genotype 1b infection (p = 0.039) and had a significantly higher mean score of bile duct damage, periportal necroinflammation, and portal inflammation in liver histologies when compared with patients without lymphoid A/F. No significant difference in sex distribution, mean age, history of blood transfusion, serum liver biochemistry, presence of serum autoantibodies/cryoglobulinemia, serum viral titer, and response to interferon therapy was noted between the two groups. Multivariate logistic regression analysis showed HCV genotype 1b infection and periportal necroinflammation were significant independent predictors associated with portal lymphoid A/F. CONCLUSIONS: The presence of portal lymphoid A/F in Chinese patients with chronic hepatitis C was significantly correlated with HCV genotype 1b infection and periportal necroinflammation.

Biopsy↗

Role of substance P in the pathogenesis of spider angiomas in patients with nonalcoholic liver cirrhosis.

OBJECTIVE: Cutaneous spider angioma is a common sign observed in patients with liver cirrhosis, but its pathogenesis is still unclear. Increased plasma levels of estrogen, vascular dilation, and neovascularization are possible etiologies. This study was designed to investigate the relationship of spider angiomas in patients with nonalcoholic liver cirrhosis to the plasma levels of sex hormones and various vasodilators and hemodynamic parameters. METHODS: A total of 60 patients with nonalcoholic liver cirrhosis and 20 healthy subjects were included in this study. The number, size, and location of the spider angiomas were recorded. Plasma levels of estradiol, testosterone, substance P, calcitonin gene-related peptide, and nitrate/nitrite and forearm hemodynamics were measured. RESULTS: Cirrhotic patients showed higher plasma estradiol/testosterone ratios (28.3+/-47.2 x 10(-3), median 10.5 x 10(-3) vs 8.2+/-8.3 x 10(-3), median 5.7 x 10(-3), p = 0.003) and levels of nitrate/ nitrite (29.9+/-17.5, median 23.8 vs 21.4+/-10.0, median 20.6 micromol/L, p = 0.01) and substance P (47.5+/-62.5, median 29.2 vs 15.2+/-7.7, median 12.3 pg/ml, p < 0.001) than healthy controls. Sixteen (27%) of the 60 cirrhotic patients had spider angiomas. Cirrhotic patients with spider angiomas disclosed higher plasma levels of substance P (84.7+/-105.3, median 53.1 vs 34.5+/-30.7, median 25.8 pg/ml, p = 0.006) and serum levels of bilirubin (3.9+/-3.8, median 1.9 vs 1.9+/-1.9, median 1.2 mg/dl, p = 0.02) than those without. Stepwise logistic regression showed substance P was the only significant and independent predictor associated with the presence of spider angiomas in cirrhotic patients (odds ratio = 3.0, 95% confidence interval = 1.4-6.6, p = 0.01). CONCLUSION: Plasma levels of substance P are elevated in patients with nonalcoholic cirrhosis and may play an important role in the pathogenesis of spider angiomas.

Aged↗

[CT findings in the recurrent oral maxillofacial tumors eroding the central skull base]

OBJECTIVE:To domonstrate the CT manifestations of the recurrent oral maxillofacial tumors invading the middle skull base.METHODS:CT detections with axial (37 cases) and coronal (26 cases) scans were performed in thirty-seven patients who suffered from the recurrent oral maxillofacial tumors.All lesions were proven histopathologically.RESULTS:Four patterns of the central skull base erosion showing on CT images were encompassed:1.resorption of the outer cortical margin (5 cases);2.resorption of both outer and inner cortical laminae (24 cases);3.enlargement of the ovale foramen (3 cases);4.combined of sclerosis and resorption of the skull base (5 cases).The sphenoid greater wing involvement by the recurrent lesions was more frequently seen in our series (36 cases).Twenty four patients with the recurrent lesions were identified as following intracranial structures affected:the cavernous sinus (n=16),temporal lobe (n=15),and pituetary (n=1).CONCLUSION:It is believed that involvement of the intracranial structures is in close relationship with the aforementioned erosive patterns of the central skull base.The role of CT examination for evaluating the oral maxillofacial recurrent lesions invading the central skull base is very important.

Journal Article↗

Differential inhibition of fluid accumulation and tumor growth in two mouse ascites tumors by an antivascular endothelial growth factor/permeability factor neutralizing antibody.

In the accompanying paper (Luo et al., Cancer Res., 58: 2652-2660, 1998), we demonstrated that vascular endothelial growth factor (VEGF), also designated vascular permeability factor (VPF), significantly accumulated in all mouse malignant ascites tested, suggesting its fundamental role in ascites tumors. Removal of VEGF may inhibit the development of ascites tumors. In this study, using a goat antimouse VEGF-neutralizing antibody, we tested this hypothesis with two well-defined syngeneic mouse ascites tumors: MM2 breast adenocarcinoma and OG/Gardner lymphoma 6C3HED (expressing moderate and low levels of VEGF, respectively). This antibody significantly inhibited MM2 and OG cell-free ascites fluid-induced hyperpermeability of mouse peritoneal microvessels and in vitro endothelial cell growth. Mice bearing tumors were administered i.p. daily with the antibody or normal goat IgG as controls for 8 days, at doses of 20-fold (for MM2-bearing mice) or 40-fold (for OG-bearing mice) the estimated amounts of VEGF that kinetically accumulated in the ascites fluid after the tumor inoculation. The average volume of ascites fluid, number of tumor cells and leaked RBCs, and the peritoneal microvessel permeability in MM2-bearing mice that received the antibody treatment were significantly lower than those in the matched controls (P < 0.01). Unexpectedly, OG-bearing mice did not show satisfactory response to the anti-VEGF treatment. This discrepancy was not likely due to inadequate doses or different host immune responses, but it was quite possibly to the different characteristics of MM2 carcinoma and OG lymphoma tumors, the latter being strongly invasive, and/or the existence of an inflammatory mediator(s), such as bradykinin or cytokine(s) other than VEGF. In summary, our results directly demonstrated, for the first time, differential roles for VEGF in ascites tumors in vivo and suggest the potential of VEGF inhibition as a specific therapy for ascites tumors of carcinoma origin, which are the major cause of the malignant ascites in adult humans.

Animals↗

Significant expression of vascular endothelial growth factor/vascular permeability factor in mouse ascites tumors.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is believed to be a potent mediator of peritoneal fluid accumulation and angiogenesis and of tumor growth in ascites tumor. Such roles, however, have not been generally established because of insufficient quantitative and systemic analyses. To address this, we examined the expression of VEGF in 13 mouse ascites tumors (5 sarcomas, 3 carcinomas, 2 lymphomas, 1 leukemia, 1 mastocytoma, and 1 plasmacytoma). Using a newly developed sensitive and specific radioreceptor binding assay and functional assays, we found that active VEGF was significantly accumulated (6-850 ng/ml) in the ascites fluids of all 13 tumors. VEGF concentrations are higher in the tumors of sarcoma and carcinoma origin (430.4 +/- 234.2 ng/ml) than in those of lymphoma and hematological tumor origin (19.2 +/- 10.45 ng/ml). VEGF that accumulated in the peritoneal fluids or expressed in the ascites tumor cells was easily visualized with immunoprecipitation Western blot analysis with a rough correlation to the expression levels of VEGF gene in these tumor cells, suggesting that the tumor cells, at least in part, contributed to the production of the VEGF that accumulated in the ascites fluid. Most ascites tumors expressed VEGF; the 164-amino acid isoform was predominant, the 120-amino acid isoform was less abundant, and the 188-amino acid isoform was least abundant. Several representative ascites tumors expressed similar, if not higher, levels of VEGF when they were cultured at normoxic states, suggesting that they expressed VEGF at high levels in a constitutive manner. The microvessel densities in the peritoneal walls of tumor-bearing mice, which are significantly higher than those in normal mice, basically correlated to but did not parallel the VEGF concentrations in their respective ascites fluids. Thus, a complicated relationship may exist between the VEGF production and angiogenesis associated with ascites tumor in vivo. Taken together, our observations suggest that VEGF plays a fundamental role in ascites tumor formation; however, its importance may vary according to tumor origin.

Animals↗

Lung function and general illness symptoms in a semiconductor manufacturing facility.

Large quantities of potent gases, dopants, photoactive chemicals (photoresists, photoinitiators), solvents, and ionizing radiation are used in the semiconductor manufacturing process, but little is known about the occurrence of respiratory disease from exposures in this industry. The purpose of this study was to assess the pulmonary risk by conducting pulmonary function tests and symptoms survey in a semiconductor plant in Taiwan. This study is part of a clinical survey conducted on 926 workers in a semiconductor plant in Taiwan in July 1995. The study items included a standard self-administered questionnaire, chest x-rays, pulmonary function tests, and physical examinations in 249 workers. There was a borderline significance of higher prevalence (P = 0.06) of restrictive lung abnormality in male photolithographic workers (4 of 21; 19.1%) than in male control workers (0 of 17; 0%), and the smoking- and age-adjusted odds ratio was 4.1 (95% confidence interval [CI], 0.41-41.6). There was a significantly higher prevalence (P = 0.02) of restrictive lung abnormality in male ion-implantation workers (5 of 19; 26.3%) than in male control workers (0 of 17; 0%), and the smoking- and age-adjusted odds ratio was 3.7 (95% CI, 0.52-26.7). There were significantly higher prevalences of airway irritation, eye irritation, headache, stress, tiredness, and poor memory in female photolithographic or etch/diffusion workers than in control workers. This study suggests that restrictive lung abnormality is a potential health effect in male silicon-wafer fabrication workers in the semiconductor industry. The tasks of male process, maintenance, and equipment engineers put them at risk for intermittent short-term peak exposure. This may account for a higher prevalence of mild restrictive lung abnormality among male engineers of photolithographic and ionimplantation sections. The findings of this medical surveillance are tentative, but they suggest that further investigation of the etiologic factors and the subsequent health effects is necessary.

Adult↗

Plasma Asp13-Ki-ras oncoprotein expression in vinyl chloride monomer workers in Taiwan.

Vinyl chloride (VC) workers are known to be at risk for development of liver angiosarcoma, a rare tumor. Previously, more than 80% of VC workers with liver angiosarcoma have been found to have an Asp-13 c-Ki-ras oncogene mutation, and more than 50% of VC-exposed workers without liver tumors were found to have Asp13-Ki-ras oncoprotein in their plasma. Some workers in Taiwan had also been exposed to VC, and some have contracted liver tumors. In this study, we used enhanced chemiluminescence Western blotting to detect Asp13-p21-Ki-ras in the sera of VC-exposed workers in Taiwan. There were 14 of 113 (12.4%) VC workers positive for the Asp13-Ki-ras oncoprotein in plasma, but 0 of 18 controls were positive. There were 10 of 69 (14.5%) plasma-positives among the more highly exposed (> 1000 ppm-months) workers and 4 of 48 (9.1%) plasma-positives among the lesser exposed (< or = 1000 ppm-months). Compared with the unexposed controls, the odds ratios (and 95% confidence intervals [CI]) for plasma-positivity were 4.11 (95% CI = 0.21, 80.4) in the lower-exposed workers and 6.53 (95% CI = 0.37, 116.9) in the higher-exposed workers, and there was a linear trend between exposure and plasma-positivity (P = 0.073). After adjusting for age and drinking status, the odds ratios (and 95% CIs) were 1.64 (95% CI = 0.17, 15.8), and 2.65 (95% CI = 0.42, 16.8), respectively, and there was a significant linear trend between exposure and plasma-positivity (P = 0.048). In summary, Asp13-Ki-ras oncoprotein can be found in the plasma of VC workers in Taiwan, and a significant dose-response relationship exists between plasma oncoprotein expression and VC exposure.

Adult↗

Clinical significance of serum auto-antibodies in Chinese patients with chronic hepatitis C: negative role of serum viral titre and genotype.

Positive serum anti-nuclear antibody (ANA) and anti-smooth muscle antibody (SMA) have been reported in 10-66% of patients with chronic hepatitis C virus (HCV) infection from Western countries. However, the mechanism involved in this immunological disorder is still unknown. This study was carried out to evaluate the prevalence and clinical significance of positive serum auto-antibodies in Chinese patients with chronic hepatitis C and to assess the role of serum HCV-RNA titre and HCV genotype in the presence of serum auto-antibodies. Serum ANA, SMA and anti-mitochondrial antibody (AMA) were measured in 122 patients with chronic hepatitis C. Clinical, biochemical and virological data (serum HCV-RNA titre and HCV genotype) were compared between patients with and without serum auto-antibodies. Fifty-eight (48%) patients were associated with positive serum auto-antibodies: 42 (34%) positive for ANA, six (5%) positive for SMA, nine (7%) positive for both ANA and SMA and one (1%) positive for AMA. Clinical parameters (age, sex, blood transfusion history), liver biochemical tests, the presence of cryoglobulinaemia or cirrhosis, and the response to interferon treatment were not significantly different between patients with and without positive serum auto-antibodies. Serum HCV-RNA levels and HCV genotypes were also not significantly different between the two groups. Logistic regression analysis showed that none of the previously mentioned parameters were significant predictors to associate with serum auto-antibodies in chronic hepatitis C. We concluded that 48% of Chinese patients with chronic hepatitis C were associated with positive serum auto-antibodies. Hepatitis C virus genotypes and serum HCV-RNA levels were not correlated to the presence of serum auto-antibodies. The clinical significance and actual pathogenesis of this phenomenon remain to be clarified.

Antibodies, Antinuclear↗

Relationships between serum aminotransferase levels, liver histologies and virological status in patients with chronic hepatitis C in Taiwan.

In patients with chronic hepatitis C, the relationships between serum alanine aminotransferase (ALT) levels, histological liver injury and serum hepatitis C virus (HCV) RNA titres remain controversial. To evaluate these relationships, 93 Chinese patients with histological diagnosis of chronic hepatitis C were enrolled for this study. Serum ALT levels, HCV-RNA titres and HCV genotypes were examined. The histology was evaluated according to a modified histological activity score based on the degree of periportal necro-inflammation, intralobular necro-inflammation, portal inflammation, total necro-inflammation and fibrosis. The mean serum ALT level was significantly higher in patients with severe intralobular necro-inflammation activity than in patients with mild or no activity (P = 0.013). However, scores of intralobular activity were only weakly correlated with serum ALT levels (r = 0.27) and could not be used to adequately predict ALT values. Serum ALT levels showed no significant correlation with the scores of portal inflammation, periportal necro-inflammation, total necro-inflammation and fibrosis. Also, there was no significant difference in the mean serum ALT level among different serum HCV-RNA levels and HCV genotypes. Serum HCV-RNA titres and genotypes showed no significant correlation with liver histology and serum HCV-RNA titres were only weakly correlated with the total necro-inflammatory score (r = 0.27). In conclusion, although serum ALT levels were higher in patients with more severe intralobular necro-inflammatory activity, the correlation was not strong enough to adequately predict ALT values. Serum HCV-RNA titres and genotypes also showed no significant correlation with serum ALT levels and liver histologies.

Alanine Transaminase↗

Flutamide-induced liver injury: a case report.

Flutamide is a nonsteroidal antiandrogen agent. Since it was marketed in February of 1989 in the USA for treatment of prostate cancer, its potential for hepatotoxicity has been reported in Western countries. Here we report the case of a 72-year-old patient who suffered from general malaise, poor appetite, nausea and jaundice after six months of flutamide therapy for the treatment of prostate cancer. He had no past history of liver disease and was not receiving other medications. Liver biochemistries revealed elevated serum alanine aminotransferase and aspartate aminotransferase concentrations of up to 1,035 U/l and 745 U/l, respectively. Serum total bilirubin concentration was elevated to 7.0 mg/dl. Serologic markers for acute viral hepatitis were all negative. Serum antinuclear antibody, antimitochondrial antibody and antismooth-muscle antibody were also negative. Percutaneous liver biopsy revealed pericentral zonal necrosis with bridging hepatic necrosis. The patient's clinical symptoms and signs began to improve after discontinuation of flutamide, and his liver function had returned to normal three months later. Roussel Uclaf causality assessment for adverse drug reaction confirmed the diagnosis of drug-induced liver injury. This case reminds us that patients who are receiving flutamide should be regularly monitored for liver function. If drug-induced liver injury is suspected, flutamide must be discontinued promptly to avoid progression of liver injury.

Aged↗

[Evaluation of 28 cases of salivary malignancies with MR imaging]

Twenty-eight cases of MRI of the salivary malignancies confirmed histopathologically were shown in this paper.By observing separately and comparatively with SE (spin echo) T2 weighted imaging and PE(field echo) imaging,the authors consider that (1)the malignant tumors within the salivary glands displaying low and intermediate signal intensities on T2 weighted image may be thought as a characteristic sign in the diagnostic processes. (2) PE imaging as an effective method is able to differentiate the tumors from the calcification and fibrosis which were low and intermediate signal intensities on T2 weighted image. (3)the locations and sizes of the tumors have directly influenced on their marginal manifestations and adjacent normal tissue structures.

Journal Article↗

Primary low grade B-cell lymphoma of colon mimicking inflammatory bowel disease: a case report.

Primary lymphoma of colon is rare in clinical practice and sometimes difficult to diagnose. We described a case of primary, low grade B-cell lymphoma of colon, whose clinical pictures were similar to inflammatory bowel disease. Although the colon mucosa showed diffuse infiltration of lymphocytes with lymphoepithelial lesions on endoscopic biopsy, immunohistochemical stains for B- and T-cell markers were negative. However, the diagnosis of lymphoma was established by positive findings on rearrangement of antigen receptor gene. Clinical symptom of blood-tinged diarrhea subsided after six courses of chemotherapy. Follow-up colonoscopy revealed normal colon mucosa. However, biopsy of colon mucosa still revealed mild proliferation of small lymphocytes. This case has drawn our attention that primary colonic lymphoma may clinically simulate inflammatory bowel disease, and gene rearrangement analysis might be helpful in the diagnosis of malignant lymphoma when traditional histological and immunohistochemical studies fail to provide a definite diagnosis.

Aged↗

Conformational effects in the p53 protein of mutations induced during chemical carcinogenesis: molecular dynamic and immunologic analyses.

The tumor suppressor gene p53 has been identified as the most frequent target of genetic alterations in human cancers. Vinyl chloride, a known human carcinogen that induces the rare sentinel neoplasm angiosarcoma of the liver, has been associated with specific A-->T transversions at the first base of codons 249 and 255 of the p53 gene. These mutations result in an Arg-->Trp amino acid substitution at residue 249 and an Ile-->Phe amino acid substitution at residue 255 in a highly conserved region in the DNA-binding core domain of the p53 protein. To determine the effects of these substitutions on the three-dimensional structure of the p53 protein, we have performed molecular dynamics calculations on this core domain of the wild-type and the Trp-249 and Phe-255 mutants to compute the average structures of each of the three forms. Comparisons of the computed average structures show that both mutants differ substantially from the wild-type structure in certain common, discrete regions. One of these regions (residues 204-217) contains the epitope for the monoclonal antibody PAb240, which is concealed in the wild-type structure but accessible in both mutant structures. In order to confirm this conformational shift, tumor tissue and serum from vinyl chloride-exposed individuals with angiosarcomas of the liver were examined by immunohistochemistry and enzyme-linked immunosorbent assay. Individuals with tumors that contained the p53 mutations were found to have detectable mutant p53 protein in their tumor tissue and serum, whereas individuals with tumors without mutations and normal controls did not.

Antibodies, Monoclonal↗

Levels of p53 antigen in the plasma of patients with adenomas and carcinomas of the colon.

Plasma levels of p53 protein were examined by an enzyme linked immunosorbent assay in 184 patients enrolled in a colonoscopy study. The mean levels among 47 individuals with normal colonoscopic examinations and no prior history of colonic neoplasia (0.12 ng/ml) and among 61 individuals with normal colonoscopic examinations and a prior history of colonic neoplasia (0.09 ng/ml) were similar. However, the mean levels among 54 individuals with newly diagnosed colonic adenomas (0.44 ng/ml) and 22 individuals with newly diagnosed colonic carcinomas (0.55 ng/ml) were statistically significantly elevated compared to the normal controls (P < 0.02). Among these tumor patients, the plasma levels tended to increase with increasing adenoma size and with increasing carcinoma stage, although these trends were not statistically significant. Defining a significant positive plasma level as any value greater than ten times background, the percentage of positive samples increased from 4% in the controls to 20% in the adenoma cases to 32% in the carcinoma cases. These results demonstrate that plasma p53 protein levels are elevated in a subgroup of individuals with colonic neoplasia.

Adenoma↗

Computed tomography of pulmonary metastases from oral and maxillofacial tumors.

Computed tomographic scans were done on 14 oral and maxillofacial malignant tumors in which pulmonary metastases occurred but were poorly delineated by conventional chest radiography and tomography. Computed tomography promotes the accurate diagnosis of small and occult pulmonary metastases. Optimal nonlinear computed tomographic windows are recommended for the diagnosis of pulmonary metastases.

Adult↗