Biomedical subjects
Publications and source records attributed to J C Luo.
A remote, small-size spectroscopic-based device called Compact Photonics Explorer (CPE) was designed, assembled, and tested for medical and non-medical spectroscopic and imaging applications. Spatial images acquired using the spectroscopic CPE are presented. Operational principles are demonstrated for various biomedical and non-medical applications.
Hypoxia inducible factors (HIF1, 2 and 3), consisting of alpha and beta subunits, play an essential role in various responses to hypoxia. Nuclear entry of alpha subunits is a necessary step for the formation of DNA-binding complex with beta subunit, which is constitutively localized in the nucleus. We show here that the nuclear accumulation of HIF2alpha induced by hypoxia is mediated through a novel variant of bipartite-type nuclear localization signal (NLS) in the C-terminus of the protein, which has an unusual length of spacer sequence between two adjacent basic domains. We further show that when the ubiquitin-proteasome system was deficient or inhibited, HIF2alpha accumulated in the nucleus even under normoxia, also mediated through the bipartite NLS. These findings indicate that the protein stability is critical for the nuclear localization of HIF2alpha and hypoxia is not a necessary factor for the process. Importantly, the NLS of HIF2alpha is also conserved in the other HIF family members, HIF1alpha and HIF3alpha. Mutational analyses proved that the NLS mediating the nuclear localization of HIF1alpha is indeed bipartite-, but not monopartite-type as thought before. Our results suggest that the newly identified NLS is crucial for the functional regulation of HIF family.
BACKGROUND: The aims of this study were to examine some of the factors that influence tibia lead concentrations, tibia lead x-ray fluorescence measurement uncertainty and blood lead concentrations, and to compare tibia lead concentrations in Taiwanese lead workers to those observed in lead workers from other countries. METHODS: A pilot evaluation of 43 adult lead workers who underwent measurements of tibia lead and blood lead concentrations. RESULTS: Mean and maximum tibia lead concentrations were 54 microg of Pb per g of bone mineral(microg/g) and 193 microg/g, respectively. Mean and maximum blood lead concentrations were 44 microg/dl and 92 microg/dl, respectively. CONCLUSION: Past occupational control of lead exposure in Taiwan, ROC, did not prevent these workers from accumulating tibia lead concentrations greater than those in similar workers elsewhere in the world.
PURPOSE: Hepatic bile duct injuries are characteristic histological findings in patients with chronic hepatitis C virus (HCV) infection. However, the pathogenesis and clinical significance of this phenomenon remain unclear. The aims of this study were to evaluate the prevalence and clinical significance of hepatic bile duct injuries in Chinese patients with chronic hepatitis C. METHODS: One hundred and seventeen Chinese patients with chronic hepatitis C were enrolled. Clinical, biochemical, immunological (serum autoantibodies and cryoglobulinemia), histological, and virological data (serum HCV RNA titer and HCV genotype) were compared between patients with and without hepatic bile duct injuries. RESULTS: Eighty-three (71%) of the 117 patients with chronic hepatitis C had hepatic bile duct injuries. Patients with hepatic bile duct injuries had a significantly higher frequency of HCV genotype 1b; a higher mean serum globulin level; significantly higher mean scores for histological periportal necro-inflammation, portal inflammation, and fibrosis; and more severe portal lymphoid aggregation/follicles when compared with patients without hepatic bile duct injuries (P < 0.05, all). No significant differences in the presence of serum autoantibodies, cryoglobulinemia, mean serum HCV RNA titer, or response to interferon treatment were noted between the two groups. Multivariate logistic regression analysis showed that HCV genotype 1b infection, portal inflammation, and lymphoid aggregation/follicles were significant independent predictors associated with hepatic bile duct injuries. CONCLUSIONS: The presence of hepatic bile duct injuries in Chinese patients with chronic hepatitis C was significantly correlated with HCV genotype 1b infection, and the patients with these injuries had more severe portal inflammation and formation of lymphoid aggregates/follicles.
BACKGROUND AND AIMS: Hepatic steatosis is a histological characteristic in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to evaluate the prevalence of hepatic steatosis in Chinese patients with chronic hepatitis C, and to look for possible correlation with various histopathological changes and to look for possible correlation with various clinical and pathologic variables. METHODS: One hundred and six patients were enrolled, and patients with alcoholism or diabetes mellitus were excluded. Clinical, biochemical and virologic data, including HCV genotype and serum HCV-RNA titer and histological findings, were compared between patients with and without hepatic steatosis. RESULTS: Fifty-five (52%) of the 106 patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis had significantly higher mean serum levels of triglyceride and gamma-glutamyl transpeptidase, higher body mass index, and a higher incidence of obesity compared with patients without hepatic steatosis. No significant differences in serum HCV-RNA titer and HCV genotype or the response to interferon therapy were noted between the two groups. Histological analysis showed patients with hepatic steatosis had a significantly higher mean fibrotic score than patients without hepatic steatosis (1.9 +/- 1.2 vs 1.3 +/- 1.0; P = 0.016). There were no significant differences in the severity of necroinflammation, the presence of lymphoid aggregation/follicle or bile duct damage between the two groups. Multivariate logistic regression analysis showed that independent predictors associated with hepatic steatosis were obesity or a histology fibrotic score of > or = 2. CONCLUSION: It was found that 52% of Chinese patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis were more frequently obese and had more severe hepatic fibrosis.
BACKGROUND AND AIMS: The clinical outcomes of adult-acquired acute infection of hepatitis C virus (HCV) and hepatitis B virus (HBV) are quite different. In order to compare the clinical, biochemical, virologic and pathologic pictures in these two groups of patients, we enrolled 22 adult patients with acute hepatitis C and 16 adult patients with acute hepatitis B, on whom liver biopsies were performed within 3 months of acute onset of the illness. RESULTS: The results showed that a significantly younger age, a higher ratio of the clinical symptoms of jaundice, nausea, vomiting, and poor appetite, a higher mean serum level of alanine transaminase, aspartate transaminase, and total bilirubin were present in patients with acute hepatitis B patients than in those with acute hepatitis C (P < 0.05). There was a significantly higher degree of periportal inflammation and total necro-inflammatory activity in the acute hepatitis B patients (P = 0.002 and 0.049, respectively). Fifteen (68.2%) of the 22 patients with acute hepatitis C had detectable serum HCV-RNA, but only two (14.3%) of the 14 tested patients with acute hepatitis B had detectable serum HBV-DNA, detected by using the branched DNA signal amplification assay. Eighteen (82%) of the 22 acute hepatitis C patients and none of the 16 acute hepatitis B patients progressed into a chronic hepatitis stage (P < 0.001). CONCLUSION: The manifestations of mild clinical symptoms, lower mean serum transaminases and bilirubin levels, a lesser degree of histological periportal necroinflammation, and more patients with a high circulatory viral load among the acute hepatitis C patients, may lead to more of that group developing chronicity than patients with acute hepatitis B.
Elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C is not uncommonly seen, but the pathogenesis of this phenomenon remains unclear. The aims of this study were to assess the prevalence of elevated serum AFP in patients with chronic hepatitis C and to evaluate the clinical, virologic, and histopathologic significance of this phenomenon. One hundred and fifteen Chinese patients with a histologic diagnosis of chronic hepatitis C were enrolled. None had evidence of hepatocellular carcinoma by image study at enrollment and for at least 2 years' follow-up. Of the 115 patients, 33 (29%) had elevated serum AFP (more than 12 ng/mL). There was a significantly lower mean serum albumin (4.0 +/- 0.1 vs. 4.3 +/- 0.1 gm/dL, p <0.001) and higher mean scores for periportal necroinflammation (3.3 +/- 0.3 vs. 2.3 +/- 0.2, p = 0.007) and fibrosis (2.3 +/- 0.2 vs. 1.1 +/- 0.1, p < 0.001) in patients with elevated serum AFP when compared with patients without elevated serum AFP. Patients with elevated serum AFP had significantly more incidences of genotype 1b infection when compared with patients without elevated serum AFP (77% vs. 51%, p = 0.021). Mean serum hepatitis C virus (HCV) RNA titer showed no significant difference between the two groups. Multivariate logistic regression analysis showed that as serum albumin of less than 4.2 gm/dL, a histology fibrotic score of more than 3, and HCV genotype 1b infection were significantly independent predictors associated with elevated serum AFP. In conclusion, elevated serum AFP levels were significantly correlated with lower serum albumin levels, advanced fibrosis/cirrhosis, and genotype 1b infection in patients with chronic hepatitis C.
OBJECTIVE: Hepatocellular carcinoma is the most common malignancy in Taiwan, and spinal metastasis is a serious complication in cancer patients. In this study, we aimed to delineate the clinical features, evaluate the radiotherapy response and analyse the prognostic features in hepatocellular carcinoma subjects with spinal metastasis. METHODS: From 1981 to 1997, 102 patients with spinal metastasis were enrolled, taken from the 5887 documented hepatocellular carcinoma patients treated at Taipei Veterans General Hospital. All the clinical and laboratory data were recorded, including: age; gender; liver biochemistry; tumour characteristics; Child-Pugh's score; performance status; number and location of vertebral metastasis; motor capacity; neurological symptoms and signs; response to radiotherapy of the spinal lesion; and survival. Prognostic factors in hepatocellular carcinoma patients with spinal metastasis were analysed using Cox's regression model. RESULTS: The most common symptoms in hepatocellular carcinoma patients with spinal metastasis were lower back pain (74.5%), thoracic numbness (52.9%) and lower limb weakness (51.0%). Of the 102 patients, 84 received palliative radiotherapy using 3000 cGy for spinal lesions. Of these 84 patients, 32.1% showed a complete response, 26.2% a partial response and 41.7% a non-response to the radiotherapy. Multivariate Cox's regression analysis revealed that responsive radiotherapy (complete response + partial response) and good performance status (score <or= 2) were significant positive prognostic factors for survival in hepatocellular carcinoma patients with spinal metastasis. CONCLUSIONS: Responsive radiotherapy can improve a hepatocellular carcinoma patient's quality of life by ameliorating the neurological condition and relieving pain, and can prolong survival in hepatocellular carcinoma patients with spinal metastasis.
N,N-Dimethylformamide (DMF) has excellent solvent properties and is used intensively in the production of synthetic leather and resins. It has caused hepatoxicity in human and animal studies. Hepatitis B virus (HBV) and hepatitis C virus infections are reported to be the major causes of chronic liver diseases (including liver cirrhosis and liver cancer) in Taiwan. This study examined the dose-response relationship of the observed abnormal liver function among the DMF-exposed workers and the interactions among DMF, other chemical exposures, HBV infection, and potential confounders on liver abnormalities. The average DMF exposure concentration was 11.6 ppm (median, 5.9 ppm; range, 0.1 to 86.6 ppm); 65 of 176 workers (36.9%) had high (> 10 ppm) DMF exposure, 37 (21%) had middle (> 5 ppm, < or = 10 ppm) exposure, and 74 (42%) had low (< or = 5 ppm) exposure. There were 24 of 65 abnormal liver function test results (LFTs) (36.9%) (elevations of either glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, or gamma-glutamyl transpeptidase) among the workers with high DMF exposure, 10 of 37 abnormal LFTs (27%) among workers with middle DMF exposure, and 11 of 74 abnormal LFTs (22%) among workers with low DMF exposure. Compared with the workers having low DMF exposure, the HBV, drinking, body mass index (BMI), sex, duration of employment, epichlorohydrin, and toluene exposure adjusted odds ratios (ORs) (and 95% confidence intervals [CIs]) for abnormal LFTs were 1.62 (0.61, 4.28) for workers with middle DMF exposure and 2.93 (1.27, 6.8) for those with high DMF exposure, and there was a significant dose response between DMF exposure and the prevalence of abnormal LFTs (P = 0.006). There were significant associations between abnormal LFTs and HBV carriers (adjusted OR: 3.11; 95% CI: 1.29, 7.5; P = 0.01) and between abnormal LFTs and increased BMI (adjusted OR: 2.2; 95% CI: 1.02, 4.72; P = 0.041). Ultrasonography showed significant associations between chronic liver diseases and HBV carrier status, increased BMI, and high cumulative (> 100 ppm-years) DMF exposure (respectively, adjusted OR: 9.58, 95% CI: 1.79, 51.4, P = 0.007; adjusted OR: 13.2, 95% CI: 1.32, 132, P = 0.025; and adjusted OR: 6.2, 95% CI: 1.14, 34.1, P = 0.032). Drinking and BMI were significantly associated with fatty liver (respectively, adjusted OR: 4.9, 95% CI: 1.39, 17.3, P = 0.012; and adjusted OR: 7.93, 95% CI: 1.6, 39.3, P = 0.01). In conclusion, this study demonstrated that (1) a significant dose-response relationship existed between liver function abnormalities and DMF exposure among workers in Taiwan, (2) HBV carrier status or increased BMI had synergistic effects with DMF in causing liver abnormalities (abnormal LFTs and clinical chronic liver diseases).
OBJECTIVE: To detect the occult cervical metastasis with MRI so as to find out its diagnostic accurate rate. METHODS: 41 lateral necks(negative by clinical palpation) with malignant tumor of head and neck were examined by MRI before operation and correlated with postoperative pathologic finding. RESULTS: With MRI evaluation occult cervical metastasis has higher accurate rate(75%), nine of 12 lateral metastatic positive necks were detected on MRI, other three false negative necks were not found, owing to no change of the shape of the metastatic nodes. CONCLUSION: At present, MRI is one of the effective methods evaluating occult cervical metastasis with malignant tumor of head and neck, but it has still a certain limitation.
We report a 42-year-old Chinese female with elevated serum levels of liver aminotransferases, alkaline phosphatase, gamma-glutamyl transpeptidase, cholesterol and immunoglobulin M. Serum antimitochondrial antibody was negative, but antinuclear antibody was strongly positive. Liver histology showed features of both autoimmune cholangitis and autoimmune hepatitis. Combination therapy with immunosuppressive (prednisone and azathioprine) and choleuretic agents (ursodeoxycholic acid) was given. Serum aminotransferases and biliary enzymes showed much improvement after treatment. A follow-up liver biopsy showed improvement of both hepatic necroinflammation and bile duct damage. Biliary enzymes rose after withdrawal of the immunosuppressive agents and declined again with reinstitution of prednisone. This case demonstrates that a combination of immunosuppressive agents and ursodeoxycholic acid may effectively treat patients with features of both autoimmune cholangitis and autoimmune hepatitis.
BACKGROUND: Elevated serum gamma-glutamyl transpeptidase (GGT) is often seen in patients with chronic hepatitis C virus (HCV) infection and is associated with a poor response to interferon treatment. The pathogenesis of these phenomena is unclear. Therefore, we assessed the prevalence of elevated serum GGT in Chinese patients with chronic hepatitis C and evaluated the clinical, biochemical, virologic and histologic features of this phenomenon. METHODS: One hundred and twelve patients with biopsy-proven chronic hepatitis C were enrolled. Patients who were habitual alcohol drinkers, alcoholics or had diabetes mellitus were excluded. RESULTS: Forty-three (38.4%) of 112 patients had elevated serum GGT (> 60 U/l). Patients with elevated serum GGT had significantly higher serum levels of alanine and aspartate aminotransferases, alkaline phosphatase and total bilirubin, significantly higher histologic scores of liver lobular necro-inflammation and fibrosis when compared to patients with normal serum GGT. Elevated serum GGT was not correlated to serum HCV RNA titer or HCV genotype. Multivariate logistic regression analysis showed that a histologic fibrotic score > or = 2 was the only significantly independent predictor associated with elevated serum GGT. Fifty-seven of 112 patients completed a six-month course of interferon treatment. Patients with elevated serum GGT had a significantly lower sustained response rate to interferon when compared to patients with normal serum GGT (8% vs 30%, p = 0.042). CONCLUSIONS: Elevated serum GGT in chronic hepatitis C patients was frequently associated with more severe hepatic fibrosis or cirrhosis and may, in part, account for poor response to interferon therapy.
OBJECTIVE: The aim of this study was to measure certain diameters of the pterygopalatine fossa (PPF) and to discuss the anatomic appearance of PPF on CT images. METHODS: 20 dry skulls were scanned by CT on axial and coronal plane with 2 mm slice thickness. RESULTS: On CT imaging, the shape of superior 1/4 part of PPF is mainly shown as biconcavity. The maximal posteroanterial (PA)diameter was (6.6+/-2.2)mm. The maximal medialateral diameter (ML)was (13.7+/-3.7)mm. The shape of the middle 1/4 part of PPF was biconvexity with the PA and ML of (6.6+/-2.1)mm and (12.1+/-2.7)mm. The shape of the inferior 1/2 part of PPF just liked a tube with the diameter of (3.8+/-1.7)mm. The foramen rotudum lied (5.2+/-2.3)mm under the inferior orbital fissure. The pterygoid canal lied (7.4+/-2.5)mm medial and (6.2.+/-4.2)mm inferior to the foramen rotudum. CONCLUSION: PPF has various shapes on axial and coronal CT images. Based on the distances and the relationship between the foramen and fissures, the normal and abnormal status of PPF can be evaluated.
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignancy in Taiwan. Some patients may manifest paraneoplastic syndromes during the clinical course of the disease. In this study, the authors evaluated the clinical significance of these paraneoplastic syndromes, compared the prevalence of these syndromes between cases of hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related HCC, and estimated significant predictors associated with the syndromes. METHODS: Clinical data on 1197 HCC patients, including age, gender, Child-Pugh score, survival time, laboratory data (including liver biochemistry, hepatitis markers, and serum alpha-fetoprotein [AFP]), and tumor features (including tumor size, portal vein thrombosis, and histologic pictures), were retrospectively reviewed. RESULTS: A total of 232 of 1197 patients (19.4%) had paraneoplastic syndromes. HCC patients with paraneoplastic syndromes had significantly higher serum AFP; higher rates of initial main portal vein thrombosis, metastasis, and bilobal tumor involvement; larger tumor volume; and shorter survival than those without these syndromes. Patients with HBV-related HCC had a significantly higher prevalence of paraneoplastic syndromes than patients with HCV-related HCC (20.1% vs. 11.2%, P = 0.005). In a stepwise multivariate logistic regression analysis, AFP >50,000 ng/mL and tumor volume >30% were significant predictive variables associated with the presence of paraneoplastic syndromes in HCC patients. CONCLUSIONS: HCC patients with paraneoplastic syndromes usually had higher levels of serum AFP and larger tumor volumes than those without. Patients with HBV-related HCC had a significantly higher prevalence of paraneoplastic syndromes than those with HCV-related HCC.
Vascular endothelial growth factor (VEGF) has potent endothelial cell mitotic and vascular permeability activity. Several reports have suggested that VEGF may be one of the major factors regulating ascites formation, although no quantitative and systematic analyses have been carried out. To determine the role of VEGF in ascites formation, we examined the expression of VEGF in 13 mouse ascites tumors (5 sarcomas, 3 carcinomas, and 5 hematopoietic malignancies). We found that significant amounts (6-850 ng/mL) of biologically active VEGF accumulated in the ascites fluid of all 13 tumors, particularly in tumors of sarcoma and carcinoma origin (430 +/- 234 ng/mL). The microvessel densities in the peritoneal walls of tumor-bearing mice, which are significantly higher than those in healthy mice, basically correlated with but did not parallel VEGF concentrations, suggesting the existence of an additional modulator(s) of the angiogenic process. Administration of anti-mouse VEGF-neutralizing antibody to mice bearing the carcinoma-derived ascites tumor MM2 suppressed ascites accumulation, tumor growth, and tendency to bleed. These results directly demonstrate the crucial role of VEGF in carcinoma-derived ascites tumor formation in vivo.
Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-beta-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) and human malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with the relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.
BACKGROUND: Hypercholesterolaemia, hypoglycaemia, hypercalcaemia and erythrocytosis, are well-known paraneoplastic manifestations in patients with hepatocellular carcinoma (HCC). Hepatocellular carcinoma patients manifesting with two or three paraneoplastic manifestations have been previously reported. However, HCC patients presenting with four paraneoplastic syndromes have not been previously reported. METHODS AND RESULTS: This manuscript describes two HCC patients who manifested with hypercholesterolaemia, hypoglycaemia, hypercalcaemia and erythrocytosis during their clinical course. Erythrocytosis appeared early when HCC was diagnosed and declined to within normal range after optimal therapy for HCC. Hypercholesterolaemia manifested initially after the diagnosis in case 1, declined to within normal range after lobectomy and was re-elevated after tumour recurred. With disease progression, hypercalcaemia and hypoglycaemia occurred 1-3 months after diagnosis and the both patients subsequently died several days later. CONCLUSIONS: Similar features found in both patients were large tumour burden, high serum alpha-fetoprotein level and rapid downhill clinical course even with optimal therapy. The clinical significance of these paraneoplastic manifestations is discussed.
BACKGROUND: Spider angioma is a common sign in patients with liver cirrhosis, but the pathogenesis is still unclear. Alcohol and hyperestrogenemia are both possible etiologies. This study was designed to investigate the relationship of spider angiomas in patients with liver cirrhosis to alcohol, liver function test results, and plasma levels of sex hormones. METHODS: Eighty-two patients with liver cirrhosis and 18 healthy subjects were enrolled in this study. The number, size, and location of the spider angiomas were recorded for all subjects. Plasma levels of estradiol and testosterone were measured. RESULTS: Cirrhotic patients had significantly higher estradiol/testosterone ratios (26.8 +/- 5.1 x 10(-3) versus 8.8 +/- 2.0 x 10(-3); P = 0.002) than healthy controls. Twenty-seven (33%) of the 82 cirrhotic patients had spider angiomas. Cirrhotic patients with spider angiomas were younger (56 +/- 3 versus 66 +/- 1 years; P = 0.002) and had higher serum bilirubin levels (3.3 +/- 0.6 versus 1.7 +/- 0.2 mg/dl; P = 0.002), longer prothrombin time (16.8 +/- 0.8 versus 14.8 +/- 0.4 sec; P = 0.01), and higher prevalence of alcoholism (41% versus 20%; P = 0.04) than those without. Stepwise logistic regression showed that alcoholism and serum bilirubin level were the only significant and independent predictors associated with the presence of spider angiomas in cirrhotic patients (odds ratio = 3.5; 95% confidence interval = 1.2-10.8; P = 0.03, and odds ratio = 2.8; 95% confidence interval = 1.3-5.7; P = 0.006, respectively). CONCLUSIONS: Alcoholism and impaired liver function are important predictors of the presence of spider angiomas in patients with liver cirrhosis.