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Biomedical subjects

T M Chan

Publications and source records attributed to T M Chan.

At least 145 records · Page 8Linked to original sources

Secular changes in the clinical manifestation and pathologic pattern of early gastric cancer in Taiwan.

To investigate whether there has been a time trend change in the percentage of early gastric cancer to gastric cancer and the clinicopathologic features of early gastric cancer in Taiwan, we reviewed 208 patients diagnosed between 1964 and 1992. Patients were divided into group I from 1964-1980 (n = 106) and group II from 1981-1992 (n = 102). The percentage of early gastric cancer among total gastric resections in group II (14.7%) did not differ from group I (12.7%; p = 0.19). Epigastralgia (58.2%) was the most common complaint; 11.8% (12/102) of cancers in group II were incidentally detected by endoscopy. Endoscopy provided a better diagnostic aid than did radiology. Tumors were frequently located in the antrum (50.9%) with a mean diameter of 2.8 cm. Small cancers of less than 1 cm in diameter were more prevalent in group II (37.3%) than group I (10.4%; p < 0.001). Cancers of the elevated type (17.8%) were uncommon in contrast to depressed ones (82.2%; p < 0.001). The frequency of mucosal carcinoma (51.0%) was similar to submucosal carcinoma (49.0%). Mucosal carcinoma had less lymph node metastases (3.1%) than submucosal carcinoma (12.2%; p < 0.05) with an overall frequency of metastases of 7.5% (14/186). The five-year survival rate of group I (91.7%) was not statistically different from group II (94.6%). We concluded that, except for the symptomatology and the ability to diagnose, the clinicopathologic features of early gastric cancer were similar between these two time periods. Repeated investigation of suspicious lesions and endoscopic screening on asymptomatic subjects may increase the rate of detection and thus guarantee a favorable outcome.

Adult↗

Antiendothelial cell antibodies in lupus: correlations with renal injury and circulating markers of endothelial damage.

Systemic lupus erythematosus is characterized by the production of a broad spectrum of autoantibodies. Autoantibodies directed against endothelial cells (AECA) have been particularly well documented. We investigated associations between such antibodies, double-stranded DNA (dsDNAb), phospholipid (cardiolipin, ACA), and indices of activity and chronicity scored on renal biopsy specimens from 22 patients with acute lupus. AECA were present in 73% of these patients, and both the percentage of patients with AECA and the mean antibody titre fell significantly as patients entered remission. When patients already on immunosuppressive therapy were excluded from analysis (n = 7), only levels of AECA and DNAb (p = 0.02) correlated with histological evidence of active lesions and the presence of glomerular epithelial cell crescents; no correlation was found with chronic changes in the renal biopsies. Serum von Willebrand factor (vWf) and serum total protein S levels, two parameters reflecting endothelial cell function, were also measured during acute disease and remission. vWf concentrations were elevated during acute disease (m = 1.9 IU/ml, p = 0.02), but the values did not correlate with AECA titres. In contrast, total protein S levels were reduced (0.81 IU/ml vs. 0.97 IU/ml, p = 0.01) during active disease, but remained within the normal range (0.56-1.16 IU/ml). Furthermore, protein S levels were inversely related to levels of AECA (r = -0.4, p = 0.01). AECA were therefore present in most patients with acute lupus nephritis and were associated with histological evidence of active renal injury and serological evidence of endothelial cell dysfunction. These data provide indirect support for a pathogenic role for AECA in lupus nephritis.

Antibodies, Anticardiolipin↗

Different mechanisms by which anti-DNA MoAbs bind to human endothelial cells and glomerular mesangial cells.

The mechanisms by which anti-DNA MoAbs derived from MRL-lpr/lpr mice, bind to human umbilical vein endothelial cells (HUVEC) and glomerular mesangial cells were studied using a cellular ELISA. DNAse-treatment of either the MoAb or HUVEC followed by reconstitution with DNA and/or histones was performed to determine whether DNA and histones mediated such binding. It was found that MoAb410 bound to HUVEC and mesangial cells in the form of preformed DNA/anti-DNA immune complex, and such binding was facilitated by histones. In contrast, MoAb 152 bound directly to cell membrane-associated DNA, and adding DNA to MoAb 152 reduced its cellular binding. DNA binds endothelial cell surface and histones enhance the binding of both MoAb 410 and MoAb 152 to HUVEC by increasing cell membrane-associated DNA. Finally, the degree of MoAb binding to HUVEC is critically influenced by the relative concentrations of antibody, DNA, and histones.

Antibodies, Antinuclear↗

Total and regional bone densities in dialysis patients.

Total and regional bone mineral densities (BMD) of ten male haemodialysis (HD) patients and ten male patients on continuous ambulatory peritoneal dialysis (CAPD) were measured using dual-energy X-ray absorptiometry (DEXA), and compared with that of age- and sex-matched controls. Our data showed that patients with renal failure on dialysis had reduced bone densities as manifested by a reduction in total body BMD, femoral neck BMD, and Ward's triangle BMD. In addition, head BMD and femoral trochanter BMD were also reduced in HD patients. Among HD patients, the length of the period of dialysis correlated with serum level of parathyroid hormone and the reductions in total body BMD and head BMD. Furthermore, there was a strong negative correlation between bone density of the skull and serum parathyroid hormone. Our results demonstrated regional variations in the reduction of bone density in patients with asymptomatic renal bone disease. DEXA bone scan is a useful adjunct in the early assessment of renal osteodystrophy and bone density of the skull can be used as a monitor in hyperparathyroid bone disease.

Adult↗

Overestimation of the prevalence of antibody to hepatitis C virus in retrospective studies on stored sera.

Serum samples (1,428) from 1,149 patients with chronic liver diseases and polytransfused subjects were tested for antibody to hepatitis C virus by first-generation enzyme immunoassays. Antibody to hepatitis C virus was detected in 87% of patients with transfusion-related chronic non-A, non-B hepatitis; 17.6% of patients with nonmalignant, chronic hepatitis B virus infection; 37.3% of patients with hepatocellular carcinoma; 14.3% of patients with alcoholic liver diseases; 22.2% of patients with cryptogenic cirrhosis; 76% of intravenous drug abusers; 16.4% of patients on hemodialysis; 1.8% of patients on peritoneal dialysis; 6.2% of kidney transplant recipients; and 3.1% of normal subjects. A high frequency of weakly positive results was found in "aged" samples: 61.9% of antibody to hepatitis C virus-positive patients whose sera had been stored for more than 2 yr had optical densities less than two times the cut-off values in contrast to 7.9% of those whose sera had been stored for less than 2 yr (p less than 0.0001). A significantly lower proportion of patients who had optical densities less than two times the cut-off values were reactive in subsequent samples, 27.5% vs. 87.5% (p less than 0.0001). On retests, only 70% and 56% of sera that were initially positive for antibody to hepatitis C virus remained antibody to hepatitis C virus positive using second-generation enzyme immunoassays and neutralization enzyme immunoassays, respectively. Our results suggest that retrospective studies on stored sera may have overestimated the prevalence of antibody to hepatitis C virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗

Hepatitis C infection among dialysis patients: a comparison between patients on maintenance haemodialysis and continuous ambulatory peritoneal dialysis.

Three hundred and thirty-nine dialysis patients from two centres (278 patients on continuous ambulatory peritoneal dialysis (CAPD) and 61 on maintenance haemodialysis (HD) were tested for antibody against hepatitis C virus (anti-HCV) using first-generation enzyme immunoassay kits (Ortho Diagnostics). Anti-HCV was detected in five (1.8%) CAPD patients and ten (16.4%) HD patients (P less than 0.00001). Anti-HCV was confirmed to be positive in three (1.1%) CAPD patients and eight (13.2%) HD patients using neutralisation enzyme immunoassay kits (Abbott Laboratories). The marked difference in prevalence of anti-HCV among CAPD and HD patients was related to a significantly greater transfusion requirement of the HD patients. All the anti-HCV positive patients had been transfused. The risk of HCV infection was significantly increased in those who had received more than five units of blood. Four (26.7%) anti-HCV positive patients had one or more episodes of elevated serum alanine aminotransferase (ALT) values.

Adult↗

Hepatitis C in renal transplant recipients.

Sera from 130 renal transplant recipients were tested for antibody to hepatitis C virus (anti-HCV). Anti-HCV was detected in 6.2% of patients: 15.4% of patients who had maintenance hemodialysis (HD) and 2.2% of those who had continuous ambulatory peritoneal dialysis (CAPD) before transplantation (P less than 0.05). The similarity in prevalence of anti-HCV with patients currently on dialysis and the absence of transfusion during posttransplant follow-up suggest that most patients acquired HCV infection through transfusion during dialysis. The proportion of anti-HCV-positive patients who had one or more episodes of elevation in serum transaminase level was similar to that of hepatitis B surface antigen (HBsAg)-positive patients, 75% vs. 72.2%. However, anti-HCV was only detected in 25% of HBsAg-negative patients who had recurrent elevations in serum transaminase level. It is not clear whether the low prevalence of anti-HCV in these patients is related to the presence of other non-A, non-B hepatitis virus (es) or a decrease in titer of anti-HCV secondary to immunosuppression posttransplantation.

Adolescent↗

Crescentic IgA glomerulonephritis following interleukin-2 therapy for hepatocellular carcinoma of the liver.

A patient who developed crescentic IgA nephropathy following treatment with recombinant interleukin-2 (rIL2) and lymphokine-activated killer (LAK) cell therapy for hepatocellular carcinoma was reported. Cessation of rIL2 and LAK cell treatment plus plasmapheresis and steroid therapy was successful in achieving partial improvement and stabilization of renal function. This is the first case report of biopsy-documented glomerulonephritis developing after IL2 and LAK cell therapy. This provides indirect in vivo evidence for the role of IL2 in mediating glomerular injury in IgA nephropathy.

Biopsy↗

Peripheral insulin insensitivity in the hyperglycemic athymic nude mouse: similarity to noninsulin-dependent diabetes mellitus.

Previous studies in the homozygous athymic nude mouse (USC colony) have indicated a diabetic state characterized by spontaneous hyperglycemia, abnormal glucose tolerance, and normal or relatively decreased plasma insulin levels. Pancreatic islet cell population assessed by morphometric and immunohistochemical studies demonstrated normal insulin-secreting cells in the hyperglycemic nude mouse. To further elucidate the pathogenesis of the hyperglycemic state in the athymic nude mouse, we have studied the effects of insulin on the transport of glucose in skeletal muscle by measuring basal and insulin-stimulated uptake of a nonmetabolizable glucose analogue, 2-deoxy-D-glucose by using the perfused hindquarter preparation. Although basal 2-deoxy-D-glucose uptake by peripheral skeletal muscle was similar in the hyperglycemic and control mice, the insulin-stimulated uptake of 2-deoxy-D-glucose was significantly decreased in the athymic nude mouse at both 0.1 milliunits/ml and supraphysiologic concentrations of insulin (1 milliunit/ml) when compared with control mice (P less than 0.05 and P less than 0.001, respectively). This form of peripheral insulin insensitivity with normal pancreatic beta cell reserve, in addition to the lean body mass of the diabetic animal, mimics in part the peripheral insulin insensitivity seen in non-insulin-dependent diabetes mellitus.

Animals↗

Activation of a membrane-associated phosphatidylinositol kinase through tyrosine-protein phosphorylation by naphthoquinones and orthovanadate.

We have previously reported that several naphthoquinones stimulated tyrosine-specific protein phosphorylation in isolated rat liver membranes. Our more recent study demonstrated a similar effect by orthovanadate, which concomitantly stimulated phosphorylation of protein-tyrosine and phosphatidylinositol (Ptd-Ins). Results presented here show a simultaneous increase in PtdIns phosphorylation along with stimulation of tyrosine-protein phosphorylation by naphthoquinones. This PtdIns kinase resembles the type I PtdIns kinase in that it was insensitive to adenosine inhibition. The product, nevertheless, comigrated with a PtdIns-4-phosphate standard in TLC using three different solvent systems. Stimulation of PtdIns phosphorylation by vanadate or naphthoquinones could be achieved in the following preparations: intact rat liver membranes, Triton X-100-solubilized membranes, solubilized membranes partially purified by Sephacryl chromatography, solubilized membranes purified by wheat germ agglutinin chromatography. The naphthoquinone or vanadate-activated PtdIns kinase activity could be isolated by antiphosphotyrosine antibody-agarose affinity chromatography. The relative potencies of a series of ring-substituted naphthoquinones in the stimulation of tyrosine-protein phosphorylation, PtdIns kinase activity, dithiothreitol-dependent oxygen consumption, and cytochrome c reduction were highly correlated. We conclude that oxidant(s) produced by redox cycling of naphthoquinones stimulated an adenosine-insensitive PtdIns kinase through tyrosine phosphorylation of the enzyme.

1-Phosphatidylinositol 4-Kinase↗

Stimulation of tyrosine-specific protein phosphorylation and phosphatidylinositol phosphorylation by orthovanadate in rat liver plasma membrane.

Orthovanadate stimulated the incorporation of 32P from [gamma-32P]ATP by Triton X-100-solubilized rat liver plasma membrane into endogenous, trichloroacetic acid-precipitable materials as well as added (Glu4:Tyr1) copolymers. Extraction of incubation mixture with chloroform-methanol-HCl revealed that the increase in 32P incorporation by vanadate was predominantly into endogenous phospholipids. [32P]Phosphatidylinositol 4-phosphate (PtdIns-4-P) was identified by thin-layer chromatography as the major phosphorylated product of vanadate stimulation, which also resulted in elevated 32P, predominantly in P-Tyr in endogenous membrane proteins. Vanadate effects on protein tyrosine and phosphatidylinositol phosphorylation were concomitant and exhibited similar sensitivity. These effects of vanadate were enhanced by the presence of either dithiothreitol or NAD(P)H. Phosphatidylinositol phosphorylation could also be stimulated by a substrate of and inhibited by a synthetic inhibitory copolymer of tyrosine kinase. These results suggest that vanadate, an oxygen radical producer, stimulates a tyrosine kinase-PtdIns kinase coupled system much like those described for a number of growth factors and oncogene encoded products.

Animals↗

Effects of dexamethasone on glucose transport by skeletal muscles of obese (ob/ob) mice.

Adrenalectomy normalized basal and insulin-stimulated glucose transport in the perfused hindquarter of the obese (ob/ob) mouse. Dexamethasone treatment of adrenalectomized obese mice for 9 days significantly reduced both the basal and insulin-stimulated uptake of (3H)-2-deoxy-D-glucose in hindlimbs of adrenalectomized mice to levels similar to those of intact ob/ob mice. Five hours after injection of dexamethasone in vivo and following 5 hours of perfusion in vitro there was a 10 percent reduction in basal 2-deoxy-D-glucose uptake in both groups. In muscles perfused with dexamethasone in vitro, the stimulation of 2-deoxy-D-glucose uptake by insulin was greater than in those muscles perfused with vehicle alone. Five hours of treatment in vivo also resulted in a significant increase in liver tyrosine aminotransferase activity, and a decrease in muscle glycogen synthetase activity ratio. These data suggest that the effect of glucocorticoids on lowering glucose transport in the skeletal muscle of obese ob/ob mice is a direct one.

Adrenalectomy↗

Fungal peritonitis complicating peritoneal dialysis: report of 27 cases and review of treatment.

The clinical features, treatment and outcome of 27 cases of fungal peritonitis were studied. Twenty-one cases occurred in patients receiving CAPD and six in patients on intermittent peritoneal dialysis. Twenty-five cases were due to Candida spp., one was due to Trichosporon spp. and in one, both Candida and Trichosporon and an unidentified acid-fast bacillus were isolated. Clinical features of fungal peritonitis and bacterial peritonitis were the same. A direct comparison with patients without fungal peritonitis failed to reveal an increased incidence of diabetes mellitus. However, a history of recent bacterial peritonitis and antibiotic treatment was frequently obtained. We found that the combination of oral ketoconazole and intraperitoneal miconazole is successful in treating fungal peritonitis complicating peritoneal dialysis but catheter removal and replacement is often necessary. Analysis of the relationship between clinical outcome and various treatment strategies in cases reported in the literature and in our own showed that an initial trial of antifungal drugs consisting of oral ketoconazole and i.p. 5-fluorocytosine or miconazole is warranted in most cases before contemplating catheter removal.

Adolescent↗

Stimulation of tyrosine-specific protein phosphorylation in the rat liver plasma membrane by oxygen radicals.

Incorporation of 32P from [gamma-32P]ATP into endogenous proteins, added histone and the copolymers Glu 80 Tyr 20 by rat liver plasma membranes was markedly increased by several naphthoquinones, including menadione. This stimulation was most marked with Glu 80 Tyr 20, has an absolute requirement for either dithiothreitol or reduced glutathione, and was inhibited by superoxide dismutase, catalase, and desferrioxamine to varying degrees depending on the quinones used. Their effectiveness in stimulating the apparent tyrosine-specific protein phosphorylation correlated with the rates of DTT-dependent redox cycling measured by oxygen consumption. Increased protein phosphorylation was also seen with particulate fractions isolated from hepatocytes incubated with quinones. A free radical-mediated mechanism is suggested for the quinone stimulation of protein phosphorylation.

Adenosine Triphosphate↗