Expression of Epstein-Barr virus genome in nude-mouse-growth nasopharyngeal carcinoma cells.
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Biomedical subjects
Publications and source records attributed to T K Chan.
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Human endothelial cells in culture is shown to synthesize antithrombin III (At-III). The endothelial cell At-III (EC-At-III) consists of a small fraction similar to plasma At-III and a larger fraction with decreased heparin-binding as tested by crossed immunoelectrophoresis. However, both the anti-Xa and thrombin-neutralizing activities of the EC-At-III were rapid and active even in the absence of added heparin. It is concluded that the major portion was probably bound to endogenous heparin-like substance, thus accounting for its decreased exogenous heparin binding. The presence of At-III and other antithrombotic factors in the vascular endothelium offer protection against thrombosis and possibly atherosclerosis.
An adult Chinese man presented with tendinous and tuberous xanthomatosis and severe atheromatous changes in the coronary arteries. In addition, he had chronic hemolytic anemia, with spherostomatocytic erythrocytes. Cerebrotendinous xanthomatosis was diagnosed on the basis of increased cholestanol levels in his plasma, red cells and xanthoma, changes in bile acid composition due to the defective synthesis of chenodeoxycholic acid. Coexisting beta-sitosterolemia was confirmed by the finding of large amounts of the plant sterols such as beta-sitosterol and campesterol. This is the first report of these two rare lipid storage disorders in the same patient.
1. The metabolism of human antithrombin III (ATIII) was studied by using 125I-labelled tracer. 2. The plasma half-life (t0.5) was 2.71 +/- 0.26 days in normal subjects and was similar in patients with cirrhosis or primary carcinoma of liver. 3. Patients with cirrhosis had low ATIII levels, decreased intravascular mass, total body mass and decreased absolute catabolic rate, suggesting decreased synthesis. The positive correlation of ATIII level with fractional catabolic rate (K10) indicated that the decreased catabolic might exert a positive inhibition on ATIII production. 4. These abnormalities were more exaggerated in patients with macronodular cirrhosis associated with hepatitis surface antigen or in those with ascites. 5. In cirrhotic patients with ascites an additional extravascular pool of ATIII was present which did not turn over at the same rate as the intravascular pool. 6. Patients with primary carcinoma of liver had moderately low ATIII, but normal intravascular mass and total body mass because of the increased plasma volume and normal absolute catabolic rate. 7. The negative correlation of ATIII levels with K10 suggested that the low levels could be due to increased catabolism or consumption. 8. One patient with disseminated malignancy and active superficial thrombophlebitis had normal ATIII metabolism.
Liddle's syndrome was diagnosed in a 23-yr-old Chinese girl with hypertension and hypokalemia by the presence of suppressed renin and negligible plasma and urinary aldosterone secretion. Adrenal corticosteroids, including aldosterone, were suppressed by dexamethasone and stimulated by ACTH. While spironolactone was ineffective, triamterene (2,4,7-triamino-6-phenyl-pteridine) treatment corrected the hypertension and hypokalemia and restored PRA to normal provided that sodium intake was not excessive. During long term treatment with triamterene, blood pressure was extremely sensitive to salt intake, increasing promptly with high intake and decreasing with low salt intake. As a result of the chronic hypervolemia and sodium retention consequent upon the patient's persistent high salt intake and increased renal tubular sodium reabsorption, plasma renin and aldosterone remained low. Erythrocyte sodium concentration and membrane permeability were increased. Triamterene with salt restriction was able to lower the intracellular sodium concentration but did not correct the increased sodium permeability. This suggests that there is an abnormality of sodium transport in Liddle's syndrome which affects the erythrocytes as well as the renal tubular cells.
After at least four courses of intermittent chemotherapy, 14 of the 15 men with malignant lymphoma had elevated serum follicle-stimulating hormone (FSH). In three of these subjects, serial studies showed progressive increases in basal FSH and exaggerated FSH responses to luteinizing hormone releasing hormone (LHRH). Although gonadal biopsies were not done, this elevation of FSH is indicative of progressive and severe damage to the germinal epithelium by chemotherapy. Elevated leutinizing hormone (LH) was found in seven and decreased testosterone (T) in two of these subjects. Increased LH responses to LHRH stimulation were also found in the three subjects studied. These findings suggest that the testicular damage is not restricted to the germinal tissue. In four male subjects with acute myeloid leukemia treated by intermittent chemotherapy not containing any alkylating agents, FSH, LH, and T levels were normal. Three of the 4 female patients with malignant lymphoma and two with acute myeloid leukemia had normal basal, serial, and LHRH-stimulated FSH, LH, and estradiol (E2) levels. Elevated gonadotropins and low E2 were found only in subjects who had received abdominal irradiation.
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The presence of Hb New York was confirmed in a Chinese family in which affected members have occasional red cells with Hb-H-like inclusions and a relative decrease in alpha chain synthesis, suggestive of a coexisting alpha thalassaemia trait. However, globin gene mapping and DNA hybridization revealed no deletion of the alpha genome. Timed-incubation experiments showed that the rate of synthesis of beta NY chain was greater than that of normal beta chain in the early periods. Chromatographic separation of Hb NY and Hb A before chain analysis revealed preferential binding of newly synthesized alpha chains to beta NY, with a four-fold increase in specific activity of the alpha Hb NY chains. It is concluded that beta NY chain is being synthesized more rapidly and its increased turnover may account for this presentation of apparent alpha chain deficiency.
Of 154 Chinese patients who underwent gynaecological operations, four showed a positive 125I fibrinogen leg scan for venous thrombosis, and overall incidence of 2 . 6%. In those who were on oral contraceptives and had major pelvic surgery for benign conditions, the incidence was 10 . 5%; in those who had Wertheim hysterectomy for carcinoma of cervix, it was 6 . 7%. This confirms the rarity of post-operative thromboembolism in the Chinese. Fragment E showed a biphasic rise after major operation due to tissue injury and venous thrombosis. In patients with malignancy, the postoperative 'fibrinolytic shutdown', represented by decreased plasminogen activator together with increased alpha 1 antitrypsin and C1- inhibitor levels, was more marked. In addition, alpha 2 macroglobulin level was lower and fell significantly after operation. In patients on oral contraceptives, fragment E levels were higher after surgery and there was no decrease in plasminogen activator levels. Antithrombin III levels did not fall except in three of the four patients with venous thrombosis. A marked increase in fragment E level and a decrease in antithrombin III level might be useful diagnostic markers for postoperative venous thrombosis.
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A radioimmunoassay (RIA) had been developed for the determination of antithrombin III (AT III) in man. The detection limit was 25 microgram/dl. AT III-RIA level and biological activity (anti-Xa) was significantly correlated (r = 0.737, P less than 0.001). Plasma levels in 36 healthy males (mean +/- SD, 19.9 +/- 2.5 mg/dl) and 21 healthy females (19.1 +/- 2.4 mg/dl) were similar. Serial AT III measurements in normal menstruating females showed lower levels during midcycle and higher concentrations during menstruation. In carcinomas, the AT III levels were lower than normal, particularly in hepatocellular carcinoma. In cirrhosis of liver, the levels were markedly decreased and in some patients were below that found in congenital AT III deficiency. Patients with deep vein thrombosis and patients with heart valve replacement had lower levels than normal, while patients with cerebral vascular occlusion had normal levels. The possible use of AT III as a diagnostic tool of post-operative deep vein thrombosis was demonstrated in one patient after hysterectomy. The increased sensitivity, specificity and precision of this type of assay offer distinct advantages over existing methods of AT III estimation.
Heparin antithrombin III binding was studied by crossed immunoelectrophoresis. In plasma and purified antithrombin III standard, multicomponent patterns were obtained with low concentrations of mucosal heparin. There is evidence that antithrombin III may bind more than one heparin molecule. At high heparin concentration (greater than 16 U/ml), single symmetrical peaks were obtained. Serum samples showed two antithrombin III peaks due to a decreased heparin binding of the slower peak (2.1-3.9 times), which was probably antithrombin III-activated procoagulant complexes. Heparin analogue (A 73025) also bound antithrombin III in vitro but the mobility of the peak was slower than with mucosal heparin and only a single peak was obtained in serum samples. Radioimmunoassay showed a decreased binding of antithrombin III antibody to heparin-antithrombin III complex. Venous occlusion to the forearm resulted in a slow second peak in the plasma. Heparin therapy gave rise to a double peak in the plasma antithrombin III profile and with continuous infusion, quantitative decreases were noted in all subjects studied, two of whom rethrombosed at the end of 7 days therapy.
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One hundred and twenty-nine Chinese patients with aplastic anaemia, were studied. In ten it was induced by drugs, one followed hepatitis and the remainder were of unkown cause. Mortality within the first six months was 47.3 per cent. Features associated with poor prognosis included a short duration of symptoms of three months or less, neutropenia of less than 0.5 x 10(9)/l and severe thrombocytopenia. On the other hand, some preservation of erythroid activity of the bone marrow was associated with long survival. Remission occurred in 47 patients and this was associated with androgen therapy in 33. Remission was complete in 18 and partial in 29. In the latter group, persistent thrombocytopenia was the main abnormality and treatment with calusterone led to an increase in platelets although the effect was not sustained after its withdrawal. Hepatotoxicity was seen in 16.0 per cent of patients treated with androgens and this occurred even with non-17alpha-alkylated compounds. It is concluded that androgen therapy was useful and should be started as early as possible after diagnosis. Hepatic intolerance to androgens may be an indication for bone marrow transplantation.