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Biomedical subjects

M F Tsan

Publications and source records attributed to M F Tsan.

At least 73 records · Page 4Linked to original sources
PubMed1986

Pure red-cell aplasia in patients with chronic lymphocytic leukemia.

Four cases of pure red-cell aplasia (PRCA) in association with chronic lymphocytic leukemia (CLL) are summarized. In addition, all reported cases of CLL-PRCA (27, including our 4 cases) are reviewed to consolidate their clinical features and compare them with those of 26 patients with CLL who were anemic (Stage III) and 52 who were not anemic (Stages O-II). The incidence of PRCA in our patients with CLL is about 6%. Eighty-seven percent of patients with PRCA had B-lymphocyte (B-cell) CLL and 13% had T-lymphocyte (T-cell) CLL. In 4 of 17 patients PRCA was the presenting feature, and in 13 of 17 it developed in patients previously diagnosed as having CLL. In the latter group, the average time from the diagnosis of CLL to the development of PRCA was 50.2 months (range, 1 to 96). The average age at presentation with PRCA was 61.6 years (range, 37 to 79), and the male to female ratio was 1.6 to 3:1. Eighty-one percent had splenomegaly and 65% had lymphadenopathy. The average hematocrit was 17 +/- 3.6% with zero reticulocyte count, and the lymphocyte count was 134 X 10(3)/microliter. Normoblasts were absent in the marrow and lymphocytes constituted 50 to 100% of the marrow cells. In patients with B-cell CLL and those with T-cell CLL, the T cells were found to inhibit the growth of the marrow erythroid progenitors in in vitro cultures. These abnormal T cells (Tr cells) possessed IgG Fc receptors on their surface, which may be responsible for induction of PRCA in these patients. Continued administration of cyclophosphamide and prednisone in moderate doses appears to induce remission from PRCA, but not until the leukemic mass and abnormal Tr cells are markedly reduced. Daily or alternate-day cyclophosphamide administration in small to moderate doses seems to be essential to maintain remission.

Erythrocyte Count↗
PubMed1986

Enhancement of hepatic gallium-67 uptake by asialo-transferrin.

A significant fraction of intravenously injected 67Ga localizes in the liver. The mechanism of 67Ga uptake by the liver is not clear. Hepatocyte membranes contain galactose-specific receptors which selectively remove asialo-glycoproteins from the circulation by way of endocytosis. In this investigation, we examined whether endocytic uptake of asialo-transferrin would involve 67Ga transport into hepatocytes. We demonstrated that asialo-transferrin bound 67Ga as effectively as apotransferrin. Human asialo-transferrin markedly enhanced 67Ga uptake by isolated, perfused rat livers. Human asialo-orosomucoid, but not orosomucoid competitively inhibited hepatic uptake of the 67Ga asialo-transferrin complex, indicating that hepatic 67Ga uptake in the presence of asialo-transferrin occurred by way of galactose-specific receptors. Our results point to a novel pathway for metal ion transport into hepatocytes by way of galactose receptor mediated endocytosis.

Animals↗
PubMed1986

Mechanism of gallium-67 accumulation in tumors.

Neoplasms are characterized by increased perfusion, increased permeability of their capillary beds to macromolecules, and a delay in new lymphatic vessel growth. These lead to the increased entry and residency time of macromolecules in the interstitial space of tumors. Multiple factors contribute to the localization of 67Ga in tumors. Adequate blood supply is essential; at areas with no blood supply such as the necrotic center of a large tumor, there is no 67Ga accumulation. Gallium-67, mainly in the form of transferrin-67Ga complex, is delivered to the tumor through capillaries with increased permeability. In tumors, some 67Ga is taken up by tumor cells; some may also be taken up by inflammatory cells when they are present. Gallium-67 binding proteins, such as lactoferrin or ferritin, may also contribute to the accumulation and retention of 67Ga in tumors; however, their roles are less clear. The intensity of these various factors determine their relative contribution and the degree of 67Ga accumulation in tumors.

Animals↗
PubMed1985

Enhancement of intracellular glutathione protects endothelial cells against oxidant damage.

We studied the role of glutathione in the endothelial cell defense against H2O2 damage. Treatment of endothelial cells with buthionine sulfoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase, depleted the cells of GSH, while L-2-oxothiazolidine-4-carboxylate, an effective intracellular cysteine delivery agent, markedly enhanced endothelial cell GSH concentration. Depletion of intracellular GSH sensitized the endothelial cells to injury by H2O2 either preformed or generated by the glucose-glucose oxidase system. In contrast, an increase of intracellular GSH protected the cells from H2O2 damage. There was an inverse, linear relationship between the intracellular GSH concentrations and killing of endothelial cells by H2O2. Our results suggest that enhancement of endothelial cell GSH may be an alternative approach toward the prevention of oxidant-induced endothelial damage such as adult respiratory distress syndrome.

Animals↗
PubMed1985

Transferrin sialic acid contents of patients with hereditary hemochromatosis.

Recent evidence suggests that asialotransferrin may enhance hepatic uptake of trivalent metal ions through the asialoglycoprotein-receptor pathway. In hereditary hemochromatosis, there is preferential uptake of iron by hepatocytes. We purified transferrin from two patients with this disease. Their transferrins had normal electrophoretic patterns and contained normal amounts of sialic acid. We conclude that the preferential uptake of iron by hepatocytes in hereditary hemochromatosis is not due to the presence of asialotransferrin in their plasma.

Asialoglycoproteins↗
PubMed1985

Membrane endopeptidases of human neutrophil.

Recent studies using inhibitors or synthetic substrates of serine protease suggest that membrane protease activity may be essential for neutrophil chemotaxis, phagocytosis, degranulation, and superoxide production. However, little is known about the nature and localization of the proteases. In this study, we demonstrated that intact human neutrophils hydrolyzed [125I]glucagon. The degradation of glucagon was temperature dependent and was not dependent on the release of lysosomal enzymes. Two endopeptidases were demonstrated: a metalloendopeptidase which accounted for two thirds of the intact cell activity, and a serine endopeptidase, accounting for the rest of the activity. Both enzymes had a neutral to alkaline pH optimum (pH 7-9). The metalloendopeptidase had a Km of 15.3 microM and Vmax of 5.9 nmol/5 X 10(6) cells/45 min. The corresponding values for the serine endopeptidase were 33.3 microM and 5.0 nmol/5 X 10(6) cells/45 min, respectively. Inhibition of the membrane metalloendopeptidase or serine endopeptidase by 1,10-phenanthroline or diisopropylfluorophosphate, respectively, did not inhibit the production of superoxide by phorbol myristate acetate-stimulated neutrophils.

Cell Membrane↗
PubMed1985

Gallium-67 uptake by hepatoma: studies in cell cultures, perfused livers, and intact rats.

In this investigation, the effect of transferrin on 67Ga uptake by rat hepatoma was studied at three levels: at the level of individual tumor cells in culture; at the level of isolated, perfused livers with implanted intrahepatic tumors; and in intact animals bearing intrahepatic tumors. This approach was possible using H-4-II-E hepatoma cells which grew into discrete tumors when implanted intrahepatically. Transferrin at low concentrations (0.05-0.5 mg/ml) stimulated, while at a higher concentration (1.0 mg/ml) it inhibited 67Ga uptake by tumor cells in culture. In contrast, in isolated, perfused livers with intrahepatic tumors, transferrin at concentration levels of 0.05 and 0.1 mg/ml had no effect, while at 0.25-1.0 mg/ml transferrin inhibited 67Ga uptake by intact tumors. Administration of transferrin which markedly enhanced the serum unsaturated iron binding capacity, had no effect on 67Ga accumulation in the intrahepatic tumors in vivo. These results indicate that, although transferrin at low concentration promotes the uptake of 67Ga by individual tumor cells in culture, it does not do so in intact tumors in isolated rat liver preparations or in tumor bearing rats. We conclude that the mechanism of 67Ga uptake by intact tumors is different from that of tumor cells growing in culture.

Animals↗
PubMed1985

Mechanism of gallium-67 accumulation in inflammatory lesions.

Multiple factors contribute to the accumulation and retention of gallium-67 in inflammatory lesions. Adequate blood supply is essential. Gallium-67, mainly in the form of transferrin-Ga-67 complex, is delivered to the inflammatory lesions through capillaries with increased permeability. At the site of inflammation, some Ga-67 is taken up by leukocytes and bacteria when they are present. In addition, Ga-67 may also bind to lactoferrin and bacterial siderophores. Multiple contributing factors often coexist at any given inflammatory lesion. The nature and intensity of the inflammation affects the relative contribution of these factors. Thus, there may be situations in which all the contributing factors are present, but in such a low intensity that they escape clinical detection by Ga-67 scans. On the other hand, there may be situations in which one or more contributing factors are missing, such as in patients with agranulocytosis, while they are readily detected by Ga-67 scans.

Biological Transport↗
PubMed1984

Kinetics and distribution of platelets in man.

51Cr sodium-chromate, though having been widely used in the last two decades for labeling platelets, suffers from several serious drawbacks, ie, low labeling efficiency, long physical half-life, and low gamma photon yields. 111In-oxine and 111In-tropolone overcome these shortcomings and have the potential of precise determination of platelet kinetics as well as visualization and in vivo quantification of the temporal and spatial distribution of platelets in man. Computer analysis of platelet kinetics reveals that the multiple-hit model fits the survival curve better than the linear or the exponential model. The multiple-hit model provides not only the mean platelet survival time but also information on the initial recovery and the shape of the survival curve. The application of these techniques in normal and disease states should greatly enhance our understanding of the physiology and pathophysiology of platelets.

Blood Platelets↗
PubMed1984

Gallium-67 uptake by the liver: studies using isolated rat hepatocytes and perfused livers.

We studied the hepatic uptake of carrier-free Ga-67 using isolated rat hepatocytes and perfused livers. The results indicate that: (a) the liver can take up Ga-67 and secrete it into the bile, even in the absence of transferrin; (b) transferrin inhibits hepatic uptake of Ga-67 and its biliary excretion; and (c) iron deficiency markedly enhances hepatic uptake of Ga-67.

Animals↗
PubMed1983

Inhibition of neutrophil sulfhydryl groups by choloromethyl ketones. A mechanism for their inhibition of superoxide production.

The inhibition of O2- production by serine protease inhibitors such as chloromethyl ketone derivatives, has been used as evidence to indicate that protease activity is essential for the production of O2- by neutrophils. However, chloromethyl ketones are potent inhibitors of sulfhydryl groups. This study demonstrates that chloromethyl ketones inhibited non-protein sulfhydryl groups as well as O2- production by human neutrophils stimulated with phorbol myristate acetate (PMA). Their inhibition of O2- production could be prevented by reduced glutathione. The results suggest that inhibition of O2- production by chloromethyl ketones is largely due to their inhibition of sulfhydryl groups.

Amino Acid Chloromethyl Ketones↗
PubMed1983

Evaluation of arterial injury due to balloon angioplasty by 111In-labelled platelets.

The sensitivity of 111In-labelled platelets for the detection of intimal trauma following balloon angioplasty was evaluated in 8 arteries in 6 patients. Focal platelet accumulation was detected at all 3 iliacs, one superficial femoral and the anterior tibial artery angioplasty sites. Minimal platelet accumulation was present at the superficial femoral artery angioplasty site in another patient whereas in both renal arteries no focal platelet accumulation was detectable. These results indicate that 111In-labelled platelets may provide a sensitive method for evaluation platelet accumulation at the balloon angioplasty site in the peripheral circulation.

Angioplasty, Balloon↗
PubMed1983

Functional asplenia in patients with chronic graft-versus-host disease: concise communication.

Liver/spleen images were performed with technetium-99m sulfur colloid in 53 patients who had undergone bone-marrow transplantation. The spleen was not seen in the images in five out of the ten patients with chronic graft-versus-host disease (GVHD). None of the five had a history of splenectomy. In two of these patients, anatomical presence of the spleen had been documented earlier by scintigram. The spleen was visible in all seven patients with acute and in all 36 patients without GVHD. Neither the differences in methods of treating the patients before bone-marrow transplantation nor the time lapse between transplantation and the liver/spleen image correlated with the observed effect among these three groups of transplant patients. We conclude that there is a high association between chronic GVHD and functional asplenia.

Adolescent↗
PubMed1983

111In oxine-labeled rabbit platelets: in vivo distribution and sites of destruction.

We have studied the kinetics, biodistribution, and fate of autologous platelets labeled with 111In-oxine in rabbits. The initial recovery was 75% and mean survival time was 2.8 days when the data were analyzed by the multiple-hit gamma function model. Using a modified geometric mean for correction of attenuation, there was good correlation between the values obtained by in vivo quantification and those obtained by postmortem measurements of the radioactivity in the liver and the spleen (i.e., r = 0.854 and 0.899, respectively, n = 32). Using this method, it was shown that after infusion, the 111In-platelets rapidly accumulated in these two organs reaching 35% and 12% of the injected dose in the liver and spleen, respectively, by 1 day. Thereafter, there was little subsequent change. On the sixth day, when essentially all of the 111In-platelets had cleared from the circulation, a total of 82% of the injected dose was deposited in the three major reticuloendothelial organs: liver (40%), spleen (14%), and bone marrow (28%). Our results suggest that in addition to liver and spleen, bone marrow played an important role in sequestering platelets in rabbits.

Animals↗
PubMed1982

Kinetics and distribution of 111Indium-labeled platelets in patients with homocystinuria.

Homocystinuria is an inborn error of metabolism involving a high incidence of thromboembolism. It sometimes improves with large doses of pyridoxine. We investigated the kinetics and distribution of 111Indoxine-labeled platelets in 11 normal volunteers and 12 patients with homocystinuria, none of whom had clinical evidence of acute thrombosis at the time of the study. Six of the patients were resistant to pyridoxine and had homocystinemia. There were no statistical differences in mean platelet-survival times between pyridoxine responders and nonresponders or between normal subjects and pyridoxine responders or nonresponders, regardless of whether a linear, exponential, or multiple-hit model was used to analyze the kinetic data. Plasma homocystine levels had no apparent effect on mean platelet-survival time. There was no abnormal accumulation of platelets in any of the patients, and the distribution of platelets in liver and spleen was similar to that in normal subjects. Our results suggest that the kinetics and distribution of platelets in patients with homocystinuria who have no clinical evidence of thromboembolism are normal. Thus, the data do not provide evidence for disordered platelet function or for an ongoing interaction of platelets with vessel walls in this condition.

Adolescent↗
PubMed1982

Myeloperoxidase-mediated oxidation of methionine.

The myeloperoxidase-mediated oxidation of methionine was studied using a purified canine myeloperoxidase preparation. The system required the simultaneous presence of myeloperoxidase, H2O2, and a halide anion. When 0.1 mM H2O2 was used, the system has a Ph optimum of approximately pH 5-5.5. Bromide and iodide were much more effective than chloride in the myeloperoxidase-mediated oxidation of methionine. Horseradish peroxidase was unable to oxidize methionine whether chloride or iodide was used. In contrast, lactoperoxidase oxidized methionine in the presence of iodide but not chloride. Based on studies of 1) the effect of various inhibitors and singlet oxygen quenchers, as well as 2) the effect of D2O on the oxidation of methionine, by the myeloperoxidase system, OCI-, or methylene blue, it was shown that the oxidation of methionine by the myeloperoxidase system was not mediated by OCI- or 1O2. The mechanism of the myeloperoxidase-mediated oxidation of methionine remains unclear. However, it may be one mechanism by which the myeloperoxidase system damage microorganisms.

Animals↗
PubMed1982

Transferrin receptors and gallium-67 uptake in vitro.

The relationship was studied between the number of transferrin-receptor positive cells and in vitro uptake of 67Ga and 125I-labeled transferrin in human cell lines, including two normal cell lines (WI-38 and foreskin fibroblasts), two transformed cell lines (AV-3 amnionic cells and Chang liver cells), and two neoplastic cell lines (HEp-2, larynx cancer and HeLa, cervical cancer). Transferrin receptors were determined by an indirect immunofluorescence technique based on their ability to bind purified human transferrin. Gallium-67 uptake was determined after a 24-h incubation of cells with Ga-67 in the presence and absence of transferrin (0-2.5 mg/ml). 125I-labeled transferrin uptake was also obtained after a 24-h incubation. The fraction of cells with transferrin receptors was low in normal cell lines (3% and 9%), intermediate with transformed cell lines (33% and 61%). Transferrin stimulated 67Ga uptake by all six cell lines. However, there was poor correlation between the number of transferrin-receptor positive cells and 67Ga uptake either in the presence (r = 0.21) or absence (r = 0.46) of human transferrin. Likewise, there was poor correlation between the number of transferrin-receptor positive cells and 125I-labeled transferrin uptake (r = 0.35). In contrast, the correlation between 67Ga uptake (in the presence of transferrin) and 125I-labeled transferrin uptake was highly significant (r = 0.96). These results suggest that human cell lines in culture are capable of both transferrin-dependent and transferrin-independent uptake of 67Ga.

Amnion↗