Search PubMed⌕ Search

Biomedical subjects

D Kessel

Publications and source records attributed to D Kessel.

At least 217 records · Page 12Linked to original sources
PubMed1980

Transport and binding of mesoporphyrin IX by leukemia L1210 cells.

The combination of mesoporphyrin IX and light is cytotoxic to leukemia L1210 cells, resulting in membrane damage and loss of viability. In this study, mesoporphyrin transport and the cellular environment of accumulated drug were examined. The latter was characterized by measurements of absorbance and fluorescence spectra and of effects of irradiation on subsequent capacity of cells for transport of the nonmetabolized amino acid cycloleucine. We observed a rapid accumulation of drug at a relatively hydrophilic cellular environment (dielectric constant, 20) from which light-catalyzed inhibition of cycloleucine transport was clearly demonstrable. Washing at 37 degrees rapidly depleted this cellular region of drug. Longer incubations resulted in accumulation of porphyrin at more hydrophobic locci (dielectric constant, approximately 10) from which the drug was not readily washed and from which the efficiency of light-catalyzed damage to membrane transport was relatively low. These findings are consistent with the hydrophobic nature of mesoporphyrin (octanol:water partition ratio, 10).

Animals↗
PubMed1980

Cell surface alterations associated with exposure of leukemia L1210 cells to fluorouracil.

Exposure of murine leukemia L1210 cells to graded doses of 5-fluorouracil for 24 hr led to a progressive increase in cell surface hydrophobicity, inhibition of cell division, an an increased cell volume. Among the effects associated with fluorouracil treatment were inhibition of thymidylate synthetase, decreased incorporation of leucine into glycoprotein, and an apparently increased incorporation of thymidine into DNA and of glucosamine into glycoprotein. The latter effects are believed to be caused by depleted metabolite pools. Short-term treatment of L1210 cells with the drug altered only levels of thymidylate synthetase. Cell surface changes therefore appear to be related to long-term effects of fluorouracil associated with impaired synthesis of membrane glycoprotein.

Animals↗
PubMed1979

Delineation of fucosyltransferase activities with thiol reagents.

The thiol reagent dithiothreitol inhibits the activity of a core GDP-fucose-N-acetylglucosaminide alpha-6-fucosyltransferase in plasma and blood-cell homogenates, while promoting the activity of alpha-2- and alpha-3-fucosyltransferases. The latter enzymes catalyse transfer of fucose on to terminal galactose and subterminal N-acetylglucosamine residues respectively. A thiol-blocking reagent N-ethylmaleimide does not affect the activity of the alpha-6-fucosyltransferase, but inhibits the other two enzymes. These results indicate the presence of a critical disulphide linkage in the alpha-6-fucosyltransferase, and provide a means of delineation of different fucosyltransferases.

Chemical Phenomena↗
PubMed1979

Electrofocusing patterns of fucosyltransferases in plasma of patients with neoplastic disease.

Electrofocusing patterns of plasma fucosyltransferases provide information concerning marrow status of patients with myeloproliferative disorders. Three enzymes were detected in normal plasmas using an acceptor terminating in the sequence N-acetylglucosamine-galactose. The enzyme which focused at pH 4.7 was elevated during rapid proliferation of myeloid cells, e.g., acute myelogenous leukemias and certain infectious diseases. Activity at pI = 5.1 was decreased in acute myelogenous leukemia patients, and from other observations, appears related to the level of erythropoietic activity. Acceptor studies show this enzyme to be specified by the H gene. A third enzyme focused at pH 5.5 and appeared to be correlated with a later step in granulocytes maturation. Two other plasma fucosyltransferases (pl = 5.6 and 8.3) were detected with a high-molecular-weight acceptor terminating in N-acetylglucosamine. This activity was markedly elevated during regeneration of a normal marrow population during drug-induced remission of acute myelogenous leukemia. Additional isoenzymes were detected, using this acceptor, in plasma of patients with certain solid tumors and multiple myeloma. However, the new isoelectric points observed (pH 6.0, 6.9, and 7.8) suggest these enzymes are probably not derived from hematopoietic tissues.

Acetylglucosamine↗
PubMed1978

Transport of a nonphosphorylated nucleoside, 5'-deoxyadenosine, by murine leukemia L1210 cells.

The mode of transport of a nonphosphorylated adenosine analog, 5'-deoxyadenosine, was studied in murine leukemia L1210 cells. This compound is not subject to the action of intracellular nucleoside-trapping kinases, and its transport can be examined without regard for effects of experimental conditions on kinase activity. Accumulation of 5'-deoxyadenosine was rapid, and nonconcentrative, with equilibrium attained within 12 s at 37 degrees. Kinetic studies were carried out at 20 degrees. We found both a nonmediated (diffusion) and a mediated transport process. The latter had an apparent Km fo 115 micrometer, Vmax = 105 pmol/10(6) cells/min. Uptake of 5'-deoxyadenosine was inhibited by several heterologous nucleosides including adenosine, 2'-deoxyadenosine, thymine riboside, and inosine. Like 2'-deoxyadenosine, 5'-deoxyadenosine was more lipid-soluble than adenosine (from octanol/water partition studies). Compared with 5'-deoxyadenosine, adenosine had a much lower apparent Km (5 micrometer) and a higher Q10 over the 27-37 degrees range (3.0 versus 1.3). Data obtained with adenosine might, however, reflect properties of intracellular adenosine kinase interacting with a transport process.

Animals↗
PubMed1978

Some properties of sialyltransferase in plasma and lymphocytes of patients with chronic lymphocytic leukemia.

Some properties of sialyltransferase activity in plasma and lymphocytes from patients with chronic lymphocytic leukemia were compared. Three distinct enzyme fractions were identified in plasma: (1) cation independent, irreversibly bound to agarose; (2) cation dependent, weakly bound to agarose; (3) strongly bound to agarose, lost upon dialysis. Lowering of the peripheral lymphocyte count by leukapheresis markedly decreased the level of serum sialyltransferase, suggesting the circulating lymphocyte is a source of the serum enzyme. The enzyme solubilized by detergent from lymphocytes showed a substantially lower Km for CMP-sialic acid than did the serum enzyme, was less sensitive to several inhibitors, was not irreversible bound to Agarose, and had a substantial cation requirement. The enzyme solubilized from the lymphocyte therefore generally resembles fraction 2 of serum.

Cations, Divalent↗
PubMed1978

Evaluation of two plasma fucosyltransferases as marker enzymes in non-Hodgkin's lymphoma.

Levels of two fusosyltransferases were measured in plasmas of patients with non-Hodgkin's lymphoma at different phases of the disease. The level of a GDP-fucose: galactoside fucosyltransferase (EC 2.4.1.69) was found elevated in nonresponding patients and was correlated with estimated tumor burden. Enzyme levels in the normal range were found in patients in remission, maintained on chemotherapy, or unmaintained. The plasma level of a GDP-fucose; N-acetylglucosaminide fucosyltransferase (EC 2.4.1.68) was elevated in all individuals receiving drug therapy regardless of diesease status, but returned to normal levels during unmaintained remissions.

Acetylglucosamine↗
PubMed1978

Guanosine diphosphate-L-fucose plasma: N-acetylglucosaminide fucosyltransferase as in index of bone marrow hyperplasia after chemotherapy.

We have measured the plasma level of a fucosyltransferase in patients with acute myelogenous leukemia and non-Hodgkin's lymphoma at various stages of the disease and in normal controls. This enzyme transfers the sugar fucose from a guanosine diphosphate-L-fucose donor to high-molecular-weight acceptors with a terminal N-acetyl-glucosamine residue. The enzyme levels of fucosyltransferase in individuals free from disease and in patients with untreated leukemia or lymphoma were comparable. A substantial increase in plasma enzyme level was measured during drug-induced remissions, three weeks after drug therapy. The enzyme level fell to the normal range during unmaintained remissions inpatients with lymphomas; comparable information for the leukemia is not available since all remissions were drug maintained. These data, together with microscopic examination of marrow samples, indicate that the level of this fucosyltransferase is correlated with regeneration of a normal marrow population after chemotherapy. The enzyme assay may prove useful in defining normal bone marrow recovery and in timing cyclic combination chemotherapy in patients with neoplastic disease.

Antineoplastic Agents↗