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Biomedical subjects

O Kucuk

Publications and source records attributed to O Kucuk.

69 records · Page 4Linked to original sources
PubMed1986

Hypogammaglobulinemia and hemophagocytic syndrome associated with lymphoproliferative disorders.

Four patients with lymphohistiocytic disorders had or subsequently experienced severe hypogammaglobulinemia and pancytopenia due to hemophagocytosis. The percentages of B- and T-lymphocytes and the ratios of helper (OKT4) cells to suppressor (OKT8) cells in the peripheral blood were variably altered. Mitogenic response to pokeweed mitogen and phytohemagglutinin was depressed but could be restored to near normal by the in vitro addition of indomethacin or interleukin-2. The half-life of intravenously administered immunoglobulin was markedly shortened. The data indicate that hyperactive monocytes/histiocytes are capable of simultaneously ingesting apparently normal blood cells and immunoglobulin, leading to pancytopenia and hypogammaglobulinemia. The monocytes with suppressor activity (which could be abrogated with indomethacin or interleukin-2) appeared to additionally contribute to the hypogammaglobulinemia, possibly by interfering with the terminal differentiation of the B-lymphocytes. Hemophagocytosis occurs frequently in histiocytic and occasionally in lymphoproliferative disorders or viral diseases. More frequent and serial determination of serum immunoglobulin levels in such situations may lead to the discovery of additional cases.

Adult↗
PubMed1986

Increased fibrinolytic activity in patients undergoing cardiopulmonary bypass operation.

The influence of cardiopulmonary bypass on fibrinolytic activity was assessed by a sensitive clot lysis assay in eight patients undergoing coronary artery bypass operations. Fibrinolytic activity increased immediately after cardiopulmonary bypass was begun and remained elevated throughout the period of extracorporeal circulation. At the conclusion of the operative procedure, fibrinolytic activity returned to the normal range in all patients, and no subject had postoperative bleeding.

Blood Cell Count↗
PubMed1986

The influence of oxygenated sterol compounds on dipalmitoylphosphatidylcholine bilayer structure and packing.

Fourier Transform Infra-red and Raman Spectroscopies indicate that 7 alpha-hydroxycholesterol and 7-ketocholesterol have a diminished capacity to condense (increase the packing order of) fluid-state dipalmitoylphosphatidylcholine (DPPC) acyl chains when compared with the effects of cholesterol and the other oxidized sterols studied. DPPC head groups were also more ordered by 7-ketocholesterol over the temperature range 10 degrees - 70 degrees C. Primary effects of these sterols appear to be associated with the hydrophillic regions of the DPPC bilayer, although packing arrangements with acyl chains are also involved. Phosphate and acyl chain ester groups were observed to possess a packing order which was invariant which indicates that these may be the target groups in the interaction with 7-ketocholesterol. A surprising observation was the synergistic amplification of the effects of 7-ketocholesterol by the presence of cholesterol in the DPPC bilayer.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1985

Oxygenated cholesterols synergistically immobilize acyl chains and enhance protein helical structure in human erythrocyte membranes.

Fourier transform infrared spectroscopy revealed that insertion of 20 alpha-hydroxycholesterol into human erythrocyte membranes (10% of total membrane sterol) immobilized the lipid acyl chains to a degree equivalent to enriching total membrane cholesterol by 50% (Rooney, M.W., Lange, Y. and Kauffman, J.W. (1984) J. Biol. Chem. 259, 8281-8285). Raman spectroscopy showed that the amount of acyl chain rotamers was not significantly altered by the presence of 20 alpha-hydroxycholesterol, indicating that acyl chain immobilization was limited to an inhibition of lateral motion. The presence of 20 alpha-hydroxycholesterol may synergistically enhance the acyl-chain-immobilizing behavior of membrane cholesterol. In addition, protein helical structure was not altered by 20 alpha-hydroxycholesterol. The insertion of 7 alpha-hydroxycholesterol into erythrocyte membranes resulted in an increase in protein helical structure which was comparable to that observed for erythrocyte membranes enriched with pure cholesterol by 50%. However, both acyl chain mobility and conformation were unchanged. These results suggest a synergistic behavior between oxysterols and cholesterol in modifying erythrocyte membrane packing.

Cholesterol↗
PubMed1985

Thromboembolic complications associated with L-asparaginase therapy. Etiologic role of low antithrombin III and plasminogen levels and therapeutic correction by fresh frozen plasma.

A case of an 18-year-old woman with acute lymphoblastic leukemia who developed L-asparaginase-associated stroke and subclavian vein thrombosis is presented. The latter was also associated with a Hickman central venous catheter. Thrombotic complications occurred when plasma levels of plasminogen and antithrombin III were still markedly reduced as a result of L-asparaginase therapy, although the fibrinogen had recovered from its lower levels. The stroke was treated with fresh frozen plasma and the subclavian vein thrombosis was treated with streptokinase and fresh frozen plasma. L-asparaginase and Hickman-associated coagulopathy is reviewed and the treatment is discussed.

Adolescent↗
PubMed1984

Separation of clonogenic tumor cells from small cell lung cancer bone marrow and small cell lung cancer cell lines.

One of the major obstacles to successful autologous bone marrow transplantation is tumor contamination of the marrow. We attempted to separate tumor cells from the marrow of patients with small cell lung cancer by layering bone marrow on a discontinuous albumin gradient and then assessing hematopoietic potential (CFUc) and clonogenic tumor cells (TCFUc) by standard techniques. In the six of seven patients whose bone marrow grew tumor colonies, 75 to 80% of CFUc could be found in Fraction 3 of the gradient; while 80 to 90% of TCFUc could be found in light-density Fraction 1 + 2. Furthermore, we observed tumor colony growth in Fraction 1 + 2 in some patients whose unfractionated bone marrow failed to grow tumor colonies. In separate experiments, we layered five cell lines established in patients with small cell lung cancer on the gradient and found that cells from four of the five lines also migrated to Fraction 1 + 2, and TCFUc from these lines were observed in Fractions 1 + 2 in three of four lines tested. We conclude that gradient fractionation may be one way of removing clonogenic tumor cells from the bone marrow of small cell lung cancer patients prior to autologous transplantation.

Bone Marrow↗
PubMed1984

Estimation of hemopoietic potential by CFU-c and bone marrow scan in cancer patients.

The concentration of granulocyte-macrophage colonies in culture (CFU-c) in bone marrow cells was estimated, and bone marrow radionuclide scans were performed in a group of 15 cancer patients prior to bone marrow harvest for autologous transplantation. Preharvest CFU-c counts on iliac-crest bone marrow aspirates correlated very well with CFU-c counts from fresh and frozen-thawed bone marrows. Technetium-99m-sulfur colloid radionuclide scans showed that the distribution of total-body bone marrow and increased peripheral radionuclide uptake correlated with higher preharvest and harvest CFU-c counts. Bone marrow scan results were available in 1 h, whereas CFU-c counts took 14 days to obtain. Bone marrow scans may facilitate the clinical estimation of hemopoietic activity in patients under consideration for autologous bone marrow transplantation.

Bone Marrow↗
PubMed1983

H-2-linked resistance to mastocytoma in male mice: immune response to a histocompatibility antigen on the X chromosome.

Male hybrids from a cross between female mice of strain C57BL/6Kh and males of strain DBA/2J lived longer after injection of P815 mastocytoma cells of DBA/2 origin than did their female siblings. Responses to the histocompatibility antigen on the X chromosome of the DBA/2 strain may be involved in resistance to the tumor. When the female parent was replaced with a C57BL/6Kh carrying one of several mutations in the H-2 region, this sex effect disappeared in some of the hybrid combinations. Thus, the H-2 complex appears to be involved in the regulation of the immune response to the X-linked histocompatibility antigen in this tumor model.

Animals↗
PubMed1983

Estrogen receptor analysis in chronic lymphocytic leukemia.

Estrogen receptor (ER) determinations were performed on cytosol preparations of Ficoll-Hypaque density separated mononuclear cells from 11 patients with chronic lymphocytic leukemia (CLL). The presence of ER was noted in 8 of 11 specimens (73%). ER ranged from 431 fmole/mg to 4.3 fmole/mg cytosol protein. Two types of receptor subunits were observed at the 8S and 4S region of the sucrose gradient. In addition, 1 of 3 Epstein-Barr virus (EBV) transformed B-lymphoblastoid cell lines from healthy donors had a measurable amount of ER. Patient R.L., who was refractory to standard chemotherapy and radiation and was ER positive, experienced a minor response to Tamoxifen therapy, with subsequent loss of ER. The demonstration of ER in CLL suggests that this malignancy may have a hormone-dependent subpopulation of cells.

Aged↗
PubMed1983

H-2 gene control of resistance to P815-X2 mastocytoma.

Some, but not all, mutations at H-2 loci can alter, in either direction, histocompatible tumor resistance in the model system of P815-X2 mastocytoma (DBA/2 origin) transplanted into DBA/2J or (C57BL/6 X DBA/2J)F1 mice. This hybrid effect has been shown previously to depend on the immune system. We have examined eight mutants at H-2Kb (bm1, bm4, bm6, bm7, bm8, bm10, bm11, and bm16, two at H-2Db (bm13 and bm14), and one I-Ab mutant (bm12). When one parent is an H-2b mutant (C57BL/6 mutant), the hybrid progeny (C57BL/6 mutant X DBA/2J)F1 may have increased (bm7 and bm8) or decreased (bm10, bm11, bm12, and bm16) survival times when compared to C57BL/6 X DBA/2J)F1 controls. Hybrids from bm1, bm4, bm6 (all H-2Kb), and bm13 and bm14 (both H-2Db) mutants showed no differences in survival. Several of the mutant molecules differ from those of the parental strain by only one or two amino acids. Apparently, these small changes in H-2 antigens are capable of altering resistance to a histocompatible tumor to produce an immune response gene-like effect. The availability of H-2 mutant strains and detailed data on the molecular nature of the gene products make the model presented in this report a particularly useful system to study.

Alleles↗
PubMedDate not supplied

In vitro studies of natural killer cell activity in post traumatic stress disorder patients. Response to methionine-enkephalin challenge.

Attempts to define biological parameters that may be specifically associated with the pathophysiology of post traumatic stress disorder (PTSD) have met with only limited success, reflecting perhaps the practical limitations resulting from the high frequency of comorbidity of this condition with Axis I, II and III psychiatric diagnoses. We now report our studies on natural killer cell activity (NKCA), and the response of this cellular immune function to an in vitro methionine-enkephalin (MET) challenge in a population of Vietnam veterans with PTSD. Due to the characteristics of our PTSD patients, our protocol included four sex-matched, age-comparable control groups: (1) chronic alcoholics, (2) chronic drug abusers excluding alcohol, (3) chronic users of alcohol and other drugs of abuse and (4) drug-free, healthy volunteers. Although these groups did not significantly differ in their "baseline" NKCA, significant findings emerged from their response to preincubation with MET (10(-10), 10(-8) and 10(-6) M; 40:1 effector-to-target cell ratio). To minimize interindividual variations in the expression of NKCA each subject was used as its own control. Whereas peptide challenge resulted in an increase in NK lytic function in a subpopulation of group four (one or more MET concentrations, 8 out of 22 subjects), it produced mixed results in samples from individuals in group 2, and in general failed to elicit NKCA changes in the samples from participants in groups 1 and 3. Nine of the thirteen PTSD patients responded to MET preincubation with decreases in NKCA, which in five of them reached values below 20% of baseline for the three peptide concentrations tested. These findings may suggest that the "stress factor" in Vietnam veterans with PTSD plays a role in downmodulating NK lytic function in response to an in vitro MET challenge, an effect that appears to be potentiated by the use of drugs of abuse other than alcohol. The possible clinical relevance of these findings, including the identification of a subgroup of PTSD patients on the basis of immunological tests such as the one described in this work, deserves further investigation.

Adult↗