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Biomedical subjects

N Kamada

Publications and source records attributed to N Kamada.

At least 271 records · Page 15Linked to original sources
PubMed1991

[Inhibitory effects of interferon and inhibitors of polyamine biosynthesis on clonal growth of Raji cells derived from Burkitt's lymphoma].

Interferon (IFN)-alpha, -gamma, and two inhibitors of polyamine biosynthesis (alpha-difluoromethyl ornithine; DFMO and methyl glyoxal bis-guanyl hydrazone; MGBG) inhibited the clonal growth of Raji cells. The combination-treatment using two agents, particularly IFN-alpha and DFMO represented synergistic effects. In order to investigate the mechanism of the synergism between IFNs and inhibitors of polyamine biosynthesis, the concentrations of polyamines and the levels of 2'-5' oligo-adenylate synthetase (2-5 AS) activity in the treated Raji cells were determined. Not only the inhibitors of polyamine biosynthesis, but also IFNs decreased the content of spermidine in the cells. Furthermore, the clonogenic growth-inhibition by IFN-alpha was recovered partially by exogenous spermidine. On the other hand, 2-5AS activity in the cells was elevated to 57 times by the treatment with interferon-alpha and further more, the combinations of IFN and the inhibitors of polyamine biosynthesis induced higher activities of 2-5AS as compared with those by each agent. From these results, it was suggested that the synergistic effects of IFNs in combinations with inhibitors of polyamine biosynthesis on the inhibition of clonal growth of Raji cells were closely associated with the decrease of intracellular polyamine level and the increase of 2-5AS activity in the treated cells.

2',5'-Oligoadenylate Synthetase↗
PubMed1991

[Parallel loss of c-FMS and GM-CSF genes in myeloid leukemias with 5q-chromosome].

DNA contents of c-FMS and GM-CSF genes were analyzed by densitometer in nine patients with myelodysplastic syndrome or acute myeloid leukemia associated with abnormality of chromosome 5. Five patients with deletion in the long arm of chromosome 5 had loss of both c-FMS and GM-CSF genes. These findings suggest that c-FMS oncogene and GM-CSF gene locating in the critical region on chromosome 5 seem to have an important role in the process of leukemogenesis.

Aged↗
PubMed1991

[Molecular construction of Philadelphia chromosome and its relation to the clinical features].

In 1960, Nowell and Hungerford found, for the first time, a minute chromosome at the metaphase in chronic myelocytic leukemia (CML) cells, which was called Philadelphia chromosome (Ph1 chromosome) later. Ph1 chromosome was considered to be specific for the disease and was frequently used as an important marker for the definite diagnosis. However, in mid-1970s, some cases with acute lymphocytic leukemia (ALL) were also found to have Ph1 chromosome in the leukemic cells. Therefore, Ph1 chromosome seemed to be non-specific for the diagnosis of CML. In 1980s, molecular-biology techniques were applied in the fields of leukemia research. As a result, clear differences were demonstrated between the two diseases (CML and ALL with Ph1 chromosome, respectively) at the molecular level using oncogene concept. In this review, molecular-genetic constructions of ABL, BCR and BCR-ABL hybrid genes in CML, as well as m-BCR-ABL hybrid gene in Ph1 positive ALL are focused in detail. Relationship between these molecular-genetic changes with the clinical features and the mechanism of cell growth in these cells with BCR-ABL or m-BCR-ABL hybrid genes are also discussed.

Chromosome Fragility↗
PubMed1990

Acute T-lymphocytic leukemia with Ph1 and 5q-chromosome abnormalities and rearrangements of bcr and TCR-delta genes.

Almost all cases of Ph1-positive acute lymphocytic leukemia (ALL) have an immature B-cell phenotype and are CD10-positive. A very rare case of Ph1-positive ALL with T-cell features (T-ALL) is presented. Cytogenetic analyses revealed a clone with a Ph1 chromosome and 5q- at diagnosis, and mosaic clones with an additional complex abnormal karyotype at relapse. DNA analysis revealed rearrangement of the breakpoint cluster region (bcr) gene with deletion of the 5' side and of the T-cell receptor (TCR) delta gene, without any rearrangement of other immune-associated genes. From the results of immunophenotypic and genetic analyses, the origin of leukemic cells seemed to be an immature T-cell at a very early stage on T-cell ontogeny.

Chromosome Deletion↗
PubMed1990

Evidence that soluble class I antigen in donor serum induces the suppression of heart allograft rejection in rats.

The effect on heart allograft rejection in the rat of continuous slow infusion of donor MHC type serum is described. DA (RT1a) serum delayed significantly the rejection of PVG.RT1a heart grafts in PVG recipients (p less than 0.01), but did not affect survival of third-party WAG grafts. Grafts at both early and late stages of rejection were prolonged by serum infusion. Removal of soluble class I MHC antigen from DA serum by affinity chromatography on a monoclonal anti-class I antibody column completely abolished the immunosuppressive effect. The results may indicate that soluble class I antigen can act as a specific immunosuppressive agent in allograft rejection.

Animals↗
PubMed1990

Isolation and characterization of VP-16 resistant human leukemia cell line.

VP-16 resistant cells, designated VP-16K6-1 (K6-1) were isolated from human acute lymphoblastic leukemia cell line RPMI 8402. IC50 value against VP-16 were 11-fold higher than their sensitive parental cell line. The membrane permeability of the drug was not responsible for resistance in K6-1 cells. K6-1 cells showed resistance in drug-induced DNA strand breaks (single strand breaks) determined by the alkaline sucrose gradient sedimentation method. Dot-blot analysis of RNA extracted from 2 cell lines showed that the mRNA levels of DNA topoisomerase II in K6-1 cells decreased slightly compared with that of parent cells. However, Topo II activities were similar in wild-type and K6-1 cells. In addition, K6-1 cells exhibited cross-resistance only to VM-26. These data suggest that a reduced intracellular Topo II level may contribute to drug resistance as an important factor in K6-1 cells.

DNA Replication↗
PubMed1990

Reduced DNA topoisomerase II in VP-16 resistant mouse breast cancer cell line.

VP-16 resistant cells, FvprB350 (50B-3), were isolated from mouse breast cancer cell line FM3A. 50B-3 cells showed 84-fold higher resistance than their parent cells. Reduced drug uptake was not found in resistant cells. Quantitative analysis of drug-stimulated DNA cleavage activity using 3'32P end-labeled pBR322 restriction fragments showed that VP-16 stimulated DNA-topoisomerase II cleavable complex forming activity in crude nuclear extract from 50B-3 cells was approximately one-fifth as compared with that of FM3A wild-type cells. Dot-blot analysis of RNA extracted from the two cell lines showed that mRNA levels of topoisomerase II in 50B-3 cells drastically decreased and catalytic activity was also 1/2-1/3 as compared with that of parent cells. 50B-3 cells showed cross resistance to VM-26, m-AMSA, adriamycin. These findings suggest that reduced topoisomerase II activity (cellular levels) and cleavable complex forming activity may be significant factors in the marked drug resistance.

Animals↗
PubMed1990

Rat liver arginase suppresses mixed lymphocyte reaction.

An inhibitory factor to mixed lymphocyte reaction (MLR) was purified from the supernatant of rat liver homogenate by procedures including chloroform treatment, ammonium sulfate precipitation, ion-exchange column chromatography, and gel filtration. The molecular weight of the purified inhibitor was 34,000 on SDS-PAGE. We determined the amino acid sequence of the N-terminal region of the purified inhibitor to be Glu-Glu-Pro-Trp-Met-Ser-Met-Ser-Ser-Lys-Pro-Lys-Pro-Ile-Glu-. This sequence shows a high homology to a rat arginase, the amino acid sequence of which was predicted from the nucleic acid sequence of cloned rat arginase cDNA. The amino acid sequence of the purified arginase is 6 amino acid residues longer than the predicted one. The purified MLR inhibitor showed a high arginase activity. The inhibition mechanism was studied and it was discovered that L-arginine was depleted in the culture medium, and that the supply of L-arginine to the cell culture caused recovery of the incorporation of tritium thymidine. Here we present evidence that the MLR inhibitor from rat liver homogenate is the liver arginase. It is noteworthy that immune response may be controlled by a liver factor.

Amino Acid Sequence↗
PubMed1990

DNA synthesis in hepatocytes during liver allograft rejection in rats.

We have investigated DNA synthesis in hepatocytes after orthotopic liver transplantation in four rat combinations--DA into DA (isogeneic), DA into PVG (allogeneic, nonrejector), DA into BN (allogeneic, rejector), and DA into (BN X PVG)F1 (allogeneic, intermediate nonrejector). The methods used were assay of thymidine kinase activity in graft homogenate and staining of hepatocytes in liver sections by an antibromodeoxyuridine monoclonal antibody. Both demonstrated increased DNA synthesis in grafts in all combinations except isogeneic, and showed that its intensity and timing paralleled the occurrence of the rejection reaction. The significance of hepatocyte regeneration after liver grafting is discussed.

Animals↗