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Biomedical subjects

K Kohda

Publications and source records attributed to K Kohda.

At least 91 records · Page 5Linked to original sources
PubMed1993

Is personality involved in the expression of dysmenorrhea in patients with endometriosis?

OBJECTIVE: To investigate whether a relationship exists between personality and expression of pain in women with endometriosis. STUDY DESIGN: With use of the Rosenzweig picture frustration study, the personality of women with endometriosis was assessed. These results were then correlated with the manifestation of pain. RESULTS: Women without dysmenorrhea tended to be less assertive compared with women who complained of dysmenorrhea and women without endometriosis. Those women without dysmenorrhea showed a destructive attitude in face of a problem. CONCLUSIONS: Personality affected the expression of pain. Pain caused by endometriosis was influenced by each personality type.

Adult↗
PubMed1993

Identification of N4-(guanosin-7-yl)-4-aminoquinoline 1-oxide and its possible role in guanine C8 adduction.

A novel base adduct of the carcinogen, 4-nitroquinoline 1-oxide, N4-(guanin-7-yl)-4-amino-quinoline 1-oxide was identified from RNA, which was bioactivated 4-hydroxyaminoquinoline 1-oxide. In addition of base adducts, we uncovered the formation of 8-hydroxyguanine residue (8-OH-G) in DNA and RNA after treatment of 4NQO, in vivo and in vitro. A conceivable mechanism of formation of 8-OH-G and guanine C8-substituted quinoline adducts is proposed.

4-Hydroxyaminoquinoline-1-oxide↗
PubMed1993

[NEO-MACOP-B chemotherapy for the treatment of advanced-stage aggressive non-Hodgkin's lymphoma].

We conducted a new chemotherapy, NEO-MAC OP-B (addition of etoposide and mitoxantrone to MACOP-B with half dose of methotrexate and half administration of doxorubicin), to reduce severe mucositis, which is a major toxic effect of MACOP-B, and to increase its effect with etoposide and mitoxantrone as new non-cross resistant drugs. Between Jan. 1989 and Mar. 1993, 12 patients with previously untreated advanced aggressive non-Hodgkin's lymphoma (NHL), 2 patients with adult T cell lymphoma, and 3 patients with relapsed NHL, were treated with NEO-MACOP-B. After termination of NEO-MACOP-B therapy, 83.3% of 12 patients with previously untreated NHL were in complete remission (CR). After median follow-up of 22 months, Kaplan-Meier estimates showed that overall survival of 12 previously untreated patients was 71.4%, and relapse-free survival of complete responder was 83.3%. Toxic effects on all 17 patients were moderate with a lower incidence of severe mucositis (only one patient with relatively severe stomatitis, WHO Grade 3). No treatment related deaths were observed. Thus, NEO-MACOP-B is an effective and safe treatment for advanced stage aggressive NHL.

Adult↗
PubMed1993

Chemical characteristics of complexes of O6,9-dimethylguanine with cis-platin and debenzylation rates of O6-benzylguanines.

Complexes of O6,9-dimethylguanine with cisplatin were synthesized and their chemical characteristics were studied in relation to the function of the repair enzyme, O6-alkylguanine-DNA alkyltransferase (AGAT). In addition, dealkylation rates of O6-benzylguanine derivatives, that are though to be better substrates for AGAT, were determined by the thiophenol-Et3N system.

Alkylation↗
PubMed1993

Chemical characteristics of N-aminated nucleic acid bases. Nitrosation of aromatic N-amino group and accompanying reductive deamination.

Primary NH2 group attached to the pyridine-type or pyrrole-type nitrogen underwent sequential nitrosation and reductive deamination by the treatment with NaNO2-AcOH. Secondary NHR group attached to the pyridine-type nitrogen underwent also the reductive deamination. In contrast, secondary NHR group attached to the pyrrole-type nitrogen gave the corresponding N-nitroso derivative under the same conditions. Mechanism of the reductive deamination is discussed.

Amines↗
PubMed1993

Bone marrow transplantation for hematological diseases in Hokkaido--June 1985 to December 1991.

Bone marrow transplantation (BMT) was started in Hokkaido in 1985. In the present report we have reviewed the clinical outcome of patients treated with BMT for hematological diseases in Hokkaido. Fifty-eight allogeneic and 19 autologous transplants were registered by December 1991. The underlying diseases consisted of 47 leukemias, 14 lymphomas, 10 aplastic anemias and six myelodysplastic syndromes. Among the allogeneic BMT cases, 55 were human leucocyte antigen (HLA) identical and three were mismatched. Among the autologous BMT patients, two received their marrow purged with 4-hydroperoxycyclophosphamide and five, with monoclonal antibodies and complements. The conditioning regimens used for malignancies were chiefly cyclophosphamide (CY) plus total body irradiation, or busulfan plus CY. In many cases, cytokines were used for rapid recovery of decreased leukocytes. Engraftment was observed in 50 out of 52 evaluated allogeneic and 18 out of 19 autologous transplants. Ten allogeneic patients suffered from severe acute graft-versus-host diseases (GVHD), and extensive chronic GVHD appeared in 16 patients. Relapses were observed in four cases of allogeneic BMT and six of autologous BMT. The major complications were interstitial pneumonitis (IP) and severe infections. Long-term survival rates were almost 60% in both allogeneic and autologous transplants. Mild acute GVHD and limited chronic GVHD increased the survival rates. The results indicated that substantial problems such as GVHD, IP and relapses must be controlled in the near future for an improved outcome to be made possible.

Adolescent↗
PubMed1991

Exaggerated prolactin response to thyrotropin-releasing hormone in infertile women with the luteinized unruptured follicle syndrome.

Ten cases of luteinized unruptured follicle (LUF) syndrome out of 250 women with unexplained infertility were detected on ultrasonography, giving a frequency of 4%. Hormonal analysis revealed lower serum progesterone levels at mid-luteal phase in LUF cases, suggesting a link between LUF syndrome and inadequate luteal phase. Prolactin response to thyrotropin-releasing hormone was exaggerated in LUF cases as compared with ovulatory cases. Aberrant prolactin release may be a contributory factor in the pathophysiology of the LUF syndrome.

Anovulation↗
PubMed1991

Dealkylation rates of O6-alkyldeoxyguanosine, O4-alkylthymidine and related compounds in an alkyl-transfer system.

Bacterial O6-alkylguanine-DNA alkyltransferase (AGT) removes alkyl group from O6-alkylguanine and O4-alkylthymine residues in DNA, both of which are considered to be DNA damages most related to the induction of cancer and/or mutation. The repair process involves alkyl-transfer of an O-alkyl group to the active site of the enzyme, where an SH-group of cysteine residue plays the role of alkyl acceptor. In order to elucidate the chemical characteristics of substrates for this enzyme, dealkylation rates of O6-alkyldeoxyguanosine, O4-alkylthymidine and related compounds were measured using an alkyl-transfer system. Thiophenol-triethylamine system was employed as an alkyl acceptor and twenty-one O-alkyl compounds were tested. Dealkylation proceeded with pseudo first order kinetics. The half-life of O6-methyldeoxyguanosine (MedG) was 122 h and no remarkable dependence on N-9 substituents (H, CH3 and deoxyribose) was observed. A compound lacking 2-NH2 group underwent demethylation about three times faster than O6-methylguanines did, while, a compound lacking imidazole moiety underwent demethylation about 2.5 times more slowly. The half-life of O4-methylthymidine (MedT) was 38 h and no remarkable dependence on N-1 (H, CH3 and deoxyribose) and C-5 (H and CH3) substituents was observed. Deethylation proceeded much more slowly than demethylation. Substitution of selenophenol for thiophenol resulted in a 4.5 times faster MedG demethylation rate. Demethylation rates were moderately correlated with values for NMR chemical shift of CH3 group, an indicator of electron density, although the correlation curves of a series of MedG and MedT derivatives were quite different. This result suggests that some different rate-determining factors other than electron density are playing a role. These findings may be of help in resolving the details of the mechanisms of enzymic repair by bacterial and mammalian AGT.

Alkylation↗
PubMed1991

Diagnostic value of measurement of serum type I procollagen carboxy terminal peptides in patients with scirrhous carcinoma of the stomach.

We have evaluated the radioimmunoassay for type I procollagen carboxy terminal peptide (type I C-peptide), which is liberated from type I procollagen during its conversion to collagen, in the serodiagnosis of scirrhous carcinoma of the stomach. The mean (SD) serum concentration of type I C-peptide in 39 normal subjects was 41.7 (19.7) ng/ml. The mean serum values and the positive ratio of type I C-peptide in 11 patients with stages II and III scirrhous carcinoma of the stomach were 91.2 (41.9) ng/ml and 54.5%, respectively. In 10 patients with other types of gastric carcinoma, the mean type I C-peptide values were not significantly different from the normal value. Serum type I C-peptide values reflected the clinical course of scirrhous gastric carcinoma in five patients who underwent either operation or chemotherapy. The measurement of serum type I C-peptide concentrations could provide a useful way of diagnosing and monitoring scirrhous carcinoma of the stomach.

Adenocarcinoma, Scirrhous↗
PubMed1991

Some cytotoxicological aspects of ethyl and fluoroethyl alkanesulfonates in Escherichia coli: role of fluorine substitution.

Several fluoroethyl derivatives of alkanesulfonates and N-nitrosourea were tested for cytotoxicity and mutagenicity in E. coli K12 AB1157. Cytotoxicity was potentiated by fluorine substitution in the alkyl moiety of the ethylating agents. Mutagenicity was strongly suppressed by fluorine substitution in the alkanesulfonates, but not in the N-nitrosourea. The capacity to induce the SOS repair network was suppressed, as was mutagenicity, in alkanesulfonates, but not in N-nitrosourea. The potentiating effect of fluorine on the cytotoxicity of alkanesulfonates seems to be due to an as yet unknown killing mechanism. An appreciable suppressive effect on the mutagenicity and the SOS induction is worth notice for the biological role of fluorine substitution in alkylating agents.

Alkylating Agents↗
PubMed1991

Detection of 8-hydroxy-2'-deoxyguanosine in deoxyribonucleic acid by the 32P-postlabeling method.

Using synthesized 8-hydroxy-2'-deoxyguanosine 3'-monophosphate as a marker, the 32P-postlabeling method was adapted with minimum modifications for the analysis of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) content in deoxyribonucleic acid (DNA). This method allows the analysis of one 8-OH-dG per 10(4) DNA nucleotides with only 10 pmoles of nucleotides required. The amounts of 8-OH-dG in DNA detected by the postlabeling method correlated well with the electrochemical detection method but were consistently lower.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1991

Formation of O6,7-dimethylguanine residues in calf thymus deoxyribonucleic acid treated with carcinogenic N-methyl-N-nitrosourea in vitro.

Treatment of calf thymus deoxyribonucleic acid (DNA) in vitro with a methylating carcinogen, N-methyl-N-nitrosourea (MNU), in phosphate buffer (pH 7.2) resulted in formation of O6,7-dimethylguanine residues in DNA besides the well-known methylated DNA adducts, 7-methylguanine, O6-methylguanine and 3-methyladenine. The product ratio (%) of O6,7-dimethylguanine versus 7-methylguanine was 0.32 after one MNU treatment. The significance of formation of O6,7-dimethylguanine residues in DNA is discussed briefly in relation to the carcinogenicity of MNU.

Animals↗
PubMed1991

Lignified materials as a potential medicinal resource. IV. Dehydrogenation polymers of some phenylpropenoids and their capacity to stimulate polymorphonuclear cell iodination.

Based on our recent finding regarding diverse biological activities of natural lignified materials, synthetic dehydrogenation homo- and copolymers were prepared using 3 p-hydroxylated cinnamic acids and coniferyl alcohol in order to explore the role of lignin skeleton in the activities displayed by natural lignins. The synthetic polymers stimulated polymorphonuclear cell iodination as potently as the natural lignified materials.

Electron Spin Resonance Spectroscopy↗
PubMed1990

Induction of covalent DNA modifications and micronucleated erythrocytes by 4-nitroquinoline 1-oxide in adult and fetal mice.

Pregnancy and development are known to modify carcinogenesis. Little is known about the mechanism for the modulation. These studies investigated the relative sensitivity of nonpregnant, pregnant, and fetal mice to the induction of covalent DNA modifications and micronucleated erythrocytes by 4-nitroquinoline 1-oxide (4-NQO). Our results revealed that 4-NQO was bound to guanine nucleotides of DNA in all maternal and fetal organs tested. The adduct levels ranged from 2-60 base modifications per 10(9) DNA bases when 4-NQO was administered s.c. Overall, 4-NQO bound preferentially to DNA of the maternal tissues compared with that of the corresponding fetal tissues, with the exception of the liver. The adduct levels in maternal and fetal organs fell into 3 distinct levels. The greatest binding was in maternal lungs and pancreas (the target organs for carcinogenesis). The lowest binding levels were in maternal liver and all fetal organs studied. Gestation age at the time of 4-NQO treatment did not produce a significant effect on the amounts of adduct formation in the tissues examined, with the exception of placenta and bone marrow. Chronic treatment did not affect binding preference. At the cellular level, 4-NQO treatment induced twice the frequency of micronucleated erythrocytes in the bone marrow of pregnant mice compared with the nonpregnant mice and fetal liver, on a mg/kg basis. However, the polychromatic erythrocytes of fetal liver were more sensitive than those of adult bone marrow to the induction of micronuclei, when adduct levels were taken into account. A positive correlation of organotropsim between 4-NQO-induced DNA adducts and carcinogenicity was observed for maternal tissues, but not for fetal tissues. Fetal tissues, overall, lack the enzymes to metabolically activate 4-NQO. Fetal cells elicit greater biological responses, compared with adult cells, at equal adduct levels. This study reveals that the effective doses in maternal and fetal tissues may differ and, therefore, will be a better basis for further understanding the molecular mechanism of transplacental carcinogenesis.

4-Nitroquinoline-1-oxide↗