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Biomedical subjects

K Kohno

Publications and source records attributed to K Kohno.

At least 361 records · Page 20Linked to original sources
PubMed1991

Foramen magnum decompression for syringomyelia associated with basilar impression and Chiari I malformation--report of three cases.

Anterior or posterior decompression of the foramen magnum was performed in three patients with syringomyelia associated with basilar impression and Chiari I malformation. The operative results were evaluated using the pre- and postoperative magnetic resonance (MR) images. Two patients with combined anterior and posterior cervicomedullary compression due to basilar impression and tonsillar descent received suboccipital craniectomy, upper cervical laminectomy, and dural plasty without any intradural manipulations via the posterior approach. One patient with prominent anterior cervicomedullary compression due to basilar impression and a sharp clivoaxial angle was operated on by the transoral anterior approach. Postoperatively, all patients showed a sustained shrinkage of the syrinx and rounding of the flattened cerebellar tonsils. Two patients showed upward movement of the herniated tonsils. All patients had improved symptoms during 2-4 years follow-up. Treatment of syringomyelia associated with basilar impression and Chiari I malformation requires more efficient decompressive procedures at the foramen magnum based on neurological and MR findings.

Adult↗
PubMed1991

[Mechanisms of resistance to DNA topoisomerase II inhibitors].

Cytotoxicity of anticancer drugs are depended on cellular differences of drug transport processes, drug metabolism or proliferation process including DNA synthesis. Thus, resistance to anticancer drugs is likely due to many cellular changes. Mechanisms of resistance to anticancer drugs have been studied with cells selected for their ability to grow in the presence of drugs. In this paper, the mechanisms of cellular resistance to DNA topoisomerase II inhibitors was described.

Animals↗
PubMed1991

Induced natural killer-like cytotoxic function in the TCR delta-1 positive human leukemic T-cell lines.

Four human leukemic T-cell lines with a T-cell receptor (TCR) gamma/delta heterodimer (MOLT-13, MOLT-14, and PEER) or beta/delta-heterodimer (DND-41), as determined by monoclonal antibody (mAb), TCR delta-1, were identified by phenotypic and genotypic analysis. Two similar human leukemic T-cell lines with a TCR alpha/beta heterodimer (CCRF-CEM and MOLT-16) were used in this study. Natural killer (NK)-like activity was investigated in the TCR gamma/delta+ cell lines and TCR alpha/beta+ cell lines induced by exogenous recombinant human IL-2 (rIL-2), or phorbol 12-myristate 13-acetate (PMA). Three (MOLT-13, MOLT-14, and DND-41 cells) of the four TCR delta-1 positive cell lines, after 48 h treatment with exogenous rIL-2 or PMA (except DND-41), showed NK-like activity to K562, but not to Daudi cells. Furthermore, when MOLT-13, MOLT-14, and DND-41 cells were co-cultured with rIL-2 or PMA, 5-20% of these cells expressed the beta-subunit of IL-2R. Treatment with rIL-2 or PMA induced the expression of the beta-subunit of IL-2R, which in turn induced IL-2R. Subsequently these cells could transmit the signal for the induction of NK-like cytotoxicity. These findings indicate that changes in the beta-subunit of IL-2R expression may be responsible for the target cell specificity of activated effector cells.

CD4 Antigens↗
PubMed1991

Hepatocellular carcinoma presenting with pyrexia and leukocytosis: report of five cases.

In the past 26 years we have encountered five patients with primary liver malignancy clinically characterized by high remittent fever and leukocytosis mimicking liver abscess. Two patients underwent exploratory laparotomy, and drainage was carried out in another. The clinical courses went rapidly downhill. The liver was cirrhotic in two patients. The interior of the main mass was almost totally necrotic in four cases. Histologically, the malignant cells in the main portion resembled sarcoma, but in some areas cells appeared epithelial with eosinophilic cytoplasm and were in a trabecular arrangement, except for one case not subjected to autopsy in which histological study was inadequate because of extensive necrosis. It seems that these neoplasms were very poorly differentiated hepatocellular carcinomas rather than combinations of sarcoma and hepatocellular carcinoma. These patients, therefore, may represent a distinct clinicopathological type of hepatocellular carcinoma that is very rare in Japan but perhaps more common in South Africa, where similar cases have been clinically described in larger numbers.

Adult↗
PubMed1991

Potentiation of etoposide and vincristine by two synthetic 1,4-dihydropyridine derivatives in multidrug-resistant and atypical multidrug-resistant human cancer cells.

Newly synthesized 1,4-dihydropyridine derivatives had been screened to determine whether they could overcome vincristine (VCR)-resistance in VCR-resistant (P388/VCR) leukemia-bearing mice, and six compounds had strong reversing ability among the screened compounds. We further determined whether NK-250 and NK-252 among the six compounds could potentiate cytocidal activities of etoposide (VP16) as well as VCR against both multidrug-resistant (MDR) cell line (VJ-300) and atypical MDR cell line (KB/VM-4). Both VJ-300 and KB/VM-4 were derived from the same parental human cancer KB cell line: VJ-300 cells showed enhanced expression of a MDR-specific glycoprotein of molecular weight of 170,000 Da (gp170) while KB/VM-4 cells were selected as teniposide (VM26)-resistant cell line with no expression of gp170. NK-250 and NK-252 potentiated the cytotoxic action of VCR about 2- to 10-fold against KB and KB/VM-4 cells, and they almost completely reversed VCR-resistance in VJ-300 cells. By contrast, NK-250 and NK-252 potentiated the cytotoxic action of VP16 about 2-fold against KB cells while they reversed 5- to 10-fold VP16-resistance in both VJ-300 and KB/VM-4 cells. The reversal effect by NK-250 and NK-252 of VCR-resistance in VJ-300 cells appeared to be due to enhanced cellular accumulation of radioactive VCR through interaction to 170-kDa P-glycoprotein. The potentiation effects by these dihydropyridines of VCR and VP16 on KB or KB/VM-4 cells also appeared to be due to enhanced accumulation of radioactive VP16 or VCR, but the effects might be mediated through other mechanisms, plausibly enhanced cellular uptake of the drugs.

Antineoplastic Agents↗
PubMed1991

[Massive hemorrhage induced by tracheo-innominate artery fistula in two infants].

Two cases of massive hemorrhagic shock induced by tracheo-innominate artery fistula are reported. The first case is a 4 year-old girl with encephalitis under prolonged mechanical ventilation. The second case is a 6 year-old tracheostomized girl with mental and motor retardation of congenital origin who has been taken care of at her home. This catastrophic complication is usually caused by long term placement of tracheostomy tube with the cuff inflated especially in malnourished pediatric patients. The cuff pressure is apt to be concentrated on one side of the tracheal wall especially in mechanically ventilated immobilized patients. Although this complication is rare because cuffed tube is currently avoided in pediatric patient, sophisticated care should be taken in managing tracheostomized patients.

Brachiocephalic Trunk↗
PubMed1990

HU-1 mutants of Escherichia coli deficient in DNA binding.

We constructed four mutants of the Escherichia coli hupB gene, encoding HU-1 protein, by synthetic oligodeoxyribonucleotide-directed, site-specific mutagenesis on M13mp18 vectors. The HupBR45 protein contained alterations of Arg58----Gly and Arg61----Gly, and the HupBF3, HupBK2 and HupBA1 proteins contained Phe47----Thr, Lys37----Gln and Ala30----Asp alterations, respectively. HupBF3 and HupBR45 were unable to maintain normal cell growth in a hupA-hupB-himA triple mutant at 42 degrees C, mini-F or RSF1010 proliferation, or Mu phage development in a hupA-hupB double mutant, whereas HupBA1 and HupBK2 supported these cellular activities. DNA-affinity column chromatography showed that the HupBF3 and HupBR45 had reduced affinities to DNA. These observations indicate that two highly conserved Arg residues in the arm structure of the C-terminal half of the HU-1 molecule and a Phe residue in the short beta-sheet connecting the two halves of the molecule are important for the DNA-binding ability and biological functions of this protein.

Amino Acid Sequence↗
PubMed1990

Tissue-specific enhancer of the human multidrug-resistance (MDR1) gene.

Identification of cis-regulatory sequences is a first step in analyzing the regulation of the human multidrug-resistant 1 (MDR1) gene which encodes the 170-kilodalton membrane P-glycoprotein in normal tissues and tumor cells. We have studied several overlapping genomic clones containing the 5'-flanking region of the gene. These clones span about 30 kilobases (kb) of contiguous DNA containing 10 kb of the gene and 20 kb of the 5'-flanking sequence. The nucleotide sequence of the first exon and the 2 kb preceding the exon were determined. DNA sequences containing the 5'-flanking regions were linked to the chloramphenicol acetyltransferase (CAT) gene. For transient CAT assay, we have employed six cell lines, including human cancer KB, vincristine-resistant VJ-300 derived from KB, mouse adrenal tumor Y-1, African green monkey kidney CV-1, mouse fibroblast NIH3T3, and human adrenal carcinoma SW-13 cells. Promoter activity was very weak regardless of the length of the promoter region in mouse adrenal tumor Y-1 and monkey kidney CV-1 cells, in which endogenous P-glycoprotein was expressed. Introduction of a 700-base genomic DNA fragment from a site located at 10 kb far upstream of the initiation site increased the transcription of the CAT gene in Y-1, CV-1, and SW-13 cells. However, no significant increase in the CAT activity could be observed in NIH3T3, KB, and VJ-300 cells. This fragment markedly augmented the expression of the CAT gene regardless of orientation or position, and it acted in a cell type-specific manner even with heterogenous promoters. Our present study suggests that the 700-base pair fragment may carry a tissue-specific transcriptional enhancer that is active in at least some adrenal and kidney-derived cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Reduction of drug accumulation and DNA topoisomerase II activity in acquired teniposide-resistant human cancer KB cell lines.

We have isolated stable teniposide (VM26)-resistant cell lines from human cancer KB cells by stepwise exposure to increasing doses of the drug. At each step, we have purified VM26-resistant cell lines. KB/VM-a, KB/VM-b, KB/VM-1, KB/VM-2, KB/VM-3, and KB/VM-4 showed 3-, 6-, 12-, 16-, 74-, and 95-fold higher resistance to VM26 than did KB. We have further characterized KB/VM-2 and KB/VM-4 which showed about 15- and 100-fold higher resistance to VM26 or etoposide (VP16) than did KB. Both VM26-resistant cell lines showed 4- to 11-fold higher relative resistance to daunomycin and Adriamycin than did KB. Steady-state levels of the cellular accumulation of radioactive VP16 in KB/VM-2 and KB/VM-4 cells were about 40% of that of KB cells, whereas similar levels of radioactive daunomycin accumulation were observed in KB/VM-2 and KB/VM-4 cells as KB cells. Topoisomerase II activity of nuclear extracts of both KB/VM-2 and KB/VM-4 assayed by decatenation of kinetoplast DNA was consistently two-thirds or less the activity of KB cells. A similar reduction was seen in both immunoblot assays with specific anti-topoisomerase II antibody and Northern blot analysis with specific human DNA topoisomerase II complementary DNA. DNA topoisomerase I activity, however, was similar between the mutants and their parent. Furthermore, cell growth of KB/VM-2 and KB/VM-4 was more thermolabile than that of KB, while KB/VM-b already showed temperature-sensitive growth. KB/VM-1 did show reduced accumulation of VP16 as in KB/VM-2 or KB/VM-4, but it had a normal level of topoisomerase II content as in KB cells. These data suggest that the reduced expression of DNA topoisomerase II, possibly combined with decreased permeability to the drugs, can account for the acquired VM26 resistance of KB/VM-2 and KB/VM-4 cells and also that the temperature-sensitive phenotype might not be obligatorily coupled with the reduced expression of topoisomerase II or the decreased permeability.

DNA Topoisomerases, Type I↗
PubMed1990

Enhanced production of tissue-type plasminogen activator by estradiol in a novel type variant of human breast cancer MCF-7 cell line.

ES-1 cells, which showed a higher sensitivity to the cytocidal action of estradiol were isolated from a human breast cancer MCF-7 cell line. Growth of ES-1 cells was inhibited by a dose of 17-beta estradiol that stimulated the growth of the parental MCF-7 cells. Proteins secreted from MCF-7 and ES-1 cells when cultured with 17-beta estradiol were compared by sodium dodecyl sulfate-containing polyacrylamide gel electrophoresis (SDS-PAGE). Addition of estradiol to culture medium enhanced secretion of a protein of molecular mass of 52 kDa in media for both MCF-7 and ES-1 cell lines, but the secretion of a second 67 kDa protein was enhanced about 10-fold only in ES-1 cells. The analysis by SDS-PAGE of culture medium immunoprecipitated with anti-tissue-type plasminogen activator (t-PA) antibody demonstrated that the band of 67 kDa protein specifically secreted from estradiol-treated ES-1 cells contained t-PA. Zymography assays, quantitative immunoreactive assays, and Northern analysis showed about 5-fold specific increase by estradiol of t-PA with molecular mass of 65-70 kDa in ES-1 but not in its parental MCF-7 cells. Cellular level of the plasminogen activity was also specifically enhanced in ES-1 cells by estradiol, but only a slightly in MCF-7 cells. By contrast, another urokinase-type PA (u-PA) with molecular weight of 55 kDa showed very low level activity in both MCF-7 and ES-1 cell lines in the presence of estradiol. Formation of t-PA mRNA was specifically enhanced in ES-1 cells when ES-1 cells were treated for more than 12 h with 10(-8) M 17-beta estradiol. Estradiol did not elongate the lifetime of t-PA mRNA in ES-1 cells. A unique phenotype of ES-1 cells in response to estradiol is discussed in relation to activating expression of the t-PA gene.

Breast Neoplasms↗
PubMed1990

Inverse correlation between expression of multidrug resistance gene and N-myc oncogene in human neuroblastomas.

Genomic amplification of N-myc is an important prognostic indicator in neuroblastoma. The tumors with amplified N-myc are initially sensitive to chemotherapy but often acquire resistance to therapy, recur, and ultimately kill the patients. We measured amplification and expression of N-myc and expression of mdr-1 in 35 surgically resected neuroblastomas, before acquisition of drug resistance and in 4 recurrent tumors resistant to chemotherapy. The mdr-1 mRNA expression was found to be inversely correlated with the N-myc expression. The mdr-1 gene expression was at a low level in advanced stage and histologically undifferentiated neuroblastomas, the same group of tumors in which N-myc expression is elevated. A significantly better prognosis was noted in those patients whose tumors had a high level of mdr-1 expression and a low level of N-myc expression. The role, if any, of increased expression of mdr-1 in the acquisition of multidrug resistance in neuroblastoma remains unclear. However, the aggressive clinical behavior associated with N-myc amplification and/or expression appears to be linked to down-regulation of mdr-1 expression.

Cell Differentiation↗
PubMed1990

Promoters and autogenous control of the Escherichia coli hupA and hupB genes.

Three start sites and a single start site for transcription of the hupB and hupA genes, respectively, have been identified in Escherichia coli. Preceding the RNA start sites are DNA sequences that conform to canonical promoter consensus sequences. The two most upstream promoters of the hupB gene function in vivo at comparable efficiency, while the third is not expressed significantly. Both hupB and hupA genes possess a DNA sequence with a rho-independent transcriptional terminator in their respective regions downstream from the coding regions. The hup genes are both transcribed in vivo into monocistronic mRNA molecules. Upon introduction of an HU-overproducing plasmid carrying either the hupB or the hupA gene into the wild-type and hup single deletion mutants, the intracellular levels of mRNA from the chromosomal hup genes are reduced. The HU-1 and HU-2 proteins both repress both hup genes, repression of the hupB gene being less efficient. The HU protein selectively represses mRNA synthesis starting at the hup promoters in the hupB promoter-CmR and hupA promoter-KmR fusion genes, but does not have a negative regulatory effect on mRNA synthesis from the true CmR and KmR promoters. These findings suggest that the signals for the actions of HU proteins are located in the DNA regions upstream from the sites near the 5' extremities of the coding regions of the hupB and hupA genes.

Bacterial Proteins↗
PubMed1990

Drug resistance to cis-diamminedichloroplatinum (II) in Chinese hamster ovary cell lines transfected with glutathione S-transferase pi gene.

Establishment of Chinese hamster ovary (CHO) cell lines expressing human glutathione S-transferase-pi (GST-pi) was performed after cotransfection of pSV2-neo and human GST-pi cDNA-carrying plasmid p beta actGPi-2. About 30 G418-resistant clones were tested for their expression of GST-pi by Northern blot analysis. Two clones, beta 2-3 and beta 2-5, expressed a significant amount of GST-pi mRNA; and one clone, beta 1-1, that did not was also used for further study. Western blot analysis with anti-GST-pi antibody showed significant increases of GST-pi in beta 2-3 and beta 2-5, but not in beta 1-1. Northern blot analysis with the human GST-pi cDNA probe showed that the increase in the expression of GST-pi-mRNA in beta 2-3 and beta 2-5 was respectively 2- and 4-fold higher than that in beta 1-1. Southern blotting analysis showed that beta 1-1, beta 2-3 and beta 2-5 contained about one copy of the human GST-pi cDNA sequence. beta 2-3 and beta 2-5 were resistant to 1.4- and 3.0-fold higher doses of CDDP than CHO, respectively, but beta 1-1 was not. Increased expression of GST-pi might be associated with CDDP-resistance in CHO cells.

Animals↗
PubMed1990

Activities of newly synthesized dihydropyridines in overcoming of vincristine resistance, calcium antagonism, and inhibition of photoaffinity labeling of P-glycoprotein in rodents.

Newly synthesized 1,4-dihydropyridine derivatives (NK-compounds) were screened to determine whether they could overcome vincristine (VCR) resistance in VCR-resistant (P388/VCR) leukemia-bearing mice. Among the 57 NK-compounds examined, six compounds had strong reversing ability (Grade A), 18 partially overcame the resistance (Grade B), and 33 did not reverse the resistance (Grade C). The ability to overcome resistance varied considerably with the nature of substituents at positions 3.5 of the 1,4-dihydropyridine, and the most suitable substituents were the pyridylalkyl-including esters. Calcium antagonistic activity of NK-compounds having pyridylalkyl-including esters at positions 3.5 and dithiene ring at position 4 of the 1,4-dihydropyridine was greater than in those compounds having the dioxene ring at position 4. NK-242, which was assessed at Grade A and had no calcium antagonistic activity, improved therapeutic effects in both VCR-sensitive (P388/S) leukemia- and P388/VCR leukemia-bearing mice when combined with VCR. Fourteen NK-compounds were screened to determine whether they could inhibit photoaffinity labeling of the P-glycoprotein (Mr 170,000 glycoprotein) in a multidrug-resistant cell line by [3H]azidopine. All six compounds of Grade A and two of the three compounds of Grade B almost completely inhibited the labeling of Mr 170,000 glycoprotein at 1 to 10 microM. Thus there was a good correlation between the ability to reverse VCR resistance in vivo and the inhibition of photoaffinity labeling of Mr 170,000 glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Pharmacokinetic analysis of absorption and metabolism of dopamine and a dopamine prodrug in dogs.

Pharmacokinetic compartment models were constructed to describe the absorption and metabolism of dopamine (DA) and DA prodrug, N-(N-acetyl-L-methionyl)0,0-bis-eth-oxycarbonyl) dopamine(1). Plasma concentrations of DA, DA-SO4, and DOPAC after oral administration of DA to dogs, were analysed using the pharmacokinetic model assuming the contribution of first-pass metabolism for the formation of DA-SO4 and DOPAC. Though plasma concentration of DA was quite different from that of DA-SO4 or DOPAC, these data were simultaneously analysed with a good fitting curve. The apparent absorption rate constant of DA(K1) was proved to be much smaller than the apparent formation rate constants of DA-SO4(K2) or DOPAC(K3). It was found that the compartment model is useful for the evaluation of absorption and metabolic inactivation of DA. Plasma concentration of DA, N-(N-acetyl-L-methionyl)dopamine(2), DA-SO4, and DOPAC after oral administration of 1 were simultaneously analysed using the compartment model including the first-pass metabolism and two-fraction dissolution process. Good fitting curves were obtained. The apparent formation rate constant of 2(K4) is larger than that of DA-SO4(K5) or DOPAC(K6); thus it was shown that two protective groups of 1 reduced the metabolism of DA and 2 specially played an important role to the reduction of first-pass metabolism. From these results, it was found to be possible to give a pharmacokinetic interpretation for the mechanism of reduction of first-pass metabolism of DA.

3,4-Dihydroxyphenylacetic Acid↗