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N Kanda

Publications and source records attributed to N Kanda.

At least 91 records · Page 5Linked to original sources
PubMed1988

Structure-activity relationship of aldose reductase inhibitors based on X-ray crystal structures of oxazolecarbamate derivatives.

In order to elucidate the key atoms and/or stereostructures necessary for the inhibitory emergence of aldose reductase, crystal structure determinations were carried out for 11 oxazolecarbamate analogues, which have similar chemical and physicochemical properties but different inhibitory activities. The molecular conformations, revealed by X-ray analyses, were also ascertained to be energetically stable from theoretical conformational energy calculations. A surprising degree of conformational similarity was observed for the potent inhibitors. The analyses of the quantitative structure--activity relationships showed that the molecular conformation and the dipole moment, as well as the hydrophobicity at the oxazole C5-site, were important for high activity.

Aldehyde Reductase↗
PubMed1987

Nature of recombination involved in excision and rearrangement of human repetitive DNA.

An alphoid-like human repetitive DNA of the Sau3A family is present extrachromosomally and in the chromosomes. In the chromosomes, the DNA is located on chromosome 11 but related sequences are present in chromosome 17. We characterized the nature of the recombination involved in the excision of the extrachromosomal DNA from chromosome 11. The results show that the recombination occurs both between the homologous subunits and between the heterologous subunits with only a 70 to 80% sequence homology among them, suggesting that a DNA structure other than a sequence homology mediates the recombination process. The same type of recombination is responsible for the rearrangement of the related sequences in chromosome 17.

Base Sequence↗
PubMed1987

Amplification of IMR-32 clones 8, G21, and N-myc in human neuroblastoma xenografts.

Amplification of clones 8, G21, and N-myc, which were derived from human neuroblastoma cell lines IMR-32 and NB-19, were studied in nine neuroblastoma xenografts. N-myc was amplified from 50- to 120-fold in eight of nine xenografts, clone 8 was amplified in five of the xenografts, and clone G21 was amplified in four of these five. Each of these clones was localized by in situ hybridization to homogeneously staining regions in metaphase spreads of xenograft chromosomes. In one xenograft a DNA rearrangement of clone 8 was observed, and only two of the sequences detected by G21 were amplified. Restriction enzyme mapping indicated that the rearrangement within clone 8 occurred at a position close to the rearrangement previously noted in neuroblastoma cell line NB-9.

Cell Line↗
PubMed1987

Different karyotypic patterns in early and advanced stage neuroblastomas.

Of 23 untreated and 7 treated (relapsed) neuroblastomas, 14 (11 untreated, 3 treated) had modal chromosome numbers in the diploid (45 to 51), 9 (8 untreated, 1 treated) in the triploid (60 to 77), and 6 (3 untreated, 3 treated) in the hypotetraploid (81 to 88) range, and one (untreated) had hypertetraploidy (100). The near-or-pseudodiploid and hypotetraploid tumors were characterized by numerous structural abnormalities, most frequently of 1p, and frequent presence of double minutes or homogeneously staining regions. The near-triploid tumors were characterized by three almost complete haploid sets of chromosomes, and few structural abnormalities. N-myc amplification was found in five of the near-or-pseudodiploid or hypotetraploid tumors but in none of the near-triploid tumors. Most near-triploid tumors were found in infants at stage I or II, and the near-or-pseudodiploid or hypotetraploid tumors in children at stage II or IV mostly 1 year old or older. Among the untreated patients, all 8 with a near-triploid tumor were alive with no evidence of the disease, and the 11 with a near-or-pseudodiploid tumor had a median survival of only 376 days (P less than 0.05), 7 of the 11 being dead. Thus, the near-triploid patients had well recognized favorable prognostic factors and an excellent prognosis, and the near-or-pseudodiploid patients had unfavorable prognostic factors and a dismal prognosis. The hypotetraploid tumors seemed to have karyotypic and clinical features in common with the near-or-pseudodiploid tumors. We presume that the near-triploid tumors and the near-or-pseudodiploid or hypotepraploid tumors may constitute distinctly different subcategories within neuroblastomas.

Age Factors↗
PubMed1987

Human gene coding for granulocyte-colony stimulating factor is assigned to the q21-q22 region of chromosome 17.

Granulocyte-colony stimulating factor (G-CSF) is a member of colony stimulating factors which regulate the proliferation and differentiation of hematopoietic progenitor cells. A full-length cDNA clone coding human G-CSF was used as a hybridization probe to detect homologous sequence in human-mouse somatic cell hybrids, flow-sorted human chromosomes, and in situ human metaphase chromosomes. The results indicate that the gene encoding human G-CSF is on the q21-q22 region of chromosome 17, which is involved in translocation of t(15;17) (q23;21) in human acute promyelocytic leukemia.

Animals↗
PubMed1987

[Amplification of oncogene N-myc in human neuroblastomas].

The basic mechanisms of oncogene activation are gene amplification, increased expression of a single copy gene and somatic mutation, resulting in a genetic product with increased oncogenic potential. Gene amplification appears to be a more common mechanism of oncogene overexpression and its clinical significance is beginning to be appreciated. In human neuroblastomas, N-myc amplification is highly correlated with advanced stages of disease and rapid disease progression, suggesting that the N-myc gene plays a crucial part in determining the degree of malignancy of neuroblastomas. Chromosome aberrations such as double minutes and homogeneously staining region which observed frequently in neuroblastomas are the cytological manifestation of N-myc amplification and its surrounding DNA fragments.

Animals↗
PubMed1986

Effects of cyclophosphamide, cis-platinum, nitrosourea (ACNU), melphalan, and dacarbazine on a cytogenetically highly malignant neuroblastoma xenograft.

The effects of eight different chemotherapeutic agents were studied on a human neuroblastoma xenograft, designated TNB9, according to the standard Battelle Columbus Laboratories protocol. Cytogenetically and molecular-cytogenetically, this xenograft is known to have a homogeneously staining region (HSR) on chromosome 20 and to exhibit 60- to 80-fold amplification of clone #8 (1.75 kb) and N-myc (2.1 kb) in the HSR. Our previous analyses of cytogenetic and phenotypic characteristics on nine human neuroblastoma xenografts demonstrated that TNB9 is one of the most malignant strains of neuroblastoma. The in vivo chemotherapeutic sensitivity assessment disclosed that cyclophosphamide, cis-platinum, nitrosourea (ACNU), melphalan, and dacarbazine (DTIC) are effective, while aclarubicin, vincristine, and cytosine arabinoside are quite ineffective against this neuroblastoma xenograft.

Adolescent↗
PubMed1986

Prostaglandins: a possible mediator to inhibit hepatic drug metabolism in adjuvant arthritic rats.

In the liver of adjuvant arthritic rats perfused with a hemoglobin-free buffer solution, the rate of metabolism of a model drug, 2,6-dichloro-4-nitroanisole, was approximately half that of the control, while the bile flow rate was normal. Granulation tissue extracts and arthritic rat serum had no effect on the activity of CNA metabolism in normal rat liver preparations. In the perfused normal rat liver, the rate of CNA metabolism was inhibited by addition of prostaglandin (PG) E1, PGE2, and PGF2 alpha, respectively, in a final concentration of 0.5 microM. The inhibition by PGE1 was increased in the concentration range from 0.1 to 2.5 microM. The bile flow rate was not affected by the added PGs. However, these PGs had no direct effect on the CNA demethylating activity of the isolated hepatocytes from normal rat liver in a high concentration of 10 microM. Serotonin stimulated slightly CNA metabolism and bile production in the perfused livers by the intermittent infusion, but was without effect in the isolated hepatocytes. Epinephrine and histamine had no significant effect on CNA metabolism in both liver preparations. A similar pattern of the inhibition of CNA metabolism by PGs was reproduced in the normal rat liver perfused with the medium containing the supernatant of the hepatic nonparenchymal cells incubated in the presence of PGE1. The involvement of liver sinusoidal cells as secretory cells in depression of hepatic drug metabolism has been discussed.

Alprostadil↗
PubMed1986

Amplification and rearrangement of DNA sequences from the chromosomal region 2p24 in human neuroblastomas.

Seven DNA fragments which map to or very near human chromosome band 2p24 are shown to be differentially amplified in DNA from specific subsets of an enlarged series of human neuroblastoma cell lines and primary neuroblastomas. Of these DNA fragments, the probe NB-19-21 for the oncogene N-myc is the most frequently amplified, with a second expressed sequence (pG21) amplified in 9 of those 11 cell lines and 16 of those 25 tumors exhibiting amplification of N-myc. The remaining probes are in turn each amplified in progressively smaller, nested subsets of the cell lines and tumors in which both N-myc and pG21 are amplified. These data permit construction of models for the organization of a "neuroblastoma amplicon," i.e., an originally amplified DNA domain, with N-myc positioned most central and the other DNA fragments increasingly peripheral; comparable models result for the cell lines and the tumors. Five of the seven probes examined detect novel DNA fragments in these specimens, reinforcing previous observations that extensive DNA rearrangement can occur during DNA amplification in neuroblastoma cell lines and in primary neuroblastomas. Such rearrangements could contribute significantly to the evolution of the neuroblastoma amplicon in different specimens to progressively smaller units, preserving, in the limit, amplification of N-myc.

Base Sequence↗
PubMed1986

[Oncogene amplification in human neuroblastomas].

N-myc, which has partial sequence homology to the oncogene c-myc, was isolated from human neuroblastoma cell lines. We have surveyed amplification of N-myc, clone 8 and pG21 in human neuroblastoma cell lines, xenografts and in primary tumors and found that amplification frequently occurred in tumors classified as stage III and IV. In situ hybridization studies demonstrated that in neuroblastomas, chromosome aberrations such as HSR (homogeneously staining region) and DMs (double minutes) are cytological manifestations of the amplification of these clones. The N-myc-related gene seems to contribute to cell growth or differentiation of the nerve cell and its amplification with enhanced expression promotes the progression of the tumor with poor prognosis.

Animals↗