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Biomedical subjects

M Kaneko

Publications and source records attributed to M Kaneko.

At least 199 records · Page 11Linked to original sources
PubMed1998

The sensitivity to DNA single strand breakage in mitochondria, but not in nuclei, of Chinese hamster V79 and variant cells correlates with their cellular sensitivity to hydrogen peroxide.

To investigate whether a relation exists between the level of DNA damage by and cytotoxicity of hydrogen peroxide, we measured the initial level of H2O2-induced nuclear and mitochondrial DNA single strand breaks in Chinese hamster V79 and H2O2-resistant variant cells (Hpr-4) with an alkaline elution technique and a quantitative Southern blot technique, respectively. The frequency of DNA single strand breaks in mitochondrial DNA induced by H2O2 was more than one hundred times that of nuclear DNA in the parent V79 cells. While a similar frequency of nuclear DNA single strand breaks was generated in V79 and Hpr-4 cells at an equidose of H2O2, a lower number of mitochondrial DNA single strand breaks were generated in Hpr-4 cells than in V79 cells by H2O2 in the range of 100 microM to 5 mM. The sensitivity to mitochondrial DNA single strand break-induction correlated with the cellular sensitivity to H2O2 in Chinese hamster V79 and variant cells.

Alkalies↗
PubMed1998

Biologically active oligodeoxyribonucleotides. 5. 5'-End-substituted d(TGGGAG) possesses anti-human immunodeficiency virus type 1 activity by forming a G-quadruplex structure.

A series of hexadeoxyribonucleotides (6-mers), d(TGGGAG), substituted with a variety of aromatic groups at the 5'-end were synthesized and tested for anti-human immunodeficiency virus type 1 (HIV-1) activity. While unmodified d(TGGGAG) (31) had no anti-HIV-1 activity, compound 23 with a 3,4-di(benzyloxy)benzyl (DBB) group at the 5'-end potently inhibited the HIV-1IIIB-induced cytopathicity of MT-4 cells in vitro (IC50 = 0.37 microM) without cytotoxicity up to 40 microM. A thermal denaturation study on the 5'-end-substituted 6-mers by means of the circular dichroism (CD) spectra demonstrated that the aromatic substituent attached at the 5'-end of the 6-mer strongly enhanced the formation of a parallel helical structure consisting of four strands (quadruplex). On the contrary, compound 36, in which one of the guanosines of 23 was replaced by a thymidine, did not form a quadruplex, thus exhibiting no anti-HIV-1 activity. Moreover, both compound 15, with a tert-butyldiphenylsilyl group solely at its 3'-end, and compound 21, with a relatively small substituent, a benzyl group, at the 5'-end, formed quadruplexes but had no anti-HIV-1 activity. These findings led us to the conclusion that both the quadruplex structure and the aromatic substituent with adequate size at the 5'-end are crucial for the interaction of the 5'-end-substituted 6-mers with the V3 loop as well as the CD4 binding site on viral gp120, resulting in anti-HIV-1 activity.

Anti-HIV Agents↗
PubMed1998

Increased risk of hepatoblastoma among immature children with a lower birth weight.

Hepatoblastomas among children with very low birth weights have significantly increased recently, according to the data from the Japan Children's Cancer Registry for the years 1985-1993. We then analyzed more Registry data for 1969-1994 to clarify the possible relationship between low birth weight and hepatoblastoma. The percentage of low birth weights was compared between 543 hepatoblastoma children in the Registry and all live births in Japan in four successive periods during the 26 years from 1969 to 1994, in relation to the given birth year. The percentage of children with birth weights of 1500-1999 g among hepatoblastomas was higher, at 2.94-1.60%, than that among all live births in each of the four periods (0.79-0.92%), and the percentage of children with birth weights of 2000-2499 g was slightly higher. The percentage of children with birth weights of <1500 g and, especially, <1000 g, has increased rapidly among children born after 1988 (1.60 and 6.40%, respectively), when most very low birth weight infants began to survive. Compared with children with a birth weight of 2500 g or more, the relative risks of hepatoblastoma among children with birth weights of <1000, 1000-1499, 1500-1999, and 2000-2499 g were 15.64 (P < 0.001), 2.53 (P = 0.129), 2.71 (P = 0.001), and 1.21 (P = 0.381), respectively, suggesting the lower the birth weight, the higher the risk of hepatoblastoma. There was no association between hepatoblastomas with a low birth weight and either age at diagnosis or congenital malformations or light-for-date weight. The risk of hepatoblastoma for low birth weight children may be inherently high, especially for lower birth weights, and the recent rapid increase may be a result of an increase in the number of more immature infants with a more sensitive liver and also more frequent exposure to risk factors related to perinatal treatment.

Adolescent↗
PubMed1998

Long-term postmortem survival of mitochondrial genomes in mouse synaptosomes and their rescue in a mitochondrial DNA-less mouse cell line.

Mitochondrial DNA (mtDNA) transfer was carried out from postmortem mouse tissues to mouse mtDNA-less (rho0) cells to determine how long it takes for autolysis of mtDNA after death and whether mtDNA in postmortem tissues can recover its function in rho0 cells. The results showed that mtDNA was stable in postmitotic tissues stored at 4 degreesC. Moreover, mtDNA in postmortem brain tissues stored for up to 1 month still retained functional properties, causing complete recovery of mitochondrial respiratory function, when it was transferred to rho0 cells. These observations suggest that mtDNA in brain tissue can survive for 1 month after death and can start replication and gene expression in rho0 cells without showing any functional defects. This procedure might be applied to human autopsy brain tissues for examination of the influence of accumulated somatic mutations in mtDNA from aged subjects.

Aging↗
PubMed1998

CEP-1347/KT7515 prevents motor neuronal programmed cell death and injury-induced dedifferentiation in vivo.

CEP-1347, also known as KT7515, a derivative of a natural product indolocarbazole, inhibited motor neuronal death in vitro, inhibited activation of the stress-activated kinase JNK1 (c-jun NH terminal kinase) in cultured spinal motor neurons, but had no effect on the mitogen-activated protein kinase ERK1 in these cells. Results reported here profile the functional activity of CEP-1347/KT7515 in vivo in models of motor neuronal death or dedifferentiation. Application of CEP-1347/KT7515 to the chorioallantoic membrane of embryonic chicks rescued 40% of the lumbar motor neurons that normally die during the developmental period assessed. Peripheral administration of low doses (0.5 and 1 mg/kg daily) of CEP-1347/KT7515 reduced death of motor neurons of the spinal nucleus of the bulbocavernosus in postnatal female rats, with efficacy comparable to testosterone. Strikingly, daily administration of CEP-1347/KT7515 during the 4-day postnatal window of motor neuronal death resulted in persistent long-term motor neuronal survival in adult animals that received no additional CEP-1347/KT7515. In a model of adult motor neuronal dedifferentiation following axotomy, local application of CEP-1347/KT7515 to the transected hypoglossal nerve substantially reduced the loss of choline acetyl transferase immunoreactivity observed 7 days postaxotomy compared to untreated animals. Results from these experiments demonstrate that a small organic molecule that inhibits a signaling pathway associated with stress and injury also reduces neuronal death and degeneration in vivo.

Animals↗
PubMed1998

Intrathecal bicuculline does not increase formalin-induced inflammation.

Intrathecal (i.t.) administration of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline enhances pain behaviors in the formalin test. This study examined whether bicuculline also increases the peripheral inflammation induced by formalin. Subcutaneous injection of 0.25 to 5.0% formalin in the plantar surface of one hindpaw of the rat produced a concentration-dependent increase in plasma extravasation as measured by the Evans Blue method. Pretreatment with 0.3 microg i.t. bicuculline neither enhanced nor suppressed formalin-induced plasma extravasation. This dose of bicuculline also did not affect plasma extravasation induced by injection of 3% kaolin/3% carrageenan in the knee of the rat. These data indicate that the enhancement of formalin-induced pain behaviors by i.t. bicuculline is not secondary to enhanced peripheral inflammation, but more likely reflects enhancement of nociceptive transmission in the spinal cord.

Animals↗
PubMed1998

Effects of gamma-glutamylcysteine ethyl ester on heart mitochondrial creatine kinase activity: involvement of sulfhydryl groups.

To study the mechanism of the protective effect of gamma-glutamylcysteine ethyl ester, mitochondrial creatine kinase activity of rat heart was measured. Gamma-glutamylcysteine ethyl ester had a protective effect against the depression of creatine kinase activity induced by xanthine + xanthine oxidase or hydrogen peroxide. Gamma-glutamylcysteine ethyl ester also prevented the depression of creatine kinase activity induced by N-ethylmaleimide. It is suggested that the protective effect of gamma-glutamylcysteine ethyl ester is related to oxygen free radicals or to reduction of the sulfhydryl groups of the enzyme which were previously oxidized by oxygen free radicals.

Animals↗
PubMed1998

Loss of CD9 with Expression of CD31 and VEGF in Breast Carcinoma, as Predictive Factors of Lymph Node Metastasis.

Immunohistochemical staining for CD9, CD31 and vascular endothelial growth factor(VEGF)was performed in breast carcinoma specimens. CD9 was expressed in the membrane of carcinoma cells in 61 of 93 cases(67%), CD31 in the membrane of carcinoma cells in 23 of 86 cases(27%), and VEGF in the cytoplasm of carcinoma cellsin 26 of 86 cases(30%). The expression of CD9, CD31 and VEGF did not singly correlate with any clinicopathological factors. However, a loss of CD9 with concurrent expression of CD31 or VEGF in the invasive component showed a slight correlation with lymph node metastasis. These findings suggest that the potential for metastatic spread to lymph nodes in breast carcinoma may be synergically affectedby various factors.

Journal Article↗
PubMed1998

Normal developing rat brain expresses a platelet-derived growth factor B chain (c-sis) mRNA truncated at the 5' end.

The 5' untranslated sequence (5' UTS) of platelet-derived growth factor B (PDGF-B/c-sis) mRNA is highly preserved through evolution, and inhibits translation of downstream coding sequences. In this study, using Northern analysis we identified two PDGF-B/c-sis mRNAs (3.5 kb and 2.6 kb) expressed in normal developing rat brain. In contrast to the constitutive expression of 3.5 kb mRNA, the expression of 2.6 kb mRNA increased markedly in accordance with those stages of brain development at which we had previously demonstrated an increased immunoreactivity for PDGF-B/c-SIS in neurons (Sasahara et al., 1992). By PCR cloning and the RNase protection assay, we determined the complete sequence of rat PDGF-B/c-sis, and found that the 2.6 kb transcript was a form of the 3.5 kb message truncated at the 5' end, and that the predominant 2.6 kb mRNA commenced 15 nt upstream of the signal peptide. Accordingly, it is suggested that the truncation of 5' UTS contributes to the expression of PDGF-B/c-SIS protein in the CNS. Lack of translational inhibitory 5' UTS of PDGF-B/c-sis transcript and resultant efficient protein translation have been reported in only a few transformed cells and cultured umbilical vein endothelial cells. We have extended this knowledge to the developing rat brain, and suggest that a similar mechanism could operate widely in non-transformed tissue in vivo.

Animals↗
PubMed1998

Suppression of cell proliferation and the expression of a bcr-abl fusion gene and apoptotic cell death in a new human chronic myelogenous leukemia cell line, KT-1, by interferon-alpha.

A new human leukemia cell line, KT-1, was established from a patient in the blastic crisis phase of chronic myelogenous leukemia (CML). This cell line had a positive reaction for intracytoplasmic myeloperoxidase and two Philadelphia chromosomes (Ph1) [t(9;22)(q34;q11)] and lacked normal copies of chromosomes 9 and 22. Molecular characterization of the breakpoint in the t(9;22)(q34;q11) showed that KT-1 had a bcr-2/abl-2 splice junction. When the KT-1 cells were cultured with interferon (IFN)-alpha or IFN-gamma, the growth of the cells were dose-dependently suppressed. IFN-alpha and IFN-gamma exerted synergistic suppressive effects on the growth of KT-1 cells. Furthermore, IFN-alpha suppressed the expression of the bcr-abl fusion gene in KT-1 cells, and induced G1 cell-cycle arrest and apoptotic cell death. The KT-1 cell line should be a valuable tool for studying the molecular mechanism of the suppression of Ph1 clone cells from CML by IFN.

Apoptosis↗
PubMed1998

Stratification of treatment of stage 4 neuroblastoma patients based on N-myc amplification status. Study Group of Japan for Treatment of Advanced Neuroblastoma, Tokyo, Japan.

BACKGROUND: It has been shown that children aged more than 12 months with stage 3 and 4 neuroblastoma with N-myc amplification do worse than those without amplification. Development of an innovative chemotherapeutic protocol for patients in such an extremely poor-risk group was the purpose of this study. PROCEDURE: Since March 1991 a new protocol for the treatment of advanced neuroblastoma was started. When N-myc was amplified more than 10-fold, patients received regimen A3, in which cyclophosphamide 1,200 mg/m2 was given on days 1 and 2; hence the dose of cytotoxic drugs was doubled. Patients with fewer than 10 copies of N-myc received regimen new A1, which is very similar to regimen A1 that had been used until March 1991 for all patients with advanced neuroblastoma with/without N-myc amplification. The efficacy of regimen A3 was evaluated. RESULTS: The relapse-free survival rate at 1 and 2 years for stage 4 patients older than 12 months of age with N-myc amplification of more than 10-fold was 43% and 29%, respectively, with regimen A1 and that for the same subgroup of patients treated with regimen A3 since March 1991 was 79% and 49%, respectively; the difference is statistically significant. On the other hand, there were no differences in the relapse-free survival rate at 1 year and 2 years for stage 4 patients with fewer than 10 copies of N-myc between those treated with regimen A1 and those treated with new A1 since March 1991. CONCLUSIONS: Stratification based on N-myc amplification into new A1 and A3 treatment protocols is of significant clinical importance. Regimen A3 was well tolerated and showed an improvement in clinical results in stage 4 patients with N-myc amplified more than 10-fold.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Soluble Fas ligand in the joints of patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To investigate the expression and function of Fas ligand (FasL),which can be in a membrane-bound or soluble form, in the joints of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The concentration of soluble FasL (sFasL) in serum and synovial fluid (SF) from 24 OA and 38 RA patients was measured using an enzyme-linked immunosorbent assay. The expression of FasL on SF lymphocytes (SFL) and peripheral blood lymphocytes (PBL) was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. A cytotoxic killing assay of membrane-bound FasL and purified sFasL against cultured synovial cells was also performed. RESULTS: Soluble FasL was detected in the SF of patients with RA and OA, but not in their serum. The concentration of SF sFasL was remarkably higher in patients with severe RA than in patients with mild RA or with OA. RT-PCR showed that SFL, but not PBL, from RA patients expressed messenger RNA for FasL. Membrane-bound FasL induced apoptosis in cultured synovial cells from the RA and OA patients, but naturally processed human sFasL did not. CONCLUSION: SFL from RA patients expressed FasL, and cleaved sFasL accumulated in the SF of inflamed joints. The different killing activity of membrane-bound FasL and sFasL against synovial cells may regulate Fas-mediated apoptosis in synovial cells.

Aged↗
PubMed1998

Enhanced Formation of Roots and Subsequent Promotion of Growth of Shoots on Cryopreserved Nodal Segments of Asparagus officinalis L.

This study was designed to investigate the effects of cryopreservation on the survival, organogenesis, and growth of plants regenerated from nodal segments of asparagus (Asparagus officinalis L.) that had been cut from cultures in vitro. The addition of dimethylsulfoxide (Me2SO) to the freezing solution at 8-16% (v/v) with or without a sugar (glucose, sorbitol, or sucrose) was effective for successful cryopreservation by a slow prefreezing method. Frequencies of root formation (average, 59.3%) from cryopreserved and surviving nodal segments were significantly higher (P < 0.005) than those (average, 13.9%) from nodal segments that had only been treated with freezing solution supplemented with 12% (v/v) Me2SO and various sugars without freeze-thawing. The increased frequency of root formation from cryopreserved nodal segments appears to have been induced by the freeze-thaw step of the cryopreservation procedure. Numbers and lengths of shoots derived from cryopreserved nodal segments were initially lower but were subsequently higher, after 60-90 days of culture, than those of shoots derived from nodal segments without freeze-thawing. The promotion of growth of shoots from cryopreserved nodal segments seemed to have been due to the increased percentage of root formation. Histological observations revealed that only dome-shaped meristematic tissue and a few cells of cladophyll primordia survived in cryopreserved nodal segments that had been cultured for 5 days after thawing. Many mitochondria and well developed rER were observed in these cells. Disorganization and/or physiological changes might have occurred in the surviving tissues and/or cells of the cryopreserved nodal segments that were responsible for the subsequent increased formation of roots. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Asymmetric imine-ene reactions: diastereofacial selective reactions with chiral glyoxylate-derived alpha-imino esters and asymmetric catalysis of enantiofacial selective reactions with prochiral alpha-imino esters.

The diastereofacial selective "imine-ene" reactions with alpha-imino esters, prepared from (-)-8-phenylmenthyl glyoxylate, are shown to provide an efficient entry to the asymmetric synthesis of alpha-amino acids. The feasibility study of the asymmetric catalysis is also reported on the enantiofacial selective ene reactions with prochiral alpha-imino esters.

Amino Acids↗
PubMed1998

[Transcatheter stent-graft implantation for the treatment of acute aortic dissection--rupture of aneurysm because of perigraft leakage].

An 82-year-old woman was diagnosed as having acute type B aortic dissection. At bed rest, her systolic blood pressure was kept less than 120 mmHg. Four days later the aneurysm threatened to rupture. Because she presented a high operative risk for open-chest surgery, a stent-graft was implanted across the dissection site via transcatheter. The entry site to the aneurysm was closed by the stent-graft, and postoperative aortograph demonstrated that contrast medium did not enter the false lumen except for a trivial projection. A CT scan 6 days after the stent-graft implantation unexpectedly demonstrated the false lumen not only had not thrombosed, but had expanded. As a result, 8 days after the operation the aneurysm ruptured into the left pleural cavity, and the patient died. An autopsy revealed the stent-graft was exactly implanted across the entry site, but that the diameter of the graft was slightly larger than that of the aorta. Consequently, a portion of the rim of the graft had been wraped after implantation, causing perigraft leakage. Leakage is one of the gravest complications of the stent-graft implantation, to prevent it, a new design for stent-graft device is essential.

Acute Disease↗
PubMed1998

Expression of platelet-derived growth factor after transient forebrain ischemia in the gerbil hippocampus.

The present study was conducted to clarify the role of platelet-derived growth factor-B chain (PDGF-B) in neuronal death after ischemia. Transient forebrain ischemia was induced in Mongolian gerbils by occluding the bilateral carotid arteries for 5 min. We investigated PDGF-B expression in the hippocampus after ischemia by immunohistochemistry, Northern blotting and in situ hybridization histochemistry. The results showed that PDGF-B is expressed in control CAI and CA3 neurons. In CA1, the amount of the PDGF-B transcript immediately increased, then disappeared 2 days after ischemia. Delayed neuronal death followed 1 day later. However, PDGF-B immunoreactivity in CA1 rapidly decreased and disappeared 12 h after transient forebrain ischemia, proceeding to delayed neuronal death. In contrast, the expression of both PDGF-B protein and the transcript was well preserved throughout the study in CA3, which remained viable even after ischemia. Accordingly, the selective neuronal susceptibility in the CA1 to ischemia corresponded with rapid disappearance of PDGF-B. PDGF-B expression may contribute to neuroprotective effect after ischemia.

Actins↗
PubMed1998

Hepatocellular carcinoma with chondrosarcomatous variation: case report with immunohistochemical findings, and review of the literature.

Hepatocellular carcinoma with chondrosarcomatous variation is very rare. We report a case with the results of pathology examination, and review the literature. The patient, a 72-year-old may had a very large tumor in the liver revealed during follow-up for diabetes mellitus. The liver mass, which was 14 cm in diameter, was diagnosed as hepatocellular carcinoma by abdominal ultrasonography. Anterior segmentectomy and partial liver resection were performed. Histopathology examination revealed that the tumor consisted of two different components: the major one was hepatocellular carcinoma (HCC), which occupied most of the tumor; and a sarcomatous component, which occupied a smaller area, and included spindle-shaped cells with chondroscarcomatous variation. Intrahepatic metastases and tumor thrombi of HCC were also found in portal and hepatic veins. Investigations of the immunohistochemical localization of keratin (KRT), vimentin (VMT), and S-100 protein (S 100) were performed by the avidin-biotin complex method. Some of the spindle cells were immunohistochemically positive for both KRT and VMT, and the chondrosarcomatous cells were positive for S 100. These results strongly suggested that the sarcomatous lesion resulted from a sarcomatous change of HCC.

Aged↗