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M Kanno

Publications and source records attributed to M Kanno.

At least 181 records · Page 10Linked to original sources
PubMed1993

[New evolvement of antiarrhythmic drugs].

The Cardiac Arrhythmia Suppression Trial (CAST) casted serious doubts on the usefulness of Class I antiarrhythmic drugs, causing us to turn our attention from drugs impairing conduction of excitation in the myocardium by blocking sodium channels toward those producing increased refractoriness of myocardial cells by blocking potassium channels. This change in the direction of thinking from the "Na+ channel paradigm" to "K+ channel paradigm" resulted in the generation of newly synthetized Class III drugs that have the common electrophysiological property of suppressing outward K+ currents (IK, IK1, Ito) without affecting inward currents (INa, ICa). However, their reversed use-dependence of action potential duration prolonging effect contributes to their untoward action of proarrhythmias. It is still controversial if ion channel blockers acting solely on a certain kind of ion channels are more beneficial than drugs having compound actions such as amiodarone or sotalol. Molecular biology, if combined with arrhythmology, is expected to provide new chemical and pharmacological bases for creating novel antiarrhythmic drugs.

Action Potentials↗
PubMed1993

The mouse Mel-18 "RING-finger" gene: genomic organization, promoter analysis and chromosomal assignment.

The chromosome gene for mouse Mel-18 (mMel-18) protein has been isolated and characterized. The entire mMel-18 gene is composed of thirteen exons spanning about 15 kilobases, in which the protein is encoded by exons 5-13. The "RING-finger" motif of Mel-18 protein that displays a significant evolutionary resemblance to other RING-finger nuclear proteins is encoded by exons 5 and 6. Exon 13 encodes a C-terminal proline/serine-rich domain that is homologous to some transactivator proteins. Sequence analysis of the 5'-flanking region revealed the presence of potential binding sites for transcription factors such as SP-1, NF-1, NF-kappa B and c-myc/max. At least two major cap sites and three minor cap sites were identified by S1 mapping and primer extension analysis. We propose that the mMel-18 gene is regulated by two different types of promoters, the CAAT-TATA box promoter and the GC-rich TATA-less promoter. The 2.4 kb DNA fragment of the 5'-flanking region exhibited constitutive promoter activity when transfected into L cells. By the in situ hybridization method, the mMel-18 gene was assigned to mouse chromosome 10C3.

Animals↗
PubMed1993

A dual-component positive inotropic effect of endothelin-1 in guinea pig left atria: a role of protein kinase C.

This study was designed to analyze the mechanism(s) underlying the positive inotropic effect (PIE) of endothelin-1 (ET-1) in the guinea pig left atrium. ET-1 exhibited a greater PIE at lower frequencies of pacing and potentiated significantly the postrest contraction similar to isoproterenol. However, ET-1 prolonged the duration of a single contraction, whereas isoproterenol shortened it. ET-1 was similar to methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate in the prolonged duration of a single contraction but different from this drug in the force-frequency relationship. ET-1 at concentrations of 10 nM and higher caused a dual-component PIE composed of an initial increasing phase (early component) and a second greater positive inotropic phase (late component). The early component was correlated to the ET-1-induced prolongation of the duration of the action potential in the time course. Both nifedipine and ryanodine suppressed the late component much more than the early component. ET-1 (> or = 3 nM) produced significant stimulation of phosphoinositide hydrolysis as measured by [3H]inositol monophosphate accumulation. ET-1 was found to activate protein kinase C (PKC) instantaneously but transiently (evaluated by the translocation of PKC activity to the particulate fraction). Pretreatment with 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine and staurosporine, PKC inhibitors, markedly inhibited the late component of the PIE of ET-1 without affecting the early component. These data indicate that the two components of the PIE induced by ET-1 in the guinea pig left atrium may be mediated by different mechanisms. The early component may be attributed to the increased Ca++ influx as a result of the prolongation of the duration of the action potential, whereas the late component may be linked to stimulation of phosphoinositide hydrolysis and subsequent PKC activation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Transfusion-associated graft-versus-host disease.

We reported two patients showed similar clinical course after blood transfusion. Case 1 was 74-year-old female, received transfusion of 200 ml of whole blood from her son, because of hemorrhagic shock for fematemesis from gastric ulcer. After transfusion, she died of liver dysfunction and severe aplastic anemia. Case 2 was a 73-year-old male, received transfusion of three unites of concentrated red blood cells for anemia following the orthopaedic treatment. High fever and erythema was appeared suddenly after transfusion. He died of liver dysfunction and the autopsy was performed. In case 1 the diagnosis was transfusion-associated graft-versus-host disease (GVHD) and in case 2 drug-induced-aplastic anemia (DIAA) was suspected. Differentiating the diagnosis between GVHD and DIAA is clinically difficult.

Aged↗
PubMed1993

[A case of Fontan operation for complex heart disease with good post-operative course by the management of hypothermia in coming off from cardiopulmonary bypass].

A 8-year-old boy with a complex heart disease was underwent Fontan operation with Glenn operation, and had a good post-operative course by the management of hypothermia in coming off from cardiopulmonary bypass around 31 degrees C. The hypothermic therapy was thought to be effective in acute stage after Fontan operation, because it improved tachycardia, decreased the systemic metabolism, redistributed the systemic arterial blood flow and increased the urinary output.

Child↗
PubMed1993

Association between gallbladder cancer and anomalous union of the pancreaticobiliary ductal system.

Between 1978 and 1989, gallbladder cancer was diagnosed in 17 out of 48 patients with anomalous union of the pancreaticobiliary system. The clinical, surgical, and pathological features of these 17 patients are described. We classified them into two groups, those with and those without dilation of the common bile duct, and compared the clinicopathological features. Patients with dilation of the bile duct often had early onset of symptoms, so that cancer was detected at a relatively early stage. Most of those without dilation of the common bile duct already had a number of severe symptoms at the first consultation, and the cancer was usually at an advanced stage. We believe that early diagnosis of patients without dilation of the bile duct is an important clinical problem that needs to be resolved.

Adult↗
PubMed1992

Expression of p53 protein in colorectal cancer and its relationship to short-term prognosis.

BACKGROUND AND METHODS: The expression of p53 protein in 100 large bowel cancers was studied immunohistochemically by use of a monoclonal antibody (PAb1801). RESULTS: Immunoreactivity was found in 61.0% of specimens from 100 patients with colorectal cancer. The pattern of p53 expression was mainly detected in the nuclei of the cancer cells. There was no significant correlation between the expression of p53 and the histologic grade, tumor size, serosal invasion, lymphatic invasion, venous invasion, lymph node metastasis, or liver metastasis. However, patients with p53-positive tumors had a greater relative risk of death compared with those with p53-negative tumors. The p53 negative-tumors showed a recurrence rate of 5.9%; for the p53 positive-tumors, a recurrence rate of 23.8% was recorded. The 3-year survival rate was 96.7% of 39 patients with p53-negative carcinomas and 61.8% for the patients with p53-positive tumors; there was a significant difference in the rate between the two groups of patients (P < 0.05). The growth fraction of p53-positive tumors determined with a monoclonal antibody against DNA polymerase alpha (49.0%) was significantly higher than that of p53-negative tumors (40.7%, P < 0.01). CONCLUSIONS: These results suggest that the immunoreactivity of p53 may be a biologic marker of prognostic significance.

Analysis of Variance↗
PubMed1992

Cloning of the 62-kilodalton component of basic transcription factor BTF2.

Cloning of the mammalian basic transcription factors serves as a major step in understanding the mechanism of transcription initiation. The 62-kilodalton component (p62) of one of these transcription factors, BTF2 was cloned and overexpressed. A monoclonal antibody to this polypeptide inhibited transcription in vitro. Immunoaffinity experiments demonstrated that the 62-kilodalton component is closely associated with the other polypeptides present in the BTF2 factor. Sequence similarity suggests that BTF2 may be the human counterpart of RNA polymerase II initiation factor b from yeast.

Amino Acid Sequence↗
PubMed1992

Genomic structure of the putative BTF3 transcription factor.

On the basis of the amino acid (aa) sequence of the putative BTF3 transcription factor, two complementary DNAs coding for the two proteins, BTF3a and BTF3b, have been cloned from a HeLa cell cDNA library. The two proteins are identical, except that BTF3b lacks the first 44 N-terminal aa present in BTF3a. These proteins originate from the same gene, which contains seven exons, and are the products of alternative splicing. The promoter region, containing a putative TATA box(es) and a CAAT box sequence, was identified. In addition, three other BTF3-like genes were characterized.

Amino Acid Sequence↗
PubMed1992

Molecular cloning and characterization of the gene encoding mouse melanoma antigen by cDNA library transfection.

We have isolated a cDNA (H52) of 2.8-kb-long encoding an 80-kDa mouse melanoma Ag that is defined by a syngeneic anti-B16 melanoma mAb with an ability to block anti-melanoma cytotoxic T cell responses. H52 transfectants were brightly stained with the antibody, and the 80-kDa molecule was immunoprecipitated from the transfectants. Northern blot analysis showed that this transcript was detected in mouse melanoma cells of C57BL/6 and DBA/2 origin, C1300 A/J neuroblastoma, L cell (C3H) and EL-4 T lymphoma (C57BL/6), faintly in BW5147 (AKR) T lymphoma, but not in other tumors, such as S913 fibrosarcoma (C57BL/10), NIH3T3, 70 Z/3 pre-B lymphoma, and P3U1 plasmacytoma (BALB/c). Since the transcripts were not found in normal C57BL/6 tissues of fetus, newborn, and adult origin, the H52 expression is associated with transforming phenotypes. However, no tissue- or cell type-specific expression was observed. Nucleotide sequence analysis has clearly demonstrated that H52 cDNA encodes the full length of the env gene and long terminal repeat region of endogenous ecotropic murine leukemia provirus of AKV-type, which is defective in C57BL/6. The H52 envelope protein has several amino acid changes compared to those of AKV, one of which is in the env 14 peptide region preferentially associated with MHC molecule, suggesting the possible reason for the difference of antibody reactivity even in H52-positive tumors. We also demonstrate that CTL against H52 transfectant kills B16 melanoma. Thus, the above results are direct evidence that even the endogenous self molecule, when constitutively expressed, does act as a tumor Ag.

Amino Acid Sequence↗
PubMed1992

Expansion of murine T cells bearing a unique T cell receptor beta-chain in Friend virus-induced tumor in situ.

Heterogeneity of V alpha 1+ and V beta 10+ TCR alpha beta-chains, which are predominantly used in anti-FBL-3 CTL clones established in vitro, was investigated at a nucleotide level in FBL-3 tumor-infiltrating lymphocytes (TIL) in vivo. The majority (90%) of V beta 10+ beta-chains dominated in TIL used homogeneous V beta 10D beta 2.1 sequences identical to that used in the T cell clones with cytotoxic functions. The homogeneous TCR beta-chain expression was dominant and found to be about 10% of the total TCR beta-chains in the TIL population, which was a greater than 300-to 900-fold increase than in the regional lymph nodes. This is in good agreement with the in vitro data showing that about 11% CTL clones used the homogeneous V beta 10D beta 2.1+ beta-chain. However, the J beta segment does not seem to contribute greatly to the recognition and selection of this TCR because some of homogeneous VD+ beta-chains were associated with J beta segments other than J beta 2.7 of the CTL clones. The frequency of the V alpha 1J alpha 112-2+ alpha-chain expression of the CTL type was much less (3- to 80-fold increase compared to that of lymph node) and also varied in sample materials, indicating the lower contribution of the alpha-chain for the oligoclonality of the TCR. The results were also confirmed by quantitative PCR and RNase protection assays. This suggests that the dominant expression of the homogeneous TCR beta-chain is due to the expansion of the particular anti-FBL-3 CTL in the tumor in situ. Also, the TCR beta-chain, especially the V beta D beta region, rather than alpha-chain is more important for the recognition and selection of the anti-FBL-3 TIL with cytotoxic functions.

Amino Acid Sequence↗
PubMed1992

Glibenclamide does not block arterial relaxation caused by vasoactive intestinal polypeptide.

Vasoactive intestinal polypeptide (VIP) caused a concentration-dependent relaxation in rabbit mesenteric artery with intact endothelium. The relaxant response to VIP was inhibited by the removal of the endothelium or by pretreatment with methylene blue, but not by pretreatment with glibenclamide. A small but significant relaxant response to VIP in the endothelium-denuded artery was also unaffected by glibenclamide. These findings indicate that ATP-sensitive K+ channels are not involved in the endothelium-dependent or endothelium-independent arterial relaxation elicited by VIP.

Animals↗
PubMed1992

Effects of Cl- channel blockers on beta-adrenoceptor-mediated decreases in resting potential and intracellular Cl- activity in guinea-pig heart.

In order to find a more specific blocker of the cardiac Cl- channel, we examined the effects of anthracene-9-carboxylic acid (9AC) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) on the beta-adrenoceptor-mediated decreases in resting potential and intracellular chloride ion activity (aiCl) in guinea-pig papillary muscles by using Cl- ion selective microelectrodes. 9AC (1 mM) significantly inhibited the isoproterenol (1 microM)-induced decreases in resting potential and aiCl in quiescent preparations. However, 1 mM DIDS did not significantly affect the changes in aiCl and resting potential during beta-adrenergic stimulation. Thus, in cardiac cells, 9AC is a more potent blocker of the Cl- channels activated by beta-adrenergic stimulation than DIDS.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Electrophysiologic and anticholinergic effects of pirmenol enantiomers in guinea-pig myocardium.

Since it has been reported that several class I drugs stereoselectively block sodium channels, potassium channels and muscarinic receptors in cardiac tissues, electrophysiologic and anticholinergic effects of enantiomers of pirmenol, a class I antiarrhythmic drug, were examined. Both (+) and (-) pirmenol depressed the maximum upstroke velocity (Vmax) of the action potential in a concentration-dependent manner in guinea-pig papillary muscles driven at 1.0 Hz, and there was no significant difference in the potency of the class I effect between the enantiomers. The onset rates of use-dependent block (UDB) of Vmax at 2.0 Hz for 10 mumol/l (+) and (-) pirmenol were 0.30 +/- 0.03 and 0.29 +/- 0.01 per action potential, and the recovery time constants from UDB for (+) and (-) pirmenol were 27.0 +/- 2.7 and 27.7 +/- 1.9 s, respectively, indicating no difference in the binding and unbinding kinetics to the sodium channel between the enantiomers. Both (+) pirmenol and (-) pirmenol prolonged action potential duration (APD) at low concentrations (1-10 mumol/l) and shortened it at high concentrations (30-100 mumol/l). Again, there was little difference with respect to the effects on APD between the enantiomers. However, in the isolated guinea-pig left atria (-) pirmenol more potently antagonized the negative inotropic effect of carbachol than (+) pirmenol, and the pA2 values for (+) and (-) pirmenol were 6.41 and 6.71, respectively. The functional study was supported by the radioligand binding experiments using [3H]N-methylscopolamine ([3H]NMS) in guinea-pig left atrial membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1992

Intraperitoneal hyperthermic treatment for peritoneal dissemination of colorectal cancers.

Continuous hyperthermic peritoneal perfusion (CHPP) combined with administration of anticancer drugs was performed in eight colorectal cancer patients with peritoneal dissemination. An overall response rate of 50 percent was achieved in the eight patients. Two of three complete responders are long, recurrence-free survivors for 15 and 30 months. The two-year survival has been achieved in 18.8 percent of the patients receiving CHPP, and this rate is significantly higher than the rates in P2 and P3 patients who did not receive CHPP. The complications of CHPP with administration of anticancer drugs were mild bone marrow suppression in two (25 percent) of the eight patients and also a mild grade of renal dysfunction in one (12.5 percent), though not lethal. The results suggest that the combination of CHPP with the administration of anticancer drugs is a safe and effective therapy for peritoneal dissemination of colorectal cancers.

Adult↗
PubMed1992

Effect of SMS 201-995 on exocrine pancreatic secretion in a patient with external pancreatic fistula.

The effect of SMS 201-995 on pancreatic exocrine function was studied. The SMS 201-995 was administered to a patient with an artificial external pancreatic fistula following pancreaticoduodenectomy. Variations in pancreatic exocrine function were assessed by determining the volume and components of the fistula fluid during the following periods: 5 d prior to SMS 201-995 administration, for 5 d during actual administration, and for 5 d after it had been discontinued. The SMS 201-995 was administered by subcutaneous injection of 100 micrograms every 12 h for the first 2 d and then 100 micrograms every 6 h for 3 d. This experiment demonstrated that SMS 201-995 has a strong inhibitory effect on pancreatic exocrine function, markedly reducing the amount of fistula fluid and the production of amylase, total protein, and bicarbonate.

Female↗