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Biomedical subjects

K Matsubara

Publications and source records attributed to K Matsubara.

At least 127 records · Page 7Linked to original sources
PubMed1998

Endogenously occurring beta-carboline induces parkinsonism in nonprimate animals: a possible causative protoxin in idiopathic Parkinson's disease.

To examine whether simple beta-carbolines induce parkinsonian-like symptoms in vivo via N-methylation, the simple beta-carbolines norharman (NH), 2-mono-N-methylated norharmanium cation (2-MeNH+), and 9-mono-N'-methylnorharman (9-MeNH) were systematically administered to C57BL/6 mice for 7 days. These substances induced bradykinesia with reduction of locomotion activity. NH or 2-MeNH+ decreased dopamine (DA) contents to 50-70% of values in controls in the striatum and midbrain. 9-MeNH potently decreased not only DA but also serotonin content in various regions. Immunohistochemical examination revealed that the numbers of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta of NH- and 9-MeNH-treated mice were diminished to 76 and 66% of values in control mice, respectively. The formation of a toxic metabolite, 2,9-di-N,N'-methylated norharmanium cation (2,9-Me2NH+), was 14 and eight times higher in the brain of mice receiving 9-MeNH than that in NH- and 2-MeNH+-treated mice, respectively. In cultured mesencephalic cells from rat embryo, 2,9-Me2NH+ selectively killed TH-positive neurons only at a lower dose but was toxic to all neurons at higher doses. Thus, the excess formation of 2,9-Me2NH+ would induce nonspecific neurotoxicity. These results indicated that 9-indole nitrogen methylation should be the limiting step in the development of the toxicity. NH, a selective dopaminergic toxin precursor, is sequentially methylated to form 2,9-Me2NH+, which could be an underlying factor in idiopathic Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Significance of a diastolic notch in the uterine artery flow velocity waveform induced by uterine embolisation in the pregnant ewe.

OBJECTIVE: To investigate the relation between placental embolisation and the diastolic notch in the uterine artery flow velocity waveform of pregnant ewes under general anaesthesia. METHODS: Seven pregnant ewes at a gestation 16 to 17 weeks were anaesthesized and microbeads of gelfoam were injected into the uterine artery; changes in the uterine circulation were assessed by Doppler velocimetry. RESULTS: Gelfoam embolisation reduced uterine blood flow in a dose-dependent manner, from a mean (95%, CI) of 568 mL/min (495-641) to 159 mL/min (131-187) after the injection of 30 mg of gelfoam, and increased the uterine vascular resistance from 135 mmHg x min x L(-1)(103-167) to 498 mmHg x min x L(-1) (422-574). A diastolic notch in uterine artery flow velocity waveform was observed after 20 mg to 25 mg of gelfoam in two ewes and after injection of 30 mg of gelfoam in all seven animals. Injection of 30 mg of gelfoam increased the pulsatility index to 2.4 (1.9-2.9) from 0.6 (0.5-0.7). The mean uterine vascular resistance at the time of the appearance of a diastolic notch was 414 mmHg x min x L(-1)(377-451). CONCLUSION: These findings suggest that an elevated pulsatility index and the presence of a diastolic notch in the uterine artery flow velocity waveform are indicators of increased uterine vascular resistance and impaired uterine circulation.

Animals↗
PubMed1998

[A case of human infection with Clinostomum sp].

The genus Clinostomum is a cause of parasitic laryngo-pharyngitis. We report the 15th case of Clinostomum sp. infection in Japan. A 29-year-old female visited our hospital because of throat discomfort and expectoration of a worm by sneezing on November 17, 1997. The pharyngitis was caused by the worm. The worm was morphologically identified as the adult of the genus Clinostomum.

Adult↗
PubMed1998

Disturbance of consciousness associated with hypophosphatemia in a chronically alcoholic patient.

A 69-year-old man with chronic alcoholism was admitted to our hospital due to disturbance of consciousness and oliguria. Emergency laboratory examination revealed metabolic acidosis, hypoglycemia, hyponatremia, mild liver dysfunction, acute renal failure and rhabdomyolysis. After administration of fluids and nutrients and continuous hemodiafiltration, he recovered from all signs and symptoms except for disturbance of consciousness after 7 days. Since severe hypophosphatemia persisted, we administered adequate phosphates, and then his level of consciousness normalized. We discuss the relationships among alcohol abuse, hypophosphatemia and disturbance of consciousness, and recommend that hypophosphatemia be considered a potential cause of disturbance of consciousness in alcoholic patients.

Acidosis↗
PubMed1998

[Metabolic activation of azaheterocyclics induced dopaminergic toxicity: possible candidate neurotoxins underlying idiopathic Parkinson's disease].

In 1983, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a contaminant of "synthetic heroin", has been reported to induce parkinsonian symptoms in humans, who were responsive to L-DOPA therapy, as a result of the degeneration of nigrostriatal neurons. The "MPTP story" hypothesizes that Parkinson's disease may be initiated or percipitated by environmental and/or endogenous toxins by a mechanism similar to that of MPTP in genetically-predisposed individuals. Several classes of heterocyclic molecules structurally related to MPTP have been advanced as possible neurotoxicant precursors underlying the nigrostriatal degeneration in Parkinson's disease. Indoleamine-related beta-carbolines (beta Cs), a class of heterocyclics which are basically plant alkaloids, are proposed as the most promising natural MPTP-like toxicants or protoxicants. In this article, beta Cs and N-methylated beta C cations are reviewed with regards to their formation, bioactivation, toxicity and presence in the human central nervous system. The enzymes in mammalian brain particulate fractions methylate beta Cs, sequentially forming 2-mono-[N]-methylated (2-Me beta C+s) and neurotoxic 2,9-di-[N, N']-methylated (2,9-Me2 beta C+s) beta-carbolinium cations. These beta C+s are structural analogs of 1-methyl-4-phenylpyridinium ion (MPP+), an active metabolite of MPTP, with a nitrogen bridge. The beta C+s not only inhibit DA reuptake and tyrosine hydroxylase, but also function as NADH-linked respiratory inhibitors in isolated mitochondria. The quarternization of beta C strikingly increased the affinity for dopamine transporter with 2-10 times greater Km and 10 times smaller Vmax values than MPP+. Furthermore, we have found higher concentrations of beta C+s localized in the nigra than in the cortex, and observed the S-adenosyl-L-methionine-dependent methylation of 2[beta]- and 9[indole]-nitrogens of beta Cs in non-parkinsonian human brains. Moreover, the cerebrospinal fluid levels of these beta C+s are higher in parkinsonian than non-parkinsonian patients. Simple beta-carboline induced parkinsonian-like symptoms in mice via N-methylation. These results indicated that beta C is a selective dopaminergic toxin precursor, that is sequentially methylated to form 2,9-Me2 beta C+ that could be an underlying factor in idiopathic Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

[Effects of institutional therapy and factors which influence the prognosis].

We examined the effect of institutional therapy on asthmatic children and evaluating the factors influencing the prognosis. We analyzed the questionnaires and laboratory findings obtained form the 565 children who had been treated with the therapy in National Higashi-Saitama Hospital from April 1978 to March 1997. The institutional therapy seems to be effective in the following 3 aspects. 1) Pulmonary function test such as FEV1.0, and bronchial hypersensitivity test such as acetylcholine inhalation test were improved. 2) Exercise abilities such as free running were improved. 3) More than 40% of the patients had no asthma attack or only a few mild asthma attacks requiring no medication. When compared the group whose symptoms were not improved with the remission group, who had no asthma attack, significant differences were seen in the following points, 1) The dose and the number of the medicines at the end of the hospitalization, 2) the bronchial hypersensitivity test, 3) the age of onset, 4) the age of the symptoms become perennial and 5) the term from the symptoms become perennial to the hospitalization were significantly different. The therapy principles including the recipes for exercise training were not different between the two groups. It is concluded that we should consider institutional therapy or, a combination of physical training and environmental control as one of the most important therepeutic methods when asthmatic symptoms become perennial in spite of the conventional medication.

Asthma↗
PubMed1998

Elevation of serum thrombopoietin precedes thrombocytosis in Kawasaki disease.

Kawasaki disease (KD) is an acute systemic vasculitis causing coronary arterial aneurysms and myocardial infarction in young children. Prominent thrombocytosis with increased megakaryocytes develops during the convalescent period. To clarify the mechanisms of thrombocytosis, we studied serum levels of thrombopoietin (TPO) and other thrombopoietic cytokines in 40 patients with KD (149 samples) and 106 age-matched controls using ELISA. TPO values in the controls were 1.94 +/- 0.69 fmol/ml (mean +/- SD) with a 95% reference interval of 0.85 to 3.27 fmol/ml. In the first week of KD, platelet counts were normal but TPO values increased (approximately 15.5 fmol/ml). TPO levels peaked on day 6 +/- 2 at 5.94 +/- 2.64 fmol/ml and then fell gradually. When platelet counts peaked in the second to third weeks, TPO levels were still high or comparable with the controls. TPO levels in KD patients with normal platelet counts were significantly higher than control levels. Interleukin (IL)-6 levels in the first week rose, but neither IL-11 nor leukemia inhibitory factor was detectable. These results suggest that TPO contributes to thrombocytosis in KD in conjunction with IL-6 and TPO production may be enhanced during the acute phase.

Child↗
PubMed1998

Isolation and characterization of human cathepsin V: a major proteinase in corneal epithelium.

PURPOSE: To isolate and characterize a novel cathepsin gene, as part of the systematic isolation of genes uniquely active in corneal epithelium. METHODS: For the isolation of a full-length cDNA clone, a probe was selected from a set of expressed sequence tag clones classified as unique to corneal epithelium. Inserted cDNA was introduced into insect cells using a baculovirus expression system, and the secretion of recombinant protein was identified using antisera against a synthetic peptide. Proteolytic activity was determined using bovine serum albumin (BSA) as substrate. The expressions of the novel cathepsin in human cornea and other tissues were examined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The full-length cDNA clone encoded a peptide of 334 amino acids with 82% identity with bovine cathepsin L and 77% identity with human cathepsin L when aligned. The recombinant protein produced in the baculovirus expression system cleaves BSA, and its activity was inhibited by the cysteine proteinase inhibitors E-64 and leupeptin, but not by pepstatin A, phenylmethylsulfonyl fluoride, and EDTA. By RT-PCR, a low level of expression was observed in some other epithelial tissues of ectodermal origin, but only in cornea was it higher than cathepsin L, which is known to be a general lysosomal cathepsin. Cathepsin V protein was detected in human corneal epithelium by western blot analysis, but not in tear fluid. CONCLUSIONS: The amino acid homology and proteolytic activity of the recombinant protein indicate that the novel gene is a new member of the cathepsins that have features of cysteine proteinase. Its uniquely high expression in corneal epithelium strongly implies an important role in corneal physiology.

Amino Acid Sequence↗
PubMed1998

[Clinical efficacy of concurrent carboplatin, etoposide, and definitive radiotherapy for stage III non-small-cell lung cancer: consideration as to therapeutic outcomes and morbidity].

To improve the therapeutic outcome for inoperable non-small-cell lung cancer, we applied definitive thoracic radiotherapy combined with concurrent administration of carboplatin and etoposide. We retrospectively analyzed 55 eligible patients with Stage III disease. The one-year rate of overall survival (OAS) and distant metastasis-free survival (DMFS) of the total group were 46.1% and 36.1%, respectively. Twenty-nine patients developed thoracic failures (52.7%) and 23 (41.8%) distant failures. Using univariate and multivariate analyses, radiation dose, performance status and LDH were revealed as significant prognostic factors of OAS, and LDH had a strong adverse effect on DMFS. Leucopenia of Grade 3 or higher was noted in 75.9%, anemia in 55.6%, thrombocytopenia in 59.3%, esophagitis in 20.4%, and lung injury in 10.9%. Sufficient gain was not obtained by our strategy, and higher morbidity, especially of lung, was noted than was expected. It was suspected that simultaneous use of oral etoposide might increase radiation pneumonitis, so one should take special care of unexpected toxicity in concurrent chemoradiotherapy. Both the hyperfractionated technique of radiotherapy and the time-dose modification of anti-tumor drugs should be considered in further steps.

Aged↗
PubMed1997

Colocalization of Ras and Ral on the membrane is required for Ras-dependent Ral activation through Ral GDP dissociation stimulator.

Ral GDP dissociation stimulator (RalGDS), a putative effector protein of Ras, stimulated the GDP/GTP exchange reaction of the post-tanslationally lipid-modified but not the unmodified form of Ral in response to epidermal growth factor in COS cells. The RalGDS action on Ral was enhanced by an active form of Ras but not a Ras mutant which was not post-translationally modified in the cells. The RalGDS activity was inhibited by acidic membrane phospholipids such as phosphatidylinositol and phosphatidylserine but not by phosphatidylcholine or phosphatidylethanolamine in vitro. The post-translationally modified form but not unmodified form of Ras, Ral, and Rap were incorporated in liposomes consisting of these phospholipids. When Ral was incorporated alone in the liposomes, RalGDS did not stimulate the dissociation of GDP from Ral. When Ral was incorporated with the GTP-bound form of Ras in the liposomes, RalGDS stimulated the dissociation of GDP from Ral, while the GDP-bound form of Ras did not affect the RalGDS action. The Ras-dependent Ral activation through RalGDS required the Ras-binding domain of RalGDS. Rap, which shared the same effector loop as Ras, also stimulated the dissociation of GDP from Ral through RalGDS in the liposomes, although Rap did not enhance the RalGDS action in COS cells. Taken together with our previous observations that Ras recruits RalGDS to the membrane, these results indicate that the post-translational modifications of Ras and Ral are important for Ras-dependent Ral activation through RalGDS and that colocalization of Ras and Ral on the membrane is necessary for Ral activation in intact cells.

Animals↗
PubMed1997

Molecular cloning and expression of a novel human aquaporin from adipose tissue with glycerol permeability.

In a systematic analysis of genes expressed in human adipose tissue, we detected a novel gene that is expressed uniquely in adipose tissue. The sequence showed that it encodes a 342-amino-acid protein containing six putative transmembrane domains, and is a new member of the aquaporin family of water-selective membrane channels. We named this gene aquaporin 9. It features a cyclic-AMP protein kinase phosphorylation consensus site in the NH3-terminal domain. Expression of the cRNA in Xenopus oocytes yielded a 7-fold increase in osmotic water permeability blocked by 0.3 mM HgCl2, and also facilitated the uptake of glycerol. Northern blot analysis demonstrated that the mRNA is abundant in adipose tissue, but not in other tissues. Thus, this gene product may participate in glycerol transport in adipocytes.

Adipose Tissue↗
PubMed1997

Eighteen novel human genes regionally mapped on chromosome 11.

Expression sequence tags (EST) obtained by sequencing a randomly primed cDNA library and gene signatures (GS) obtained by sequencing a 3'-directed cDNA library can identify genes that are active in the source cells. Eight ESTs and ten GSs which represent novel human genes, except for one GS, and which have been assigned to human chromosome 11 were used to select cosmids from a chromosome 11-specific cosmid library. These cosmids were regionally mapped using the fluorescence in situ hybridization technique.

Animals↗
PubMed1997

A neutral N-methyltransferase activity in the striatum determines the level of an endogenous MPP+-like neurotoxin, 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion, in the substantia nigra of human brains.

An endogenous MPTP-like dopaminergic neurotoxin, N-methyl(R)salsolinol, increases in the parkinsonian cerebrospinal fluid and accumulates in the human nigro-striatum. An N-methyltransferase specific for (R)salsolinol was found in human brain with optimal pH at 7.0 and 8.5. The correlation of the enzyme activity with the level of N-methyl(R)salsolinol and its oxidation product, 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion was examined in the brain regions. Neutral N-methyltransferase activity in the striatum was found to correlate with the level of the endogenous MPP+-like isoquinolinium ion in the substantia nigra (P < 0.001). Considering that this neutral N-methyltransferase activity increases in parkinsonian lymphocytes, the enzyme may be an endogenous factor in the pathogenesis of Parkinson's disease.

Caudate Nucleus↗
PubMed1997

Chromosome assignment of aberrant NotI restriction DNA fragments in primary hepatocellular carcinoma.

DNA aberrations in human hepatocellular carcinoma (HCC) were studied by two-dimensional DNA electrophoresis analysis. Five intensified and 60 dwindling spots were detected recurrently in the two-dimensional profile which showed about 3000 restriction DNA fragments as distinctive spots. We assigned these aberrant spots to chromosomes, using the chromosome-assigned two-dimensional profile. Four of the five intensified, and 53 of the 60 dwindling spots were given chromosome assignments. Intensified spots were assigned to chromosomes 5, 6, 9 through 12, 16 and 18. Among the dwindling spots, the highest incidence of aberrations was found on chromosome 16, followed by 9 through 12 and chromosome 2. No aberrations were detected in chromosomes 7, 21, 22 or Y.

Carcinoma, Hepatocellular↗
PubMed1997

Cloning of a cDNA encoding a novel sugar transporter expressed in the neonatal mouse hippocampus.

While analyzing active genes in the neonatal mouse hippocampus, we observed several novel genes that were abundantly expressed in this tissue. We report here cloning and sequencing of one of these transcripts, HiAT1 (Hippocampus Abundant Gene Transcript 1). The mRNA was 2.7 Kb in length, and the deduced amino acid sequence consisted of 490 amino acids with characteristics typical of members of the sugar transporter family. However, its overall sequence homology to known transporter cDNAs was only about 30%, suggesting strongly that it represents a novel sugar transporter gene. Northern hybridization analyses showed this transcript is detected in adult and embryonic brains, as well as in other tissues.

Amino Acid Sequence↗
PubMed1997

Isolation of a cDNA encoding a widely expressed novel zinc finger protein with the LeR and KRAB-A domains.

We have isolated a human cDNA clone representing a novel human gene. The predicted 683-amino-acid protein, designated FPM315, contains nine C2H2-type zinc finger motifs and two regions homologous to the LeR domain, a finger-associated structural domain, and the A element of the Kruppel-associated box (KRAB) domain involved in transcriptional repression. The FPM315 mRNAs were expressed in all human tissues so far examined. A cross-species genomic hybridization indicates that the FPM315 gene is highly conserved among eukaryotes. These data suggest that FPM315 might play an important role in basic cellular processes.

Amino Acid Sequence↗