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Biomedical subjects

M Kitahara

Publications and source records attributed to M Kitahara.

At least 55 records · Page 3Linked to original sources
PubMed1999

[A case of SLE with positive antiphospholipid antibody and various coagulopathy].

We described an 11 year-old boy with systemic lupus erythematosus (SLE) and various coagulopathy. He had purpura on the legs, pancytopenia, positive anti-DNA antibodies and hypocomplementia. Hematological examination also showed that platelet counts were 80 x 10(3)/microliter, lupus anticoagulant and anticardiolipin antibodies were positive. The aPTT was remarkably prolonged. Those laboratory findings fulfilled the criteria of antiphospholipid syndrome. Following treatment with predonisolone and heparin, thrombocytopenia improved. When heparin discontinued and renal biopsy was performed, severe thrombocytopenia recureded. FDP and FDP-DD became high, but the aPTT was not prolonged. Thrombocytopenia didn't improved by the therapy with heparin, high dose of methylpredonisolone, FOY and gamma-globulin. However by the therapy with both warfarin and cyclophosphamide, remarkable improvement of coagulopathy was absorbed. Probably anticardiolipin antibodies and disseminated intravascular coagulation (DIC) participate in the various coagulopathy in this case.

Antibodies, Antiphospholipid↗
PubMed1999

Lupus nephritis in juvenile myelomonocytic leukemia.

A 13-year-old girl developed lupus nephritis and Hashimoto thyroiditis in the chronic phase of juvenile myelomonocytic leukemia (JMML). At age 7 months, she was diagnosed as having JMML based on the hepatosplenomegaly, leukocytosis, thrombocytopenia, increased levels of fetal hemoglobin, and spontaneous in vitro growth of granulocyte-macrophage progenitors. At the onset of JMML, she had hypergammaglobulinemia, antinuclear antibodies, rheumatoid factors and anti-smooth muscle antibody. She had been placed on oral 6-mercaptopurine for about 12 years, with clinical improvement. At age 13 years, she was found to have hematuria and proteinuria. She also developed arthritis and Raynaud's phenomenon as well. She had antinuclear antibodies, rheumatoid factors, LE phenomenon, beta-1C (C3) nephritic factor (C3NeF), antithyroid antibodies, and hypocomplementemia. The renal biopsy specimens revealed a diffuse increase in the mesangial cells and matrix by light microscopy, and intense staining of IgG, Clq and C3 by immunofluorescence microscopy. The hormonal study ultimately showed decreased thyroid functions. So she was diagnosed as lupus nephritis and Hashimoto thyroiditis. The patient is the first example to show close relationship between stem cell abnormalities in JMML and development of overt autoimmune disorders.

Adolescent↗
PubMed1999

[T cell non-depleted bone marrow transplantation for primary refractory erythroleukemia using a partially HLA-mismatched related donor].

We performed an HLA-mismatched T cell non-depleted bone marrow transplant on a 53-year-old man with acute erythroleukemia that was highly resistant to conventional remission-induction chemotherapy. After conditioning that included total body irradiation, the patient received a two-HLA-antigen-mismatched bone marrow graft harvested from his sister using tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis. He successfully established rapid engraftment accompanied by steroid-responsive GVHD localized to the skin. Although bone marrow samples on day 31 and day 66 disclosed a complete remission with full donor chimerism, the patient relapsed and died of pulmonary infection on day 154. There is evidence that tacrolimus is effective in alleviating GVHD. Selected patients who have partially mismatched related donors with less HLA disparity may benefit from tacrolimus-based T cell non-depleted bone marrow transplants because of the more potent graft-versus-leukemia effect that can be expected compared to transplants using T cell depleted inoculum.

Bone Marrow Transplantation↗
PubMed1998

cDNA cloning and genomic organization of peroxisome proliferator-inducible long-chain acyl-CoA hydrolase from rat liver cytosol.

The cDNA for a peroxisome proliferator-inducible long-chain acyl-CoA hydrolase from rat liver cytosol, referred to as rLACH2, was isolated and its genomic structure was determined. The cDNA encoded a 419-amino-acid polypeptide with a calculated molecular weight of 46,011. Sequence analysis identified an active-site serine motif (Gly-x-Ser-x-Gly) common to carboxylesterases and lipases. When expressed in Escherichia coli, the cDNA directed expression of a protein immunoreactive to an anti-rLACH2 antibody with a molecular mass of 47 kDa, identical to that of purified rLACH2. Northern blot analysis showed marked induction of rLACH2 mRNA in the liver after feeding rats with di(2-ethylhexyl)phthalate, a peroxisome proliferator. The rLACH2 gene spanned about 19 kb and comprised 3 exons, the intron/exon boundaries of which were consistent with the donor/acceptor splice rule. A putative peroxisome proliferator response element (AGGTCATGGTTCA) was identified in the 5'-flanking region, suggesting the involvement of peroxisome proliferator-activated receptors in the regulation of rLACH2 gene expression.

Amino Acid Sequence↗
PubMed1998

The inhibitory effect of lycorine on tumor cell apoptosis induced by polymorphonuclear leukocyte-derived calprotectin.

We recently demonstrated that calprotectin, an abundant calcium-binding protein complex in polymorphonuclear leukocytes (PMNs), has the capacity to induce growth inhibition and apoptotic cell death against a variety of tumor cell lines and normal cells such as fibroblasts. Therefore, calprotectin which is released to extracellular spaces, might cause tissue destruction in severe inflammatory conditions. In search of drugs to suppress the cytotoxic effects of calprotectin, we screened plant products that have been used as Chinese medicines. Using MM46 mouse mammary carcinoma cells as targets, we found that hot water extracts of Crinum asiaticum showed strong inhibition of calprotectin-induced cytotoxicity in vitro. By purification studies, we identified the alkaloid, lycorine, as the active inhibitory molecule. Lycorine inhibits not only induction of MM46 cell death by calprotectin but also inhibits the suppressive effect of calprotectin on target DNA synthesis at a half effective concentration of 0.1-0.5 microg/ml. Lycorine has been reported to posses inhibitory activity against protein translation. Since we previously showed that target protein synthesis is necessary for induction of cell death and that calprotectin actually upregulates the net protein synthesis of MM46 cells, we compared the dose-response relationship between the inhibitory effects of lycorine on calprotectin action and target protein synthesis. Although 1 microg/ml lycorine did not bring about marked inhibition of protein synthesis in MM46 cells without calprotectin, it attenuated the protein synthesis that was augmented by calprotectin to the level of protein synthesis in cells not treated with calprotectin. These results suggest that lycorine inhibition for calprotectin cytotoxicity is not solely due to its inhibitory effect on protein synthesis.

Amaryllidaceae Alkaloids↗
PubMed1998

NK-104, a newly developed HMG-CoA reductase inhibitor, suppresses neointimal thickening by inhibiting smooth muscle cell growth and fibronectin production in balloon-injured rabbit carotid artery.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to suppress smooth muscle cell growth and arterial neointimal thickening. In this study, to elucidate the potency and mechanisms of NK-104 ((+)-monocalcium bis[(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoate], CAS 147526-32-7) in neointimal thickening, the effect of NK-104 on the neointimal thickening, Br-dU-labeled cell number and extracellular matrix immunohistochemistry were examined in balloon-injured rabbit carotid artery. NK-104 suppressed the neointimal thickening dose-dependently, and the suppression was 69.5% at 1.0 mg/kg. NK-104 suppressed the intimal total and Br-dU-labeled cell number. Fibronectin and type I collagen were observed in 81% and 38% of the total intimal area in the control arteries, respectively, and the areas occupied by fibronectin and type I collagen were significantly decreased by 1.0 mg/kg NK-104 to 39% and 22%, respectively. The decrease in fibronectin per cell was more potently demonstrated. Aortic total and activated TGF-beta contents that were markedly increased in the injured artery were increased further by NK-104. NK-104 concentration-dependently suppressed fibronectin content of the basement lesion in rabbit primary cultured smooth muscle cells. These findings suggest that NK-104 suppresses balloon-injury-induced neointimal thickening through inhibition of intimal smooth muscle cell growth and extracellular matrix accumulation.

Animals↗
PubMed1997

A conjugative linear plasmid in Streptomyces laurentii ATCC31255.

Plasmid pSLL of Streptomyces laurentii ATCC31255 (wild-type strain P0) is a 93-kilobase linear DNA plasmid that carries a protein bound to each 5' end of the DNA. It was self-transmitted to the pSLL-cured strain by conjugation in solid culture. The pSLL-cured strain carried a circular plasmid, pSLS, and showed a marked decrease in spore formation and thiostrepton productivity, owing to the pSLS. However, by retransmission of pSLL, these things reverted to levels seen in strain P0. Thus, plasmid pSLL suppressed the injurious effects of pSLS on the host mycelia.

Anti-Bacterial Agents↗
PubMed1997

Pharmacological profile of a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

Pharmacological properties of NK-104 ((+)-monocalcium bis¿(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl++ +]-3,5-dihydroxy-6- heptenoate¿, CAS 147526-32-7), a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, were investigated. The kinetic study, using rat liver microsomal HMG-CoA reductase, revealed that NK-104 is a competitive inhibitor of HMG-CoA reductase with a Ki of 1.7 nmol/l. To examine the inhibitory effect on sterol synthesis in vivo, de novo synthesis of sterols from [14C]acetate 3 h after oral administration of NK-104 was measured in rats. NK-104 showed marked inhibition in liver (ED50 0.13 mg/kg) and in ileum (ED50 0.20 mg/kg), but much weaker in the other tissues. The inhibitory effect of NK-104 on liver sterol synthesis lasted over 6 h, while that of pravastatin and simvastatin disappeared 6 h after administration of the drugs twice the ED50s. Due to induction of HMG-CoA reductase, initial suppression of hepatic sterol synthesis by pravastatin and simvastatin was compensated, and the cumulative change in hepatic sterol synthesis during 12 h after drug administration was remarkably negative only with long-acting NK-104. Hypolipidemic effects of NK-104 (0.03, 0.1, 0.3 and 1 mg/kg p.o. for 2 weeks) were examined in beagle dogs. NK-104 reduced plasma total cholesterol dose-dependently (13.1, 18.5 and 20.2% at doses of 0.1, 0.3 and 1 mg/kg, respectively), and also plasma triglycerides by 0.1 mg/kg or more. Pravastatin (1 and 3 mg/kg) and simvastatin (3 mg/kg) lowered plasma total cholesterol (14.0, 15.4 and 17.4%, respectively), but did not significantly affect plasma triglyceride levels. These results indicate that NK-104 is a potent, liver-selective, long-acting HMG-CoA reductase inhibitor with a high cholesterol- and triglyceride-lowering potency.

Animals↗
PubMed1997

[A slowly progressed case of brain metastasis and meningeal carcinomatosis from lung cancer].

We reported a case of long survival brain metastasis and meningeal carcinomatosis from lung cancer without radiochemotherapy. A 59-year-old female admitted to our hospital suffered from headache, anorexia and nausea. Papilledema was noticed, and examinations showed a brain tumor in the left parietal lobe and cancer cells in cerebrospinal fluid. Removal of the tumor and ventriculoperitoneal shunt were performed. Pathology showed adenocarcinoma. No neurological deficit was found during the postoperative course and the patient asked for home treatment. She survived for 25 months and spent a useful life in the 15 months after the onset in spite of no radiochemotherapy for meningeal carcinomatosis. In this case, because of the slow progression of the clinical symptoms, it is considered that cancer cells in the cerebrospinal fluid space grow slowly. The first CT and MRI findings of metastatic tumor of this case showed atypical for brain metastasis. Calcifications were found in plain CT and a high intensive tumor in both T1 and T2 weighted images of MRI. Enhancement due to contrast media was very slight in both CT and MRI. We considered that these findings were related to the slow growing of cancer cells.

Adenocarcinoma↗
PubMed1997

[A case of chronic expanding epidural hematoma].

A 7-year-old female was admitted to our hospital with complaints of headache and nausea following mild head injury. Computed tomography (CT) showed a small epidural hematoma (EH) in the right frontal area, but she was kept under observation because of these mild symptoms. Two weeks after admission, repeat CT showed that the EH had gradually increased in size with decreased clot density. A rim of high density was observed on the dural surface. Craniotomy was performed on the 15th day after admission to evacuate the EH. The brown-fluid hematoma was encapsulated by membrane on the dural surface and under the skull. CT 4 months after the operation-showed complete resolution of the EH. Histological examination suggested that chronic expansion of EH had occurred due to repeated hemorrhages from the dural surface membrane.

Child↗
PubMed1995

Identification of the human ERK gene as a putative receptor tyrosine kinase and its chromosomal localization to 1p36.1: a comparative mapping of human, mouse, and rat chromosomes.

From a newly determined cDNA sequence of the human ERK gene, a highly hydrophobic portion was identified upstream of the putative tyrosine kinase domain. This is the first evidence that the ERK protein possesses a receptor-like membrane-spanning structure. Fluorescence in situ hybridization analysis of R-banded metaphase chromosomes revealed that the ERK gene is located in chromosome region 1p36.1. This locus is near the frequent translocation breakpoint or deletion region of neuroblastoma and some other cancers. A comparative mapping study of the mouse and rat homologues indicated that each counterpart maps to the mouse chromosome 4D2.2-D3 and rat chromosome 5q36.13 regions, both of which have conserved linkage homology to human chromosome 1p.

Amino Acid Sequence↗
PubMed1995

CD27/CD70 interaction directly drives B cell IgG and IgM synthesis.

CD27 is a T cell activation antigen expressed on a majority of peripheral blood T cells. CD27 is also expressed on a subpopulation of human B cells, and it is reported that CD27+ B cells secrete both IgG and IgM. CD70, a ligand for CD27, is expressed on activated T and B cells, suggesting an interaction between T and B cells via CD27/CD70 ligation. Here, we analyze B cell immunoglobulin synthesis using a CD70 transfectant and present functional data showing that B cells secrete large amounts of IgG and IgM as a result of the CD27/CD70 interaction. A flow cytometric analysis showed that CD27 expression was increased and CD70 was expressed on tonsillar and peripheral blood B cells after activation with Staphylococcus aureus Cowan strain (SAC) plus interleukin (IL-2). In addition, the proliferation of B cells was enhanced mildly by the addition of CD70 transfectant, and its proliferation was blocked by anti-CD70 mAb. More importantly, the CD70 transfectant enhanced IgG and IgM production by purified B cells greatly in the presence of SAC plus IL-2. The enhancement was completely blocked by the addition of either anti-CD70 mAb or anti-CD27 mAb. Strongly suggesting that the interaction of CD27 with its ligand, CD70, on B cells plays an important role in B cell growth and differentiation to produce IgG and IgM.

Adult↗
PubMed1995

Frequently relapsing minimal change nephrotic syndrome with natural killer cell deficiency prior to the overt relapse of Hodgkin's disease.

A 15-year-old boy developed minimal change nephrotic syndrome (MCNS) during remission of Hodgkin's disease. Natural killer (NK) cell activity was practically absent at the onset of MCNS, with a value of 3% compared with the normal value of 44.1% +/- 7.8% (mean +/- SD). Treatment with prednisolone resulted in transient remission of MCNS and partial improvement of NK cell activity. Extensive investigations for Hodgkin's disease were performed at 1- to 3-month intervals; a relapse finally became apparent 25 months after the diagnosis of MCNS. Successful treatment of Hodgkin's disease resulted in complete disappearance of proteinuria and normalisation of NK cell activity. Frequently relapsing MCNS with NK cells deficiency during remission of Hodgkin's disease appears to imply its subclinical relapse.

Child↗
PubMed1995

Effects of efonidipine hydrochloride on cholesterol esterification mediated by beta-very low density lipoprotein in J774 macrophages.

The effects of efonidipine hydrochloride (efonidipine), a dihydropyridine calcium antagonist, on the cholesterol ester metabolism induced by beta-migrating very low density lipoprotein (beta-VLDL) in J774 macrophages were studied. The cholesteryl ester content in the macrophages was increased by incubation with beta-VLDL, and the increase was inhibited by efonidipine. Oleic acid incorporation into cellular cholesteryl ester was increased by beta-VLDL in J774 macrophages. The incorporation at an early phase of beta-VLDL induction (0-3 hr) was inhibited by efonidipine. This inhibitory effect of efonidipine was greater at an early phase of beta-VLDL induction (0-3 hr) than at a late phase of the induction (8-11 hr). Pretreatment of the cells with efonidipine enhanced the inhibitory effect. Efonidipine also inhibited beta-VLDL degradation but not the binding and association in macrophages without pretreatment. beta-VLDL binding and association to macrophages were decreased by pretreatment of the cells with efonidipine. beta-VLDL metabolism was also decreased by dibutyryl cyclic AMP pretreatment. The decrease of beta-VLDL metabolism by efonidipine was prevented by co-treatment with efonidipine and HA1004, a protein kinase A inhibitor. Furthermore, efonidipine increased the intracellular cyclic AMP content in J774 macrophages. These findings suggest that efonidipine suppresses cholesterol ester deposition in atherosclerotic foam cells by inhibiting the modified lipoprotein metabolism and cholesterol esterification mainly through elevation of the cellular cyclic AMP level.

Animals↗
PubMed1995

Air caloric test with continuous thermal change in patients with vestibular disorders.

In a previous report (1) the author described a new air caloric test with continuous thermal change. In this study, 19 patients with vestibular disorders were examined with this technique, and the results were compared with the results of the water caloric test (30 degrees C, 50 ml, 20 s) in the same subjects. A difference in interaural response to the air caloric test was noted in 9 of the 19 patients (47.4%), greater than with the water caloric test, 5 of 19 (26.3%). The detectability of vestibular disorders with the air caloric test (28 of 38 ears; 73.7%) was significantly higher than that with the water caloric test (8 of 38 ears; 21.1%) (p < 0.01). The air test appeared to estimate vestibular function more precisely, as stimulation by this method is too weak to cause vestibular recruitment.

Adult↗
PubMed1995

Epidemiological and clinical characteristics of Menière's disease in Japan.

From 1975 to 1990, nationwide surveys on Menière's disease were performed three times by the Research Committee of Menière's disease (1975-76) and the Research Committee of Peripheral Vestibular Disorders (1982-84 and 1990) in Japan. Nine hundred and fifty-eight definite Menière cases, 520 in the 1st, 230 in the 2nd and 148 in the 3rd survey, were sampled by the members of the Committees. The epidemiological and clinical characteristics of Menière's disease were analyzed and compared with such control cases as other vertiginous patients, ENT patients without vertigo, and healthy subjects. In Menière's disease, the male to female ratio has changed from even to female predominance over the 15 years the study ran. The age distribution at onset peaked in the forties for males and thirties for females. Significant epidemiological results are summarized as follows: Definite Menière's disease has a higher incidence in married persons and in people with a nervous and precise character, whereas the incidence is lower in obese people. Physical and mental fatigue induced the onset of attacks. Menière's disease happened in day time in many cases, especially during the afternoon. As these epidemiological findings were commonly observed in all the surveys, the results are considered to be universal epidemiological characteristics of Menière's disease in Japan. In the same period, regional investigations were performed by Toyama Medical Association and our University. The male to female ratio in Toyama indicated a more significant female predominance than in the nationwide surveys. The prevalence of Menière's disease in Toyama Prefecture has been almost constant in all surveys, about 17/100,000 since 1974.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗