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Biomedical subjects

M Umeno

Publications and source records attributed to M Umeno.

At least 19 recordsLinked to original sources

Synchrotron-radiation X-ray topography of surface strain in large-diameter silicon wafers.

Using a 300 mm-wide monochromatic X-ray beam obtained at beamline BL20B2 of SPring-8, the difference in surface-strain distribution caused by various steps of silicon-wafer manufacturing, i.e. slicing, lapping, etching, grinding and polishing, was studied. The asymmetric 511 reflection of 21.45 keV X-rays, incident at a glancing angle of 0.26 degrees, was used to obtain topographs over the whole surface of a 200 mm-diameter (100) CZ silicon wafer. Differences in crystallinity and in warp between the surfaces at different steps of the manufacturing process (firstly after the lapping following the slicing, and then after successive etching, grinding and polishing) were clearly observed. The former gave a topographic image over the whole area with a one-shot exposure because of their wide rocking curves (50-70 arcsec FWHM), which indicate poor crystallinity. The latter, on the other hand, showed sharper curves (4-5 arcsec FWHM), which indicate good crystallinity in local areas, and the existence of warp, and therefore required step scanning of omega-rotation to cover the whole surface in topography measurements. The effect of each step in the process is also discussed.

Journal Article↗

Thermal stability of nanocrystalline diamond films grown by biased enhanced microwave plasma chemical vapor deposition.

The thermal stability of nanocrystalline diamond (NCD) films grown on mirror-polished silicon substrates by biased enhanced microwave plasma chemical vapor deposition was investigated. Different pieces of a NCD sample were annealed for 1 h in an ambient argon atmosphere at 200, 400, 600, and 800 degrees C. The structural and mechanical properties of as-grown and annealed samples were assessed. The surface roughness and high hardness of the samples remained fairly constant with annealing temperature.

Argon↗

Gelatinous bone marrow transformation complicated by self-induced malnutrition.

A 48-year-old woman with a history of anorexia nervosa was admitted to our hospital because of malaise, anorexia and edema in the face and legs. She was diagnosed with gelatinous bone marrow and iron deficiency anemia due to severe malnutrition. She was intravenously treated by saccharated ferric oxide and her anemia was improved, but her bone marrow still showed much gelatinous material.

Anorexia Nervosa↗

[A case of lymphocytic interstitial pneumonia].

A 56-year-old female was admitted on November 1995 to our hospital because of the abnormal shadow on her chest X-ray. Although the chest X ray film revealed diffuse reticulonodular shadows in the bilateral lung fields and right hilar lymphadenopathy, she had not any complaints. Furthermore, mediastinal lymphadenopathy and polyclonal hypergammaglobulinemia were noted. For a further examination, transcutaneous thoracoscopic lung biopsy was performed on August 1996. The lung specimens showed a interstitial infiltration of small lymphocytes exclusively around bronchioles. And the diagnosis of lymphocytic interstitial pneumonia (LIP) was made. She had been suffered from bronchial asthma for 27 years. This is the first report of LIP accompanied with bronchial asthma. Its relationship between LIP and bronchial asthma remains unclear. In the 2 years of follow-up, she remained asymptomatic with unchanged chest radiogram. And her pulmonary function was preserved for the 2 years. But lymphocytic interstitial pneumonia may induce malignant lymphoproliferative disease potentially, we should carefully follow up.

Asthma↗

[Anti-platelet antibody and severe thrombocytopenia during interferon-alpha therapy for chronic active hepatitis C].

We herein report a case of chronic hepatitis C where the patient developed severe thrombocytopenia during interferon therapy. The patient was a 61-year-old woman, who received interferon therapy on April 27, 1993 under the diagnosis of C type chronic active hepatitis. After 4 weeks, her platelet count had decreased to 18,000/microliters and intraoral hemorrhage had begun. Although she received 250 mg of methylprednisolone and 20 U of platelet transfusion three times, her platelet count continued to decrease to 4,000/microliters on both May 28, and on June 3, 1993, and so she was transferred to our hospital on June 4. On her second admission to our hospital, although the platelet-associated IgG (PA-IgG) had increased markedly and the megakaryocytes in her bone marrow had decreased, her platelet count had already increased to 37,000/ microliters, and this gradually returned to a normal level accompanied with a decrease of PA-IgG within one month In this case, although we found immunological abnormalities (high level of IgG, positive ANA and positive anti-smooth muscle antibody) prior to interferon treatment, we could not diagnose the patient as having suffered from autoimmune disease, including autoimmune hepatitis, because she did not satisfy the necessary criteria and because she did not have any symptoms suggesting autoimmune disease. We consider that there may be the possibility that interferon induced only an anti-platelet antibodies that caused the high level of PA-IgG and decreased the production level of platelets within the bone marrow.

Adolescent↗

Chronic Prototheca meningitis.

A case of chronic meningitis caused by the achloric alga Prototheca wickerhamii is described, which has persisted for more than 6 years despite treatment with various antifungal agents. For the last year no treatment has been given, but the patient has no complaints.

Adult↗

[A case of SLE with the onset of pleuritis showing eosinophilia and elevation of serum IgE].

A 19 year old female was admitted to our hospital with complaints of fever, dyspnea and chest pain. Chest x-ray film showed a massive right pleural effusion. She was diagnosed to have systemic lupus erythematosus (SLE) because of malar rash, serositis (pleuritis), positive antinuclear antibody and positive anti-DNA antibody. Then she was successfully treated with 50 mg/d prednisolone. This case was unusual and of interest in that she had eosinophilia in the peripheral blood and exudative pleural effusion and a marked elevation of serum IgE level despite no history of allergic diseases and no evidence of parasite infections.

Adult↗

[A case of myelofibrosis that developed polycythemia vera following treatment with ranimustine and then acute myelogenous leukemia (M0)].

A 60-year-old Japanese woman was admitted to our hospital because of fatigue, weight loss and abdominal distension. Myelofibrosis was diagnosed, based on anemia, huge hepatosplenomegaly, leukoerythroblastosis and bone marrow fibrosis. Following treatment with ranimustine, anemia and splenomegaly improved. Seven months after initial therapy of ranimustine, however, polycythemia (RBC 7.39 x 10(6)/microliter; Hb 19.1 g/dl, Ht 65.9%) developed gradually, then RBC decreased to normal level following venesection (total 1,200 ml). After 32 months, blastic transformation occurred. The blasts were negative for myeloperoxidase. By flow cytometric analysis, the cells were positive for CD2, CD13, CD33 and HLA DR. Thus, AML (M0) was diagnosed. Despite of treatment with multicytotoxic agents, she died of DIC 36 months after the initial diagnosis of myelofibrosis. The progression from myelofibrosis to polycythemia is rare and only 15 cases have been reported so far. In addition, although a chromosomal abnormality, 46, XX, t(3; 12) (q25; p11), was present at the time of first diagnosis of myelofibrosis, the development of an additional abnormality, del(11) (q-), might be related to the transformation to AML.

Antineoplastic Agents↗

[Clinical efficacy of sulbactam/cefoperazone for the treatment of geriatric patients with respiratory tract infections].

We performed clinical studies on sulbactam/cefoperazone (SBT/CPZ) for the treatment of geriatric patients with respiratory tract infections. Seven patients with pneumonia, 7 with acute bronchitis, 6 with chronic respiratory tract infections were treated with SBT/CPZ. The patients were administered with a daily dose of 2.0 g or 4.0 g for 4-14 days. The clinical responses were excellent in 3, good in 13, fair in 3, and poor in 1 patients. The efficacy rate was 80.0%. No side effects were observed in any patients, but elevations of GOT, GPT were observed in two cases. Causative organisms were E. coli (2 strains), P. aeruginosa (2), MSSA (1), MRSA (1), S. pneumoniae (1), H. influenzae (1), K. oxytoca (1), and E. aerogenes (1). The bacteriological effect rate was 60%. One strain of MRSA and one of two strains of P. aeruginosa persisted in 2 patients.

Aged↗

Analysis of serum elements and the contaminations from devices used for serum preparation by inductively coupled plasma mass spectrometry.

Two different samples of serum were prepared from a blood specimen by using two types of serum-separation tubes. Each serum sample was diluted by 100 times with deionized and sub-boiling distilled water. Thirty-six elements in the serum and exudate, from devices used for the serum preparation, were determined by inductively coupled plasma mass spectrometry (ICP-MS). From the comparison of elemental concentrations in two groups of 11 serum samples, it was found that the exudate from serum-separation tubes, as well as from disposable stainless steel needles, had serious effects on the elemental concentrations in the serum. Means for the concentrations of Li, Co, Ga, Cd, Sn, Sb, Ba, La, and Ce in the two serum groups were statistically different from each other. The concentrations of Cr, Mn, Fe, and Mo in both groups were apparently higher than those reported in the literature, suggesting contamination from the disposable stainless steel needle and spectral interferences due to molecular species produced in the argon plasma.

Disposable Equipment↗

A multicenter comparison of nicorandil and diltiazem on serum lipid, apolipoprotein, and lipoprotein levels in patients with ischemic heart disease.

The effects of nicorandil and diltiazem on serum lipid, apolipoprotein, and lipoprotein levels in 37 patients with ischemic heart disease were examined in a randomized, multicenter study. Nicorandil (n = 20, 10-40 mg/day, b.i.d.) and diltiazem (n = 17, 60-240 mg/day, b.i.d.) were administered for 12 weeks. Both nicorandil and diltiazem administration showed an effective antianginal effect. Diltiazem administration showed a significant hypotensive action. There were no significant changes in serum lipids, apolipoproteins, and lipoproteins for both nicorandil and diltiazem. There were no significant changes in body weight, uric acid, and fasting blood sugar levels during the test period for both drugs. These data show that nicorandil, like diltiazem, does not have any adverse effects on lipid metabolism and that it is a favorable drug to use as an agent for treating arteriosclerotic heart disease.

Aged↗

Microsomal ethanol oxidizing system: transcriptional and posttranscriptional regulation of cytochrome P450, CYP2E1.

CYP2E1 is solely responsible for microsomal P450-mediated ethanol oxidation activity. This enzyme is also involved in a pathway leading to gluconeogenesis from ketone bodies and in metabolic activation of numerous foreign compounds to intermediates that can be toxic to cells. Metabolic activation of certain procarcinogens by CYP2E1 may also lead to cell transformation. Regulation of CYP2E1 is especially intriguing. The CYP2E1 gene is transcriptionally activated in rat liver from a dormant state within a few hours after birth. This activation is due in part to the participation of a transcription factor designated hepatocyte nuclear factor 1 or HNF-1. In adult animals, constitutive expression of the enzyme is controlled to some degree by growth hormone. CYP2E1 is also regulated by many of its substrates through a substrate-induced stabilization of the enzyme. Under extreme conditions of fasting and uncontrolled diabetes CYP2E1 mRNA is stabilized.

Animals↗

The rat P450 IID subfamily: complete sequences of four closely linked genes and evidence that gene conversions maintained sequence homogeneity at the heme-binding region of the cytochrome P450 active site.

Four genes in the P450 IID gene subfamily were isolated from Sprague-Dawley rat lambda EMBL 3 and Charon 4A genomic libraries and completely sequenced. Their transcription start sites were determined by primer extension analysis. The four genes designated IID2, IID3, IID4, and IID5 span 4036, 4371, 4678, and 4567 bp, respectively, and are closely linked head to tail on a 60-kb segment of DNA. All IID genes contained nine exons, and interestingly, the IID2, IID3, and IID4 genes possessed an atypical GC5' splice junction in intron 2. All four genes are transcribed, however, IID4 mRNA is produced at a level of less than one-tenth of those of IID2, IID3, and IID5. The exonic regions of these genes displayed from 79 to 84% sequence similarties. Several regions of extremely high nucleotide similarity were found within the introns, exons, and in the flanking regions of the four genes. These localized areas of high nucleotide similarities are the result of former gene conversion events. Of interest was the finding that the most highly similar region of all IID genes that was maintained by gene conversion covers portions of the eighth and ninth exons and the eighth intron. The ninth exon codes for a region of the P450 protein that is well conserved among all P450 gene families and in all species and that is associated with the noncovalently bound heme iron at the enzyme's active site. These data indicate that gene conversions have maintained sequence homogeneity within a critical region of the four P450 IID proteins.

Amino Acid Sequence↗

The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene.

The debrisoquine-4-hydroxylase polymorphism is a genetic variation in oxidative drug metabolism characterized by two phenotypes, the extensive metabolizer (EM) and poor metabolizer (PM). Of the Caucasian populations of Europe and North America, 5%-10% are of the PM phenotype and are unable to metabolize debrisoquine and numerous other drugs. The defect is caused by several mutant alleles of the CYP2D6 gene, two of which are detected in about 70% of PMs. We have constructed a genomic library from lymphocyte DNA of an EM positively identified by pedigree analysis to be homozygous for the normal CYP2D6 allele. The normal CYP2D6 gene was isolated; was completely sequenced, including 1,531 and 3,522 bp of 5' and 3' flanking DNA, respectively; and was found to contain nine exons within 4,378 bp. Two other genes, designated CYP2D7 and CYP2D8P, were also cloned and sequenced. CYP2D8P contains several gene-disrupting insertions, deletions, and termination codons within its exons, indicating that this is a pseudogene. CYP2D7, which is just downstream of CYP2D8P, is apparently normal, except for the presence, in the first exon, of an insertion that disrupts the reading frame. A hypothesis is presented that the presence of a pseudogene within the CYP2D subfamily transfers detrimental mutations via gene conversions into the CYP2D6 gene, thus accounting for the high frequency of mutations observed in the CYP2D6 gene in humans.

Amino Acid Sequence↗

Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4.

The metabolism of midazolam and triazolam to their 1'-hydroxy and 4-hydroxy metabolites was studied in microsomes of 15 human livers. The formation of both metabolites was inhibited by more than 90% by an antiserum directed against a pregnenolone 16 alpha-carbonitrile-inducible cytochrome P450 (P450PCN1) of rat liver. Moreover, midazolam hydroxylase activity was immunoprecipitated from solubilized human microsomes with polyclonal antibodies against rat P450PCN1 and the closely related human isozyme P450NF. A close correlation was observed between the amount of protein detected in immunoblots with these antibodies and the midazolam or triazolam hydrxylase activity. The formation of both metabolites of midazolam was inhibited by triacetyloleandomycin, a known inhibitor of cytochromes P450 of the IIIA family. Direct evidence that P450IIIA4 catalyzes the metabolism of midazolam was provided through the use of cDNA-directed expression. Monkey COS cells transfected with human P450PCN1 cDNA were able to catalyze both the 1'- and the 4-hydroxylation of midazolam. We conclude that the metabolism of midazolam and triazolam in human liver is predominantly mediated by cytochrome P450IIIA4. Two of 15 human livers expressed a second immunoreactive microsomal protein of higher apparent Mr and were more active in midazolam 1'-hydroxylation. Our data also provide evidence that the marked interindividual variation in the response to these widely used benzodiazepine drugs is due to variable hepatic metabolism.

Animals↗