Search PubMed⌕ Search

Biomedical subjects

M Ohmori

Publications and source records attributed to M Ohmori.

At least 181 records · Page 10Linked to original sources

Characterization of thrombin- and plasmin-resistant mutants of recombinant human single chain urokinase-type plasminogen activator.

Recombinant human single-chain urokinase-type plasminogen activator (suc-PA) (SM0: wild type) and its variants resistant to plasmin and/or thrombin (SM1: Lys135 to Gln; SM3: Phe157 to Asp; and SM4: Lys135 to Gln and Phe157 to Asp) have been constructed by site-directed mutagenesis with the aim of producing more efficient thrombolytic agents [Miyake, T. et al. (1988) J. Biochem. 104, 643-647]. In the present study, we characterized the recombinant variant scu-PAs expressed in Escherichia coli. They appeared to have structural integrity because their heat-stabilities, immunological reactivities, and circular dichroism spectra were essentially identical to those of each other and of native scu-PA (nscu-PA). In the presence of thrombin, SM3 and SM4 showed efficient clot lysis by all of the assays used, compared with SM0, SM1, and nscu-PA. While in the absence of thrombin, when measured by a fibrin plate method in a purified system, SM3 and SM4 had lower specific activities than SM0, SM1, and nscu-PA, because of their catalytic constants for conversion to the two-chain form (tcu-PA) by plasmin are lower. However, SM4 lysed clots as efficiently as SM0 in plasma by retaining the single-chain form, whereas SM0 was partly converted to the two-chain form.

Autoradiography↗

Myelodysplastic syndrome (MDS)-associated inhibitory activity on haemopoietic progenitor cells.

We studied MDS-associated inhibitory activity, which inhibited colony formation in vitro of granulocyte-macrophage progenitors (CFU-GM). Macrophages obtained from MDS bone marrow mononuclear cells (BM-MNC) when pretreated with granulocyte-macrophage colony stimulating factor (GM-CSF) suppressed the growth of normal CFU-GM. These macrophages were designated as 'MDS-derived inhibitory macrophages'. Media conditioned by MDS-derived inhibitory macrophages (MDS-CM) also suppressed the growth of normal CFU-GM. In the MDS-CM, high levels of prostaglandin E2 (PGE2) and ferritin were found. However, MDS-CM did not contain detectable levels of tumour necrosis factor (TNF) or gamma-interferon (gamma-IFN). Antiserum against human placental ferritin and/or against PGE2 blocked the haemopoietic inhibitory activity to some extent. These results suggest that inhibitory macrophages may be responsible for the suppression of granulopoiesis in patients with MDS and that the suppression may be mediated by soluble factors including PGE2 and ferritin.

Adult↗

Gaucher's disease type I. Report of a case with prominent deposition of ceroid in splenic endothelial cells and intestinal smooth muscle fibers.

A case of type I Gaucher's disease in a 39-year-old male is reported. Autopsy showed marked enlargement of the spleen (3,070 g) and infiltration of typical Gaucher's cells in the spleen, liver, bone, marrow, gastrointestinal tract, lymph nodes and adrenal glands. The diagnosis of Gaucher's disease was ascertained by the very low beta-glucosidase activity of cultured subcutaneous fibroblasts and the high content of glucocerebroside in the spleen tissue. A peculiar finding in this case was prominent deposition of brown pigment in endothelial cells of the spleen and smooth muscles fibers of the gastrointestinal tract, urinary bladder and prostate. Histochemical examination revealed that the granules in endothelial cells and smooth muscle fibers were ceroid. Such deposition of ceroid has never been reported previously in Gaucher's disease. Ceroid deposition in generalized smooth muscle fibers is known as brown bowel syndrome, and is highly suggestive of severe vitamin E deficiency. Although other symptoms of vitamin E deficiency were not noticed in this case, some malnutritional condition might play a role in prominent deposition of ceroid in lysosomes, possibly together with deficient activity of a lysosomal enzyme.

Adult↗

[A case of histiocytosis X of the penis].

A case of localized histiocytosis X of the penis was reported. The patient was a 9-year-old boy who had several tumor lesions on the glans penis and inner layer of prepuce. Biopsy specimens were studied by H-E staining and immunohistochemical staining for S-100 protein (S-100), lysozyme (Lys), leucocyte common antigen (LCA), and Leu-M1. They revealed diffuse infiltration of many atypical histiocytes, which were shown to be S-100+, Lys+, LCA- and Leu-M1-. This indicates that these cells were derived from T-zone histiocyte system. After complete remission of these tumors, the other one arose from anal mucosa. In the literature we could find only one case of a primary penile lesion reported by Myers and others.

Anus Neoplasms↗

[An epithelial myoepithelial carcinoma of the parotid gland].

A case of epithelial myoepithelial carcinoma is reported. Histologically, this tumor shows tubular and solid growth pattern. The inner layer of the tubules is composed of cells with an eosinophilic cytoplasm that is surrounded by cells with clear cytoplasms. Clear cells also manifest a solid growth pattern. Immunohistochemical and electron microscopic examinations has revealed that the cells with an eosinophilic cytoplasm have the characteristics of the ductal epithelium and that the clear cells have the characteristics of the myoepithelium. Immunohistochemically, keratin positive clear cells and S-100 protein positive ductal cells were found in our case. This suggests the existence of cells having both ductal and myoepithelial characteristics and this inspected tumor had derived from multipotential cells of intercalated ducts.

Actin Cytoskeleton↗

[An autopsy case of lethal midline granuloma that terminated in an intracranial hemorrhage].

Reported is an autopsy case of a lethal midline granuloma (LMG) that originally had been manifested as chronic sinusitis and that terminated in intracranial hemorrhage. A 30-year-old woman developed a necrosis of the nasal cavity while being treated for chronic sinusitis for approximately four months. She subsequently died of an intracranial hemorrhage, and an autopsy revealed a necrosis that had progressed from the nasal cavity to the frontal base of the brain, and an infiltration of atypical cells that had an immunoreactivity to the T-cell antigens was observed. Recent studies have strongly suggested the possibility that some cases of an LMG, if not all, may be identical to a T-cell lymphoma. Our case is described and this disease is discussed.

Adult↗

Prognostic implication of sequential bone marrow cultures in the myelodysplastic syndromes.

Twenty-five patients with newly-diagnosed myelodysplastic syndromes were studied by the clonal culture method at least three times during the clinical course. Clinical outcomes of the patients were classified into: a stable disease (ten patients); subsequent leukemic transformation (eight patients) and nonleukemic death (seven patients). The growth of the marrow granulocyte-macrophage progenitors (CFU-GM) at the time of diagnosis was significantly related to the survival. In addition, sequential changes in the CFU-GM growth patterns correlated with the different clinical outcome of myelodysplastic syndromes patients.

Aged↗

Genetically engineered mutant of the cyanobacterium Synechococcus PCC 7942 defective in nitrate transport.

Nitrate-grown cells of Synechococcus PCC 7942 (Anacystis nidulans R2) contain a 45-kDa protein as a major protein in the cytoplasmic membrane but ammonium-grown cells lack it. A mutant (M45) was constructed by inactivating the gene encoding the 45-kDa protein. M45 did not grow under low concentrations of nitrate but high concentrations of nitrate could support its growth, with the optimal concentration being 40-70 mM. The growth rate of M45 was as high as that of the wild-type cells when ammonium was the nitrogen source. The 45-kDa protein was absent in M45 irrespective of the growth conditions. The activities of nitrate and nitrite reductases were higher in M45 than in wild type. The rate of nitrate-dependent O(2) evolution in wild type measured in the presence of L-methionine D,L-sulfoximine and D,L-glyceraldehyde showed saturation kinetics with respect to nitrate concentration in the external medium. The nitrate concentration required to produce half the maximal rate was 1 muM. In M45, the rate of nitrate-dependent O(2) evolution was nearly zero at nitrate concentrations <1 mM and was linearly increased as the concentration increased. The presumed absence of nitrate transport in M45 demonstrated by these results suggested that the 45-kDa protein is a nitrate transporter.

Journal Article↗

Lymphotoxin cDNA clones from a HTLV-I-carrying T cell line HUT-102.

The conditioned medium of a HTLV-I-carrying T cell line HUT-102 showed cytotoxic activity against a mouse fibroblast cell line L-M. We prepared the cDNA library from HUT-102 poly(A)+ RNA and screened it using oligonucleotide probes that correspond to the amino acid sequences conserved in tumor necrosis factor (TNF) and lymphotoxin (LT). As a result we obtained two kinds of cDNA clones encoding LT in which amino acid residue 26t of mature LT is different; one is Asn and another is Thr. The sequence of the genomic clones obtained using a polymerase chain reaction method showed that the HUT-102 genome also contains two types of LT genes. Recombinant LTs expressed in Escherichia coli exhibited the same level of cytolytic activity against L-M cells. These results indicate that the cytotoxin constitutively produced by HUT-102 cells include two kinds of LT.

Amino Acid Sequence↗

[Diagnosis and treatment of endometrial hyperplasia].

Endometrial hyperplasia (EH) was found to coexist in 13 of 21 patients (cystic glandular hyperplasia, 13; adenomatous hyperplasia, 9) with endometrial adenocarcinoma (EC), but in only 44 of 940 patients with other than EC. In this study, blood type (A, B, H), c-myc translation products, estrogen receptor and DNA polymerase alpha were examined on endometrium of proliferative phase (EPP), EH and EC. Patient blood type products were shown in EH surrounding EC, and yet they were detected in only small portion or none of EC itself. H products were detected in EC of other than O type. c-myc translation products were shown in only a small portion of cancer cells. EPP had many ER positive cells and a few proliferating cells as they were shown by staining with anti-DNA polymerase alpha monoclonal antibody. EC can be divided into two types, one has few ER positive cells and many proliferating cells, other many ER positive cells and a few proliferating cells. In EH, the numbers of ER positive cells and DNA polymerase alpha positive cells were between those of EPP and EC. In a patient with atypical hyperplasia, high dose Medroxyprogesterone acetate (MPA) therapy induced that stratification and papillary growth of gland lining epithelia disappeared, and that cytoplasmic enlargement and vacuolation appeared. These findings were important histopathological changes in high dose MPA administration to EH and EC.

ABO Blood-Group System↗

Small intestinal perforation in Wegener's granulomatosis.

Wegener's granulomatosis is a disease characterized by necrotizing vasculitis and granulomatous inflammation. Gastrointestinal (GI) involvement is uncommon in this disorder. Only a few cases of perforation of GI tract have been reported, but vasculitis has not been demonstrated to be a cause of perforation in these cases. We report a case of Wegener's granulomatosis in which a single perforation in the terminal ileum was disclosed on laparotomy and active necrotizing vasculitis was found in the submucosal layer of the resected specimen.

Adult↗

[An autopsied case of idiopathic interstitial pneumonia, showing a remarkably elevated serum level of CA 19-9].

Discussed herein is an autopsied case of a 30-year-old male with Idiopathic Interstitial Pneumonia (IIP) manifesting a markedly elevated CA 19-9 in the serum (maximum, over 120,000 U/ml). Despite a careful examination, no malignant lesion was found. The postmortem examination revealed a marked elevation of CA 19-9 in the serum and in the lung tissue. Further immunohistochemically regenerative bronchiolar and alveolar epithelial cells were more intensely positive for CA 19-9 than in our controls. These CA 19-9 positive cells for the most part, were found to stain with alcian blue. It is considered that IIP induces activation of sialyl-transferase in these cells.

Adult↗

Cloning and nucleotide sequencing of phenylalanine dehydrogenase gene of Bacillus sphaericus.

The gene coding for phenylalanine dehydrogenase [PDH; L-phenylalanine: NAD+ oxidoreductase (deaminating); EC 1.4.1.-] from Bacillus sphaericus SCRC-79a was cloned onto plasmid pUC9, and the nucleotide sequence of the 2-kb DNA region of the insert was determined. A 1143-bp open reading frame consisting of 381 codons was identified as a pdh gene coding for PDH.

Amino Acid Oxidoreductases↗

GTP-binding proteins in a cyanobacterium Anabaena cylindrica.

GTP-binding proteins were detected in a crude extract containing membrane components of Anabaena cylindrica. The crude extract was treated with 1% Lubrol PX and was fractionated by gel filtration. The binding of [35S]GTP gamma S to GTP-binding proteins was prevented in the presence of 0.1 mM GTP and in the presence of 0.1 mM ATP. Six fractions of these GTP-binding proteins, tentatively designated GA1 to GA6, were ADP-ribosylated by pertussis toxin. GA3, GA4 and GA5 had Km values of 10, 60 and 7 nM, respectively. The molecular weights of some of these GTP-binding proteins were reduced after being labelled with [35S]GTP gamma S.

Binding, Competitive↗

Hepatotoxicity of gardenia yellow color in rats.

Acute toxicity by gardenia yellow color was studied in rats. Oral administration of the colorant at doses of 800 mg/kg up to 5000 mg/kg caused diarrhea and increases in serum alanine aminotransferase and aspartate aminotransferase activities in a dose-dependent manner. After 24 h of oral treatment with 2000 mg/kg of the colorant, liver showed partially hemorrhagic changes and the intestinal tract, especially the duodenum, appeared blue. The toxicity induced by the colorant was stronger by oral administration than by intraperitoneal administration. The content of geniposide, an iridoid compound, was estimated to be 28% of the colorant, and this iridoid accounted for almost all the hepatotoxic activity of the colorant.

Administration, Oral↗

Synthesis of recombinant human single-chain urokinase-type plasminogen activator variants resistant to plasmin and thrombin.

Single-chain urokinase-type plasminogen activator (scu-PA), a potential therapeutic reagent for thrombosis, is activated in plasma by plasmin. The activated enzyme is further digested by plasmin to generate low-molecular-weight urokinase (LMW-UK), which has no affinity for fibrin. To circumvent this dual effect of plasmin, we synthesized in Escherichia coli a variant of scu-PA, which is not converted to LMW-UK on treatment with plasmin. In another variant, the activation cleavage site was modified such that activation by plasmin was slowed down and that inactivation by thrombin was greatly diminished. The combination of these variants may be applicable as an effective thrombolytic reagent for clinical use.

Drug Resistance↗

Assessment of warfarin therapy under full dose using indium-111 platelet scintigraphy in patients with intracardiac thrombi.

Twenty patients in whom intracardiac thrombi were detected by indium-111 platelet scintigraphy (the first platelet scintigraphy) were prospectively studied to examine the effect of warfarin therapy under full dose on the intracardiac thrombogenicity. Eleven patients (group I) who received 2-6 mg/day of warfarin and 9 patients (group II) who did not receive warfarin had the second platelet scintigraphies 14-71 days after the first platelet scintigraphies. In group I, 10 platelet scintigraphies became negative and one remained positive for intracardiac thrombi after administration of warfarin, while in group II 8 platelet scintigraphies remained positive and only one changed to negative. The incidence of negative image at the second platelet scintigraphy was significantly lower in group II than that in group I. In group I, the degree of accumulation of platelets onto the surface of the thrombus (%IE), showed significant reduction (0.69 +/- 0.48 to 0.11 +/- 0.21) after warfarin therapy, while in group II %IE at the second scintigraphy (1.07 +/- 1.03) were not significantly different from those at the first scintigraphy (1.13 +/- 0.79). These results indicated that warfarin therapy under full dose inhibited the deposition of platelets on the intracardiac thrombi and thrombogenicity in the patients with intracardiac thrombi which were detected by indium-111 platelet scintigraphy.

Adult↗

[Two cases of IBL-like T-cell lymphoma showing helper/inducer characteristics].

Two cases of an IBL-like T-cell lymphoma are reported, in one case of which the histological changes could be observed throughout its course. Although both cases were difficult to differentiate from true IBL in their early stage, focal proliferation of pale cells appeared in their first specimens and gradually, the characteristics of lymphoma grew manifest. Immunohistochemical studies of both cases revealed lymphoma cells having the characteristics of helper/inducer T lymphocytes. Electron-Microscopic examination showed no particular differences in the morphology of the tumor cells between our case and the case previously reported as being an IBL-like T-cell lymphoma of a suppressor/cytotoxic character.

Aged↗