Biomedical subjects

M Ohtsuka

Publications and source records attributed to M Ohtsuka.

At least 145 records · Page 8Linked to original sources

PubMed1993

Effect of FK409, a novel nitric oxide donor, on acute experimental myocardial ischemia.

The anti-ischemic heart effect of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]- 5-nitro-3-hexenamide (FK409), a novel nitric oxide donor, was studied in dog and rat preparations in vivo and in vitro. In anesthetized dogs with partially occluded coronary artery that were subjected to atrial pacing at a constant blood pressure, FK409 (1-100 micrograms/kg, i.v.) suppressed the ST-segment elevation on epicardial electrocardiograms. Glyceryl trinitrate (GTN; 10, 32 micrograms/kg) or dipyridamole (1000 micrograms/kg) failed to suppress the ST-segment elevation, although continuous i.v. infusion of GTN (32, 100 micrograms/kg/min) was effective. FK409 also suppressed the ST-segment elevation induced by methacholine in anesthetized rats by both i.v. (10, 100 micrograms/kg) and intraduodenal (i.d., 100, 1000 micrograms/kg) injections, while GTN (100 micrograms/kg, i.v.; 1000 micrograms/kg, i.d.) was effective only by the i.v. route. FK409 (0.32 microgram/kg/min, i.v.) and GTN (10 micrograms/kg/min) increased the blood flows of the endomyocardium (ENDO) and the epicardium (EPI) and the flow ratio of ENDO/EPI in the ischemic zone in anesthetized dogs with occluded coronary artery. Furthermore, in isolated dog vascular preparations, FK409 (4.6 x 10(-10)-4.6 x 10(-7) M) had a greater vasorelaxing effect on the large coronary artery [2.0-2.5-mm outer diameter (od)] than on the small coronary artery (0.3-0.5-mm od) or the saphenous artery. The results suggest that FK409 protects against acute experimental myocardial ischemia through relaxation of the large conductive coronary artery, and may be a useful oral drug for the treatment of angina pectoris.

Animals↗

PubMed1993

A neopullulanase-type alpha-amylase gene from Thermoactinomyces vulgaris R-47.

Shimizu et al. and ourselves have reported some enzymatic properties of an alpha-amylase from Thermoactinomyces vulgaris R-47 that hydrolyzed pullulan to produce panose [M. Shimizu et al., Agric. Biol. Chem., 42, 1681-1688 (1978); Y. Sakano et al., Agric. Biol. Chem., 46, 1121-1129 (1982)]. In this study, we cloned a gene for an alpha-amylase, which was different from the one mentioned above but also hydrolyzed pullulan to produce panose, from T. vulgaris R-47, and analyzed the entire primary structure of the gene. We designated the previously reported enzyme as T. vulgaris alpha-amylase I (TVA I), and this novel enzyme as T. vulgaris alpha-amylase II (TVA II). The nucleotide sequence had an open reading frame of 1755 base pairs corresponding to a protein of 585 amino acid residues. Although this novel alpha-amylase, TVA II, hydrolyzed both pullulan and starch, the ratio of pullulan-hydrolyzing activity to starch-hydrolyzing activity of the enzyme was higher than that of TVA I, and the primary structure of the enzyme resembled neopullulanase, which scarcely hydrolyzed starch, rather than that of TVA I.

Amino Acid Sequence↗

PubMed1993

Lung fibrosis in hypersensitivity pneumonitis. Association with CD4+ but not CD8+ cell dominant alveolitis and insidious onset.

Seventeen cases of hypersensitivity pneumonitis (HP) at a symptomatic phase were categorized into two groups based on computed tomographic (CT) findings and histologic features of transbronchial lung biopsy specimens, HP accompanied by lung fibrosis (fibrosis group), and HP unaccompanied by lung fibrosis (nonfibrosis group). The fibrosis group comprised bird fancier's lung and HP of unknown etiology, whereas the nonfibrosis group mainly comprised summer-type HP. Comparison of results of pulmonary function tests between these two groups confirmed a restrictive impairment in the fibrosis group. Analyses of cellular components of bronchoalveolar lavage (BAL) fluids revealed lymphocytes, especially CD8+ T lymphocytes, were significantly increased in the nonfibrosis group in comparison with the fibrosis group, whereas CD4+ T cells were increased to the same level in the both groups. Analyses of the onset of disease showed that acute onset was observed mainly in nonfibrosis group and strongly correlated with increased CD8+ T lymphocytes in BAL fluids, while insidious onset was related to lung fibrosis and relatively increased CD4+ T lymphocytes in BAL fluids. These findings raise the possibility that highly elevated CD8+ T cells might have a protective effect on pulmonary fibrosis or that relatively increased CD4+ T cells might play an important role in the pathogenesis of pulmonary fibrosis of HP at the chronic phase.

Adult↗

PubMed1993

[Pathogenesis of development of lung cancer in idiopathic interstitial pneumonia--growth factors in bronchoalveolar lavage fluid].

It has been generally accepted that lung fibrosis as in idiopathic interstitial pneumonia (IIP) is frequently associated with the development of lung cancer. This observation implies that the mechanism involved in carcinogenesis and/or enhanced proliferation of cancer cells is common to the fibrosing process. However, there are few studies reported on the pathogenesis of associated lung cancer except for several studies assessed from the point of view of surgical pathology. This study was undertaken to learn whether BAL fluid, which reflects the local milieu of the fibrosing process, enhances the proliferation of human lung cancer cell line Lu-99, Lu-65 and rat lung fibroblasts as assessed by 3H-thymidine incorporation. BAL fluid was obtained from patients with IIP (n = 8) and normal volunteers (n = 8). BAL fluids from patients with IIP enhanced the mean incorporation of 3H-thymidine of Lu-99 up to 3.6 times (p < 0.01) compared to that of normal volunteers. Furthermore, the mean incorporation of Lu-65 was increased up to 1.8 times (p < 0.05) by BAL fluids from patients with IIP. In contrast, BAL fluids from patients caused no significant increase of the mean incorporation of rat lung fibroblasts as compared to normal BAL fluids. The enhancing activities on the growth of cancer cell line Lu-99, Lu-65 were eluted in several fractions by high performance liquid chromatography using Superose 12. These observations indicate that the BAL fluid of IIP patients contains factors enhancing the growth of cancer cells.

Aged↗

PubMed1993

[Subclass distribution of IgG and IgA antibodies in summer-type hypersensitivity pneumonitis].

The present study was undertaken to determine the most specific of the 3 serotypes of Trichosporon cutaneum responsible for summer type hypersensitivity pneumonitis and to elucidate the subclass distribution of the antibody response, which is partly dependent on the nature of the causative antigen. Western blot analysis revealed that serotype II (TIMM 1318) is the most specific antigen for summer type hypersensitivity pneumonitis. The subclass distributions of anti-Trichosporon cutaneum IgG antibodies and IgA antibodies in sera and bronchoalveolar lavage fluids (BALF) from 13 patients with summer type hypersensitivity pneumonitis and 10 normal volunteers were measured by biotin-avidin-linked immunosorbent assay. The results were as follows, (1) high levels of IgA2 antibodies were found in BALF, but minute amounts in sera, (2) IgG1 antibodies were the predominant subclass in sera and BALF, (3) three out of 13 cases showed high levels of IgG3 antibodies in sera and BALF associated with low levels of IgG1 antibodies, (4) IgA1 antibodies were found in both sera and BALF. (5) the levels of all antibody subclasses were higher in BALF than in sera. The subclass distributions suggest that the protein components of Trichosporon cutaneum are predominantly immunogen, although polysaccharides may participate as an antigen in the respiratory tract.

Alveolitis, Extrinsic Allergic↗

PubMed1992

Tumor-associated M(r) 34,000 and M(r) 32,000 membrane glycoproteins that are serine phosphorylated specifically in bovine leukemia virus-induced lymphosarcoma cells.

Tumor-associated antigens that are expressed in tumor cells of cattle with enzootic bovine leukosis (EBL) were analyzed previously by use of 13 monoclonal antibodies. We biochemically identified one of the tumor-associated antigens, which is recognized by the c143 monoclonal antibody, as two glycoproteins, each having an apparent molecular weight of 32,000 or 34,000. These glycoproteins were found in the plasma membrane of peripheral blood lymphocytes of both bovine leukemia virus (BLV)-free normal and BLV-infected cattle. With the progression of EBL, the proportion and the absolute number of cells positive for the tumor-associated antigen increased. Moreover, the level of the M(r) 34,000 component, which was susceptible to cell-surface labeling, increased over the level of the M(r) 32,000 component. Partial proteolytic peptide mapping with V8 protease and deglycosylation analysis revealed that the two glycoproteins most likely have an identical M(r) 30,000 polypeptide portion but have different N-linked oligosaccharide portions. Both glycoproteins were found to be phosphorylated at serine residue(s) in EBL-derived B-lymphoid cell lines and in tumor cells and peripheral blood lymphocytes from cattle with EBL, but not in peripheral blood lymphocytes from BLV-free normal cattle and BLV-infected cattle without any evidence of tumor, suggesting that the phosphorylation of these glycoproteins is related to the transformed state of the BLV-infected B-lymphoid cells.

Animals↗

PubMed1992

A straight correlation between mutagenic activity and beta-galactosidase activity induced by monofunctional alkylating agents.

Eight monofunctional alkylating agents were examined for their ability to induce mutation in Salmonella typhimurium. The assay was carried out in S. typhimurium TA100 with the preincubation method. The SN1-type agents were more mutagenic than the SN2-type ones; besides, methylating agents exerted more mutagenic activity than ethylating ones. Those responses in the reversion assay were quite similar to the results obtained previously with the beta-galactosidase assay in Escherichia coli CSH26/pMCP1000 (alkA'-lacZ') as to the induction of the adaptive response. A good correlation was found between mutagenic potency in the reverse mutation assay and inducing potency in the beta-galactosidase assay.

Alkylating Agents↗

PubMed1992

Agents for the treatment of overactive detrusor. II. Synthesis and inhibitory activity on detrusor contraction of 1,1'-biphenyl-2,6-dicarboxylic acid diesters with an aminoalkyl group in the ester function.

A series of 1,1'-biphenyl-2,6-dicarboxylic acid diesters with an aminoalkyl group in the ester function were synthesized and examined for their inhibitory activity on detrusor contraction in vitro and in vivo. In the in vivo test, arrhythmia was observed as a side effect. Among those compounds synthesized, 2-methyl 6-[4-(1-methylpiperidinyl)] 3-hydroxy-5-methyl-2'-nitro-1,1'-biphenyl-2,6-dicarboxylate (18) showed strong inhibitory activity on detrusor contractions in vivo (ED50 = 0.54 mg/kg i.v., ED50 = 7.2mg/kg i.d.) and good separation from the side effect. Compound 18 was chosen for further pharmacological evaluation as an agent for the treatment of overactive detrusor.

Animals↗

PubMed1992

[A case of small liver cancer presenting as a huge mediastinal mass].

A 61-year-old male was admitted because of hemoptysis. He had a 9 year history of liver cirrhosis associated with HB viral chronic hepatitis. Physical examination revealed no abnormalities. Laboratory investigations revealed positive HBs antigen with normal alpha-fetoprotein. Chest X-ray film showed large mediastinal lymph nodes and an endobronchial polypoid mass in the distal end of the right main bronchus. The right main PA was narrowed due to compression by the mediastinal mass. Bronchoscopic examination revealed a polypoid mass in the right main bronchus. The biopsy specimen was histologically diagnosed as undifferentiated large cell carcinoma. The patient developed respiratory failure, and died 3 weeks after admission. Autopsy revealed a small liver cancer of 1.3 cm diameter within the cirrhotic liver, associated with a small abdominal lymph node metastasis and large mediastinal lymph node swellings. Thromboembolism in the bilateral main pulmonary arteries was concluded to be the cause of death. The mediastinal mass which directly invaded into the right main bronchus had a close histological similarity with the liver cancer, showing undifferentiated carcinoma cells with bizarre nuclei and abundant cytoplasm. An immunohistological study revealed cells positive for alpha-fetoprotein in the mediastinal lymph nodes. The patient was diagnosed as having small liver cancer with mediastinal lymph node metastases. A survey of the literature revealed only a few cases of advanced hepatoma associated with prominent mediastinal metastases. This is the first reported case of small liver cancer presenting with large mediastinal lymph node metastases.

Carcinoma↗

PubMed1992

[A case of intrabronchial dissemination of candida pseudohyphae presenting as respiratory failure].

A 63-year-old man was admitted to our hospital because of fever, skin eruption, leukocytopenia and liver dysfunction. He was receiving H2-blocker for gastric ulcer of the time he developed his symptoms. The H2-blocker was discontinued because of its possible association with leukocytopenia, and steroids were administered. On the 4th day of hospitalization, he suddenly developed expiratory wheeze and dyspnea, resembling an asthmatic attack. WBC was 400/mm3 with 65% neutrophils. Chest X-ray showed hyper inflation and increased thickness of bronchiolar walls. Bronchodilators had no effect and the patient died of respiratory failure on the 8th day. At autopsy, most bronchioles were filled with candida pseudohyphae. The large airways and lung parenchyma were not involved, except for focal bacterial pneumonia. Histological findings suggestive of bronchial asthma such as constriction of bronchial smooth muscle or infiltration of eosinophils were not observed Candida infection was also found in the pharynx, stomach, bowel, and kidneys. Candidiasis is becoming a more important contributory cause of death in compromised hosts. Although rare, this case suggests that patients with bronchopulmonary candidiasis present with expiratory wheeze resembling asthmatic attack.

Airway Obstruction↗

PubMed1992

[The influence of lung volume and body position on pulmonary blood flow under hypoxic exposure].

We examined the changes in the electromagnetically measured left lower lobe blood flow (QLLL) when the left lower lobe (LLL) was exposed to alveolar hypoxia selectively under two different positions (supine and right lateral position in 18 dogs. QLLL/CO, Qs/Qt and other cardiopulmonary parameters were obtained during the following experimental sequence; 1) the whole lung ventilated with 100% O2 (control), 2) LLL collapsed and the remainder ventilated with 100% O2, 3) N2 expansion of LLL (N2 CPAP) and the remainder ventilated with 100% O2, 4) O2 expansion of LLL (O2 CPAP) and the remainder ventilated with 100% O2, and 5) The whole lung ventilated with 100% O2. In the supine position group (n = 9), both selective collapse and N2 CPAP of LLL caused QLLL/CO to decrease significantly (P less than 0.02) from control values (14.9 +/- 1.7%) to 10.6 +/- 0.9% and 11.9 +/- 1.6%, respectively. But there was no difference in QLLL/CO between collapse and N2 CPAP of LLL. In the right lateral position group (n = 9), hypoxic exposure of LLL caused no decrease in QLLL/CO from control values. But QLLL/CO during N2 CPAP (8.5 +/- 1.1%) decreased significantly than that during collapse (10.8 +/- 1.5%) (P less than 0.02). Qs/Qt during N2 CPAP (15.6 +/- 1.4%) also decreased significantly (P less than 0.05) from that during collapse (18.5 +/- 2.2%). We conclude that the difference of the changes in QLLL/CO under hypoxic exposure between supine and right lateral position was caused by hydrostatic pressure which influenced more during lateral position than during supine position.

Animals↗

PubMed1991

Sequential changes in lung injury induced by preformed immune complexes.

Immune complexes formed in the airside may be involved in the early parenchymal changes in hypersensitivity pneumonitis. The present study was undertaken to compare the responses of animals after an intratracheal injection with preformed immune complexes to those of patients with acute hypersensitivity pneumonitis, with special emphasis on sequential bronchoalveolar lavage findings and the possible role of chemotactic factors in the immune complex-induced lung injury. An increased number and percentage of polymorphonuclear cells could be detected in bronchoalveolar lavage fluids of guinea pigs within 48 hr following an intratracheal injection of preformed immune complexes. Chemotactic factor activity preceded the observed increase of polymorphonuclear cells in bronchoalveolar lavage fluids, suggesting a role for chemotactic factors in the sequestration of these cells in the lung. In addition, this study confirmed the usefulness of bronchoalveolar lavage in evaluating the pulmonary findings because the changes in bronchoalveolar lavage cell populations correlated with sequential histological findings. The sequential characteristics of the involved areas were noted to be of a peribronchial or bronchiolar infiltration with polymorphonuclear cells at early stages, then alveolar sac infiltration, followed by mild infiltration of mononuclear cells into the alveolar walls. The findings suggest a possible role for chemotactic factors in the accumulation of polymorphonuclear cells, and the sequential changes of bronchoalveolar lavage and histological findings in animals are comparable to those in patients with acute hypersensitivity pneumonitis.

Alveolitis, Extrinsic Allergic↗

PubMed1991

Clinical significance of serum levels of a carbohydrate antigen, sialyl SSEA-1, in patients with fibrosing lung disease.

Serum levels of sialyl SSEA-1 antigen, a carbohydrate antigen, were measured by radioimmunoassay in 142 patients with nonmalignant lung diseases. In 20 of 41 patients with fibrosing lung disease, either idiopathic or associated with collagen disease, the serum sialyl SSEA-1 levels were abnormally elevated. In patients with other lung diseases, the serum levels were almost within normal limits, less than 38.0 units/ml. In fibrosing lung disease the serum levels ranged from 13.8 to 147.0 units/ml and were largely concurrent with the degree of disease activity. The therapeutic effects of corticosteroid, which were evaluated with clinical-radiographic-physiologic scores and survivals in the patients with elevated serum levels, were significantly lower than those of the patients with the normal range of antigen levels. An immunohistochemical study performed on autopsied lungs from five patients with fibrosing lung disease indicated that the antigen was selectively expressed in the pulmonary epithelial cells that covered the remodeling alveolar septi in the lungs. No antigen was detectable by immunostaining in normal pulmonary epithelium among five normal lungs. From these findings, it is thought that the elevated levels of serum sialyl SSEA-1 may be derived from proliferating epithelial cells that were dominant in the late stage of fibrosing lung disorders. The measurements of serum sialyl SSEA-1 in patients with fibrosing lung disease may be clinically useful in establishing the degree of disease activity that has an influence on patient prognosis and therapeutic response.

Adrenal Cortex Hormones↗

PubMed1991

Agents for the treatment of overactive detrusor. I. Synthesis and structure-activity relationships of 1,1'-biphenyl derivatives.

A series of 1,1'-biphenyl-2,6-dicarboxylic acid diesters were synthesized and examined for their inhibitory activity on guinea-pig detrusor muscle contraction at electrical field stimulation in vitro. Among them, 6-isopropyl 2-methyl 3-hydroxy-5-methyl-2'-nitro-(1,1'-biphenyl)-2,6-dicarboxylate, FR75513 (8a) was one of the potent compounds (IC50 = 3.3 x 10(-6) g/ml). This compound (8a) exhibited a strong inhibitory activity on detrusor contraction after intravenous administration in anesthetized rats (ID50 = 0.04 mg/kg).

Animals↗

PubMed1991

[Utilization of D-histidine by the derivative strain TA100 of Salmonella typhimurium LT 2].

In general, wild-type gram-negative enteric bacteria are not able to utilize D-amino acids as the precursors of respective L-amino acids. We found, however, that an L-histidine auxotroph mutant, TA100, derived from Salmonella typhimurium strain LT 2 and used in the Ames test, showed a biphasic growth curve in the presence of both L- and D-histidine at concentrations of 5 micrograms/ml and 100 micrograms/ml, respectively. L-histidine may be utilized preferentially and then, after a short lag, D-histidine may be utilized. The short lag time is therefore considered to be the time required for induction of such an enzyme that converts D-histidine to L-histidine and for uptake of D-histidine by the bacterial cells.

Culture Media↗

PubMed1991

Effects of the anticholinergic drug prifinium bromide on urinary bladder contractions in rat in vivo and in guinea-pig in vitro.

The parenteral and enteral effects of prifinium bromide (CAS 4630-95-9; in the following referred to as prifinium), a quaternary ammonium anticholinergic drug, were investigated on contractions of the rat urinary bladder by cystometry and compared with those of atropine, oxybutynin and terodiline. Additionally, in vitro experiments were carried out with the isolated guinea-pig detrusor muscle to clarify the mechanisms of action of these effects. In intravenous doses, all the drugs reduced the amplitude of the contractions in the cystometric studies. The inhibition was dose-dependent, but was not entirely even at the respective largest doses. According to the 40% inhibitory doses, prifinium was as active as atropine, and 10 and 100 times more active than oxybutynin and terodiline, respectively. The potency ratios of the drugs in their in vivo effects were in good agreement with those of their in vitro anticholinergic effects, which were determined with carbachol-induced contractions in the isolated guinea-pig detrusor muscle. On the other hand, in the in vitro studies, prifinium and atropine had little or no effect on contractions induced by electrical stimulation, KCl and BaCl2, whereas oxybutynin and terodiline antagonized all of the stimuli to a similar extent. These findings indicate that the anticholinergic activity of prifinium may be only one factor in the mechanisms of its in vivo inhibition of the rat bladder contractions. Finally, intraduodenal doses of prifinium also inhibited the contractions of the rat bladder, and the effects of the drug by this route were almost the same as those of oxybutynin and terodiline.

Animals↗

PubMed1990

Antimetastatic effect of defibrinogenation with batroxobin depends on the natural killer activity of host in mice.

Using batroxobin, a thrombin-like enzyme found in snake venom, the effects of defibrinogenation on artificial lung metastasis in mice were studied. The role of natural killer (NK) cells in the inhibitory effects of defibrinogenation on metastasis was also investigated. Artificial lung metastasis experiments were performed by inoculating either B16-F10 cells or B16-BL/6 cells, highly metastatic strains of B16 melanoma cells, into C57BL/6 mice via the tail vein. The administration of batroxobin significantly inhibited lung metastasis, as did NK activity augmented by poly (I).poly (C) were administered, lung metastasis was more markedly inhibited. When NK activity was suppressed by administration of anti-(asialo GM1) antibody, lung metastasis was markedly increased. When batroxobin was administered with anti-(asialo GM1) antibody, no inhibitory effects on lung metastasis, such as those seen with batroxobin alone, were observed. The administration of batroxobin had no effect at all on spleen lymphocyte NK activity. These results indicated that defibrinogenation due to batroxobin inhibits lung metastasis, and these effects depend on NK activity of the host.

Animals↗

PubMed1990

Ligand-induced phosphorylation of the colony-stimulating factor 1 receptor can occur through an intermolecular reaction that triggers receptor down modulation.

Ligand-induced tyrosine phosphorylation of the human colony-stimulating factor 1 receptor (CSF-1R) could involve either an intra- or intermolecular mechanism. We therefore examined the ability of a CSF-1R carboxy-terminal truncation mutant to phosphorylate a kinase-defective receptor, CSF-1R[met 616], that contains a methionine-for-lysine substitution at its ATP-binding site. By using an antipeptide serum that specifically reacts with epitopes deleted from the enzymatically competent truncation mutant, cross-phosphorylation of CSF-1R[met 616] on tyrosine was demonstrated, both in immune-complex kinase reactions and in intact cells stimulated with CSF-1. Both in vitro and in vivo, CSF-1R[met 616] was phosphorylated on tryptic peptides identical to those derived from wild-type CSF-1R, suggesting that receptor phosphorylation on tyrosine can proceed via an intermolecular interaction between receptor monomers. When expressed alone, CSF-1R[met 616] did not undergo ligand-induced down modulation, but its phosphorylation in cells coexpressing the kinase-active truncation mutant accelerated its degradation.

Amino Acids↗