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S Okamoto

Publications and source records attributed to S Okamoto.

At least 253 records · Page 14Linked to original sources
PubMed1997

Probing the ubiquinone reduction site of mitochondrial complex I using novel cationic inhibitors.

A wide variety of N-methylpyridinium and quinolinium cationic inhibitors of mitochondrial complex I was synthesized to develop potent and specific inhibitors acting selectively at one of the two proposed ubiquinone binding sites of this enzyme (Gluck, M. R., Krueger, M. J., Ramsay, R. R., Sablin, S. O., Singer, T. P., and Nicklas, W. J. (1994) J. Biol. Chem. 269, 3167-3174). N-Methyl-2-n-dodecyl-3-methylquinolinium (MQ18) inhibited electron transfer of complex I at under microM order regardless of whether exogenous or endogenous ubiquinone was used as an electron acceptor. The presence of tetraphenylboron (TPB-) potentiated the inhibition by MQ18 in a different way depending upon the molar ratio of TPB- to MQ18. In the presence of a catalytic amount of TPB-, the inhibitory potency of MQ18 was remarkably enhanced, and the extent of inhibition was almost complete. The presence of equimolar TPB- partially reactivated the enzyme activity, and the inhibition was saturated at an incomplete level (approximately 50%). These results are explained by the proposed dual binding sites model for ubiquinone (cited above). The inhibition behavior of MQ18 for proton pumping activity was similar to that for electron transfer activity. The good correlation of the inhibition behavior for the two activities indicates that both ubiquinone binding sites contribute to redox-driven proton pumping. On the other hand, N-methyl-4-[2-methyl-3-(p-tert-butylphenyl)]propylpyridinium (MP6) without TPB- brought about approximately 50% inhibition at 5 microM, but the inhibition reached a plateau at this level over a wide range of concentrations. Almost complete inhibition was readily obtained at low concentrations of MP6 in the presence of TPB-. Thus MP6 appears to be a selective inhibitor of one of the two ubiquinone binding sites. With a combined use of MP6 and 2,3-diethoxy-5-methyl-6-geranyl-1,4-benzoquinone, we also provided kinetic evidence for the existence of two ubiquinone binding sites.

1-Methyl-4-phenylpyridinium↗
PubMed1997

A physiological role of interferon (IFN)-beta derived from tumor: tumor growth of a mouse bladder carcinoma line MBT-2 is partially suppressed by autocrine IFN-beta.

Although some tumor cells endogenously produce a wide variety of cytokines, their physiological roles remain to be fully understood. In this study, we found that mouse subcutaneous tumor induced by inoculation of bladder tumor MBT-2 cells into syngeneic mice secreted a significant amount of interferon (IFN), whereas the cells exhibited no IFN production in in vitro cell culture. Typing experiment using IFN-specific neutralizing antibodies showed that the tumor-derived IFN was exclusively beta type. Since the MBT-2 tumor tissues were homogenous and not infiltrated by immune cells, MBT-2 cells themselves were considered to be IFN-beta producers. By intraperitoneal injection of neutralizing anti-IFN-beta antibodies into MBT-2 cell-inoculated mice, the tumor growth was substantially precipitated and survival days of the tumor-bearing mice were shortened. As the in vitro cell growth of MBT-2 cells was dose-dependently inhibited by IFN-beta, it was suggested that apparent immunogenicity of MBT-2 tumor is partially mediated by tumor suppression by autocrine IFN-beta.

Animals↗
PubMed1997

Bone density and body composition in Japanese women.

Total body bone mineral content (BMCTB in g) and density (BMDTB in g/cm2) and body composition were measured in 1006 healthy Japanese women aged 20-79 years using dual X-ray absorptiometry. Peak BMDTB was 1.11 +/- 0.05 g/cm2 in women 20-49 years, and mean BMDTB was 1. 019 g/cm2 in the 6th decade, 0.956 g/cm2 in the 7th decade, and 0. 900 g/cm2 in the 8th decade. BMDTB declined by 0.007 g/cm2/year in women after age 50. This age-related decline in BMD showed a similar pattern to that seen for the lumbar spine and femoral neck, but the actual rate of loss was lower for BMDTB than for these other measurement sites. There was no significant difference between a eumenorrheic premenopausal group and a group with irregular menses. BMCTB and BMDTB were associated with body build, lean tissue mass, and fat mass (r = 0.29 approximately 0.65 and 0.26 approximately 0.41, respectively). Bone mass and density decreased significantly in older women of all body builds. Premenopausal Japanese women had a 5% lower BMDTB than U.S. and European whites, but the difference was several times greater in postmenopausal than in premenopausal women.

Adult↗
PubMed1997

Cholestyramine loading test to assess hepatic reserve for bile acid synthesis in patients with chronic liver diseases.

BACKGROUND & AIMS: Serum 7alpha-hydroxycholesterol level reflects hepatic bile acid synthesis in humans. The aim of this study was to examine the maximal bile acid synthesis in patients with chronic liver diseases. METHODS: Cholestyramine (12 g/day) was administered for 3 days to patients with compensated liver cirrhosis (n = 7), patients with chronic hepatitis (n = 10), and control subjects (n = 9), and serum total 7alpha-hydroxycholesterol level was measured by gas-liquid chromatography-mass spectrometry. RESULTS: A preliminary study showed that cholestyramine increased the serum value to the maximum by the third day. Before cholestyramine treatment, there were no significant differences in serum 7alpha-hydroxycholesterol levels among the groups. Three days of cholestyramine treatment increased the serum levels 5.71 +/- 2.90-fold in the controls, 3.25 +/- 0.85-fold in patients with chronic hepatitis, and 1.70 +/- 0.78-fold in cirrhotic patients. Cirrhotic patients had significantly lower serum 7alpha-hydroxycholesterol levels after the treatment compared with other groups. Serum 7alpha-hydroxycholesterol levels stimulated by cholestyramine significantly correlated with serum albumin levels and indocyanine green retention rate. CONCLUSIONS: Three days of cholestyramine loading increased the bile acid synthesis to its maximal level. The cholestyramine test showed that patients with chronic hepatitis had enough hepatic reserve for bile acid synthesis; however, patients with compensated liver cirrhosis had significantly decreased capacity.

Aged↗
PubMed1997

Impact of the development of a liver transplant program on the treatment of biliary atresia in an institution in Japan.

Kasai operation for biliary atresia (BA) and living-related liver transplantation (LRLT) for failed Kasai cases have been performed by the same team in our hospital. Outcome of the treatment for BA in the pretransplantation and posttransplantation era in our institution were compared. As the "pre" group, 35 children first underwent the Kasai operation between 1982 and 1989. The "post" group consisted of 25 patients who underwent Kasai after introduction of the LRLT program in our hospital (1990). As for the reconstruction procedure after portal dissection during Kasai, jejunal interposition hepatic portoduodenostomy for the pre group was intentionally changed to Roux-en-Y procedure for the post group to decrease the risk of duodenal leakage after LRLT. Patients who needed revision of the Kasai decreased from 57% for the pre group to 28% for the post group. There was only one re-revision in the post group compared with seven in the pre group. In the pre group, 10 patients (28.6%) died at age 6 to 16 (mean, 8.5) months before the transplantation program was initiated. In the pre group, three patients could receive a cadaveric liver transplantation in other countries, and seven had LRLT in our hospital. Ten patients (40%) in the post group had LRLT at 7 to 22 (mean, 9.3) months old, and no deaths occurred in this group. When the patients who had liver dysfunction were excluded, the percentage of the patients who could be expected to survive and accomplish growth without undergoing liver transplantation was similar for the two groups, (31.4% v 36%). The change in the reconstruction procedure and the tendency for fewer revisions of Kasai procedure were effects of the start of the liver transplant program. As a general strategy for BA, Kasai operation should be the initial procedure, followed by liver transplantation for failed Kasai. In the late-diagnosed patients, primary LRLT can be considered if the liver has already been cirrhotic. LRLT in the infantile period is a significant component of this strategy for helping all patients to survive.

Biliary Atresia↗
PubMed1997

Autologous bone marrow transplantation for patients with advanced chronic myelogenous leukemia.

We report on seven chronic myelogenous leukemia (CML) patients who received autologous bone marrow transplantation (ABMT) using bone marrow (BM) cells while at the chronic phase (CP) under the various treatments. Of the seven patients, four progressed to accelerated phase (AP) in 83-248 weeks after onset and three patients entered blastic crisis (BC) in 84-171 weeks after onset. All patients received high-dose chemoradiotherapy followed by infusion with 11.3 +/- 12.1 x 10(7) (average +/- S.D.) of bone marrow mononuclear cells (BM-MNCs)/kg IFN-alpha was resumed shortly after platelet recovery. Of the four patients in AP, one developed a recurrence of blastoma in 7 weeks, one progressed to second AP in 138 weeks after ABMT and two patients have survived the second CP for 159 and 330 weeks since ABMT, respectively. One of them achieved the complete disappearance of Ph1-positive metaphases for 33 weeks after ABMT. Of patients who received AMBT in BC, three relapsed within 8 weeks and died in 9, 17 and 58 weeks after ABMT, respectively. Hematological recovery was delayed in four patients. Therefore, we retrospectively re-evaluated the number of BM-MNCs collected through 50 procedures from 40 patients with CML-CP. The total MNCs obtained from 30 collections under IFN-alpha treatment was 27.4 +/- 30.9 x 10(8) cells (average +/- S.D.), being significantly lower than that obtained from 20 collections in pre-treatment state or with single chemotherapy other than IFN-alpha treatment (81.8 +/- 68.2 x 10(8) cells) (P < 0.005). The total number of MNCs correlated to white blood cell (WBC) count at BM collection (P < 0.01), which was also lower in the IFN-alpha(+) group than in the IFN-alpha(-) group (7.2 +/- 5.7 and 25.6 +/- 32.3 x 10(9)/l; P < 0.005). Our findings suggested that ABMT with the use of a sufficient number of progenitor cells might be helpful to CML patients in early AP and reach in extended periods of second CP. In addition, we suggest that BM collection is required before the start of IFN-alpha therapy because the total number of BM-MNCs correlated to the WBC count, which might be lower in IFN-alpha treatment.

Adolescent↗
PubMed1997

Fatal GVHD demonstrating an involvement of respiratory muscle following donor leukocyte transfusion (DLT).

A 41-year-old female patient with AML, who relapsed after an allogeneic BMT from her HLA-identical sister, was treated by a donor leukocyte transfusion (DLT). Thereafter, bone marrow aplasia accompanied by the disappearance of leukemic blasts following the GVHD was observed. The patient died of chronic GVHD with respiratory muscle involvement 19 months after the DLT. Although the DLT was considered helpful in suppressing the proliferation of the leukemic cells, it might also have caused the severe GVHD observed in this case. Efforts to separate the lymphocyte clones responsible for GVL from those for the GVHD thus appear to be necessary for the further development of the therapeutic approach, so-called DLT.

Adult↗
PubMed1997

Gastric corpus IL-8 concentration and neutrophil infiltration in duodenal ulcer patients.

BACKGROUND: The purpose of the present study was to examine the association between interleukin-8 (IL-8) in the gastric body due to Helicobacter pylori infection and histological gastritis, as well as elucidating the effect of acid secretion inhibitors on H. pylori associated body gastritis in duodenal ulcer patients. METHODS: Twenty H. pylori-negative patients, 20 H. pylori-positive patients with chronic gastritis without peptic ulceration, and 20 H. pylori-positive duodenal ulcer patients (DU) were studied. Four biopsy samples were taken, each from the greater curvature of the antrum and body of the stomach. Biopsies were histologically investigated by ELISA to determine the density of H. pylori, the degree of neutrophil infiltration and the IL-8 concentration in the mucosa. RESULTS: In the gastric mucosa of H. pylori-negative subjects, no IL-8 and hardly any neutrophil infiltration were observed. In contrast, enhanced IL-8 production and increased neutrophil infiltration were present in those infected with H. pylori. In H. pylori-positive patients, a significant correlation was observed between the IL-8 concentration and the degree of neutrophil infiltration, but no correlation was found in the body mucosa of those with DU. Twelve of 20 DU patients demonstrated hardly any neutrophil infiltration, despite the increased mucosal IL-8 content in the body. The administration of omeprazole in DU patients markedly increased mucosal neutrophil infiltration even though it did not cause any significant change in the H. pylori density and IL-8 concentration in the body. Although the effect of omeprazole was transient, a significant increase in neutrophil infiltration continued in comparison with the status before omeprazole administration in those subsequently undergoing maintenance treatment with H2-blockers. CONCLUSION: In H. pylori-positive chronic gastritis, IL-8 concentration is enhanced in the mucosa of the body, and is associated with increased neutrophil infiltration. However, in DU patients, despite increases in body IL-8 concentration, neutrophil infiltration is reduced and the gastritis may be localized in the antrum.

Adult↗
PubMed1997

Superantigenicity of helper T-cell mitogen (SPM-2) isolated from culture supernatants of Streptococcus pyogenes.

A superantigen (Streptococcus pyogenes mitogen-2; SPM-2) that stimulates human helper T cells bearing unique types of variable domains of T-cell receptor beta-chain (TCR V beta) was isolated from the culture supernatant of S. pyogenes strain T12. The active molecule isolated by diethylaminoethyl (DEAE)-cellulose chromatography and isoelectric focusing was a protein with a molecular weight (MW) of 29,000 and isoelectric point (pl) of 6.0. This new superantigen was found to activate preferentially V beta 4+, 7+, and 8+ T cells, whereas recombinant streptococcal pyrogenic exotoxin A and C activated V beta 12+ and V beta 2+ T cells, respectively, as determined by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) methods. This proliferative response was significantly inhibited by anti-HLA-DR monoclonal antibody, and required paraformaldehyde-fixed antigen-presenting cells (APC), indicating that this action is dependent on major histocompatibility complex (MHC) class II molecules without processing. Analysis of the amino-terminal amino acid sequence of the molecule failed to find any identical or significantly homologous proteins. We have previously reported that cytoplasmic membrane-associated protein (CAP), a streptococcal superantigen isolated from the cell membranes of S. pyogenes T12 strain, stimulated mainly V beta 8+ T cells. Both SPM-2 and CAP preferentially stimulated helper T cells, and rabbit antiserum against SPM-2 completely neutralized the T-cell-stimulating activities of CAP, suggesting that SPM-2 and CAP belong to a family of streptococcal mitogenic proteins. The SPM-2 activity with stimulation of V beta 8+ T cells was detected extensively in the culture fluids of group A streptococci, but not in those of other streptococcal species, including groups B and D streptococci, and most of the activities detected were completely inhibited by anti-SPM-2 serum. These results indicate that SPM-2 may be a newly discovered superantigen molecule, which can be commonly synthesized by group A streptococci.

Amino Acid Sequence↗
PubMed1997

Enzyme-controlling medicines: introduction.

A short history of the research work of S. Okamoto and co-workers, for the previous 50 years, is briefly described. In the 1950s, when the physiologic role of fibrinolysis had not been established, they began to seek for compounds that inhibit the action of plasmin. They examined approximately 200 lysine derivatives and discovered epsilon aminocaproic acid (EACA) and tranexamic acid (t-AMCHA). In the 1970s, we selected thrombin as the target enzyme to be controlled; structure-activity relationship studies, taking arginine as the skeleton structure, led to the discovery of the selective thrombin inhibitor No. 205 (4-ethyl-1-[N2-(5-dimethylamino-1-naphthalenesulfonyl)-L-arginyl]- 1-piperidine), and further attempts to minimize the toxicity finally led to No. 805 (argatroban, MD-805, (2R,4R)-4-methyl-1-(N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)-sulfo nyl]-L-arginyl)-2-piperidine carboxylic acid). Argatroban, without any cofactor, inhibits thrombin competitively. The high selectivity of the action of argatroban is promising for treating thrombosis in clinical practice. More recently, taking advantage of our knowledge obtained through previous studies, active center-directed plasmin inhibitors and a selective inhibitor of kallikrein have been found.

Aminocaproic Acid↗
PubMed1997

Induction of donor-specific ACAID can prolong orthotopic corneal allograft survival in "high-risk" eyes.

PURPOSE: To examine the effect of donor-specific anterior chamber-associated immune deviation (ACAID) induction on the survival of orthotopic corneal allografts in neovascularized graft beds. METHODS: To induce donor-specific ACAID in recipients, peritoneal exudate cells (PEC) from C57BL/6 mice were incubated overnight with transforming growth factor (TGF)-beta. Cultured PEC were injected intravenously (i.v.) into BALB/c mice, and, 1 week later, these animals received orthotopic corneal allografts from C57BL/6 donors into neovascularized graft beds. Control mice received i.v. injection of syngeneic (BALB/c) PEC, cultured overnight with TGF-beta, and then received orthotopic corneal allografts from C57BL/6 donors. RESULTS: All corneal allografts (15 out of 15) were rejected within 2 weeks after grafting in the neovascularized graft beds of control animals. However, only 6 out of 16 (37.5%) of corneal allografts were rejected in recipients in which donor-specific ACAID had been induced by injection of allogeneic PEC cultured with TGF-beta. CONCLUSION: Previous studies revealed that rejection of orthotopic corneal allografts in neovascularized graft beds in mice correlated with acquisition of donor-specific delayed hypersensitivity (DH). The results of this study suggest that induction of donor-specific ACAID, which selectively impairs DH responses to donor antigens, effectively prolongs corneal allograft survival in "high-risk" eyes.

Animals↗
PubMed1997

Molecular cloning of a functional murine arginine-specific mono-ADP-ribosyltransferase and its expression in lymphoid cells.

A protein mono-ADP-ribosyltransferase (ADPRT), anchored in the cell membrane as a glycosylphosphatidylinositol (GPI)-anchored cell-surface enzyme, was recently described on murine cytotoxic T cells (CTL). Expression of this enzyme was shown to exert regulatory functions on CTL proliferation and cytotoxic activity, presumably by modulating activity of the protein tyrosine kinase p56(lck), which is associated with the CTL co-receptor CD8. Here we report on the molecular cloning and expression of this important regulatory enzyme. The ADPRT coding sequence was derived by making use of ADPRT sequence homologies from different vertebrate species. A cDNA fragment of the enzyme coding sequence was generated by reverse transcription polymerase chain reaction (RT-PCR) from murine T-cell lymphoma SL12, which expresses the cell-surface ADPRT. The cDNA fragment was found to share extensive homology with the corresponding sequences of human and rabbit muscle ADPRT. In Northern blot hybridization, this cDNA fragment generates a strong hybridization signal with RNA from murine heart and skeletal muscle. Weak signals are seen with SL12, thymus, and spleen. Therefore, a murine skeletal muscle cDNA library was used to identify and obtain the coding sequence of the ADPRT gene. It is shown that the nucleic acid open reading frame sequence of the murine skeletal muscle gene shares 80.3% and 76.3% homology with the sequences of the human and rabbit muscle genes, respectively. Semiquantitative RT-PCR with intron-spanning primers shows that the ADPRT mRNA is present in lymphoid organs, cytotoxic T cells, and T-cell lines. Transfection of the ADPRT coding sequence into EL4 cells results in expression of the enzyme as a functional GPI-anchored cell-surface protein, able to ADP-ribosylate the arginine analog agmatine as well as cell-surface molecules.

ADP Ribose Transferases↗
PubMed1997

Reduced incidence of Helicobacter pylori infection in young Japanese persons between the 1970s and the 1990s.

Although the incidence of gastric carcinoma in Japan has declined in the past several decades, there is no information about trends in helicobacter pylori infection. The purpose of the study was to clarify trends in H. pylori infection and in histologic gastritis in young Japanese subjects evaluated between 1975 and 1978 (the 1970s) versus 1991 and 1994 (the 1990s). The prevalence of H. pylori infection and the grade of gastritis in biopsy specimens were evaluated in 173 young Japanese without localized lesions in the upper gastrointestinal tract. Findings in 75 specimens obtained from subjects in the 1970s were compared with those of 98 specimens obtained from subjects in the 1990s. The prevalence of H. pylori infection in the 1970s (54.7%) was significantly higher than that in the 1990s (28.6%) (p < 0.01). The grade of inflammation and the prevalence of both mucosal atrophy and intestinal metaplasia also were significantly higher in the 1970s than in the 1990s (p < 0.01 and p < 0.05). Our data thus show a trend toward a reduced prevalence of H. pylori infection and of histologically apparent gastritis (especially atrophic gastritis). This decrease may be linked to the reported decline of gastric carcinoma in Japan.

Adolescent↗
PubMed1997

Clinical observation of 14 cases of childhood polyarteritis nodosa in Japan.

An epidemiological survey of childhood polyarteritis nodosa was conducted at 1290 hospitals followed by a secondary survey of hospitals that had therapeutic experience with the disease. Fourteen cases obtained from these surveys were studied clinically. The male-female ratio was 4:3. The mean age at onset was 10.6 years. To established the diagnosis, skin biopsy was performed in 43%, retrograde aortography in 21%, and kidney biopsy in 14% of cases. Non-specific symptoms such as fever (86%), skin eruption (50%), arthritis (50%), myalgia (50%), abdominal pain (43%) and hypertension (36%) were often noted as clinical findings at the initial visit. Throughout the clinical course, symptoms considered to be caused by local angiopathy, including interrupted blood circulation, were frequently noted. On blood tests, no specific findings other than acute inflammatory reaction were observed. Steroid preparations were used for treatment in all cases but one, and about half of them are presently free from steroids. Immunosuppressants were administered in 10 cases. As for prognosis, all patients are alive, but untoward sequelae were noted in 36% of cases. The results of the present survey reinforced the difficulty of establishing a final differential diagnosis because specific findings were scarce for this disease, as stated in previous reports. Establishing a method for early diagnosis by gathering and analyzing more data in detail will be necessary in the future.

Child↗
PubMed1997

Aortitis syndrome in children: clinical observation of 35 cases in Japan.

The results of clinical observation of 35 patients with aortitis syndrome (AS) in childhood, obtained by a nationwide survey in Japan, are reported. The male to female ratio was 1:2.5, the estimated age of onset averaged 10.2 years, and the duration from the estimated age of onset to the diagnosis averaged 15 months. In HLA examination A24, Bw52, Cw7 and DR2 were relatively common. Arterial lesions tended to extensively involve the aortic arch and its branches. Fever was the most frequently noted clinical symptom, followed by abdomen, joint and muscle pain. The physical findings in order of frequency were impaired circulation of the upper extremities, cardiac and vascular murmurs, hypertension, impaired cerebral circulation, visual disorder and impaired circulation of the pulmonary artery. The murmurs were found not only over the chest wall but also over the cervical area and abdomen. Pulselessness of the upper extremities occurred in 66% of patients. Percutaneous retrograde aortography and/or intravenous digital subtraction angiography to make the final diagnosis was employed except for three cases. There were not any specific abnormal signs in laboratory data. Steroid hormones were administered in 34 cases, and immunosuppressive agents in 8 cases. Five cases had percutaneous transluminal angioplasty to the right renal artery as an interventional treatment. The high frequency of abdominal pain is considered to be one of the characteristics of AS in childhood. The high frequency of pulselessness of the upper extremities and cardiac and vascular murmurs in this report is considered significant for the diagnosis of AS in childhood.

Aortitis↗