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Y Okuyama

Publications and source records attributed to Y Okuyama.

At least 19 recordsLinked to original sources
PubMed1995

Ligand-induced polyubiquitination of receptor tyrosine kinases.

The platelet-derived growth factor beta-receptor undergoes polyubiquitination as a consequence of ligand binding. In the present study, we have examined the ligand-induced receptor ubiquitination also in the other receptor tyrosine kinase (structurally different) subfamilies by immunoblotting with anti-ubiquitin antiserum. In addition to the platelet-derived growth factor alpha- and beta-receptors, all the monomeric receptor tyrosine kinases examined, such as the receptors for epidermal growth factor (subfamily I), colony stimulating factor-1 (subfamily III), and fibroblast growth factor (subfamily IV), were found to be ubiquitinated after ligand stimulation. However, the insulin receptor (subfamily II), which is a tetrameric molecule, was not. These data suggest that the ligand-induced polyubiquitination of the receptor is a general phenomenon observed in most of the monomeric receptor tyrosine kinases.

3T3 Cells↗
PubMed1995

Activation of Fes tyrosine kinase by gp130, an interleukin-6 family cytokine signal transducer, and their association.

gp130 is a signal-transducing subunit of receptors for the interleukin-6 (IL-6)-related cytokine subfamily including IL-6, leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor, indicating that gp130-mediated signals are involved in the immune response, hematopoiesis, inflammation, and endocrine and nervous system activity. We previously showed that gp130 stimulation rapidly activates Jak, Btk, and Tec tyrosine kinases, all of which constitutively associate with gp130. To further elucidate intracellular signal transduction through gp130, we examined the possible involvement of another nonreceptor tyrosine kinase, p92c-fes (Fes). We showed that gp130 stimulation rapidly induced tyrosine phosphorylation of Fes and actually activated its kinase activity in hematopoietic lineage cells. Furthermore, Fes associated with gp130 independently of ligand stimulation like Jak, Btk, and Tec tyrosine kinases. These results indicate that multiple nonreceptor tyrosine kinases are involved in the gp130-mediated signal transduction pathway. Because both gp130 and Fes are expressed not only in hematopoietic lineage cells but also in heart and nerve cells, Fes may play a role in signal transduction through gp130 in these tissues.

Animals↗
PubMed1995

Diversity of DNA sequences among Vibrio cholerae O139 Bengal detected by PCR-based DNA fingerprinting.

Vibrio cholerae O139, a causative agent of a large epidemic of cholera-like illness, has suddenly emerged and spread widely over several months. To investigate the characteristics unique to O139, traditional typing techniques for V. cholerae, such as biochemical characteristics, antibiotic susceptibility and detection of toxin production, were performed, with the result that 145 O139 strains, except for two O139 strains isolated from Argentina and Germany, were indistinguishable from O1 strains. Thus, in order to clarify the genetical relatedness among O139 strains, and between O139 and O1 strains, the RAPD (random amplified polymorphic DNA) DNA fingerprinting method was undertaken. Although the RAPD arrays in five O139 isolates from Vellore with one arbitrary primer were slightly different from the other O139 strains, the RAPD patterns of the 145 forty-five O139 strains except for two O139 strains from Argentina and Germany were quite similar to each other, but were different from those of O1 strains, indicating that those O139 epidemic strains are closely related to each other regardless of their place of isolation. Furthermore, the RAPD patterns of the O139 strains resembled those of E1 Tor strains rather than classical strain, and a small change in the RAPD pattern of O139 strains occurred during subculture for 200 generations. These results taken together suggested that O139 V. cholerae have emerged from a common origin associated with the E1 Tor strain.

Base Sequence↗
PubMed1995

Association and activation of Btk and Tec tyrosine kinases by gp130, a signal transducer of the interleukin-6 family of cytokines.

Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor constitute the IL-6 family of cytokines and play important roles in hematopoiesis, immune response, and nervous system. The receptors for the IL-6 family of cytokines share gp130 through which signals are generated, although the cytoplasmic region of gp130 does not contain any catalytic domain. In this study we show that in addition to Jak family tyrosine kinase, the stimulation of gp130 by IL-6 plus soluble IL-6 receptor alpha induced the activation of Btk and Tec tyrosine kinases, whereas IL-3 and granulocyte colony-stimulating factor activated Tec but not Btk in a pro-B cell line. Furthermore, both Btk and Tec kinases were associated with gp130 without the ligand stimulation. Because Btk is a critical tyrosine kinase for B lymphopoiesis and Tec is considered to be involved in hematopoiesis, the results suggest the involvement of gp130-Btk-Tec signal pathway in early lymphohematopoiesis.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1995

[The survey of prevalence of Lyme borreliosis in forestry workers in Saitama prefecture].

Forestry workers in Saitama Prefecture are in high occupational risk to Lyme borreliosis transmitted by ticks. We surveyed the incidence of tick bites and the prevalence of antibodies against Borrelia burgdorferi in 80 forestry workers. ELISA with the antigen from B. burgdorferi sensu stricto B31 as well as Borrelia garinii HP3 and Borrelia japonica HO14 isolated in Japan was used for the detection of antibodies. Antibody-positive cases against B31, HP3 and HO14 was 3.8, 23.8 and 13.8%, respectively. Antibody-positive cases by ELISA were subjected to Western blotting with the antigens from three borrelias. Finally, 20.0% of the workers were antibody-positive by specific antibodies, anti-OspA antibody. The correlation between ELISA and Western blotting was better when HP3 was used as an antigen. One out of 30 normal control individuals was positive in ELISA with HP3 antigen, but negative in Western blotting. Thirty percent of the workers had a history of tick bites, and these cases had no characteristic symptoms of Lyme borreliosis. However, the rate of tick bites in antibody-positive cases was significantly higher than that in antibody-negative cases. These results suggested that the forestry workers in Saitama are very likely to be infected with Lyme borreliosis transmitted by ticks.

Adolescent↗
PubMed1994

Pharmacokinetics and safety of NM441, a new quinolone, in healthy male volunteers.

The safety and pharmacokinetics of NM441, a prodrug of a new thiazeto-quinoline carboxylic acid derivative, NM394, were evaluated in healthy male volunteers given the drug orally in single doses of 20, 50, 100, 200, and 400 mg, and multiple doses of 300 mg twice daily for 6.5 days. No remarkable abnormalities were observed in symptoms, physical tests, laboratory tests, electrocardiogram (ECG), electroencephalogram (EEG), or equilibrium test. The mean plasma concentrations of active metabolite NM394 peaked between 0.5 and 1.0 hours, and the maximum concentrations were 0.68, 1.09, and 1.88 micrograms/mL at doses of 100, 200, and 400 mg, respectively. The mean half-lives were 7.7 to 8.9 hours and were not affected by dose. The mean urinary excretion rates of NM394 were 46.0, 38.3, and 30.6% of the doses within 48 hours, respectively, and other metabolites were excreted in urine by 7% of the doses. The mean salivary concentrations of NM394 were approximately 20% of the plasma concentrations. The mean fecal excretion rates of NM394 and NM441 were 52.9 and 4.2%, respectively within 72 hours after dosing of 400 mg. The Cmax, AUC, and urinary excretion rates were not altered by food intake, whereas the Tmax was prolonged slightly. In the multiple-dose study, the steady state of plasma concentration of NM394 was achieved on day 3 or 4, and further accumulation did not occur thereafter. The mean urinary excretion rate of NM394 was 49.0% during and 48 hours after the multiple administration. The acceptable safety and tolerance and defined pharmacokinetic characteristics of NM441 support further testing.

Administration, Oral↗
PubMed1994

[Biological characters of enterohemorrhagic Escherichia coli isolates from diarrhea patients in Saitama (1990-1992)].

A total of 16 strains of Enterohemorrhagic Escherichia coli (EHEC) isolated from diarrea patients in Saitama from 1990 to 1992 were tested for their serotype, verotoxin production, biochemical characteristics, antibiotics sensitivity and plasmid profiles. By serotype analysis, 14 strains from two outbreaks and 12 sporadic cases were classified as type O157:H7, one as O111:H-(not motility) and one as O128:H2. Typing of verotoxin by gene analysis using Polymerase Chain Reaction (PCR) showed that 9 of O157:H7 strains including two cases from outbreaks and O128:H2 have VT1 and VT2 genes, other O157:H7 have the VT2 gene and O111:H-has only the VT1 gene. Biochemical characteristic analysis indicated two strains of O157:H7 type from outbreaks were biotype II and the rest of O157:H7 were biotype I. One of the O157:H7 strain from a sporadic case showed positive for urease production. According to sensitivity tests against antibiotics, out of the O157:H7 group, one strain was resistant against ABPC, one against SM and two strains resistant to SM-TC. For plasmid profiles, all strains had 94 Kb plasmids and several smaller sizes of plasmids. But 5 strains of O157:H7 had 94 Kb plasmid only.

Bacterial Toxins↗
PubMed1994

[Isolation of Group B streptococci from urine in healthy persons. Streptococcal Diseases Study Group].

It is known that the neonatal group B streptococcal disease in most cases is acquired by contamination during passage through the birth canal at the time of delivery. Therefore, to investigate the influence of colonization of group B streptococci in the female genital tract by age, we carried out the isolation of group B streptococci from the urine of healthy children of school age group, and those age groups were as follow: kindergarten primary school students, junior high school students, high school students and women over twenty years of age. The isolation rates of group B streptococci from the urine of the healthy persons by each group were as follow: 12.5-18.2% in 93 females and 0-0.3% in 90 males in kindergarten aged 3-5 years, 6.4-25.3% in 285 females and 0.3-3.2% males in primary school aged 6-11 years, 11.8-19.1% in 183 females and 0-7.1% in 233 males in junior high school aged 12-14 years, 16.4-23.7% in 416 females and 2.6-7.1% in 114 males in high school aged 15-17 years, and 35.0-50.0% in adult females aged 20-60 years. Isolation rates according to sex were 2.2% in 756 males to 17.5% in 977 females of aged 3-17 years, and there was a clearly highly significant difference between males and females (p < 0.01). Group B streptococci isolated from urine of 1,818 persons were 220 strains (12.1%), and the 146 (66.4%) in all strains could be typed by the serological test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[The first report of traveler's diarrhea associated with a newly described toxigenic Vibrio cholerae O139 strain in Japan].

A newly described Vibrio cholerae O139 was isolated from a patient who had traveled in India on April 1993. The patient experienced 5 to 6 watery diarrhea per day after he returned to Japan. The isolated strain registered as K111 did not agglutinate with O1-O138 antiserum and agglutinated with O139 antiserum. This strain resembled V. cholerae O1 strain in biochemical characters and had ctx and zot, although was resistant to the vibrio static agent O/129. This is the first report of cholera-like illness by the newly described toxigenic V. cholerae O139 strain in Japan.

Base Sequence↗
PubMed1994

[Hypoplastic leukemia successfully treated by oral administration with cytarabine ocfosfate].

A 73-year-old man was admitted to our hospital with pancytopenia in December, 1992. The data of his peripheral blood were as follows: WBC 1,100/microliters (stab 9.0, seg 11.5, eosin 3.5, mono 1.0, lymph 75.0), RBC 176 x 10(4)/microliters, Hb 6.6 g/dl, platelet 4.6 x 10(4)/microliters. Bone Marrow was hypocellular (cell count 1.4 x 10(4)/microliters) and consisted of 30% blasts (peroxidase positive). He was diagnosed as having hypoplastic leukemia. Oral administration of cytarabine ocfosfate (50 mg/day) was begun from the 5th of January, 1993. The dose of cytarabine ocfosfate was increased to 100 mg/day since the 13th of January, 1993, and he was discharged from the hospital on the 23rd of January, 1993. Since then, he has been treated with cytarabine ocfosfate alone in the outpatient clinic. Pancytopenia began to improve in one month, and the data on the 7th of May, 1993 were as follows: WBC 3,500/microliters (stab 2.0, seg 37.5, eosin 1.5, baso 1.0, mono 16.5, lymph 41.5), RBC 249 x 10(4)/microliters, Hb 10.4 g/dl, platelet 15.4 x 10(4)/microliters. Bone marrow became normocellular (cell count 22.0 x 10(4)/microliters) and blasts decreased to 3.0%, and complete remission was confirmed. There were no adverse effects.

Administration, Oral↗
PubMed1994

A randomized, controlled trial of human lymphoblastoid interferon in patients with compensated type C cirrhosis.

OBJECTIVE: To determine the efficacy of human lymphoblastoid interferon (L-IFN) in the treatment of compensated type C cirrhosis, 30 patients were assigned randomly to three groups, consisting of 10 patients each, who were treated as follows. METHODS: The 1- and 3-megaunit (MU) groups received 1 or 3 MU of L-IFN, respectively, daily for 2 wk, and three times weekly for 24 wk thereafter. The control group received no treatment. All of the patients had positive C100-3 hepatitis C virus antibody (anti-HCV) titers. RESULTS: The serum alanine aminotransferase (ALT) levels decreased 26 wk after L-IFN treatment was began, in both treatment groups. In the 3-MU group, the ALT levels became normal [complete response (CR)] in 40%, improved to less than twice the upper limit of the normal value [partial response (PR)] in 10%, and remained unchanged [no change (NC)] in 50%. In the 1-MU group, a PR occurred in 30%. There was NC in 70%, and NC occurred in the control group. Twenty-four weeks after stopping L-IFN, the CR and NC rates in the 3-MU group were 10% and 90%, respectively, and NC was observed in all of the 1-MU and control patients. 2',5'-Oligoadenylate synthetase activities increased in both treatment groups (p < 0.05), but not in the control group. The anti-HCV titers decreased in the 3-MU group (p < 0.05), but not in the 1-MU and control groups. Higher doses of L-IFN were more effective. No serious side effects occurred. CONCLUSIONS: These findings suggest that IFN administration can be effective and safe in patients with compensated type C cirrhosis, and that it would be worthwhile to evaluate IFN therapy for cirrhotic patients further.

2',5'-Oligoadenylate Synthetase↗
PubMed1994

[A combination chemotherapy of mitoxantrone, etoposide, carboplatin, and prednisolone (MECP) in recurrent or refractory non-Hodgkin's lymphomas].

Twenty-two patients with recurrent or refractory non-Hodgkin's lymphoma were treated with a combination chemotherapy of mitoxantrone, etoposide, carboplatin, and prednisolone (MECP). Of 22 evaluable patients, 11 (50%) responded to MECP and 7 (32%) achieved complete remission. Particularly in relapsed cases, 9 (75%) responded and 6 (50%) achieved complete remission. Myelosuppression was the major toxicity. Thirteen patients (59%) experienced WBC counts under 1,000/microliters, and thrombocytopenia under 50,000/microliters was seen in 12 patients (55%). During myelosuppression, 2 patients developed sepsis and 1 showed intestinal bleeding. Other gastrointestinal toxicities were well tolerated. There was no death due to chemotherapy. These results show that MECP is a well-tolerated treatment regimen, and effective for recurrent or refractory non-Hodgkin's lymphomas.

Administration, Oral↗
PubMed1993

Functional integrity of hepatocyte canalicular membrane transport of taurocholate and bilirubin diglucuronide in Eisai hyperbilirubinuria rats.

Eisai hyperbilirubinuria rats (EHBR) are characterized by conjugated hyperbilirubinemia, and impaired or defective excretion of bilirubin, reduced glutathione and other organic anions from hepatocytes. Hepatocyte canalicular membrane vesicles (CMV) from EHBR and normal SD rats were studied with regard to taurocholate (TC) transport driven by ATP or a membrane potential and bicarbonate-stimulated bilirubin diglucuronide (BDG) transport. ATP-dependent uptake or association of BDG with CMV was also studied in both strains of rats. No significant differences in the uptake of TC and BDG by CMV were observed. This indicates the functional integrity of the canalicular transporters for both organic anions in EHBR. Biliary excretion of taurolithocholic acid sulfate (TLCS) is defective in EHBR. However, TLCS inhibited ATP-dependent TC uptake by SD rat CMV competitively, which may be against the hypothesis that a common organic anion carrier is defective in canalicular membranes of jaundiced rats.

Animals↗
PubMed1993

Swelling controlled zero order and sigmoidal drug release from thermo-responsive poly(N-isopropylacrylamide-co-butyl methacrylate) hydrogel.

Thermo-responsive hydrogels of poly(N-isopropylacrylamide-co-butyl methacrylate) (poly-(IPAAm-co-BMA)) are capable of swelling-deswelling changes in response to external temperature. As poly(IPAAm-co-BMA) gels swell larger at a lower temperature, the degree and rate of the swelling could be controlled by temperature without altering the chemical structure. Therefore, drug release profiles were remarkably changed by alternation of temperature. The release profiles of indomethacin from poly(IPAAm-co-BMA) were observed to be zero-order at 20 degrees C. This release profile was explained in terms of a Case-II diffusion mechanism; which indicates relaxation of polymer chains with swelling was rate-determining. In the case of 10 degrees C, release demonstrated a sigmoidal profile. The acceleration of drug release was due to a rapid increase in swelling with disappearance of the glassy core which had constrained swelling. The regulation of the water-uptake process by changing external temperature remarkably affected drug release and resulted in several different release profiles.

Acrylic Resins↗
PubMed1993

[Acute mixed lineage leukemia showing resistance to AML and ALL therapy].

A 51-year-old female was who admitted complaining of cough and slight fever and lower limb petechia. The laboratory examinations revealed leukocytosis (49,400/microliters) with blasts (71%) in the peripheral blood. The NCC was 30 x 10(4)/microliters with 84.8% blasts in the bone marrow. Myeloperoxidase staining was positive for 6% of blasts. Auer rods were not seen in some blasts. Thus, acute myeloblastic leukemia (M1) was diagnosed according to FAB classification. In the peripheral blood, 43.3% of blasts expressed CD19, 10.3% of blasts expressed CD20 and 55.6% of blasts expressed CD33 on admission. Though she received two courses of DCMP according to the DCMP-85 protocol, and one combined course of mitoxantrone, etoposide, and Ara-C. The NCC was 20.0 x 10(4)/microliters with 70% blasts in the bone marrow. CD19 was expressed by 72.4% of blasts and 35.0% expressed CD20. The ALL-90 protocol was started, but remission was not achieved. Thus this case was considered to be acute mixed lineage leukemia.

Antigens, CD↗
PubMed1993

[Accordance of the chemosensitivity between clinical specimens and their xenografts in nude mice by SDI test and the value of in vivo chemosensitivity test using nude mice].

We assessed the sensitivity to anticancer drugs by SDI (succinate dehydrogenase inhibition) test with 11 clinical specimens obtained from operated patients. The results were compared with those of xenografted specimen in nude mice, using the adjuvant part of the specimens assayed. Chemosensitivity of clinical specimens against 3 drugs is mitomycin (MMC), adriamycin (ADM) and cisplatin (CDDP), showed a good accordance (73%) with those of xenografted tumors. The drug sensitivity was considered to be one of the features of original tumors and to be well preserved in the xenografts in nude mice. We also studied in vivo experimental chemotherapy on 19 tumor lines in nude mice to compare the chemosensitivity with clinical response to the same chemotherapy observed in each donor patient. A close correlation (83% on responder, 100% on non-responder and the overall predicting accuracy rate were 95%) was shown, suggesting in vivo nude mouse assay having an excellent predictability for clinical results.

Adult↗