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Biomedical subjects

T Miyagi

Publications and source records attributed to T Miyagi.

At least 19 recordsLinked to original sources
PubMed1992

Multiple forms of mammalian sialidase: altered expression in carcinogenesis.

We have demonstrated that rat liver contains at least four types of sialidase differing in subcellular location, in catalytic property and immunologically. They are intralysosomal, cytosolic and membrane-associated sialidases I and II. Membrane sialidase I locates mainly in plasma membrane and sialidase II in lysosomal membrane. Immunological study reveals that the same types of sialidase exist in various tissues of rat and of other mammalian species. Based on these results, we examined the sialidases in rat hepatomas and in transformed cells of JB6 mouse epidermal cell. Hepatomas were found to possess four types of sialidase and the three of them altered quantitatively. Intralysosomal sialidase activity was higher but cytosolic and lysosomal membrane sialidase activities were lower in hepatomas than in control liver. When the sialidases of transformants of JB6 cells were compared with those of control cells, the activities of two lysosomal sialidases were decreased and contrarily plasma membrane sialidase was increased. We discussed a possible significance of the sialidase alterations in carcinogenesis.

Animals↗
PubMed1992

[Clinical evaluation of flucytosine in patients with urinary fungal infections].

The clinical effectiveness of flucytosine (5-FC) was evaluated in 52 patients with urinary fungal infections which were diagnosed because of the presence of both funguria (greater than or equal to 10(4) cfu/ml) and pyuria (greater than or equal to 5 WBC/hpf). The patients received oral daily doses of 5-FC ranging 20 to 150 mg/kg, with a mean treatment duration of 11 days. The 57 fungus strains isolated from urine specimens consisted of 51 Candida spp. including 28 Candida albicans, 10 Candida glabrata, 4 Candida tropicalis and 6 Trichosporon beigelii. Forty-seven (92.2%) and 4 (66.7%) of the 51 Candida spp. and 6 T. beigelii strains isolated were eradicated by the treatment, respectively, giving an overall eradication rate of 89.5%. Clinical responses in 32 patients, from whom only fungi were submitted, were excellent in 5, moderate in 22, and poor in 5, thus the overall efficacy rate was 84.4%, based on the criteria of Japanese UTI Committee. Of the 18 strains of Candida spp. tested, 5-FC showed 0.20 micrograms/ml or less of the minimum inhibitory concentrations (MICs) against 16 strains and higher than 100 micrograms/ml against the remaining 2 strains. The MICs of the 5 T. beigelii strains tested were between 3.12 and 6.25 micrograms/ml. As adverse reactions, only 2 patients (3.8%) experienced diarrhea but did not require treatment cessation. These results suggest that flucytosine is an effective drug for urinary fungal infections.

Adult↗
PubMed1992

[Intensive induction chemotherapy of adult acute myelogenous leukemia by continuing daunorubicin, behenoyl-cytosine arabinoside, 6-mercaptopurine and prednisolone until marrow aplasia].

Intensive induction chemotherapy was applied to 25 patients with acute myelogenous leukemia by continuing drugs (daunorubicin, behenoyl-cytosine arabinoside, 6-mercaptopurine and prednisolone) until the achievement of severe bone marrow aplasia (leukemic cells less than 1,000/microliters). Complete remission (CR) was achieved in 18 (72%). Numbers of partial remission and an early death were 5 (20%) and 2 (8%), respectively. Although median nadirs of white blood cells (WBC) and platelet counts (Pl) (205/microliters and 8,200/microliters, respectively) were remarkably low, recovery of WBC (over 1,000/microliters) and Pl (over 50,000/microliters) were achieved in 23.8 and 24.5 days, after an initiation of the chemotherapy. Sepsis was a most frequently observed complication during induction stage and a duration of fever was 2-48 days (median 15). Median duration of CR was 22.9 months. Unexpectedly, 11 of 17 CR (except one with bone marrow transplanted) relapsed after 4.2-41.4 months (median; 9.4), but 6 (35.3%) still remain in first CR for 30.5-72.9 months (median; 51.4). A long-term survival might be obtained by intensifying induction chemotherapy in about one fourth of patients, but the intensification or application of non-cross resistant anti-leukemic agents in post-remission therapy may be required to avoid relapses even if induction is intensified.

Administration, Oral↗
PubMed1992

Acute megakaryoblastic leukemia: establishment of a new cell line (MKPL-1) in vitro and in vivo.

A megakaryoblastic cell line (MKPL-1) was newly established from the bone marrow of an adult patient with acute megakaryoblastic leukemia. This cell line grew in single cell suspension with a doubling time of 30 h and consisted of large primitive blasts with persistent development of giant cells carrying multilobed nuclei. MKPL-1 cells were positive for platelet GPIIb/IIIa (CD41) and GPIIIa (CD61), and expressed OKM5 (CD36), MY7 (CD13), and MY9 (CD33) antigens in the absence of erythroid and lymphoid markers. The cytochemical and morphologic characteristics of MKPL-1 were also consistent with those of megakaryoblasts. The cells did not, however, express ultrastructural platelet peroxidase which is considered to be another marker of the megakaryocytic lineage. Cytogenetic analysis of MKPL-1 revealed a model chromosome number of 92 with abnormal chromosomes including those found in the patient's bone marrow cells. Furthermore, MKPL-1 cells were serially transplanted into nude mice for nine passages with production of lethal tumors and leukemic manifestation. Thus, our megakaryoblastic cell line which can be maintained both in vitro and in vivo would be useful for further studies of the biology of megakaryopoiesis and megakaryoblastic leukemia.

Aged↗
PubMed1991

D-factor: modulation of expression in fibroblasts.

Differentiation inducing factor (D-factor) is a recently described protein. The gene has been cloned, but little is known concerning regulation of expression of the gene. Our study showed that fibroblasts from a variety of tissues (lung, bone marrow, gingiva, foreskin) constitutively expressed D-factor RNA. Levels of expression of this gene increased in fibroblasts of each of the tissues after exposure to several stimuli including products of activated macrophages and lymphocytes (tumor necrosis factor (TNF), interleukin 1 and lymphotoxin). Other stimuli were those capable of activating either protein kinase C (12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin), G-binding proteins (NaF) or those inhibiting protein synthesis (cycloheximide). Accumulation of D-factor RNA by TNF may in part be explained by stabilization of D-factor transcripts; TPA and cycloheximide clearly stabilized D-factor transcripts. We and others have shown that these same signals similarly stimulated fibroblasts to express RNAs coding for a variety of cytokines including three colony-stimulating factors as well as interleukins 1 and 6. Taken together, D-factor probably is a participant in the cascade of cytokines that are produced in mesenchymal cells after various stimuli such as bacterial invasion.

Cells, Cultured↗
PubMed1991

Bacteremia from transurethral prostatic resection under prophylactic use of antibiotics.

We studied the incidence of the postoperative bacteremia developing in 44 patients undergoing transurethral resection of the prostate under prophylactic use of antibiotics. In 15 of the patients, postoperative endotoxinemia was also investigated. Postoperative bacteremia was found in 10 (22.7%) of the patients, in only one of whom septicemia developed. The incidence of bacteremia was not influenced by the kind of antimicrobial agent administered prophylactically, but was significantly higher in the patients with preoperative urinary tract infection or prostatitis on histological examination of resected prostatic tissue (p less than 0.01). Concerning species isolated from the blood, gram-positive cocci were isolated more frequently than gram-negative bacteria, and Staphylococcus epidermidis was the most common species. In 7 (70%) of the bacteremia patients an identical species was isolated from preoperative urine cultures. In the patients with bacteremia, significant increases in white blood cell count and maximal body temperature were found within 3 hours after the procedure as compared to before the procedure. To lower the postoperative bacteremic rate, appropriate and adequate antimicrobial agents must be used preoperatively in patients with infection of the genitourinary tract. As to blood endotoxin, the endotoxin levels in the patients with postoperative fever did not significantly differ from those of the patients without this complication.

Aged↗
PubMed1990

A Ki-1 (CD30)-positive T (E+, CD4+, Ia+)-cell line, DL-40, established from aggressive large cell lymphoma.

A new human lymphoma cell line, designated DL-40, was established from the peripheral blood of a 64-year-old woman with leukemic conversion of aggressive large cell lymphoma. The cell line grew in suspension with or without forming clumps of cells and exhibited large, round, or multiple nuclei in the relatively abundant cytoplasm that was positive for acid phosphatase. The cells expressed a Ki-1 antigen (CD30), E+, CD2+, CD4+, CD45+, Ia+ phenotype and had rearranged T-cell receptor beta chain but were negative for CD15, HTLV-I, and Epstein-Barr virus nuclear antigen. Chromosome analysis of this cell line showed a human female karyotype with complex hyperdiploid abnormalities. DL-40 cells produced tumors histologically similar to the original lymphoma when transplanted into nude mice and immunosuppressed hamsters. The DL-40 cell line could provide a useful tool for the understanding of biology of the Ki-1-positive non-Hodgkin's lymphoma.

Antigens, Differentiation↗
PubMed1990

Characterization of the major sialidases of various types of rat blood cells: their comparison with rat liver sialidases.

The substrate specificity and subcellular location of the major sialidases of three types of rat blood cells were characterized and compared with those of the known three types of rat liver sialidase, which have been designated intralysosomal, cytosolic, and plasma membrane-associated sialidases. Platelets and leucocytes contain mainly an acid sialidase, which is highly active towards oligosaccharides and 4MU-NeuAc, and erythrocytes possess a high level of a sialidase acting on gangliosides. A Percoll gradient centrifugation study showed that the former is located in lysosomes and the latter in plasma membrane. When the sialidase was solubilized and partially purified from erythrocyte ghosts, the enzyme was found to hydrolyze actively gangliosides but only poorly other substrates such as 4MU-NeuAc, oligosaccharides, and glycoproteins. The sialidase partially purified from rat liver membrane fraction exhibited the same substrate specificity. It is concluded that the major sialidase of platelets and leucocytes corresponds to hepatic intralysosomal sialidase while erythrocytes contain almost exclusively a ganglioside sialidase which corresponds to hepatic plasma membrane sialidase.

Animals↗
PubMed1990

Biochemical and immunological studies on two distinct ganglioside-hydrolyzing sialidases from the particulate fraction of rat brain.

Ganglioside-hydrolyzing sialidase activity was solubilized from rat brain particulate fraction by using Triton X-100 plus sodium deoxycholate. When chromatographed on AH-Sepharose 4B, the solubilized activity was resolved into two peaks, which were designated sialidases I and II in order of elution. The two sialidases were purified by using sequential chromatographies on Octyl-Sepharose CL-4B, Phenyl-Sepharose CL-4B, and Sephadex G-200. Sialidase II was purified further by Mono Q-FPLC. Overall purification was 450- and 2,150-fold, for sialidases I and II, respectively. Purified sialidases I and II were maximally active at near pH 5.0 and exhibited M = 70,000 by gel filtration. Sialidase I hydrolyzed gangliosides but scarcely other substrates including 4-methylumbelliferyl-NeuAc (4MU-NeuAc). Sialidase II hydrolyzed oligosaccharides, glycoproteins, and 4MU-NeuAc although gangliosides appeared to be preferential substrates. Sialidase II cleaved GM2 much faster than sialidase I. An antibody raised in rabbits against sialidase I reacted with only sialidase I and an antibody against sialidase II reacted with only sialidase II. A subcellular distribution study suggested sialidase I in the synaptosomal membrane and sialidase II in the synaptosomal and lysosomal membranes, and this was verified by using the above antibodies.

Animals↗
PubMed1990

Immunological discrimination of intralysosomal, cytosolic, and two membrane sialidases present in rat tissues.

Cytosolic sialidase was purified from rat skeletal muscle, and the purified enzyme migrated as a single band of Mr 43,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A polyclonal antibody raised against the enzyme inhibited and immunoprecipitated rat liver cytosolic sialidase as well as the muscle enzyme but failed to cross-react with the intralysosomal sialidase of rat liver and membrane sialidases I (synaptosomal) and II (lysosomal) of rat brain. The antibody against brain membrane sialidase I (anti-I) and that against sialidase II (anti-II), which could be useful to discriminate the two enzymes, did not cross-react with the intralysosomal and cytosolic sialidases of liver. Although more than 90% of liver plasma membrane sialidase was immunoprecipitated with anti-I, only 60% of liver lysosomal membrane sialidase was immunoprecipitated with anti-II, the remainder being immunoprecipitated with anti-I. In confirmation of these data, liver lysosomal membrane exhibited two peaks of ganglioside sialidase corresponding to the membrane sialidases I and II on Aminohexyl-Sepharose chromatography while only one peak of ganglioside sialidase corresponding to sialidase I was observed for liver plasma membrane. These results indicate that the four types of rat sialidase are proteins distinct from one another and that the three kinds of antisera described above are useful for discriminating these sialidases qualitatively and probably quantitatively.

Animals↗
PubMed1990

Neoplastic alteration of a membrane-associated sialidase of rat liver.

Rat liver particulate fraction contains two types of membrane-associated and gangliosides-hydrolyzing sialidase, which have been shown to be identical to two membrane-associated sialidases of rat brain (I and II) chromatographically, immunologically and in substrate specificity. Chromatography on AH-Sepharose 4B of the membrane sialidases of rat primary hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene (MeDAB) further revealed that hepatocarcinogenesis induces a marked decrease in sialidase II but no decrease in sialidase I. Using antisera against sialidases I and II of rat brain, immunoprecipitation studies of the solubilized particulate fractions of rat liver and MeDAB-hepatoma gave results similar to those obtained chromatographically. Using the same immunological technique, sialidase II but not sialidase I was found to be decreased in AH109 A hepatoma and in regenerating and fetal liver.

Animals↗
PubMed1990

Tumor-promoting phorbol ester induces alterations of sialidase and sialyltransferase activities of JB6 cells.

Sialidase and sialyltransferase activities were studied in JB6 mouse epidermal cells before and after exposure to phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (TPA), which irreversibly induces anchorage-independent growth and tumorigenicity. JB6 cells exhibited sialidase activities toward 4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid (4MU-NeuAc) and gangliosides at pH 4.5 in the particulate fraction but apparently not in the cytosol at pH 4.5 or 6.0. In JB6 cells exposed to TPA and in the anchorage-independent transformants, the sialidase activity toward 4MU-NeuAc was decreased and the activity toward gangliosides was increased compared with those in untreated JB6 cells. Immunological analysis with antisera against membrane-associated sialidases I and II revealed that plasma membrane-associated sialidase I was increased and lysosomal membrane-associated sialidase II was decreased under these conditions. TPA treatment also affected the sialyltransferase activities of JB6 cells: and elevation of the transfer activities toward asialo-orosomucoid and asialo-porcine submaxillary mucin but a reduction of GM3 and GD3 synthase activities were observed on exposure to TPA and in cells transformed by TPA to retain anchorage-independency. These results suggest that an increase in sialic acid bound to glycoproteins and a decrease in that bound to glycolipids may occur in JB6 cells exposed to TPA and in the anchorage-independent transformants.

Animals↗
PubMed1990

Effects of OK-432 activation on the sialidase activities of rat peritoneal macrophages.

Intraperitoneal treatment of rat peritoneal macrophages with OK-432 results in more than 9-fold increase in the activity of ganglioside sialidase, which seems to coincide with the appearance of a cell surface antigen, asialo-GM1. The results of subsequent studies suggest that the ganglioside sialidase is located in the plasma membrane, where the enzyme may be responsible for the formation of asialo-GM1 from GM1. In the macrophages activated with OK-432, sialidase activity toward 4-methylumbelliferyl-N-acetylneuraminic acid (4MU-NeuAc) is also increased. It appears that the 4MU-NeuAc sialidase is intralysosomal and is increased together with other acid hydrolases present in the lysosomes.

Animals↗
PubMed1990

[Prophylactic effect of UFT on the recurrence of bladder cancer].

To evaluate the effect of UFT, a mixture of ftorafur and uracil in a ratio of 1:4, in preventing postoperative recurrence of bladder cancer, we performed a randomized controlled study with a non-medication group as control. UFT was given orally 400 mg a day for 6 months. Of 111 patients, 56 were given UFT and 55 were followed up without any medication. The non-recurrence rate in the group treated with UFT was 62.8% after 1 year and 36.3% after 2 years of follow up, and that of the control group was 45.7% and 39.5%, respectively. The rate of non-recurrence in the UFT group was significantly higher (p less than 0.05) than that of the control group during the period of follow up for 2 years. The incidence of side effects was 6.8% in UFT patients. These results indicate the clinical usefulness of prophylactic administration of UFT for bladder cancer patients.

Administration, Oral↗
PubMed1990

[Clinical observation on renal pelvic and ureteral tumors].

During the 18 years from October, 1971 to September, 1989, 40 patients with renal pelvic and ureteral tumors were treated at our Department of Urology. Thirty were male and 10 female, and were between 44 and 83 years old with a mean age of 65.5 years. Histopathologically, there were 38 transitional cell carcinomas and 2 squamous cell carcinomas. There was a positive correlation between grade and stage of tumor. Among the patients with transitional cell carcinoma, the five-year survival rate was 54.4% for all the patients, 57.1% for patients with renal pelvic tumors and 48.4% for those with ureteral tumors respectively, as measured by the Kaplan-Meier's method. Stage and intravascular invasion of the tumor were the most influential factors for prognosis. There was no evidence in this series to show the usefulness of postoperative adjuvant chemotherapy, such as bladder instillation or peroral administration of various anti-tumor drugs, as a prophylactic use for recurrence of the bladder tumor in low stage cases.

Adult↗
PubMed1989

Direct and serial transplantation of Ph1-positive acute lymphoblastic leukemia into nude mice.

A new Philadelphia chromosome (Ph1-positive) acute lymphoblastic leukemia (ALL) cell line was established in nude mice by direct and serial transplantation of peripheral blood leukemia cells from an adult patient. Although the patient's leukemia cells did not grow in vitro, they were successfully transplanted for 8 serial passages, giving rise to progressive growth of tumors with frequent involvement of lymph nodes, liver, spleen, bone marrow, and meninges. The tumor cells could also be passaged in an ascites form. This in vivo cell line, designated PALL-I, retained the Ph1 chromosome, t(9;22) (q34;q11), and pre-B-cell phenotype (SmIg-, CpIg-, CD10+, CD19+, OKIaI+, and CD38+), like the original leukemia cells. Molecular genetic analysis of PALL-I cells revealed neither bcr rearrangement nor 8.5-kb abI-related mRNA that is characteristically seen in Ph1-positive chronic myelogenous leukemia (CML). Thus, the PALL-I cell line is genetically distinct from CML. It may provide a useful model for an understanding of the cellular and molecular biology of Ph1-positive ALL without classical bcr rearrangement.

Acute Disease↗
PubMed1989

[Seizure and tremor occurring in acute leukemia patients treated with imipenem/cilastatin].

We report here four patients with acute leukemia, who developed seizure or tremor following treatment with imipenem, a new broad-spectrum antibiotic. All four patients had no renal dysfunction and recovered after discontinuation of the drug. Two patients who developed seizure had a past history of cerebral hemorrhage with symptoms of meningitis in one and the other had received frequent intrathecal injections of methotrexate. Seizure also occurred in another patient who was given multiple intrathecal injections of methotrexate. The remaining old patient developed tremor after the first administration of imipenem which did not progress to convulsion. Cerebral hemorrhage or meningitis is known to predispose patients for convulsion following imipenem treatment. In addition, the present study suggests that central nervous system damage related with intrathecal injections of methotrexate may be a predisposing factor. Thus, imipenem should be given with caution to acute leukemia patients who often have risk factors for developing imipenem-related complications.

Acute Disease↗