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Biomedical subjects

K Utsumi

Publications and source records attributed to K Utsumi.

At least 127 records · Page 7Linked to original sources
PubMed1995

Synthesis, antiviral, antibacterial and antitumor cell activities of 2'-deoxy-2'-fluoropuromycin.

A procedure for the synthesis of 2'-deoxy-2'-fluoropuromycin (1b) was developed. Ring opening of the lyxo-epoxide (4) or nucleophilic displacement of the 3'-O-mesylate (5) by an azide ion afforded two azido nucleosides, 6a and 7a. The major product (7a) was reacted with diethylaminosulfur trifluoride (DAST) to give the 2'-fluoronucleoside (8), which was converted to the 3'-aminonucleoside (9) by hydrogenation. Compound 9 was condensed with an amino acid by the conventional method and subsequently deprotected by acid to give 1b. Compounds 1b, 6b and 7b exhibited no selective antiviral activity against several DNA and RNA viruses. Compound 1b had weak antibacterial activity (minimum inhibitory concentration approximately 25-50 micrograms/ml) and was cytotoxic to several tumor cell lines (L1210, Molt 4, CEM) at a concentration of about 5 microM. This antitumor cell activity may be attributed to inhibition of protein biosynthesis.

Animals↗
PubMed1995

Tissue- and development-specific expression of goat insulin-like growth factor-I (IGF-I) mRNAs.

We cloned four kinds of goat insulin-like growth factor-I (IGF-I) cDNAs. Each of them encodes the same mature IGF-I and different signal peptides. In this study, we analyzed expression of the four kinds of mRNAs in tissues in various developmental stages by a reverse transcriptase-polymerase chain reaction assay. The results suggest that their expression may be controlled by different promoters, the activities of which are tissue- and development-specific.

Animals↗
PubMed1995

Fat embolism syndrome caused by vegetable oil injection.

We present a case of fat embolism syndrome following vegetable oil injection for augmentation mammaplasty. Although vegetable oil is a stable neutral fat under usual storage conditions, it caused fat embolism and pulmonary injury in this patient. We investigated this mechanism by compound analysis of the injected oil, transbronchial lung biopsy and special staining of alveolar macrophages. This is the first description of the human response to vegetable oil injection. These data should aid in the investigation of the side effects of many types of lipids which may be applied to humans for various purposes in the future.

Adult↗
PubMed1995

Inhibition of stimulus-specific neutrophil superoxide generation by alpha-tocopherol.

Alpha-tocopherol but not 2-carboxy-2,5,7,8-tetramethyl-6-chromanol (trolox or CTMC) and 2,2,5,7,8 pentamethyl-6-hydroxy chromane (PMC), derivatives of alpha-tocopherol, inhibited the superoxide (O2-.) generation of rat peritoneal neutrophils (RPMN) induced by phorbol 12-myrisate 13-acetate (PMA). ID50 for neutrophils obtained from the peritoneal cavity of rat and guinea pig was about 1microM. This concentration, however, was much lower than that for the inhibition of PMA-activated phospholipid-dependent protein kinase (PKC) (ID50 = 30 microM). The alpha-tocopherol sensitive O2-. generation was also observed in neutrophils induced by dioctanoylglycerol (diC8) and calcium ionophore A23187 but not by formylmethionyl-leucyl-phenylalanine (FMLP), opsonized zymosan (OZ) and sodium dodecyl sulfate (SDS). The pattern of inhibition by alpha-tocopherol was quite similar to that of staurosporine, a specific inhibitor of PKC. The alpha-tocopherol content of RPMN was 12 ng/10(6) cells and a linear increase to 200 ng/10(6) cells by addition of alpha-tocopherol to the cell suspension corresponded with an increased inhibition of O2-. generation. These results indicate that both the chemical structure and the content of alpha-tocopherol might be important factors in O2-. generation by neutrophils.

Animals↗
PubMed1995

Selective inhibition of human TNF-alpha action by flecainide acetate, an antiarrhythmic drug.

It is now generally accepted that human tumor necrosis factor-alpha (hTNF-alpha) affects not only tumor cells but also normal cells, providing critical tissue damage. hTNF-alpha also enhanced the response of polymorphonuclear neutrophils (PMN) by its priming action and resulted in the increased generation of active oxygen which in turn may be responsible for the tissue injury. Seeking a conventional drug to attenuate the cytolytic activity of tumor necrosis factor (TNF-alpha) and thereby prevent excessive tissue injury, we focused on the cytolytic action of hTNF-alpha against L929 cells, which are sensitive to TNF-alpha, and found that flecainide acetate [N-(2-piperidylmethyl) 1,5-bis-(2,2,2-trifluoroethoxy) benzamide acetate] inhibited specifically the cytolytic action of hTNF-alpha against L929 cells. Flecainide acetate also specifically inhibited the priming action of hTNF-alpha which enhance the formylmethionyl-leucyl-phenylalanine (FMLP)-induced receptor-mediated superoxide (O.2-) generation of human peripheral polymorphonuclear neutrophils (hPMN). The ID50 values for hTNF-alpha induced cytotoxicity in L929 cells and hTNF-alpha primed FMLP-induced O.2- generation of hPMN were 30 and 50-60 microM, respectively. However, the drug does not inhibit the FMLP- or phorbol myristate acetate (PMA)-induced O.2- generation of nonprimed hPMN and has a weak cytotoxic effect on L929 cells. From these results, it is concluded that flecainide acetate suppressed specifically the action of hTNF-alpha.

Animals↗
PubMed1995

[Gamma delta T cells in peripheral blood and in bronchoalveolar lavage fluid from patients with sarcoidosis and idiopathic pulmonary fibrosis].

We measured levels of gamma delta T cells in peripheral blood and in bronchoalveolar lavage fluid from patients with sarcoidosis, from patients with pulmonary fibrosis, and from normal subjects. In blood from both groups of patients, the percentage of lymphocytes was significantly greater than normal. The number of CD3+ cells per cubic millimeter was significantly lower than normal in patients with sarcoidosis, and tendency to be lower than normal in patients with pulmonary fibrosis. The percentage of CD3+ cells tended to be low, but there was no significant difference. The percentage and number of gamma delta T cells in patients with sarcoidosis, and the number of gamma delta T cells in patients with pulmonary fibrosis tended to be high. In bronchoalveolar lavage fluid, the percentage of lymphocyte was significantly higher than normal, and the numbers of CD3+ cells and gamma delta T cells per cubic millimeter tended to be high. In both groups of patients, cell counts of lymphocytes were significantly higher than normal. Numbers of CD3+ cells and of gamma delta T cells were significantly higher than normal in patients with sarcoidosis, and tended to be higher than normal in those with pulmonary fibrosis. These findings indicate local activation of gamma delta T cell function, recruitment of these cells into the bronchoalveolar system, and augmentation of gamma delta T cell supply in the whole body, especially in patients with sarcoidosis. In patients with pulmonary fibrosis the results were inconclusive; they were not as striking as were the results in patients with sarcoidosis.

Adult↗
PubMed1995

Development of a health administration system for inhabitants in local community without abnormal findings by health examination.

This study was to establish practical methods to apply to the community health promotion program the data obtained by surveys in a fishing village, under "The Health and Medical Services Law for the Aged." This data, together with guidelines on health counseling for inhabitants in the local community with less abnormal findings on health examination, could be used for developing a health promotion support system. In 1990, a questionnaire survey was carried out on lifestyle such as diet, exercise, and rest, of 1,497 inhabitants (557 males, 940 females) attending for a health examination under "The Health and Medical Services Law for the Aged," at Nishiizu district, Shizuoka Prefecture, Japan. The questionnaire inquired about the subjects' health behavior and consciousness, i.e., on their dietary intake and preferences, dietary habits, regular exercise, exercise habits, and rest, both in fact as well as in perception. In 1991, a survey was also carried out on the daily physical activity and exercise of 1,737 inhabitants (620 males, 1,117 females) attending for a health examination under the law in the same district. The items measured were the daily physical activity, the exercise intensity, and the frequency score derived from several exercises. The relationship to the exercise score was made on the basis of the sex, age, daily physical activity, and the findings of the health examination as well as the self-evaluation of health. In 1992, based on these results and also on the know-how about the software made for similar purposes, "The Health Promotion Support System" for the personal computer was developed in order to help public health nurses perform health counseling for the local community. By means of this system, the answers concerning the health examination findings, habits, health conditions, etc., enabled us to obtain information about the appropriate amount of exercise needed for health, and of the total exercise time needed in a week at the level of 40% maximum oxygen intake. In order to ascertain the quality and effect of the program, the system was applied practically by the public health services, both at Nishiizu district and at Maruyama, Chiba Prefecture, Japan. A questionnaire survey was also conducted in Chiba Prefecture, the subjects were seven public health nurses. The results of this survey showed that the system was successfully applied to the people who received less care because of not having abnormal findings on the health examination.

Aged↗
PubMed1995

Protection against alloxan diabetes by low-dose 60Co gamma irradiation before alloxan administration.

We evaluated the protective effects of a single low-dose whole body 60Co gamma irradiation against alloxan-induced hyperglycemia in rats. i) In rats that did not receive alloxan, the superoxide dismutase (SOD) activity in the pancreas significantly increased after irradiation at a dose of 0.5 or 1.0 Gy. ii) In rats that received alloxan, plasma lipid peroxide levels, pancreatic lipid peroxide levels and blood glucose were increased. However, the increase in pancreatic lipid peroxide level was prevented by irradiation at a dose of 0.5 or 1.0 Gy; and the increase in blood glucose, by irradiation at 0.5 Gy. iii) After alloxan administration, degranulation was observed in beta cells, but this was prevented by low-dose irradiation at 0.5 Gy.

Animals↗
PubMed1994

Evidence for defects in V(D)J rearrangements in patients with severe combined immunodeficiency.

We investigated the patterns of DNA rearrangements at loci for Ig JH genes in patients with severe combined immunodeficiency (SCID). Four SCID patients without B cells (B- SCID) and four SCID patients with B cells (B+ SCID) were examined. Bone marrow cells of these patients were transformed with EBV. The majority of the transformed cells from three B- SCID patients had the germline configuration at their JH gene loci. The rearranged fragments from one patient were analyzed extensively. The rearranged regions in all of the fragments had a common structure wherein two fragments derived from the JH-S mu region were connected inversely. The possible presence of rearranged forms of VHDJH and DHQ52JH sequences in bone marrow cells of two B- SCID patients were examined directly by the polymerase chain reaction (PCR) method. In one patient, we found neither a VHDJH sequence nor a DHQ52JH sequence within the range of sensitivity of the PCR method. In another patient, we found a VHDJH sequence at an extremely low level and DHQ52JH sequences at a relatively low level. Either RAG-1 or RAG-2 gene was not expressed in the B- SCID-derived cell lines. B+ SCID patients did not show any abnormalities in terms of VHDJH rearrangements. These results indicate that B- SCID may be caused by defects in factors involved in V(D)J rearrangements.

Base Sequence↗
PubMed1994

Myristoylation of protein at a distinct position allows its phosphorylation by protein kinase C.

A hydrophilic enzyme, lysozyme, was myristoylated in vitro by the N-hydroxysuccinimide ester of myristic acid and three monomyristoylated lysozymes modified at a distinct position (at Lys-13, Lys-33, Lys-97) were isolated by two-step column chromatography. The relationship between membrane binding and phosphorylation by protein kinase C of these monomyristoylated lysozymes were examined using phospholipid vesicles. These three lysozymes bound to phospholipid vesicles to the same extent, whereas the binding of nonmyristoylated native lysozyme was negligible. When native and three monomyristoylated lysozymes were reacted with protein kinase C in a phosphatidylserine (PS)-containing vesicle system, phosphorylation was observed with the myristoylated lysozymes, whereas that of native lysozyme was negligible. However, a remarkable (more than sixfold) difference in the extent of phosphorylation by protein kinase C was observed among three monomyristoylated lysozymes with a different myristoylated position. These results suggest that the membrane binding of substrate protein is not sufficient for the phosphorylation by protein kinase C and the topology of the substrate protein on the membrane play a crucial role in the recognition of substrate protein by protein kinase C. These results further indicate that protein myristoylation can modulate the topology of the membrane-bound protein.

Amino Acid Sequence↗
PubMed1994

Detection of manganese superoxide dismutase mRNA in the theca interna cells of rat ovary during the ovulatory process by in situ hybridization.

To determine the possible involvement of reactive oxygen species in ovulation, dynamic aspects of superoxide dismutase (SOD) isozyme were studied in the ovaries of rats by in situ hybridization histochemistry. Previously, mRNA levels of ovarian manganese superoxide dismutase (Mn-SOD) were reported markedly to increase whilst enzymic activity of Mn-SOD decreased during the ovulatory process after treating immature rats with 10 and 5 Units, respectively, of pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG). Levels of Cu/Zn-SOD activity and Cu/Zn-SOD mRNA were reported to remain unchanged throughout ovulation. This increase in the Mn-SOD mRNA level was shown in the present study by in situ hybridization to be localized to the theca interna cells throughout the PMSG/HCG-induced ovulatory process. The observations suggest that the turnover rate of Mn-SOD but not Cu/Zn-SOD increases specifically in the mitochondria of these cells. SOD has been postulated to play important roles in steroidogenesis. The relationship is discussed between mitochondrial functions in steroid-secreting cells and superoxide radicals and related metabolite(s).

Animals↗
PubMed1994

Nonspecies-specific effects of mouse oviducts on the development of bovine IVM/IVF embryos by a serum free co-culture.

In Experiment 1, development of bovine embryos derived from in vitro-matured (IVM) and in vitro-fertilized (IVF) oocytes was examined under 4 culture conditions: 1) co-culture with mouse ampullae continuously for 8 d, 2) co-culture with mouse ampullae that were replaced with fresh ampullae at 48-h intervals, 3) co-culture with bovine granulosa cell monolayers, and 4) culture in medium alone. Culture medium consisted of tissue culture medium 199 (TCM-199) supplemented with 1% fetal calf serum (FCS). Inseminated oocytes were transferred to each of the culture treatment 24 h after insemination and were cultured for 8 d. The number of blastocysts per number of cleaved ova obtained after co-culture with mouse ampullae (42.9%) was significantly (P<0.05) higher than that obtained after co-culture with granulosa cell monolayers (28.3%) or culture without cells (4.2%). In Experiment 2, the developmental ability of bovine IVM/IVF embryos co-cultured with mouse ampullae supplemented with or without serum was examined. When serum was excluded from the culture medium, 26.4% (33 125 ) of the total number of embryos cultured were able to develop to the blastocysts stage using this co-culture system. This value was comparable to that obtained in a serum-supplemented co-culture system (30.7%; 39 125 ). In addition, the developmental ability of embryos that reached to the 4-cell stage or beyond at 46 to 48 h after insemination was not significantly different when the embryos were co-cultured with mouse ampullae with (38.5 vs 44.6%) or without (37.0 vs 33.8%) serum.

Journal Article↗
PubMed1994

Synthesis and hypnotic and anti-human immunodeficiency virus-1 activities of N3-substituted 2'-deoxy-2'-fluorouridines.

Reaction of 9-[3,5-di-O-(tetrahydropyran-2-yl)-beta-D-arabinofuranosyl]uracil (2) with diethylaminosulfur trifluoride in the presence of pyridine afforded 2'-deoxy-2'-fluororiboside 3a, from which 2'-deoxy-2'-fluorocytidine (4b) has been synthesized in good yield. Compound 3a was deprotected and subsequently treated with various benzyl halides or 2-chloro-4-fluoroacetophenone to give corresponding N3-substituted 2'-deoxy-2'-fluorouridines 5a-c and 6. Compounds 5a-c, as well as 6, showed weak hypnotic activity in mice. Compound 4b showed moderate antiviral activity against human immunodeficiency virus-1 but 3b, 5a-c, and 6 were virtually inactive.

Animals↗
PubMed1994

Dysfunction of mouse liver mitochondria induced by 2,2'-azobis-(2-amidinopropane) dihydrochloride, a radical initiator, in vitro and in vivo.

Mouse liver mitochondria were uncoupled in a time dependent by intraperitoneal injection of a radical initiator, 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH) (100 mg/kg). State 3 respiration, ADP/O ratio and respiratory control ratio (RCR) were decreased 30 min after injection but there was no effect on state 4 respiration. Lipid peroxidation was increased and oxidative phosphorylation was uncoupled at one hr after drug injection but gradually recovered to normal levels after 14 hr in vivo. State 3 respiration, RCR and ADP/O ratio but not state 4 respiration of isolated mouse mitochondria were inhibited by short term incubation with AAPH in vitro. This inhibitory action was concentration dependent (ID50 = 5 mM) but was not prevented by alpha-tocopherol. AAPH had no effect on electron transport or the membrane potential of these isolated mitochondria. However, mitochondria were uncoupled via lipid peroxidation and swelling by long term incubation with AAPH. These inhibitory effects of AAPH were reduced by its spontaneous degradation not only in vitro but also in vivo. Thus AAPH induces mitochondrial dysfunction by direct action in the early period of treatment and free radicals produced from AAPH mediate mitochondrial swelling via lipid peroxidation in the late period. From these findings, it is concluded that mitochondrial phosphorylation plays an important role in the pathogenesis of liver injury induced by AAPH and that radicals generated by AAPH might be a source of liver injury and mitochondrial dysfunction in vivo.

Amidines↗
PubMed1994

[A case of large cell carcinoma of the lung producing granulocyte colony-stimulating factor].

A 48-year-old female was admitted complaining of cough and right chest pain. A chest X-ray showed a tumorous mass in the right lower lung field and hilar and mediastinal lymphadenopathy. The patient underwent transbronchial lung biopsy, and was diagnosed as having a malignant tumor. Because a metastatic lesion was detected in the left lung filed, we opted for chemotherapy. The white blood cell count rose to 103,700/mm3 and 190,000/mm3 in the fifth and sixth month after hospitalization, respectively. The serum granulocyte colony-stimulating factor (G-CSF) level by enzyme immunoassay exceeded 1000 pg/ml. The histological diagnosis of large cell carcinoma was made from the specimen obtained by percutaneous needle biopsy of the lung. The carcinoma cells in this specimen, showed positive staining with anti-G-CSF monoclonal antibody.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

Induction of two species of superoxide dismutase in some organs of rats by low dose X-irradiation.

Four hours after 0.25 Gy X-irradiation, the enzymatic activity of copper and zinc activated superoxide dismutase (Cu/Zn-SOD) in the spleen of mature rats showed a significant quantitative increase (by 25%); this was accompanied by a marked increase (by 70%) in the mRNA for this enzyme as compared to the control (sham irradiation) group. Irradiation had no effect on the enzymatic activity of manganese activated superoxide dismutase (Mn-SOD). Moreover, the expression of the mRNA for Mn-SOD was similar to that of the unirradiated control group. On the other hand, the enzymatic activity of both Cu/Zn-SOD and Mn-SOD in the liver of fetal rats showed a significant quantitative increase (by 15-35%); the expression of the mRNA for the two species of SOD increased (by 20-30%) at 4 hours after 1 Gy X-irradiation as compared to the control group. These findings suggest that the increase in SODmRNA level is due to novel transcription of SODmRNA by low dose irradiation.

Animals↗
PubMed1994

DNA damage by various forms of active oxygens and its inhibition by different scavengers using plasmid DNA.

The degree of DNA damage by the treatment with various molecular species of active oxygen and its inhibition by pretreatment with different scavengers were evaluated using pUC19 plasmid DNA. DNA damage caused by O2-. generated by xanthine-xanthine oxidase system (X-XOD), .OH by Fenton reactions, and OCl- by NaOCl involved the generation of open circle DNA demonstrating single strand breaks. Catalase (Cat), diethylenetriaminepentaacetic acid (DETAPAC), desferroxiamine (Desferal), dimethyl sulfoxide (DMSO) and ethanol (EtOH) all inhibited 60-80% of DNA damage by the generated O2-.. Superoxide dismutase (SOD) inhibited all DNA damages by O2-.. Cat, DETAPAC and Desferal effectively inhibited DNA break by .OH; complete inhibition of .OH-induced DNA break was achieved by addition of DMSO and EtOH. Desferal and EtOH completely inhibited DNA damage by OCl-. These findings suggested that metal ions are associated with the mechanism of DNA damage by all forms of active oxygen species.

DNA Damage↗