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Biomedical subjects

H Satoh

Publications and source records attributed to H Satoh.

At least 829 records · Page 46Linked to original sources

Haplotype study on C4 polymorphism in Japanese. Associations with MHC alleles, complotypes, and HLA-complement haplotypes.

Genetic polymorphism of the fourth component of human complement (C4) was investigated in 83 Japanese families which have been typed for HLA-A,-B,-C,-DR, C2, and BF. Four common C4A alleles and four common C4B alleles were observed. The allele frequencies estimated from unrelated parents were as follows: C4A3, 0.686; A4, 0.132; A2, 0.106; AQ0, 0.067; ARares, 0.009; C4B1, 0.587; B2, 0.167; B5, 0.088; and BQ0, 0.158. Eight different C4 haplotypes were observed with frequencies of more than 0.01. The estimated haplotype frequencies were as follows: C4A3-B1, 0.513; A4-B2, 0.114; A2-BQ0, 0.106; A3-B5, 0.088; AQ0-B1, 0.059; A3-BQ0, 0.047; A3-B2, 0.038; A4-B1, 0.015; and Rares, 0.021. Strong positive gametic associations were found in the following C4-HLA haplotypes: C4A2BQ0-A24, C4A2BQ0-Bw52, C4A3B5-Bw54, C4A3B5-Bw59, C4A4B2-Bw46, C4A3B5-Cw1, C4A2BQ0-DR2, and C4A3B5-DR4. Eleven complotypes were observed with frequencies of more than 0.01. C4A2BQ0 and C4A3B5 were exclusively associated with BFS-C2C. BFF was associated with C4A3B1. C2AT, C2B, and C2BH were associated with C4A3B1, A4B2, and C4A3B1, respectively. Eight different HLA-complement haplotypes were found to be characteristic of Japanese. These combinations are considerably different from those reported in Caucasoid populations.

Alleles↗

Oscillations in cell shape and size during locomotion and in contractile activities of Physarum polycephalum, Dictyostelium discoideum, Amoeba proteus and macrophages.

Changes in cell shape and size were measured during locomotion, together with the motive force of the protoplasmic streaming, in various amoeboid cells in different stages of their life cycle, and under various environmental conditions. The variations in these measurements with time were examined by Fourier spectral analysis. Notwithstanding a change in cell type in the life cycle of P. polycephalum, myxamoebae and tiny plasmodia showed a similar time pattern of locomotion, exhibiting oscillations having a mixture of several periods. A regular oscillation with protoplasmic streaming appeared in the plasmodium only above a critical cell size. D. discoideum amoebae oscillated with two periods of a few minutes in preaggregation stage, but with a period of 10 min in aggregation stage, the latter being induced by cAMP. Macrophages and A. proteus also oscillated with periods of a few minutes. Periods of all these oscillations were prolonged severalfold by respiratory inhibition with NaCN, but were unaffected by glycolytic inhibition with 2-deoxyglucose. Cell fragments of A. proteus containing fewer granules oscillated more slowly and with a larger amplitude than those containing more granules. Among the granules, the nucleus was excluded as a possible modifier of the oscillation. The oscillation in Physarum plasmodium was reversibly suppressed by combining respiratory and ATPase inhibitions in mitochondria with NaCN and oligomycin, intracellular ATP concentration being kept at an appropriate level. The present results show that amoeboid motility, as well as cell shape, is oscillatory and that mitochondria are involved in time keeping.

Adenosine Triphosphate↗

Effect of indomethacin, tiaprofenic acid and dicrofenac on rat gastric mucosal damage and content of prostacyclin and prostaglandin E2.

Gastric ulcerogenicity and depletion of endogenous prostaglandins (PGs) content induced by tiaprofenic acid, dicrofenac and indomethacin were examined using the same antiinflammatory effective doses. Male Wistar rats were given each of these drugs intragastrically 24, 18, and 3 hrs before sacrifice in the following doses (mg/kg): indomethacin (0.8, 4 and 20); tiaprofenic acid (1.2, 6 and 30); dicrofenac (0.8, 4 and 20). Endogenous prostacyclin (PGI2) and PGE2 in fundic mucosa were determined by radioimmunoassay. The three compounds produced fundic mucosal lesions in a dose-dependent manner. However, tiaprofenic acid and dicrofenac were both less potent than indomethacin in producing gastric mucosal lesions at similar antiinflammatory doses. Mucosal PGE2 content was abolished by the three compounds in the following doses (mg/kg): indomethacin (4 and 20); tiaprofenic acid (6 and 30); dicrofenac (20). Mucosal PGI2 was maintained around 50% of the control value in rats given tiaprofenic acid in a dose of 6 mg/kg or dicrofenac in a dose of 4 mg/kg, while indomethacin in a dose of 4 mg/kg markedly reduced mucosal PGI2 to 17% of the control value. In larger doses, tiaprofenic acid and dicrofenac were also significantly less potent in reducing mucosal PGI2 than indomethacin. These results suggest that the difference in ulcerogenicity between indomethacin and the other two compounds was closely related to their potency in decreasing PGI2 in the gastric (fundic) mucosa.

6-Ketoprostaglandin F1 alpha↗

Effects of 6-keto-prostaglandin E1 on ascitic hepatoma-130 in vivo comparison with chemotherapeutic agents.

The inhibitory effect of 6-keto-prostaglandin E1 (pGE1) on the growth and survival of ascitic hepatoma (AH-130) cells in vivo was compared with currently used chemotherapeutic agents. Three days after receiving an intraperitoneal injection of 3 X 10(6) AH-130 tumor cells, Donrhyu rats were injected intravenously or intraperitoneally with one of the following: Thromboxane B2 (TXB2) (0.5 mg/kg), 6-keto-pGE1 (0.5 mg/kg), Mitomycin C (MMC) (1.5 mg/kg), or MMC + 6-keto-pGE1 (1.5 mg/kg + 0.5 mg/kg). The mean survival time, median survival time, and increase of life survival percent (ILS%) during a 60 day period revealed that both 6-keto-pGE1 and 6-keto-pGE1 + MMC significantly inhibited AH-130 tumor cell growth, while TXB2 promoted tumor cell growth. We conclude that 6-keto-pGE1 like anti-tumor agents such as MMC, Diketocoriolin B, Carbazilquinon, Endoxan, and 5-Fluorouracil, can significantly inhibit growth of AH-130 tumor cells in vivo, particularly when administered in combination with the anti-tumor agent MMC.

Alprostadil↗

Development of reflexes in neonatal mice prenatally exposed to methylmercury and selenite.

The development of reflexes in neonates exposed prenatally to methylmercury and selenite was investigated. Pregnant mice were assigned to one of 4 treatments; methylmercury (MeHg), selenite(Se), combination of 2 compounds (MeHg X Se) and saline control (NaCl). Mice were injected subcutaneously (s.c.) on day 9 of gestation. The dose of each compound was 30 mumol/kg. Mercury (Hg) concentrations in the neonatal brain and liver of the MeHg X Se group were slightly lower than in the MeHg group. The results of behavioral examination revealed that the MeHg X Se group showed significantly improved development compared with the MeHg group. These facts suggest the possibility that selenium compounds have protective effects against methylmercury neurotoxicity in fetuses and neonates.

Animals↗

Gene mapping in the Chinese hamster and conservation of syntenic groups and Q-band homologies between Chinese hamster and mouse chromosomes.

Using Chinese hamster/mouse somatic cell hybrids segregating hamster chromosomes, we assigned 15 enzyme genes to six different Chinese hamster autosomes. Of the 15 loci, three genes, HK1, PEPC, and SORD, were newly assigned to chromosomes 1, 5, and 6, respectively, while ENO1, PGD, and PGM1 were assigned to the long arm of chromosome 2, in the segment 2q113----qter. The locations of the following loci were confirmed: ESD, NP, and PEPB on chromosome 1, ME1 and MPI on chromosome 4, AK1 on chromosome 6, and GPI and PEPD on chromosome 9. Comparative mapping of Chinese hamster and laboratory mouse chromosomes revealed conservation of syntenic groups and extensive banding homology between the Chinese hamster and mouse chromosomes on which homologous enzyme markers have been mapped.

Animals↗

[Pharmacological studies on pinacidil, a new antihypertensive agent. 2. Studies on the hypotensive mechanism of pinacidil].

Effects of pinacidil (PND) on the blood pressure of anesthetized cats and contraction of guinea-pig isolated hearts and blood vessels were compared with those of hydralazine (HDL) and nifedipine (NFD). PND showed a dose-dependent hypotensive effect and decrease of total peripheral resistance in a dose above 0.3 mg/kg (p.o.) in anesthetized cats. However, no involvement of the autonomic nervous system was presumed in the hypotensive effect of PND due to studies on autonomic responses. Although negative inotropic and chronotropic effects of PND in the isolated guinea-pig atria and heart (Langendorff method) were slight, PND caused a coronary vasodilation at a dose of 1 micrograms. PND inhibited the norepinephrine (NE) contracture of isolated guinea-pig thoracic aorta and portal vein at 10(-6)-10(-5) M, but concentrations of 10(-5)-10(-4) M were required for the inhibition of K contracture. In the isolated thoracic aorta, HDL markedly inhibited NE contracture, while NFD inhibited K contracture. These results suggest that the hypotensive effect of PND is more closely associated with the inhibition of Ca2+ influx caused by the receptor activation of Ca2+ release from intracellular storage sites than membrane potential-dependent Ca2+ influx.

Animals↗

Effect of forskolin on prostaglandin productions in isolated dog renal arteries.

Forskolin (1 to 100 microM), a direct activator of adenylate cyclase, did not have any effect on prostaglandin E2 and I2 productions in isolated dog renal arteries. However, forskolin at the lower concentrations (10 and 100 nM) markedly stimulated only prostaglandin E2 production. 8-Bromo-cyclic AMP (0.5 and 1 mM) failed to stimulate prostaglandin E2 and I2 productions. The results suggest that 1) forskolin stimulates only prostaglandin E2 production, not through the activation of adenylate cyclase and 2) the prostaglandin production system may be independent of the cyclic AMP-generating system in isolated dog renal arteries.

6-Ketoprostaglandin F1 alpha↗

Behavioral teratology of methylmercury.

Behavioral effects of experimental perinatal methylmercury exposure are reviewed. Studies were summarized by classification based on examined behaviors and functions as follows; Development of reflexive behaviors, Swimming ability, Spontaneous activity, Open-field behavior, Maze learning, Avoidance learning, Operant learning, Susceptibility to induced convulsion and seizure, Ultrasonic vocalization, Visual function. Findings suggest that perinatal methylmercury exposure caused changes in a wide spectrum of behaviors in offspring. It is suggested that further researches on neuro-behavioral teratogenicity of methylmercury will be awaited, especially in the area investigating interaction of the other environmental factors.

Animals↗

Synthesis and antibacterial activity of 6315-S, a new member of the oxacephem antibiotic.

The synthesis and in vitro activity of 7 beta-difluoromethylthioacetamido-7 alpha-methoxy-3-[[1-(hydroxyethyl)-1H- tetrazol-5-yl]thiomethyl]-1-oxa-3-cephem-4-carboxylic acid sodium salt, 6315-S, are described. 6315-S shows good antibacterial activity against Gram-positive and Gram-negative bacteria, being especially highly active against clinical isolates of Staphylococcus aureus resistant to either ampicillin or methicillin. The structure-activity relationship of related 1-oxa and 1-thia cephems is also presented.

Bacteria↗

Immunological studies on the mechanism of halothane-induced hepatotoxicity: immunohistochemical evidence of trifluoroacetylated hepatocytes.

The fulminant hepatotoxicity caused by halothane has been thought to have an immunological basis because this toxicity occurs most often after repeated administration of halothane and because sera from patients recovering from severe halothane hepatotoxicity contain antibodies that bind to the surface membranes of hepatocytes of rabbits treated with halothane. In order to determine whether the major reactive metabolite of halothane, trifluoroacetyl halide, covalently binds to hepatocytes, we have developed specific and sensitive peroxidase enzyme-linked immunosorbent assays and an indirect immunofluorescence staining method for identifying trifluoroacetylated (TFA)-hepatocytes. Liver sections prepared from rats at 4 hr after halothane administration were stained preferentially in the centrilobular region with anti-TFA serum whereas livers of control rats showed no staining. The specificity of the assay for the TFA group was confirmed by the complete inhibition of the staining with 200 microM N-epsilon-TFA-L-lysine in the diluted antiserum. On the other hand, 2 mM halothane or L-lysine did not inhibit this staining. Moreover, treatment of rats with deuterated halothane resulted in significantly less staining than did halothane. At 24 hr after halothane administration, hepatocytes isolated and stained by indirect immunofluorescence showed a linear and granular pattern on their surface membranes. These results indicate that trifluoroacetyl halide either reacts directly with constituents of the plasma membranes or with other cellular components which become incorporated into the plasma membranes.

Animals↗

Immunochemical evidence of trifluoroacetylated cytochrome P-450 in the liver of halothane-treated rats.

Four hours after the administration of halothane to phenobarbital-pretreated rats, subcellular fractions of liver were isolated and the proteins in the fractions were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, transferred to nitrocellulose sheets, and immunochemically stained with anti-trifluoroacetylated antibodies. The microsomal fraction contained the highest level of trifluoroacetylated adducts. Its major trifluoroacetylated component was immunochemically identified as a phenobarbital-inducible form of cytochrome P-450 (54 kDa), whereas the other observed trifluoroacetylated protein fraction (59 kDa) was not identified. The plasma membrane fraction also contained a 54-kDa trifluoroacetylated adduct, which was immunochemically related to the 54-kDa cytochrome P-450. Microsomes from untreated rats that were administered halothane contained only the 59-kDa trifluoroacetylated protein fraction. The specificity of the immunochemical staining for the bound oxidative metabolite of halothane was confirmed by the finding that rats treated with deuterated halothane had considerably less stained liver proteins than did those treated with halothane. These results suggest that the CF3COX oxidative metabolite of halothane is so reactive that it binds predominantly to the cytochrome P-450 that produced it.

Acetylation↗

[Preoperative combination therapy involving local administration of a non-specific immunoactivated preparation (OK-432) and chemotherapeutic preparations for patients with stomach cancer].

OMF therapy, which is a combination therapy consisting of OK-432 administered locally, Mitomycin C and 5-Fluorouracil, was administered to 50 cases of stomach cancer (52 episodes) preoperatively. Judging the criterion for a positive (+) effect as being the existence of degeneration or necrosis in 1/3-1/2 of carcinomas visible within whole fields, the ratio of histological effectiveness shown by this therapy was 75%. As for its effect on metastatic foci of lymph nodes, when 70 case from an n1 group and 8 from an n2 group with metastatic positive lymph nodes, including 17 cases (4 in Stage II and 13 in Stage III) ablated for curing were studied, a greater than positive (+) effect was shown in 51 out of the total of 78. Consequently the effective ratio was 65%. The survival ratio of 16 cases in Stage III on the 48th month calculated by the Kaplan Meier method was 78.6%. The survival time of 50% of 9 cases in Stage IV (absolute non-curing ablation) was 15 months. Tissue samples were examined constantly after local administration of OK-432. Exudation of neutrocytes was shown on the 1st day, and that of histiocytes, lymphocytes and plasmacytes on the 4th day. At this stage, degeneration of the primary focus or necrotizing change was observed. Interstitial reaction peaked on the 14th day, but histiocytes tended to decrease.

Adult↗