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F Sugiyama

Publications and source records attributed to F Sugiyama.

72 records · Page 4Linked to original sources

Dependence of angiotensin production in transgenic mice carrying either the human renin or human angiotensinogen genes on species-specific kinetics of the renin-angiotensin system.

In order to study the functional role of the renin-angiotensin system in the control of blood pressure, projects were initiated using transgenic mice carrying either the human renin gene or the human angiotensinogen gene. To extend the usefulness of the transgenic model system of hypertension research, a two-tiered strategy for generation of transgenic mice with high blood pressure has been developed. This unique system allows the establishment of transgenic lines with a strict species specificity of the renin-angiotensinogen reaction exhibited by transgene products that are regulated in a tissue specific manner. In this report, the strategy concerning the "two-tiered method" is presented and evidence is provided the overproduction of angiotensin occurs only in the combined reaction with human renin and human angiotensinogen expressed in transgenic mice.

Amino Acid Sequence↗

Spectral analysis of heart rate variability during isoflurane anesthesia.

The autonomic nervous system is an important neural control system for maintaining cardiovascular stability in humans. Analysis of heart rate variations may provide important clinical information on the influence of anesthesia on the autonomic nervous system and the central nervous system. Therefore, the effects of 1.0, 1.5, and 2.0 minimum alveolar concentrations of isoflurane anesthesia on beat-to-beat heart rate variations were studied in ten patients (ASA Physical Status 1). Spectral analysis was used to determine the intensity of the variations. For each power spectrum, the frequency components were identified as follows: 1) the parasympathetically mediated respiratory component (0.15-0.4 Hz) and 2) both parasympathetically and sympathetically mediated components (0.04-0.15 Hz). The latter was subdivided into the low-frequency component (0.04-0.09 Hz) of vasomotor origin and the mid-frequency component (0.09-0.15 Hz) of baroreceptor origin. Marked reductions in the power of heart rate variations, at all frequencies, were found during isoflurane anesthesia, indicating isoflurane decreased total autonomic nervous system activity. Isoflurane decreased the high-frequency and mid-frequency components in a concentration-dependent manner. The low-frequency component increased transiently at 1.5 minimum alveolar concentrations concomitant with the burst suppression in the electroencephalogram. The ratio of mid-frequency to high-frequency components did not change significantly during isoflurane anesthesia compared with the awake period. These frequency characteristics of heart rate variations during isoflurane anesthesia suggest there are dose-related decreases in autonomic nervous system activity in both the vagus and the cardiac sympathetic nerves.

Adult↗

Species-specific kinetics of mouse renin contribute to maintenance of normal blood pressure in transgenic mice with overexpressed human angiotensinogen.

Angiotensinogen, the precursor of a vasoactive octapeptide angiotensin II, is the only known natural substrate of renin, and its reaction exhibits strict species specificity and is the rate-limiting step in the renin-angiotensin system that controls the blood pressure. We measured blood pressure and heart rate of the transgenic mice with overproduced human angiotensinogen, and showed no significant difference in these parameters between transgenic and nontransgenic mice. We also provided evidence that mouse renin could not cleave human angiotensinogen, indicating a lack of angiotensin production from the human substrate. These results suggested that the blood pressure of transgenic mice is normally maintained, probably due to the inability of mouse renin to release angiotensin from the transgene products.

Angiotensinogen↗

Development of mouse oocytes superovulated at different ages.

The development of oocytes superovulated at 25, 50, or 90 days in four mouse strains (C57BL/6N, DBA/2N, ICR, and B6D2F1) was examined using the techniques of in vitro fertilization, culture, and transfer of two-cell embryos to pseudopregnant recipients. The highest number of ova were obtained from superovulated 25-day-old mice in all strains. Approximately 80% of oocytes developed to the two-cell stage after in vitro fertilization. Of these living oocytes, 60% developed to weanling stage through the recipient. These results suggested that donor age among 25, 50, or 90-day-old mice has no influence on the viability of superovulated oocytes. Consequently, we conclude that superovulated 25-day-old mice offer an economical and efficient source of viable oocytes for the production of transgenic mice.

Age Factors↗

Spontaneous leukemia occurring in aged Slc: Wistar rats and its transplantation into rats.

Spontaneous leukemia occurred in 36% of a group of 39 aged Slc: Wistar rats, which ranged in age at death from 99 to 123 (average age: 114) weeks old. The leukemic rats showed hemolytic anemia, jaundice and leukocytosis (21,000 to 360,000/mm3). Macroscopically, they were characterized by splenomegaly and hepatomegaly. The leukemia cells were rich in basophilic cytoplasm containing eosinophilic granules. Their nuclei were oval and occasionally revealed mitotic figures. These leukemia cells were consistently transplantable into both Slc: Wistar and F 344/NSlc rats. In the transplanted cases, the latency and survival periods were prolonged in proportion to decreases in the inoculated cell dose.

Animals↗

Mutagenicity screening of feed additives in the microbial system.

18 feed additives were tested for DNA-modifying effects by the repair test named "rec-assay" with Bacillus subtillis H17 (rec+) and M45 (rec-), and for mutagenicity with Escherichia coli WP2 hcr and 5 Salmonella typhimurium tester strains with the use of a top-agar overlay method. Carbadox, furazolidone, panazon and zoalene were positive in both assays. The former 3 were mutagenic for TA100, TA98 and WP2 hcr, while zoalene was mutagenic for all strains. These 4 compounds did not require a metabolic activation for their mutagenic activities. Nicarbazin was weakly mutagenic for TA1538 and TA98 with and without S9 mix. Amprolium and caprylohydroxamic acid also showed very weak mutagenicities only for TA100 with S9 mix and for WP2 hcr with and without S9 mix, resp. The mutagenic activities of carbadox, furazolidone and panazon for TA100 were reduced only by the addition of S9 mix, but not by S9 fraction or blood, whereas that of zoalene was decreased by any of the 3 factors.

Animal Feed↗

Inhibitors for the mutagenicities of colon carcinogens, 1,2-dimethylhydrazine and azoxymethane, in the host-mediated assay.

Inhibitory effects of several chemicals on the mutagenicities of 1,2-dimethylhydrazine (DMH) and azoxymethane (AOM) for Salmonella typhimurium G46 in the host-mediated assay were investigated. They were carbon disulfide (CS2), tetraethylthiuram disulfide (disulfiram, DSF), sodium diethyldithiocarbamate (SDDC), ethylene-bis(dithiocarbamato) manganese (Maneb), pyrazole (PZ), aminoacetonitrile hydrogen sulfate (AAN), and sodium selenite (SE). All the compounds, except for SE, inhibited the mutagenicities of DMH and AOM.

Aminoacetonitrile↗

Assay for mutagenicity of bile in Sprague-Dawley rats treated subcutaneously with intestinal carcinogens.

To investigate the mode of action of sc injected intestinal carcinogens, the mutagenicity assay of bile collected from noninbred Sprague-Dawley rats treated sc with carcinogens was conducted in the presence and absence of beta-glucuronidase. The bile samples from rats inoculated with 4-aminobiphenyl were mutagenic for Salmonella typhimurium TA100 only in the presence of beta-glucuronidase, whereas those from the 3,2'-dimethyl-4-aminobiphenyl-treated rats did not require the enzyme for mutagenicity toward strain TA100. On the contrary, the assays with S. typhimurium G46 and TA100 of bile from rats inoculated with 1,2-dimethylhydrazine, azoxymethane, or methylazoxymethanol acetate failed to reveal mutagenicity whether beta-glucuronidase was added or not, though these carcinogens were highly mutagenic for strain G46 in the Salmonella-microsome mutagenicity test and/or in the host-mediated assay.

Animals↗