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Biomedical subjects

N Morisaki

Publications and source records attributed to N Morisaki.

At least 127 records · Page 7Linked to original sources

The inhibitory effect of a novel antiatheromatous agent, E5050, on the intimal thickening of aorta in cholesterol-fed rabbit in vivo.

The development of atheromatous lesions in the aortic arch of 0.5% cholesterol-fed rabbits was biochemically and morphologically examined. The animals were killed at week twelve (Cont-12W) or sixteen (Cont-16W). Both the micrographic and biochemical studies showed that the main atheromatous lesions in the Cont-12W group were fatty streaks, whereas those in the Cont-16W group were fibrous plaques. In these models, oral ingestion of 0.2% and 0.4% E5050, which has an antiproliferative effect on smooth muscle cells, had no effect on the surface involvement or the lipid content of the aortic arch at the sixteenth week, but reduced the degree of intimal thickening and the DNA content in the aortic arch in a dose-dependent manner. These results strongly suggest that E5050 suppresses the intimal thickening through its inhibitory effect on the proliferation of smooth muscle cells.

Animals↗

Imprints of the tectorial membrane following acoustic overstimulation and kanamycin treatment.

Normal imprints in guinea pigs were examined mainly using a scanning electron microscope (SEM). Morphological changes in imprints after loading of the conditions mentioned below were also investigated. Imprints observed on the normal tectorial membrane were composed of small concavities lined on a W-shaped line and the W-type was of a V-type in proportion to ascend to the upper turn. The imprints occurred at the rate of one for every outer hair cell and in 3-4 lines corresponding to the outer hair cell hairs. With exposure to a high intensity of sound, small concavities of the imprints were deformed and remnant sensory hairs were observed, sporadically. Another line of new imprints was sometimes evident in the lower turn of the cochlea, in addition to the original imprints. In case of inner ear disturbances due to kanamycin (KM) loading, the imprints were little deformed, but the remnant sensory hairs were numerous and their time-course revealed a gradual decrease and the disposal required a longer time than seen in the degenerated cell fractions on the reticular membrane. With exposure to high intensity sound after KM loading, KM-type changes or high intensity sound-type changes were observed and depended on severity of the KM-induced disturbance. The imprints existed for a considerably long time even when the lower region sensory cells degenerated or disappeared in the presence of various conditions.

Animals↗

Dynemicins O, P and Q: novel antibiotics related to dynemicin A isolation, characterization and biological activity.

New antibiotics, dynemicins O (3), P (4) and Q (5), were isolated from the culture broth of Micromonospora chersina M956-1, the dynemicin A (1)-producing strain. An ethyl acetate extract of a tank culture was roughly separated by a column of Diaion SP-800 and was further purified by combining a variety of column chromatographies to afford a few mg of compounds 3, 4 and 5. Their structures, analyzed from the spectral data, had a bridging phenylene group, a vic-diol and an oxo group in place of the respective 1,5-diyn-3-ene bridge, the epoxide ring and the carboxyl group in dynemicin A. Their biological activities were evaluated against bacteria and tumor cells.

Alkenes↗

[Clinical effect of the combined use of aztreonam, amikacin and clindamycin in infectious disease in obstetrics and gynecology].

Clinical effects of combined use of aztreonam (AZT), amikacin (AMK) and clindamycin (CLDM) in 46 cases with infectious diseases in obstetrics and gynecology were retrospectively studied in 2 groups, and the following results were obtained. 1. No significant difference in efficacy rates was noted between AZT plus CLDM treated group (n = 25) and AMK plus CLDM treated group (n = 21) (96.0% vs. 95.2%), while rate of excellent efficacy was slightly higher in AZT plus CLDM group than AMK plus CLDM group (24.0% vs. 14.3%). 2. No significant difference in bacteriological clinical effects was also noted between the 2 groups, while bacteriological eradication rate was higher in the AZT plus CLDM group than in the other group (76.2% vs. 50.0%), and the difference was particularly clear in the eradication rates of aerobic, Gram-negative bacteria (88.9% vs. 30.0%). 3. Subjective and objective side effects, and abnormalities of clinical test results were not found in either group.

Adult↗

[Clinical studies on flomoxef in the perinatal period infections].

We conducted clinical efficacy and safety tests of flomoxef (FMOX, 6315-S) in the perinatal infections and obtained the following results. 1. A total of 25 patients was treated: 16 patients with intrauterine infections, 2 patients with pelvioperitonitis, 4 patients with urinary tract infections and 3 patients with other infections. FMOX was injected at a daily dose of 2-4 g for 3-15 days (6-60 g for total dose) by intravenous drip infusion, intravenous injection or their combination. 2. The clinical efficacy rate was 96.0% of 25 patients: excellent in 4 cases (16.0%), good in 20 cases (80.0%) and poor in 1 case (4.0%). Bacteriological effects obtained were: eradicated in 14/16 cases (87.5%) replaced in 3 cases. 3. There were no subjective or objective side effects, nor were any abnormal laboratory test values attributable to the drug. From these findings, we consider that FMOX treatment appears to obtain good clinical and bacteriological responses and in safe in perinatal period infections.

Adult↗

Inhibitory effects of a novel antiatheromatous agent, E5050, on aortic smooth muscle cell proliferation, in vitro.

The effect of a novel antiatheromatous agent, N-(3-[4'-(2'',6''-dimethylheptyl)phenyl]butanoyl)ethanolamin e (E5050), on the proliferation of porcine aortic smooth muscle cells was studied in vitro. E5050 dose-dependently inhibited DNA synthesis as well as proliferation of cells stimulated with 10% fetal calf serum with no cytotoxic effects. An inhibitory effect of E5050 on DNA synthesis was also confirmed in cells stimulated with human platelet extract and with a combination of platelet-derived growth factor and human plasma-derived serum. DNA synthesis in smooth muscle cells stimulated with other mitogens, such as fibroblast growth factor and insulin, was inhibited by E5050 and this inhibitory effect was positively correlated with the E5050 uptake into smooth muscle cells. These results indicate that E5050 inhibits smooth muscle cell proliferation stimulated by various mitogenic factors. It is suggested that E5050 prevents atherogenesis and inhibits the progression of fibromuscular lesions by interfering with the proliferation of arterial smooth muscle cells.

Animals↗

Bifunctional effects of transforming growth factor-beta on migration of cultured rat aortic smooth muscle cells.

Migration of smooth muscle cells (SMC) in the arterial wall is important in the pathogenesis of atherosclerosis and is presumably regulated in both normal and atherosclerotic tissues. In this study, the effect of transforming growth factor-beta (TGF-beta) on the migration of rat aortic SMC was examined. TGF-beta alone enhanced the migration of SMC at concentrations of 10 to 50 pg/ml and its maximal effect was similar to that of platelet-derived growth factor (PDGF). Checker board analysis showed that TGF-beta had a chemotactic, but not a chemokinetic effect. PDGF also enhanced the migration in a dose-dependent manner and TGF-beta inhibited the PDGF-induced migration dose-dependently at 1.0 pg/ml to 1.0 ng/ml. These data suggest that TGF-beta is a bifunctional regulator of the migration of aortic SMC.

Animals↗

Inheritable abnormal lipoprotein metabolism in Werner's syndrome similar to familial hypercholesterolaemia.

Studies were made on the abnormality of lipoprotein metabolism and its cause in 10 patients with Werner's syndrome. Seven of the 10 patients had hypercholesterolaemia (above 250 mg dl-1). Six of the seven patients with hypercholesterolaemia had thickened Achilles' tendons (greater than 9 mm). A significant positive correlation (P less than 0.01) was found between the serum total cholesterol levels and the thickness of Achilles' tendons in these 10 patients, suggesting that the substance precipitated in the thickened tendons is derived from serum cholesterol. Some first-degree relatives of three patients with both hypercholesterolaemia and xanthoma-like thickening of Achilles' tendons also suffered from hypercholesterolaemia. Moreover, the low density lipoprotein (LDL) receptor activities in peripheral lymphocytes of five patients with both hypercholesterolaemia and xanthoma-like tendons were significantly (P less than 0.001) lower than those of controls, whereas the LDL receptor activities of two patients without hypercholesterolaemia were almost the same as those of controls. These findings suggest that, at least these five patients with lower lymphocyte LDL receptor activities, and probably another patient with both hypercholesterolaemia and xanthoma-like thickening of Achilles' tendons suffered from familial hypercholesterolaemia (FH). If this is the case, this high frequency of association of Werner's syndrome with FH (in six of 10 patients) suggests some relationship between these two diseases.

Achilles Tendon↗

Effects of long-term treatment with probucol on serum lipoproteins in cases of familial hypercholesterolemia in the elderly.

The effect of probucol in lowering serum lipoprotein in young and middle-aged (YM) and elderly (E) patients with familial hypercholesterolemia were compared. Probucol at 1000 mg/day was administered orally to 37 YM patients and 14 E patients for an average of 10 months. Probucol treatment for this period caused significant reductions in the serum levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, and apoprotein AI, AII, B, and CIII in both groups. The decreases in the levels of total cholesterol, LDL-C, and apoprotein B were greater in the E group than in the YM group (total cholesterol: YM, -19.3%, E, -31.3% [P less than .001]; LDL-C: YM, -17.0%, E, -35.4% [P less than .001]; apoprotein B: YM, -12.3%, E, -28.1% [P less than .01]). The decreases in other parameters in the two groups were not significantly different. The serum probucol concentrations in the YM and E groups were not significantly different. No significant side effects were observed in any patient. Thus probucol reduced the serum level of LDL more in the E group than in the YM group, and did so without any increase in the serum concentration of the drug or in side effects, suggesting that probucol is safe and beneficial for use in elderly patients.

Administration, Oral↗

[Influences of postoperative prophylaxis treatments on vaginal bacteria flora at hysterectomy].

We performed abdominal hysterectomy and administered aztreonam (AZT) for prophylaxis of postoperative infections, and investigated influences of the antibiotics on vaginal bacterial flora. The obtained results are summarized as follows. 1. Patients administered with AZT were studied (n = 48) for bacteria isolated from their vaginae preoperatively and at the 7th and the 14th days postoperatively. Groups of patients administered with cephalothin (CET), cefamandole (CMD) and latamoxef (LMOX) were also studied for comparison. 2. In the AZT group, the rate of isolation of aerobic Gram-positive bacteria was high (68.8-81.4%) whereas those of aerobic Gram-negative and anaerobic bacteria were low. 3. When changes in isolation frequencies of bacteria from the subjects preoperatively to postoperatively were compared, the following tendencies were observed: increase in the rate of aerobic Gram-positive bacteria was larger in the LMOX group than in the AZT group whereas decrease in the rate of aerobic Gram-negative bacteria was largest in the LMOX group followed by the AZT group then by the CMD group. Rates of decrease of anaerobic bacteria showed similar tendencies to the latter. Isolation rates of Candida sp. showed the largest increase in the LMOX group, followed by CET, CMD then AZT groups.

Adult↗

[A study of tissue transfer of cefmetazole in the blood and uterus in pregnant rabbits].

Analysis was made to determine concentrations of cefmetazole (CMZ) in maternal serum, and intrauterine tissues of myometrium, placenta, fetal membrane, amniotic fluid and fetal lung after one shot intravenous infusion of 100 mg of CMZ to rabbits with 25th day-pregnancy, and the following results were obtained. 1. Concentrations of CMZ in maternal serum, myometrium and placenta reached their maximum levels in 30 minutes after administration, then decreased rapidly. 2. The concentration of CMZ in the fetal membrane reached its maximum level in 30 to 60 minutes after the administration, then it decreased to a nearly constant level. 3. The concentration of CMZ in the amniotic fluid showed its maximum level in 30 minutes after administration, then decreased, but somewhat increased again thereafter. 4. The concentration of CMZ in the fetal lung was elevated gradually after administration, then decreased after reaching its maximum level at 90 minutes, after administration to a nearly constant level. It was deemed, however, that higher concentrations would be necessary to achieve therapeutic effects because attained concentrations were lower than those in other tissues.

Amniotic Fluid↗

[Comparative study of the bacterial flora in both uterocervical and uterine regions].

The relationship between indigenous bacterial floras in the lower genitals and the uterocervical region is of importance due to a barrier-like role against ascending infections through the mechanism of the localized protection at a boundary of the uterocervical region. Therefore, bacterial flora in the uterocervical and uterine regions was studied in cases for which gynecological operations were performed (n = 77). 1. Ratios of incidences of the detection of bacteria on the uterocervical and in the uterine regions were 50/77 (64.9%) and 6/77 (7.8%), respectively. When different age groups are compared, the detection ratio from the uterocervical region was high among patients in the 40 s, and all the cases in which bacteria were detected from the uterine region were in the 40 s. 2. Gram-positive bacteria were detected at a high ratio, and anaerobic bacteria were noted in the uterocervical region, and ratios of detection of Staphylococcus epidermidis, Lactobacillus sp. and Propionibacterium acnes were high. Six strains of Gram-positive bacteria and 1 strain of Candida sp. were noted in the uterine region. 3. When cefmetazole (CMZ) was administered for the prevention of the infections after these panhysterectomy cases examined here, no postoperative infectious diseases nor adverse reactions were noted.

Adult↗

[Clinical studies on aztreonam in perinatal use].

Clinical effects of aztreonam (AZT), a monobactam antibiotic, on perinatal infections were studied with the following results: 1. Efficacy rate of AZT in the clinical application to 12 cases of perinatal infections via 2-4 g/day drip infusion (total dosage 8-24 g) was 91.7% (11/12). Breakdown of the effects according to diseases were "excellent" for mastitis (n = 3), pyelonephritis (n = 1) and urinary tract infection (n = 1), and "good" for a total of 6 cases, i.e., amnionitis (n = 2), amniotic fluid infections (n = 3) and external genital infection (n = 1). 2. Results of bacteriological studies were "eradicated" (n = 1), "replaced" (n = 4), "appeared" (n = 2) and "unknown" (n = 5). MIC values of AZT (10(6) cells/ml) were in a range of 25- greater than 100 micrograms/ml in 1 case of cervicitis (complicated with amnionitis) in the 13th week of pregnancy where AZT was found non-effective. 3. Neither subjective nor objective side effects nor abnormal clinical values were observed during the treatment with AZT.

Adult↗

Phorbol myristate enhanced specific incorporation of arachidonic acid into phospholipids through lysophospholipid acyltransferase in cultured smooth muscle cells.

The effect of stimulation of phospholipase with phorbol 12-myristate 13-acetate and lipopolysaccharide on 1-acyl-glycerophospholipid acyltransferase was studied in cultured rabbit aorta smooth muscle cells. The acyltransferase in smooth muscle cells without stimulation was active on a wide range of unsaturated fatty acids and was not arachidonic acid specific. Upon increase in phospholipase activity, acyltransferase activity only with arachidonic acid as substrate increased in a time-dependent fashion. Apparent acyltransferase activity was increased most upon increase in phospholipase activity when lysophosphatidylcholine was used as acceptor. These results suggest that arachidonic acid specific acyltransferase was induced in smooth muscle cells by increase in phospholipase activity. The role of this acyltransferase is postulated to be the specific incorporation of endogenously released arachidonic acid.

1-Acylglycerophosphocholine O-Acyltransferase↗

Effects of smooth muscle cell derived growth factor (SDGF) in combination with other growth factors on smooth muscle cells.

Recently intimal thickening was shown to be due to stimulation of proliferation of arterial smooth muscle cells (SMC) by autocrine secretion of growth factor(s). We have reported that cultured rabbit aortic SMC secrete a growth factor (SDGF) distinct from other known growth factors. This paper reports on studies on the biological characteristics of SDGF. Putative "competence" and "progression" growth factors synergistically stimulated DNA synthesis of cultured rabbit aortic SMC. Conditioned medium (CM) from SMC containing SDGF stimulated DNA synthesis in SMC synergistically with either the competence factors or the progression factors. This synergistic effect was also observed in the presence of optimal concentrations of both competence and progression factors. The continuous presence of CM was essential for its stimulation of DNA synthesis whereas the presence of PDGF for only the first 4 h of culture was sufficient to induce maximum stimulation of DNA synthesis. These results suggest that SDGF is a new growth factor distinct from either competence or progression factors and that it stimulates a different pathway in SMC from those stimulated by other known growth factors.

Animals↗