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Biomedical subjects

N Morisaki

Publications and source records attributed to N Morisaki.

At least 19 recordsLinked to original sources
PubMed1992

Regulatory effects of platelet-derived growth factor-AA homodimer on migration of vascular smooth muscle cells.

Migration of medial smooth muscle cells (SMC) into the intima is important in intimal thickening of atherosclerotic tissues. To study the functions of three isoforms of platelet-derived growth factor (PDGF) in atherosclerosis, we investigated their effects on SMC migration by Boyden's chamber method. Although PDGF-AB and PDGF-BB enhanced SMC migration dose-dependently, PDGF-AA did not enhance SMC migration, but instead inhibited SMC migration induced by PDGF-AB or PDGF-BB. PDGF-AA also inhibited SMC migration induced by two other migration factors, fibronectin and SMC-derived migration factor. PDGF-AA is considered to be coexpressed with transforming growth factor (TGF)-beta 1 in atherosclerotic tissues. Treatment of SMC with TGF-beta 1 reduced an autocrine migration activity from SMC. Studies using anti-PDGF antibody revealed that an increased secretion of PDGF-AA by TGF-beta 1 caused the reduced migration activity. cAMP increase by forskolin and dibutyryl cAMP suppressed SMC migration, whereas cAMP decrease by pertussis toxin had no effects on PDGF-AA-suppressed migration. In contrast, staurosporine, an inhibitor of protein kinase C, enhanced SMC migration and neutralized the inhibitory effect of PDGF-AA. These findings suggest that PDGF-AA regulates SMC migration in intimal thickening in atheroma formation and that protein kinase C may play an important role in the inhibitory mechanism of PDGF-AA.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Hyaluronate synthesized by cultured skin fibroblasts derived from patients with Werner's syndrome.

Hyaluronate in cultured skin fibroblasts derived from patients with Werner's syndrome, who excrete large amounts of urinary hyaluronate, was investigated. The amount of hyaluronate secreted into the medium by Werner's fibroblasts was 2-3-times that of normal fibroblasts, whereas no difference in enzyme activities related to the degradation of hyaluronate was found. Werner's fibroblasts were then cultured in the presence of [3H]glucosamine, and the amount of [3H]hyaluronate and its chain lengths in the medium and matrix (trypsinate) fractions were compared with those of normal cells. No significant difference in the chain length of hyaluronate was observed between normal and Werner's fibroblasts. On the other hand, a significant increase of hyaluronate was found in the matrix fraction of Werner's fibroblasts when the cells reached confluency. In addition, a hyaluronate of small chain length was found in the matrix fraction of Werner's fibroblasts, although this was absent from that of normal cells. It was concluded that the constituents of the extracellular matrix of Werner's fibroblasts differed from those of normal cells, characterized by the presence of a large amount of hyaluronate and a relatively small hyaluronate chain.

Adult↗
PubMed1992

Expression of M-CSF receptor encoded by c-fms on smooth muscle cells derived from arteriosclerotic lesion.

Vascular smooth muscle cells in atherosclerotic lesions are phenotypically different from those in the normal arterial wall, and no expression of macrophage colony stimulating factor (M-CSF) receptor encoded by the proto-oncogene c-fms has been demonstrated in normal smooth muscle cells. In the present study, we demonstrated expression of c-fms and high affinity binding of M-CSF in smooth muscle cells isolated from an experimental rabbit model of arteriosclerosis (intimal smooth muscle cells), while no expression of c-fms was shown in medial smooth muscle cells. In the immunocytochemical analysis, both types of smooth muscle cells similarly reacted with an antibody specific to muscle cells (HHF 35) but did not react with an antibody specific to rabbit macrophages (RAM 11). In intimal smooth muscle cells, when cells were incubated with acetylated low density lipoproteins (LDL), the binding of acetylated LDL and foam cell formation were observed. In response to M-CSF, tyrosine-phosphorylation, as analyzed by the detection of anti-phosphotyrosine-reactive proteins, and an increased rate of cell proliferation were observed in intimal smooth muscle cells. These results indicated that intimal smooth muscle cells have the characteristics of monocyte-macrophages such as the expression of c-fms, which may be related to their proliferation and phenotypic conversion into foam cells in atheromatous lesions.

Animals↗
PubMed1992

Human macrophages modulate the phenotype of cultured rabbit aortic smooth muscle cells through secretion of platelet-derived growth factor.

Phenotypic change of aortic smooth muscle cells (SMC) is a key step for their abnormal proliferation in atheromatous lesions. In this study modulation of the growth properties of SMC by macrophages was investigated to clarify the mechanism regulating the SMC phenotype. Cultured rabbit SMC preincubated with either macrophages derived from human peripheral monocytes, or conditioned medium from macrophages grew faster than control SMC in the absence of either macrophages or conditioned medium. SMC preincubated with purified platelet-derived growth factor (PDGF) also grew faster than control SMC in the absence of PDGF, and their rapid growth was maintained for at least two passages. SMC preincubated with conditioned medium of macrophages plus anti-PDGF antibody did not grow faster than control SMC. Furthermore SMC preincubated with PDGF acquired the ability to secrete some mitogen, which differed from PDGF. These results suggest that macrophages modulate the phenotype of SMC by a mechanism mediated by PDGF. As a result the SMC grow faster and at the same time secrete some mitogen probably distinct from PDGF in an autocrine manner.

Animals↗
PubMed1992

Inhibitory effect of ginsenosides on migration of arterial smooth muscle cells.

Migration of arterial smooth muscle cells (SMC) in the arterial wall plays an important role in the formation of intimal thickening of atherosclerotic lesions. In this study, we examined the effect of ginsenosides on SMC migration induced by platelet-derived growth factor (PDGF) and SMC-derived migration factor (SDMF). Ginsenosides had inhibitory effects on SMC migration and the striking effects were observed with ginsenoside-Rb2 and -Rc in a dose-dependent manner. These results suggest that the administration of ginsenosides on the patients may prevent intimal thickening, in part, by inhibiting SMC migration in the arterial wall.

Animals↗
PubMed1992

Role of obesity in development of ischemic heart disease in elderly diabetic patients.

The influence of obesity on the development of ischemic heart disease (IHD) was studied in 103 diabetic patients over 65 years of age. The patients were divided into three groups on the basis of their body mass index: lean, less than 20; normal, 20-25; obese, greater than 25. The incidence of IHD was significantly (p less than 0.01) higher in the obese group than in the other groups (43.2 vs. 18.8 and 16.3%). The age, sex distribution, duration and control of diabetes mellitus, methods of diabetic therapy, and prevalence of hypertension, hyperuricemia and smoking were not significantly different in the three groups. The level of serum triglyceride was higher and that of high-density lipoprotein cholesterol (HDL-C) was lower in the obese group than in the other groups, but the prevalence of IHD was significantly higher in the obese patients without hypertriglyceridemia and/or low HDL-C than in the normal group (p less than 0.05). These results suggest that obesity is a risk factor for development of IHD in elderly diabetic patients independently of other known risk factors.

Aged↗
PubMed1992

Syntheses of cerulenin and its analogs. II. Synthesis and biological activity of dl-carbacerulenin, a carbocyclic analog of cerulenin.

2,3-Epoxy-4-hydroxy-4-((E,E)-3,6-octadienyl)cyclopentanone (dl-carbacerulenin 5) was synthesized via the epoxyketones 15a and 15b as a mimic of the active form of the antibiotics cerulenin 1, a potent inhibitor of fatty acid synthetase (FAS). The monobenzyl ethers (12 and 13), synthetic intermediates of 15, were prepared by direct benzylation of the epoxycyclopentene (7). Inhibitory activity of synthesized 5 toward yeast FAS was less than that of cerulenin by a factor of 1000.

Cerulenin↗
PubMed1992

Effect of conditioning of beta-migrating very low-density lipoprotein with macrophages on the accumulation of cholesteryl esters in smooth muscle cells.

The mechanism of cholesteryl ester accumulation in smooth muscle cells was investigated. Incubation of smooth muscle cells with beta-migrating very low-density lipoprotein (beta-VLDL, d less than 1.006) for 24 h did not result in accumulation of oil red O-stained particles in the cells. However, incubation of smooth muscle cells with beta-VLDL in the presence of rat peritoneal macrophages induced accumulation of oil red O-stained granules in smooth muscle cells. Medium containing [3H]-cholesteryl linoleate-labelled beta-VLDL ([3H]beta-VLDL) that was conditioned with rat peritoneal macrophages increased the incorporation of [3H]-cholesterol and the cholesteryl ester content in smooth muscle cells, whereas unconditioned [3H]beta-VLDL did not. On zonal ultracentrifugation of conditioned medium containing [3H]beta-VLDL with macrophages, radioactivity was found at two peaks of density 1.150 and less than 1.006. This new fraction with d = 1.150 (peak II) migrated at beta-positions, the same as that of low-density lipoprotein (LDL) on agarose gel electrophoresis, and contained cholesteryl esters (28%), free cholesterol (15%) and phospholipid (43%). When smooth muscle cells were incubated with the peak II fraction, the radioactivity incorporated into smooth muscle cells and the cholesterol ester content of the cells increased. These results show that aortic smooth muscle cells in cooperation with macrophages can accumulate cholesteryl ester from beta-VLDL.

Animals↗
PubMed1992

[Improvement of respiratory function with weight reduction in obese elderly].

The patient was a 74-year-old woman who had been obese since age 18. Her obesity was refractory to dietary manipulation. She had been suffering from increasing dyspnea for several months and eventually could not even move. She was admitted to a hospital and diagnosed as having heart failure. Although her cardiac function recovered with medical treatment, her symptoms did not improve. The patient was then sent to our hospital. On admission, her height and weight were 149 cm and 81.9 kg, respectively, yielding a body mass index (BMI) of 36.6 kg/m2. Arterial blood gas analysis in room air revealed hypoxemia and an apnea index of 27 per hour. She was given a daily 500-1000 kcal diet. After four months of treatment, her weight decreased to 65 kg with a BMI of 29.3 kg/m2. Weight reduction together with the usage of progesterone-derivatives resulted in marked improvement of sleep apnea. The apnea index decreased to 3/h and arterial blood gas values normalized. This patient seemed to have suffered from both obesity hypoventilation syndrome and sleep apnea syndrome. Improvement of respiratory function was achieved through relief of airway obstruction and weight reduction, with activation of the respiratory center due to progesterone treatment.

Aged↗
PubMed1992

Atherosclerosis from a viewpoint of arterial wall cell function: relation to vitamin E.

Vitamin E affects many key events in atheromatous lesions. Inhibition of EC injury and platelet aggregation was already reported. Foam cell formation must be inhibited according to the data presented by us and other speakers. However, effects on cell proliferation of SMC are paradoxical. The in vivo effects will be dependent on the effective concentration of vitamin E in the loci.

Animals↗
PubMed1992

Comparisons of the bacterial flora in genital regions at non-pregnancy.

In the development of infectious diseases at non-pregnancy and at pregnancy, correlations between bacterial flora in the vagina and portio vaginalis and the ascending infections of those bacteria have recently been discussed. To clarify the cause of those infectious diseases, we studied the localization of microorganisms in genital regions. Patients undergone abdominal total hysterectomy (n = 172) were employed as subjects, and microorganisms isolated from 4 genital regions were studied. In addition, the preventive effect of cefmetazole (CMZ) against postoperative infections was analyzed in 479 cases including the hysterectomy cases mentioned above. The results obtained are summarized as follows: 1. The isolation rate of microorganisms at non-pregnancy, from subjects of 30 to 69 years old, was 65.6% (82/125) in the vagina and portio vaginalis, 52.1% (25/48) in the cervical mucus, 7.3% (9/124) in the uterine cavity and 0% (0/47) in the ovarian surface. 2. Numbers of microorganisms isolated in each region were 99 strains in the vagina and portio vaginalis, 28 in the cervical mucus, 10 in the uterine cavity and none in the ovarian surface. Isolation of aerobic Gram-positive bacteria (60-89.3%) and anaerobic Gram-positive bacteria (7.1-30%) were varied in each region. Lactobacillus spp. (38 strains), Staphylococcus epidermidis (20 strains) and Propionibacterium acnes (10 strains) were isolated from vagina and portio vaginalis, and Lactobacillus spp. (17 strains) were the most often isolated bacteria from the cervical mucus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Levofloxacin in obstetrics and gynecology].

We investigated the clinical efficacy and the safety of levofloxacin (LVFX, DR-3355) in obstetrical and gynecological infections and the following results were obtained. 1. Clinical efficacies were evaluated as excellent in 2 and good in 9 cases, hence the efficacy rate was 100%. 2. Bacteriologically, the eradication rate was 16/17 (94.1%). 3. No Side effects nor abnormal changes in laboratory test results were observed. These results indicated that LVFX was highly useful in the treatment of obstetrical and gynecological infections.

Adult↗
PubMed1991

Effects of transforming growth factor-beta 1 on growth of aortic smooth muscle cells. Influences of interaction with growth factors, cell state, cell phenotype, and cell cycle.

Transforming growth factor (TGF)-beta 1 may have different effects on cell proliferation depending on many conditions. This paper clarifies the effects of various conditions on the effect of TGF-beta 1 on proliferation of cultured rabbit aortic smooth muscle cells (SMC) and also the time of its action during the cell cycle. TGF-beta 1 at 10-10,000 pg/ml inhibited DNA synthesis of SMC in the G0 stage derived from normal media or atheromatous intima stimulated by either platelet-derived growth factor (PDGF), fibroblast growth factor, SMC-derived growth factor, or fetal bovine serum (FBS). TGF-beta 1 also inhibited the growth of SMC in the growing state stimulated by either PDGF or FBS. TGF-beta 1 was effective only when added to the culture within 2 h after stimulation of the G0 state SMC with PDGF. It also inhibited increase in transcription of the c-myc protooncogene on stimulation of SMC with PDGF. These data suggest that TGF-beta 1 inhibited proliferation of SMC irrespective of the cell phenotype, growth conditions, and growth factors present and that it exerted this inhibitory effect during the time of the G0/G1 transition.

Animals↗
PubMed1991

Secretion of a potent new migration factor for smooth muscle cells (SMC) by cultured SMC.

Migration of smooth muscle cells (SMC) in the arterial wall is important in the formation of intimal thickening. In this work, cultured SMC from the rat and rabbit aortic media at 2nd to 12th passages were found to secrete a potent migration factor for SMC which was named SMC-derived migration factor (SDMF). This factor stimulated the migration of SMC dose-dependently and its maximum activity was 2-8 times that of PDGF. Checker board analysis showed that SDMF was chemotactic, but not chemokinetic. In further studies, SDMF was found to be inactivated at 100 degrees C for 10 min or by trypsinization, but not inactivated by mercaptoethanol. This factor was not dialyzable. Molecular weight was approximately 500 kDa by a gel filtration. The activity was not inhibited by an anti-PDGF antibody or a fibronectin antiserum. These data suggest that SDMF is a potent migration factor for SMC and that SDMF is distinct from PDGF, fibronectin or other known migration factors. This autocrine system of secretion of SDMF by SMC and its induction of SMC migration may contribute to intimal thickening of the arterial wall in atherosclerosis.

Animals↗
PubMed1991

Two flavonol glycosides from seeds of Camellia sinensis.

Two novel flavonol triglycosides, camelliaside A and B, have been isolated from seeds of Camellia sinensis. The structures were determined to be kaempferol 3-O-[2-O-beta-D- galactopyranosyl-6-O-alpha-L-rhamnopyranosyl]-beta-D-glucopyranoside and kaempferol 3-O-[2-O-beta- D-xylopyranosyl-6-O-alpha-L-rhamnopyranosyl]-beta-D-glucopyranoside on the basis of spectroscopic, chemical and enzymatic studies. These types of interglycosidic linkages, Gal(1----2)[Rha(1----6)]Glc and Xyl(1----2)[Rha(1----6)]Glc, have not been reported previously in flavone and flavonol glycosides.

Carbohydrate Sequence↗
PubMed1991

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↗
PubMed1991

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↗