Search PubMed⌕ Search

Biomedical subjects

N Kanayama

Publications and source records attributed to N Kanayama.

At least 55 records · Page 3Linked to original sources
PubMed1999

Detection of decreased response to activated protein C during pregnancy by an endogenous thrombin potential-based assay.

Pregnancy has been widely recognized as a predisposing risk factor for deep vein thrombosis (DVT). However, it still remains unclear why pregnant women without a history of familial thrombophilia or antiphospholipid syndrome (APS) have a higher incidence of DVT and pulmonary embolism (PE) during pregnancy and puerperium. We examined the activated protein C (APC) system in healthy pregnant women and in patients with the onset of DVT during puerperium. Sixty unselected Japanese pregnant women without a past or family history of thrombosis or APS and 3 Japanese women with DVT during puerperium were evaluated. Endogenous thrombin potential-ratio (ETP-r) was measured by determination of thrombin-alpha2-macroglobulin complexes in thromboplastin-activated patient plasma. APC sensitivity ratio (APC-sr) was calculated by the determination of ETP-r in patient plasma in the presence and absence of APC (final concentration [conc.] 5.9 nM) to evaluate the functional APC anticoagulant activity. Mean APC-sr was significantly increased at 30 weeks' gestation (2.35 +/- 0.72) and remained high during puerperium compared with the mean APC-sr in nonpregnant women (1.15 +/- 0.63). Mean APC-sr in patients with DVT at the onset was significantly higher (3.57 +/- 0.54) than mean APC-sr during puerperium was, indicating that the sensitivity to APC was reduced in the ETP-based assay. These data suggest a significant reduction in the functional sensitivity to APC associated with an increased risk of venous thrombosis during pregnancy.

Activated Protein C Resistance↗
PubMed1999

Interleukin-8 potentiates the effect of interleukin-1-induced uterine contractions.

The aim of this research was to study the effect of exogenous interleukin (IL)-8, IL-1 and IL-8 + IL-1 on uterine contractions in rabbits. Four equal groups of non-pregnant rabbits (n = 24) were investigated using either placebo or experimental drugs in the form of vaginal suppositories. The suppositories contained human recombinant IL-8 (200 ng), IL-1 (200 ng), IL-8 (200 ng) + IL-1 (200 ng) or vehicle Witepsol base, 500 microliters). Subsequently, the plasma concentration of prostaglandin (PG) E2 was estimated 3 h after the last dose of treatment. Neutrophil infiltration in the endometrial tissue was studied with anti-rabbit RT2 staining. Suppositories with IL-1 and IL-8 + IL-1 produced contractile responses with increased frequency (P < 0.003, P < 0.0005) and amplitude (P < 0.0001) in vivo, compared with vehicle. IL-1 and IL-8 + IL-1 also caused similar contractile effects with increased frequency (P < 0.01, P < 0.0007) and amplitude (P < 0.0001) in an in-vitro experiment than vehicle. The frequency and amplitude of uterine contractions were more significant with IL-8 + IL-1 than that of IL-1, both in vivo (P < 0.002, P < 0.05) and in vitro (P < 0.005, P < 0.01). IL-8 did not induce any contractions. Prostaglandin concentration was increased approximately 8-fold with IL-8 + IL-1 (P < 0.0001) and 2.5-fold with IL-1 treatment (P < 0.0001). Neutrophil numbers were significantly increased with IL-8 + IL-1 > IL-8 > IL-1 (P < 0.002, P < 0.0003 and P < 0.008) compared with vehicle. Our data suggest that IL-8 stimulates IL-1-induced uterine contractions through PGE2 production and could be an important process during labour and delivery.

Animals↗
PubMed1999

Dehydroepiandrosterone sulphate promotes hyaluronic acid-induced cervical ripening in rabbits.

Hyaluronic acid (HA) stimulates the synthesis of interleukin (IL) 8, while dehydroepiandrosterone sulphate (DHEA-S) induces the expression of IL-8 and its receptor in the human cervical fibroblast. This has led us to investigate the effect of DHEA-S on HA-induced cervical ripening. Experiments were performed in pregnant rabbits using vaginal suppositories containing 1 mg HA, 30 mg DHEA-S, 30 mg DHEA-S + 0.1 mg HA, 30 mg DHEA-S + 1 mg HA, and 500 microl Witepsol-50 base (control). The effects were evaluated by measuring collagenase, gelatinase and elastase activities, water content, neutrophil infiltration, relative collagen concentration and histological assessment. The activities of collagenase, gelatinase and elastase were significantly increased in rabbits treated with DHEA-S + 1 mg HA compared with rabbits treated with DHEA-S + 0.1 mg HA (P < 0.009, P < 0.001, P < 0.009 respectively). Water content was markedly increased in rabbits treated with DHEA-S + 1 mg HA compared with DHEA-S + 0.1 mg HA treatment (P < 0.05). Neutrophil infiltration was markedly increased, while relative collagen concentration was significantly decreased with DHEA-S + 1 mg HA compared with the DHEA-S + 0.1 mg HA approach (P < 0.001, P < 0.002). The histology of cervices treated with DHEA-S + 1 mg HA showed the density of collagen to be markedly decreased, and collagen fibres irregularly separated. Increased vascularity with massive dilatation of blood vessels was also observed in these rabbits. We conclude that DHEA-S upregulates the HA-induced cervical ripening process.

Animals↗
PubMed1999

Binding of interleukin-8 to heparan sulphate enhances cervical maturation in rabbits.

Cervical ripening is a cytokine-triggered process with substantial remodelling of the cervical extracellular matrix. Interleukin-8 (IL-8) is an important cytokine in cervical maturation. Glycosaminoglycans are also included in this process, but their role in not clearly understood. The effects of heparan sulphate (HS), hyaluronic acid (HA), IL-8, HS + IL-8 and HA + IL-8 on biochemical properties of the cervix were examined in non-pregnant rabbits. The changes in vascular pattern with collagen structure of the cervices and immunohistochemical studies, together with the relative collagen concentrations, were determined. A reduction in relative collagen concentration was significant after HS + IL-8, IL-8 and HA + IL-8 treatment (all P < 0.0001). Gel electrophoresis analysis showed that IL-8 bound preferentially to HS than to HA. Neutrophils were significantly increased in number (P < 0.0001) and located predominantly beneath the glandular epithelium and around the blood vessels after HS + IL-8 treatment. HS + IL-8 treatment caused cervices to increase their water content and become oedematous. The collagen fibres were considerably dissociated, the interfibrillar spaces markedly dilated, and the blood vessels notably increased and dilated. We conclude that binding to HS enhances the activity of IL-8 in inducing cervical maturation.

Animals↗
PubMed1999

The role of low molecular weight hyaluronic acid contained in Wharton's jelly in necrotizing funisitis.

The purpose of this research was to study the changes in the molecular weight of hyaluronic acid in Wharton's jelly altered by necrotizing funisitis. Umbilical cords were collected at delivery from 20 newborns without funisitis, 6 newborns with acute funisitis, and 4 newborns with necrotizing funisitis. Agarose gel electrophoresis of Wharton's jelly was performed to analyze the molecular weight of hyaluronic acid (HA). We also investigated the effects of low or high molecular weight HA on the production of interleukin-8 in human umbilical fibroblasts. In Wharton's jelly without funisitis, HA was 1150 +/- 280 kD in preterm newborns, regardless of gestational week at birth, and that in full-term newborns was 1100 +/- 200 kD. When acute funisitis was present, HA was 700 +/- 250 kD, and when necrotizing funisitis was present, HA was 520 +/- 100 kD. The molecular weight of HA was significantly below normal in newborns with necrotizing funisitis. Low molecular weight HA was associated with increased levels of IL-8 in the supernatant of cultured human umbilical fibroblasts in a time- and dose-dependent manner. High molecular weight HA did not induce the production of IL-8 in the same cells. Low molecular weight HA has a potent inflammatory action. The conversion from high to low molecular weight HA in Wharton's jelly may be important in the pathophysiology of necrotizing funisitis.

Birth Weight↗
PubMed1999

Induction of eclampticlike changes by stimulation of the celiac ganglion in rats.

OBJECTIVE: To examine the relation between the stimulation of the abdominal sympathetic nervous system and vasospasm of the brain in eclamptic seizures, we analyzed brain blood flow after stimulation of the celiac ganglion by lipopolysaccharide (LPS, 5, 50, or 500 mg/mL) or normal saline before and after denovation of sympathetic trunk in pregnant and nonpregnant rats. METHODS: The brain blood flow was measured after stimulation of the celiac ganglion with 50 microL (5 mg/mL) LPS in group I, 50 microL (50 mg/mL) LPS in group II, 50 microL saline in group III, and 50 microL (500 mg/mL) LPS (after denovation of the sympathetic trunk) in group IV. A sham control experiment was also done by stimulation of the abdominal peritoneum with 50 microL (500 mg/mL) LPS in group V. Changes in water content and histological findings in the brain were also studied in this protocol. RESULTS: A significant reduction in brain blood flow was observed in pregnant rats in groups I and II on stimulation of the celiac ganglion with LPS (p < 0.0001, p < 0.001) compared with before stimulation. Celiac ganglion stimulation with saline (group III) and LPS (group IV, after denovation of the sympathetic trunk) did not affect brain blood flow. Stimulation of the abdominal peritoneum with LPS (group V) could not induce any changes in brain blood flow. Repeated seizures occurred in 60% of pregnant rats and a remarkable increase in water content was observed after LPS stimulation of the celiac ganglion in groups I and II (p < 0.0001, p < 0.001). Histologically, we found that stimulation of the celiac ganglion with LPS caused widening of perivascular spaces with compression of the vessels leading to ischemic changes in brain tissues. There were no such findings observed in other groups. However, a lesser extent effect was noticed in nonpregnant than seen in pregnant rats. CONCLUSION: Stimulation of the abdominal sympathetic ganglions could induce vasoconstriction of the brain vessels, thus decreasing brain blood flow, which results in eclampsialike changes in rats.

Animals↗
PubMed1999

Induction of hypercoagulability condition by chronic localized cold stress in rabbits.

To evaluate the effect of cold-induced stress on renal and hepatic blood flow and coagulation parameters, rabbits' soles were exposed to ice pad (0 degrees C). Renal and hepatic blood flow was measured after 1 h and 15 days of cold stress. Coagulation parameters (0, 8th and 15th days of stress) and histological studies were performed. Renal and hepatic blood flow was significantly reduced after cold-stress. Decreased platelet count, antithrombin III (AT III) activity, increased fibrinogen (Fbg) level, shortened activated partial thromboplastin time (aPTT) and prothrombin time (PT) was found after 8 and 15 days of cold-stress. Histology showed enlarged glomeruli with fibrin deposition in kidney, ischemic changes and fibrin deposition in liver and hemorrhagic necrosis in adrenal cortex. We conclude that undesirable localized cold induced sympathetic stimulation in daily life may be a predisposing factor for coagulopathy.

Animals↗
PubMed1998

Urinary trypsin inhibitor suppresses vascular smooth muscle contraction by inhibition of Ca2+ influx.

Urinary trypsin inhibitor (UTI) and its precursor form inter-alpha trypsin inhibitor (ITI) are present in plasma. To determine the action of UTI on blood vessels, we performed isometric vascular muscle contraction tests, microcirculation studies and measurement of cytosolic free Ca2+ in vascular smooth muscle cells. An isometric vascular muscle contraction test showed that the contractions stimulated by endothelin-1 or norepinephrine were suppressed in the presence of UTI, and that the contractions were not inhibited in the presence of ITI. The microcirculation study showed that the contraction of mesenteric arterioles of WKY rats induced by norepinephrine were inhibited by treatment of UTI, and that they did not alter by treatment of ITI. Pre-incubation of UTI, but not ITI, with vascular smooth muscle cells inhibited the increase of cytosolic free Ca2+ induced by endothelin-1 or norepinephrine. Cell-binding study by biotinylated UTI showed that vascular smooth muscle cells have specific binding site for UTI, but not for ITI. We propose that circulating UTI converted from ITI has a regulatory effect on local vascular tone by regulation of Ca2+ influx into smooth muscle cells.

Animals↗
PubMed1998

Decreased renal and hepatic blood flow with preeclampsia-like histologic changes was obtained by stimulation of the celiac ganglion with LPS.

Decreased renal and hepatic blood flow with preeclampsia-like histologic changes was developed by stimulation of the celiac ganglion with lipopolysaccharide (LPS) in pregnant rabbits. The renal and hepatic blood flow were measured after stimulation of the celiac ganglion with 10 microL (group 1), 100 microL (group II) and 300 microL (group III) of LPS (10 mg/mL conc.) and with 100 microL of normal saline (group IV). The bifurcation of the abdominal aorta was also stimulated with 300 microL of LPS (group V). A control experiment was also done in this study (group VI). Histopathological studies of kidney and liver tissue were also performed in this protocol. A significant reduction in renal and hepatic blood flow was observed in pregnant rabbits with the times and dosage dependent on stimulation of the celiac ganglion by LPS. Stimulation of the bifurcation of the abdominal aorta with LPS could not produce any changes in renal and hepatic blood flow. Preeclampsia-like histologic changes of kidney and liver tissue were also observed. These results suggest that exogenous stimulation of the celiac ganglion causes decreased renal and hepatic blood flow, resulting in preeclampsia-like histologic changes of kidney and liver in pregnant rabbits.

Animals↗
PubMed1998

Anticoagulant activity in non-immunoglobulin fraction from plasma of patients with antiphospholipid syndrome.

Anticoagulant activity is present in non-immunoglobulin (IgG) fractions from plasma of patients with antiphospholipid syndrome (APS). Plasma from six patients with primary or secondary APS was passed through a protein A sepharose 4B column. Anticoagulant activity in IgG samples and non-IgG samples was determined by both dilute aPTT based clotting assay and by dilute PT based clotting assay. Thrombin generation was determined by prothrombinase complex assay in the presence of IgG sample or non-IgG sample. Anticoagulant activity was detected in the IgG samples with the dilute aPTT based clotting assay and in non-IgG samples with the dilute PT based clotting assay. The activity was not detected in IgG samples with the dilute PT clotting assay. Forty percent of total thrombin generation was inhibited in the presence of non-IgG samples although thrombin generation was not inhibited in the presence of IgG samples and beta2-glycoprotein I. The anticoagulant activity detected by dilute PT based clotting assay and prothrombinase complex assay was non-IgG, phospholipid-Ca++-dependent and beta2-glycoprotein I-independent. The role of non-IgG anticoagulants should be determined as well as the role of LA Igs antibodies in the mechanisms of thrombosis.

Anticoagulants↗
PubMed1998

Genetic evaluation of physiological functions of thiolase isoenzymes in the n-alkalane-assimilating yeast Candida tropicalis.

The n-alkane-assimilating diploid yeast Candida tropicalis possesses three thiolase isozymes encoded by two pairs of alleles: cytosolic and peroxisomal acetoacetyl-coenzyme A (CoA) thiolases, encoded by CT-T1A and CT-T1B, and peroxisomal 3-ketoacyl-CoA thiolase, encoded by CT-T3A and CT-T3B. The physiological functions of these thiolases have been examined by gene disruption. The homozygous ct-t1a delta/t1bdelta null mutation abolished the activity of acetoacetyl-CoA thiolase and resulted in mevalonate auxotrophy. The homozygous ct-t3a delta/t3b delta null mutation abolished the activity of 3-ketoacyl-CoA thiolase and resulted in growth deficiency on n-alkanes (C10 to C13). All thiolase activities in this yeast disappeared with the ct-t1a delta/t1bdelta and ct-t3a delta/t3bdelta null mutations. To further clarify the function of peroxisomal acetoacetyl-CoA thiolases, the site-directed mutation leading acetoacetyl-CoA thiolase without a putative C-terminal peroxisomal targeting signal was introduced on the CT-T1A locus in the ct-t1bdelta null mutant. The truncated acetoacetyl-CoA thiolase was solely present in cytoplasm, and the absence of acetoacetyl-CoA thiolase in peroxisomes had no effect on growth on all carbon sources employed. Growth on butyrate was not affected by a lack of peroxisomal acetoacetyl-CoA thiolase, while a retardation of growth by a lack of peroxisomal 3-ketoacyl-CoA thiolase was observed. A defect of both peroxisomal isozymes completely inhibited growth on butyrate. These results demonstrated that cytosolic acetoacetyl-CoA thiolase was indispensable for the mevalonate pathway and that both peroxisomal acetoacetyl-CoA thiolase and 3-ketoacyl-CoA thiolase could participate in peroxisomal beta-oxidation. In addition to its essential contribution to the beta-oxidation of longer-chain fatty acids, 3-ketoacyl-CoA thiolase contributed greatly even to the beta-oxidation of a C4 substrate butyrate.

Acetyl-CoA C-Acetyltransferase↗
PubMed1998

Vasospasms of cerebral arteries in hyperemesis gravidarum.

Hyperemesis gravidarum is associated with nausea and vomiting during the 1st trimester of pregnancy. We report 2 cases of hyperemesis gravidarum associated with vasospasms of cerebral arteries recognized by magnetic resonance imaging angiography. The hyperemetic condition of the patients improved after fluid and electrolyte replacement therapy.

Adult↗
PubMed1998

Eclamptic plasma stimulates norepinephrine release in cultured sympathetic nerve.

The purpose of the present study was to evaluate the effect of plasma from eclamptic and preeclamptic patients on cultured sympathetic nerve. Sympathetic neurons from 12- to 14-day-old chick embryos were cultured; the neurons were then stimulated with 50% plasma from eclamptic, preeclamptic, hypertensive, normotensive pregnant, hypertensive, and normotensive nonpregnant women (n=7). Similarly, neurons were individually incubated with mixtures of 50% corresponding plasma with 0.25% bupivacaine or bupivacaine only (n=7). Furthermore, the effects of 1%, 10%, and 50% plasma from eclamptic, preeclamptic, and normotensive pregnant patients (n=7) were also evaluated. Norepinephrine concentrations were measured by high-performance liquid chromatography. Electron microscopic studies of nerve cells were also performed. Stimulation with plasma from eclamptic and preeclamptic women significantly increased norepinephrine concentration (P<0.0001) compared with control. The release of norepinephrine was found to be concentration-dependent. Conversely, norepinephrine secretion was significantly hampered by bupivacaine treatment (P<0.0001). Electron microscopic studies in eclamptic and preeclamptic plasma-stimulated nerve cells showed that perikarya were in close contact with each other and with nerve cell processes. After treatment with bupivacaine, nerve cells were irregular in shape and the cell membranes were demyelinated. These results suggest that eclamptic and preeclamptic plasma has an excitotoxic effect on sympathetic nerve via axoplasmic membrane depolarization, thus increasing norepinephrine secretion that is blocked by bupivacaine. A preeclamptic condition may be improved by depression of sympathetic nerve stimulation.

Adult↗
PubMed1998

Effect of dehydroepiandrosterone sulfate on interleukin-8 receptor during cervical ripening.

We investigated the effects of dehydroepiandrosterone sulfate (DHA-S) on the production of interleukin-8 (IL-8) and expression of the interleukin-8 receptor (IL-8 R) in human cervical tissue. DHA-S increased the levels of IL-8 in cultured human cervical fibroblasts and in the supernatant in a time- and dose-dependent manner. DHA-S induced IL-8 and IL-8 R expression in human cervical fibroblasts and human pregnant cervical tissue at term in a dose-dependent manner. In addition, it induced the expression of IL-8 R in an explant culture of human cervical tissue and cultured human cervical fibroblasts in a time- and dose-dependent manner. However, dehydroepiandrosterone (DHA) only slightly induced the production of IL-8 and the expression of IL-8 R in the same cells and tissue. These results suggest that DHA-S up-regulates the autocrine system of IL-8 through the expression of IL-8 R.

Antigens, CD↗
PubMed1997

Urinary trypsin inhibitor suppresses the production of interstitial procollagenase/proMMP-1 and prostromelysin 1/proMMP-3 in human uterine cervical fibroblasts and chorionic cells.

The mechanisms by which urinary trypsin inhibitor (UTI) prevents preterm premature rupture of fetal membrane and premature cervical ripening were investigated. We, therefore, examined the effects of UTI on the production of matrix metalloproteinases (MMPs) which closely participate in the breakdown of extracellular matrix in cultured human uterine cervical fibroblasts and human chorionic cells. UTI suppressed specifically the production of interstitial procollagenase/proMMP-1 and prostromelysin 1/proMMP-3 from both cells in a dose-dependent manner (0.32-1.28 microM). This suppression was accompanied by a decrease in steady-state levels of their mRNAs. These results indicate for the first time that UTI down-regulates the production of proMMP-1 and proMMP-3 accompanying with the decrease in the expression of their mRNAs, and therefore UTI actually participates in the maintenance of fetal membranes and/or uterine cervix by overall suppression of MMP production along with the known inhibitory actions towards serine proteinases.

Blotting, Northern↗
PubMed1997

The role of chondroitin sulfate chains of urinary trypsin inhibitor in inhibition of LPS-induced increase of cytosolic free Ca2+ in HL60 cells and HUVEC cells.

Preincubation of HL60 cells and HUVEC cells with urinary trypsin inhibitor (UTI) inhibited increase of cytosolic free Ca2+ induced by LPS. In contrast, an increase of cytosolic free Ca2+ induced by LPS was not inhibited by deglycosylated UTI, UTI treated with monoclonal antibody of chondroitin sulfate. 45Ca2+ binding showed that UTI binds 45Ca2+ dose-dependently. Scatchard plot analysis showed that UTI has two binding sites for Ca2+, a high affinity binding site (Kd=15 microM) and a low affinity site (Kd=150 microM), and that UTI has more than 70 Ca2+ binding sites per molecule. The Ca2+ binding capacity of deglycosylated UTI and UTI treated with monoclonal antibody of chondroitin sulfate was markedly depressed. Furthermore, UTI forms multi-polymers in the presence of Ca2+ as demonstrated by gel filtration and agarose gel electrophoresis. These results suggest that UTI is a physiological Ca2+ chelator on the cells and that the action is due to chondroitin sulfate chains of UTI.

Binding Sites↗
PubMed1997

Derepression of gene expression mediated by the 5' upstream region of the isocitrate lyase gene of Candida tropicalis is controlled by two distinct regulatory pathways in Saccharomyces cerevisiae.

The 5' upstream region of the gene encoding isocitrate lyase of Candida tropicalis (UPR-ICL) is functional as a promoter in Saccharomyces cerevisiae, and it is regulated by carbon source; the expression of the gene is repressed when cells are grown on glucose, while it increases to a higher level in acetate-grown cells. Therefore, we have investigated regions in UPR-ICL responsible for gene expression in glucose-grown and acetate-grown cells. In glucose-grown cells, a deletion of the region between -801 and -569 (region G1) significantly decreased gene expression compared with that observed with the complete UPR-ICL. The region from -421 to -379 (region G2) also repressed gene expression in glucose-grown cells. In acetate-grown cells, two regions were found to strongly enhance gene expression, one between -728 and -569 (region A1) and the other between -370 and -356 (region A2). Whereas region A2 contained a sequence motif similar to the carbon-source-responsive element (CSRE), which mediates regulation by carbon source of S. cerevisiae ICL1, region A1 did not show similarity to any reported cis-acting elements. Deletion mutants of UPR-ICL containing only one of these regions showed that each region could independently activate gene expression to a similar level when the cells were grown on acetate. The influences of null mutations in the MIG1, SNF1 and CAT8 genes on regulation of UPR-ICL-mediated gene expression were examined. Expression of the ICL gene with full-length UPR-ICL increased about tenfold in mig1 cells grown on glucose, while little difference was observed in acetate-grown cells. The effects of snf1 and cat8 mutations were different between region-A1-mediated and region-A2-mediated gene expression in acetate-grown cells. Region-A2-mediated expression decreased 95% and 86% in snf1 and cat8 cells, respectively, while region-A1-mediated expression decreased 72% in snf1 cells and was not affected by the cat8 mutation. This finding indicates that region-A1-mediated gene expression is regulated by a pathway independent of CAT8, which is necessary for derepression of CSRE-mediated gene expression in S. cerevisiae.

Base Sequence↗