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N Kanayama

Publications and source records attributed to N Kanayama.

At least 91 records · Page 5Linked to original sources
PubMed1996

Expression of interleukin-8 receptors in the gestational tissues before and after initiation of labor: immunohistochemical study.

BACKGROUND: Interleukin-8 (IL-8) has an essential role in the mechanism of parturition. IL-8 induces its effect through specific cell binding receptors. The main purpose of this research was to elucidate the presence of IL-8 receptors in the gestational tissues and their relation to parturition. MATERIALS AND METHODS: Fetal membranes, placenta, umbilical cord and myometrial samples were collected before the initiation of labor during elective Cesarean sections (n = 15). Similar biopsies (except myometrial samples) were also gathered after normal vaginal delivery (n = 15). Immunohistochemical staining for IL-8 receptors type I and II was carried out for the fresh frozen sections of all samples. Immunoreactive score (IRS) was calculated for the stained sections. RESULTS: IL-8 Receptors type I and II were recognized in the fetal membranes, placenta, umbilical cord and myometrial samples collected from patients before the initiation of labor. The staining of amnion and placentas were found to be more intensified in the samples collected after vaginal delivery compared to those from elective cesarean sections and before initiation of labor. CONCLUSIONS: Increased expression of IL-8 receptors after initiation of labor may indicate that IL-8 receptors might have a role during parturition.

Antigens, CD↗
PubMed1996

Induction of HELLP syndrome-like biochemical parameters by stimulation of the celiac ganglion in rats.

OBJECTIVE: An animal model of HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome was developed by means of stimulation of the celiac ganglion in rats. METHODS: The celiac ganglion in pregnant or non-pregnant rats was exposed to endotoxin (lipopolysaccharide, LPS) (500 micrograms/50 microliters), potassium chloride (0.2 mol/l/50 microliters), or saline solution (50 microliters). In another group of rats the bifurcation of the abdominal aorta was exposed to LPS (500 micrograms/50 microliters). Blood pressure, platelet count, hematocrit, serum aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and plasma norepinephrine and epinephrine were measured for 6 h after treatment. Histopathologic studies were also performed in these rats. RESULTS: A significant increase in blood pressure, AST, ALT, LDH, norepinephrine, and epinephrine was found in the endotoxin-treated pregnant rats compared with control rats treated with the saline solution. A significant decrease in platelet count was found in endotoxin-treated pregnant rats compared with the control rats. A significant increase in blood pressure, AST, norepinephrine, and epinephrine was found in the potassium chloride-treated pregnant rats compared with control rats. Blood pressure and biochemical parameters remained unchanged in the pregnant rats treated with LPS at the bifurcation of the abdominal aorta, as in those treated with saline at the celiac ganglion. Histologic examination of liver tissues treated with LPS or potassium chloride showed varying degrees of ischemic necrosis of hepatocytes similar to that observed in the human HELLP syndrome. Blood pressure, biochemical parameters, and histologic findings in non-pregnant rats were almost the same as those in pregnant rats. CONCLUSION: This study suggests that exogenous stimulation of the celiac ganglion causes an increase in the blood pressure and liver ischemia, resulting in HELLP syndrome-like disease in pregnant and non-pregnant rats.

Animals↗
PubMed1995

Endothelin-1 evoked an increase and oscillations in cytosolic calcium concentration in adherent single human platelets and increased GMP-140 (P-selectin) in platelet suspension.

The effect of endothelin-1 (ET-1) on cytosolic calcium ion concentration ([Ca2+]i) in adherent single human blood platelet was determined by fluorescence digital imaging microscopy using Fura-2 as calcium probe. A dose dependent increase and oscillatory changes in [Ca2+]i in single platelets were evoked by ET-1 as with thrombin. Half and 1 microM of ET-1 increased (p < 0.01) the [Ca2+]i in single platelets from a resting level of 83 +/-3.4 nM to 120 +/- 13 nM and 240 +/- 20 nM respectively. The ET-1 induced increase in [Ca2+]i was suppressed by 1 mM EGTA, a calcium chelating agent in the medium. ET-1 increased the production of IP3 (quantitified by IP3 3H-radioreceptor assay kit) in platelets significantly (p < 0.05) in a dose dependent way. We measured the GMP-140 (P-selectin) level in the supernatant of human platelet suspensions incubated with thrombin and ET-1. Both thrombin and ET-1 increased the secretion of soluble GMP-140 in the supernatant of platelet suspensions. Therefore, we suggested that ET-1 increased [Ca2+]i in platelets by both calcium influx and IP3 mediated Ca2+ release resulting in activation and release of GMP-140.

Adult↗
PubMed1995

Inhibition of tumor cell invasion through matrigel by a peptide derived from the domain II region in urinary trypsin inhibition.

Urinary trypsin inhibitor (UTI) has a multipotent inhibitory effect on proteases such as trypsin, chymotrypsin, plasmin, human leukocyte elastase, or hyaluronidase. UTI can bind easily to its receptors on various types of tumor cells (human ovarian cancer HOC-I cells, human choriocarcinoma SMT-cc1 cells, and murine Lewis lung carcinoma 3LL cells). Our results show that the UTI receptors of some tumor cells have a possible role in modulating plasmin activity on the cell surface and prevention of tumor cell invasion and metastasis (H. Kobayashi et al., J. Biol. Chem., 269; 20642-20647, 1994). UTI interacts with tumor cells as a negative modulator of the invasive cells. We investigated whether this effect may be mediated by UTI binding to the cell surface receptors. In addition, the role of peptide sequences from each UTI domain and their interaction with tumor cells were investigated. UTI derivatized with biotin or FITC was taken up by tumor cells in a dose-dependent manner. This cell association was inhibited with a monoclonal antibody D1, which specifically recognizes NH2 terminus (domain I) of UTI. The binding was inhibited by fluid phase UTI, but not HI-8, COOH terminus (domain II) of UTI, suggesting that UTI binds to cells through a site in the UTI domain I. Furthermore, we found that UTI, HI-8 and a number of peptides containing Arg-Gly-Pro-Cys-Arg-Ala-Phe-Ile promoted the inhibition of tumor cell invasion. This site corresponds to the plasmin-inhibiting domain within HI-8. The possibility that UTI binding to tumor cells might be involved in the prevention of tumor cell invasion in vitro was excluded since HI-8, lacking domain I, promotes the inhibition of tumor cell invasion with essentially the same affinity as UTI. All these data allow us to conclude that inhibition of tumor cell invasion is mediated by domain II, which possesses anti-plasmin activity.

Amino Acid Sequence↗
PubMed1995

Activated neutrophil by endothelin-1 caused tissue damage in human umbilical cord.

Immunostaining of human neutrophils incubated with endothelin-1 (ET-1) showed intense and spreading pattern of anti human granulocyte elastase within the cytosol. That reflected neutrophil activation followed by the release of granule contents by ET-1. In contrast, PBS (phosphate buffered saline) treated neutrophils showed localized and faintly stained granules. Intracellular calcium in fura-2 loaded neutrophils was measured at 340/380 nm. A dose and time dependent increase in intracellular calcium by ET-1 occurred in human single neutrophil. Elastase activity assay was done with chromogenic substrate S2484. ET-1 induces dose and time dependent increase in elastase activity in neutrophil suspensions like ionophore A23187. A similar time dependent increase in elastase activity was retained even after repeated wash and ET-1 treatment. That confirmed the viability of most of the neutrophils after each treatment. In umbilical cord preparations, ET-1 treated neutrophils could migrate from the venous lumen into the tissue matrix of the umbilical cords. Hematoxylin and eosin staining revealed a massive tissue destruction in ET-1 activated neutrophil treated cords when compared to sham control and untreated neutrophil injected cords. Immunostaining with monoclonal anti human elastase revealed an intense staining in former sections when compared to the others. We suggest that ET-1 activated neutrophil might play a major role in endothelial injury and tissue damage in conditions with high blood level of endothelin.

Calcium↗
PubMed1995

Kunitz-type trypsin inhibitor prevents LPS-induced increase of cytosolic free Ca2+ in human neutrophils and HUVEC cells.

The protease inhibitor part of inter-alpha trypsin inhibitor is identical to urinary trypsin inhibitor (UTI). Preincubation of neutrophils and HUVEC cells with UTI inhibited increase of cytosolic free Ca2+ induced by LPS. Increase of cytosolic free Ca2+ induced by LPS in the presence of EGTA was also inhibited by UTI. In contrast, UTI did not inhibit increase of cytosolic free Ca2+ in cells stimulated by Ca2+ ionophore with or without EGTA. The effects of nine synthetic peptides of UTI on the concentration of cytosolic free Ca2+ in the neutrophils induced by LPS were examined. Preincubation with a peptide of UTI domain 2, NLPIVRGPCRAFIQL (83-97), was completely inhibited by the increase of cytosolic free Ca2+ in neutrophils. This region is identical to the trypsin inhibitor site of UTI. We propose that a function of UTI other than as a protease inhibitor is in regulation of intracellular Ca2+ and that this is due to its trypsin inhibitor region.

Amino Acid Sequence↗
PubMed1995

Down-regulation of interleukin-8 gene expression in HL60 cell line by human Kunitz-type trypsin inhibitor.

Urinary trypsin inhibitor (UTI) is one of the Kunitz-type protease inhibitors in human. Little is known about its anti-inflammatory functions other than protease inhibition. We studied the effect of UTI on gene expression of interleukin-8 (IL-8), an inflammatory cytokine. UTI inhibited IL-8 gene expression induced by lipopolysaccharide (LPS) in HL60 cells. The IL-8 concentrations in the cells and medium after LPS stimulation increased time-dependently in the absence of UTI, but did not increase in the presence of UTI. On the other hand, UTI did not inhibit either the synthesis or the release of IL-8 induced by the calcium ionophore A23187. UTI inhibited increase of cytosolic Ca2+ stimulated by LPS but not by A23187. Our results suggest that the inhibition by UTI is due to its effect on the cell membrane involved in regulating Ca2+ influx.

Calcimycin↗
PubMed1995

Inactivation of interleukin-8 by aminopeptidase N (CD13).

Aminopeptidase (APN) was found to degrade interleukin-8 (IL-8) and inactivate its chemotactic activity. The chemotactic activity of IL-8 was decreased by APN or neutrophil plasma membranes dose- and time-dependently. The chemotactic activity was not inactivated in the presence of bestatin or WM15 monoclonal antibody. The expression of IL-8 was measured by flow cytometry. On lipopolysaccharide (LPS) stimulation, IL-8 expression increased for 60 min and then decreased markedly. In contrast, on treatment with LPS and bestatin, the expression of IL-8 increased continuously for at least 120 min. These results suggest that the expression and release of IL-8 from phagocytic cells are regulated by the proteolytic effect of APN on IL-8.

Animals↗
PubMed1995

Regulatory effect of aminopeptidase inhibitor (bestatin) on the cervix during induction of ripening by interleukin-8.

Bestatin is an immunomodulatory peptide that stimulates the humoral and cell-mediated immune system. It also has an inhibitory effect on multiple aminopeptidases. Recently we found that aminopeptidase N inactivates interleukin-8 in vitro. Bestatin successfully suppresses the effect of aminopeptidase N on interleukin-8. During cervical maturation many biochemical changes occur including decrease in collagen concentration and increase in collagenase and elastase activities. Interleukin-8, which has a potent neutrophil chemotactic effect, was found to induce cervical ripening in rabbits. The combination of interleukin-8 with bestatin also induced cervical ripening by providing approximately regular levels of neutrophil numbers, collagenase, and elastase activities. We therefore suggest that this regulatory mechanism also takes place in vivo through the inhibitory effect of bestatin on aminopeptidase N.

Animals↗
PubMed1995

Urinary trypsin inhibitor prevents uterine muscle contraction by inhibition of Ca++ influx.

OBJECTIVE: The aim of this research was to elucidate the mechanism of action of urinary trypsin inhibitor, a Kunitz-type protease inhibitor, in suppressing uterine muscle contraction. STUDY DESIGN: An isometric uterine contraction test was used to study this inhibitory effect of urinary trypsin inhibitor on the myometrium. Oxytocin, prostaglandin F2 alpha, and lipopolysaccharide were used to stimulate myometrial contraction. Prostaglandins F2 alpha and E2 were measured in the buffer solution. Influx of calcium into uterine smooth muscle cells was assessed by digital imaging microscopy. RESULTS: After incubation with urinary trypsin inhibitor or fetal urine, myometrial contractions stimulated by oxytocin, prostaglandin F2 alpha or lipopolysaccharide were suppressed completely. The concentrations of prostaglandins F2 alpha and E2 in the buffer solution during the isometric contraction test were significantly increased by lipopolysaccharide stimulation, but when urinary trypsin inhibitor was present in the buffer solution the concentrations of prostaglandins F2 alpha or E2 did not change significantly. Preincubation with urinary trypsin inhibitor also inhibited calcium influx, resulting in no detectable change in the intracellular free calcium concentration of smooth muscle cells. CONCLUSION: We proposed that urinary trypsin inhibitor from fetal urine inhibits uterine muscle contraction by regulation of intracellular Ca++.

Calcium↗
PubMed1995

The effect of interleukin-1 in rabbit cervical ripening.

OBJECTIVE: In this research we studied the effect of interleukin-1 beta (IL-1 beta) on the cervix. STUDY DESIGN: Vaginal suppositories of a low dose of IL-1 beta (200 ng) were applied to non-pregnant and pregnant rabbits. Results were compared with a control group which were treated only by placebo. Water concentration, collagen content, collagenase and elastase activities were measured. Neutrophil numbers in the cervical connective tissue were counted. Also, interleukin-8 (IL-8) was measured in the supernatant of homogenized cervical tissue treated by IL-1 beta. RESULTS: Water contents of the tested cervices were increased (P < 0.006 and 0.03, respectively), whereas collagen content was markedly decreased (P < 0.0004 and 0.001, respectively). Collagenase activity was found to be increased in non-pregnant and pregnant cervices treated by IL-1 beta (P < 0.02 and 0.002, respectively). Also, elastase activity of these cervices were significantly increased compared to the control group (P < 0.0007 and 0.001, respectively). Neutrophil invasion was observed in the cervical connective tissues after application of IL-1 beta. IL-8 was significantly elevated (P < 0.0001) in the treated cervices. CONCLUSION: Interaction between IL-1 and IL-8 is suspected to be essential for cervical ripening.

Animals↗
PubMed1995

Urinary trypsin inhibitor suppresses premature cervical ripening.

UNLABELLED: Unknown signals from the fetus are thought to be involved in the onset of parturition. We recently discovered that urinary trypsin inhibitor (UTI) from fetal urine inhibits uterine muscle contraction. OBJECTIVES: The aim of this research was to elucidate the mechanism of action of UTI in suppressing cervical maturation. STUDY DESIGN: Non-pregnant and pregnant rabbits pretreated with and without UTI suppositories containing 1000 U (400 micrograms) for 3 days were treated for 2 days with vaginal suppositories containing 100 ng of interleukin-8 (IL-8). RESULTS: IL-8 induced softening and dilatation of the rabbit cervices. In contrast UTI inhibited IL-8 induced cervical softening and dilatation. Water content, collagen content, neutrophil counts, elastase activity and collagenase activity of the cervix were increased by IL-8, but they did not increase by IL-8 with UTI. CONCLUSION: These results suggest that UTI inhibits cervical maturation induced by IL-8.

Animals↗
PubMed1995

Endothelin has a role in early pathogenesis of amniotic fluid embolism.

The early pathogenesis of amniotic fluid embolism is not completely understood. The entrance of amniotic fluid (AF) into the systemic circulation leads to an initial phase of pulmonary vasospasm, pulmonary hypertension and cor pulmonale. We studied the effect of AF on endothelin (ET) production in vivo and in vitro. Injection of rabbits (pregnant and nonpregnant) with meconium-stained AF, raw AF and supernatant AF led to a significant increase in serum ET. This result was confirmed by using human umbilical vein endothelial cell cultures incubated with the same types of AFs. After infusion of rabbits with AFs, we observed that the lung, heart and kidney were positively stained for ET and von Willebrand factor. AF was found to have an injurious effect on endothelial cells measured by using fura-2. The maximal injurious effect of AFs was observed for the meconium-stained AF. We hypothesized that the early pathological changes in AF embolism may be mediated by ET.

Animals↗
PubMed1995

Cerebral magnetic resonance angiographic findings in severe preeclampsia.

OBJECTIVE: The purpose of our study was to investigate the cerebral pathophysiology of severe preeclampsia using the noninvasive method of magnetic resonance angiography. STUDY DESIGN: We studied cerebral magnetic resonance angiography findings in 9 severely preeclamptic patients. RESULTS: Magnetic resonance angiographies were abnormal on first scanning within 48 h postpartum, followed by normal findings on repeat scanning during the 1st postpartum month in 6 patients. The most common abnormality was vascular narrowing of anterior cerebral artery and basilar artery. Three of these 6 patients complained of headaches and/or visual disturbances. CONCLUSION: This study shows that cerebral artery vasospasm is seen in some severe preeclamptic patients.

Adult↗
PubMed1995

Eclampsia-like seizures and electroencephalographic changes in pregnant rabbits with endothelin-1 injections.

To examine the possible role of endothelin and vasospasm in eclamptic seizures, we studied and analyzed the electroencephalograms (EEG) of endothelin-1 (ET-1)-treated pregnant, nonpregnant and sham control (dextrose-treated) rabbits. After multiple intravenous bolus injections of ET-1 (500 pmol/kg) or 5% dextrose in the rabbits, we recorded EEG directly from the brain cortex and analyzed by Fast Fourier Transform (FFT). Water content was measured in the brain of all groups (n = 7). Repeated seizures occurred in all of the pregnant and 2 of the nonpregnant rabbits by variable doses of ET-1. FFT analysis showed remarkable changes in frequency and power arrays characterized by mild to severe form of dysrhythmia, high-voltage spikes, high-voltage fast and slow waves after ET-1 injections. Water content was increased in brain mass in ET-1-treated rabbits (p = 0.001) suggesting an ET-1-induced edema. Histologically we confirmed that ET-1 caused ischemic changes in brain tissues. However, ET-1 induced more pronounced changes in behavior, EEG, brain edema or ischemia in pregnant than in nonpregnant groups. The injections of exogenous ET-1 into the brain substances were strongly suggested by immunohistochemical study with polyclonal antiendothelin antibody in brain tissue sections. Therefore, we assume that endothelin along with other vasoactive substances causes acute cerebral vasospasm and ischemia inducing EEG changes leading to ultimate clinical convulsions in eclampsia.

Animals↗
PubMed1995

Blood coagulation and fibrinolysis in eclamptic patients and their correlation with the clinical signs.

We studied the impact of blood coagulation and fibrinolysis on the clinical features of eclamptic patients (n = 20) in Bangladesh. The variables used were edema, proteinuria, blood pressure, number of convulsions, level of consciousness at the time of admission, thrombin antithrombin complexes (TAT), antithrombin (AT) III (%) activity and antigen, D dimer fibrin degradation product and alpha 2-plasmin inhibitor-plasmin complex (PIC) in plasma. Canonical correlation analysis was made to obtain clinical index, eclampsia index and two coagulation indices. On admission, the mean values of coagulation parameters were AT III activity: 83.2% (range 57-108), TAT complex: 47.6 ng/ml (range 11.5-60), D dimer: 1,693 ng/ml (range 417-8,276) and PIC 1.4 mg/ml (range 0.4-3.3). We found a significant correlation between the eclampsia index and clinical index (r = 0.601; p = 0.01). Gestosis index, clinical index, and eclampsia index have also a strong correlation with the coagulation index (r = 0.695, p < 0.005; r = 0.871, p < 0.0001 and r = 0.805, p < 0.0001, respectively). Coagulation and fibrinolysis were markedly activated in eclampsia. The correlation between the clinical status and coagulation status in this study suggested a close relation between the coagulation and the development and progression of the disease.

Adolescent↗
PubMed1995

Effects of neutrophil chemotactic factors on cervical ripening.

Our aim was to study the effects of infection mediated by bacterial endotoxins (lipopolysaccharides LPS) and bacterial substrate (N-formyl-methionyl-leucyl-phenylalanine FMLP) on pathological cervical ripening, and compare their effects with the normal physiological mediator interleukin-8 (IL-8). Twenty non-pregnant rabbits were treated vaginally either by placebo, LPS, FMLP or IL-8 for 3 successive days. Water concentration was measured. Neutrophils were counted in 5 random fields of each specimen. Collagen and glycosaminoglycan concentrations were assessed histologically by using picrosirius red and alcian blue staining and optical density was calculated. LPS FMLP as well as IL-8 can induce cervical ripening. Water concentration was found to be significantly increased in these groups (p < 0.0001). Also, significant numbers of neutrophils were found to accumulate in the connective tissue of these cervices (p < 0.0001). Collagen concentration was significantly decreased in the cervices treated by LPS, FMLP and IL-8 (p < 0.0001). Glycosaminoglycan concentration was significantly increased in cervices treated by LPS, FMLI as well as IL-8 (p < 0.0001, 0.006 and 0.001 respectively). LPS, FMLP and IL-8 stimulate cervical ripening in non-pregnant rabbits. This ripening was mediated through the accumulated neutrophils in the connective tissue. IL-8 has a physiological type effect to induce ripening of the cervix.

Animals↗