Biomedical subjects

K Maehara

Publications and source records attributed to K Maehara.

At least 73 records · Page 4Linked to original sources

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

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↗

PubMed1994

Endothelin-1 increased immunoreactive von Willebrand factor in endothelial cells and induced micro thrombosis in rats.

This study was performed (i) to investigate the interaction between ET-1 and endothelial cells and (ii) to study the role of ET-1 in in vivo thrombosis. Fura-2AM loaded human umbilical endothelial cell cultures were incubated with 0, 25, 50 and 100 pmol of ET-1 for 24 hours (n = 6) at 37 degrees C. Fura-2 released in the media was measured by spectroflurophotometer at wavelength of 350 nm excitation and 500 nm emission. We found significant (p < 0.01) and dose dependent decrease in Fura-2 release by the cells indicating increased intracellular calcium in HUVEC. Increased calcium by ET-1 was also confirmed at single cell level by fluorescence digital image analysis using Fura-2AM. 5 ml solution of ET-1 (100 pmol/ml) was injected within the venous lumen of umbilical cords (of normal pregnancy) clumped at both ends and incubated at a temperature 37 degrees C for 3 hours (n = 7). We found intensely stained immunoreactive von Willebrand factor (vWF) on the endothelial cells of ET treated umbilical cords when compared with sham control (Umbilical cords incubated with phosphate buffer saline; n = 7). Intravenous ET-1 infusions at a rate of 1 nmol/kg/hour for 2 hours (cases, n = 7) and 5% dextrose infusions (sham control, n = 7) were performed in rats. Aorta, kidney and liver tissues were obtained to perform immunostaining with polyclonal antibody to vWF and fibrinogen. ET-1 treated rat tissues showed intense staining for vWF and fibrinogen intravascularly at hte same site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Interleukin-8 induces cervical ripening in rabbits.

OBJECTIVE: The purpose of this study was to determine whether cervical ripening can be induced in rabbits by interleukin-8. STUDY DESIGN: Nonpregnant and pregnant rabbits were treated for 5 days with vaginal suppositories containing 100 ng of interleukin-8. Collagen and glycosaminoglycan concentration in the cervices were assessed histologically by picrosirius red and alcian blue, and the mean optical density was calculated. The mean neutrophil count in five random fields was calculated from each biopsy specimen. RESULTS: Interleukin-8 induced softening and dilatation of the rabbit cervices. Water content was significantly increased (p < 0.0001 and p < 0.001, respectively). Cervical collagen concentration was found to be significantly decreased (p < 0.0004 and p < 0.0001, respectively). Glycosaminoglycan concentration was significantly increased in nonpregnant and pregnant cervices (p < 0.0009 and p < 0.1, respectively). The mean number of neutrophils was significantly increased (p < 0.0005 and p < 0.006, respectively). CONCLUSION: Interleukin-8 can induce cervical ripening in nonpregnant and pregnant rabbits.

Animals↗

PubMed1994

Lactic acidosis as a facilitator of oxyhemoglobin dissociation during exercise.

The slow rise in O2 uptake (VO2), which has been shown to be linearly correlated with the increase in lactate concentration during heavy constant work rate exercise, led us to investigate the role of H+ from lactic acid in facilitating oxyhemoglobin (O2Hb) dissociation. We measured femoral venous PO2, O2Hb saturation, pH, PCO2, lactate, and standard HCO3- during increasing work rate and two constant work rate cycle ergometer exercise tests [below and above the lactic acidosis threshold (LAT)] in two groups of five healthy subjects. Mean end-exercise femoral vein blood and VO2 values for the below- and above-LAT square waves and the increasing work rate protocol were, respectively, PO2 of 19.8 +/- 2.1 (SD), 18.8 +/- 4.7, and 19.8 +/- 3.3 Torr; O2 saturation of 22.5 +/- 4.1, 13.8 +/- 4.2, and 18.5 +/- 6.3%; pH of 7.26 +/- 0.01, 7.02 +/- 0.11, and 7.09 +/- 0.07; lactate of 1.9 +/- 0.9, 11.0 +/- 3.8, and 8.3 +/- 2.9 mmol/l; and VO2 of 1.77 +/- 0.24, 3.36 +/- 0.4, and 3.91 +/- 0.68 l/min. End-exercise femoral vein PO2 did not differ statistically for the three protocols, whereas O2Hb saturation continued to decrease for work rates above LAT. We conclude that decreasing capillary PO2 accounted for most of the O2Hb dissociation during below-LAT exercise and that acidification of muscle capillary blood due to lactic acidosis accounted for virtually all of the O2Hb dissociation above LAT.

Acidosis, Lactic↗

PubMed1994

Urinary trypsin inhibitor has a protective effect on the amnion.

Urinary trypsin inhibitor-related substance (UTI-R) was measured in the amniotic fluid (n = 30), first neonatal urine (n = 10), meconium (n = 10), and adult urine (n = 10). The concentration of UTI-R excreted in the neonatal urine was significantly higher than in adult urine and meconium. Positive immunostaining for UTI was observed in amnion, umbilical cord and placenta. The effect of UTI was studied on the amnion using fura-2-acetoxymethyl ester. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-beta (TNF-beta) led to a significant increase in relative fluorescence release (RFR) of fura-2 (p < 0.05 and p < 0.02, respectively) while endotoxin did not show significant changes of RFR of fura-2. The effect of IL-1 beta and TNF-beta was almost abolished after incubation of UTI with the amnion cells (p < 0.03). This suggests that UTI may have a protective effect on the amnion especially against IL-1 beta and TNF-beta.

Amnion↗

PubMed1994

Nonadrenergic noncholinergic nerves regulate basal coronary flow via release of capsaicin-sensitive neuropeptides in the rat heart.

Nonadrenergic noncholinergic nerve fibers supposedly modulate basal coronary flow by releasing capsaicin-sensitive neuropeptides, but the physiological effects of this intrinsic action have not been clarified. We investigated the intrinsic function of nonadrenergic noncholinergic innervation in modulating basal coronary flow in rats. We administered capsaicin to 44 rats to deplete neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P and administered inert vehicle to 60 control rats. Four days later, we measured the coronary pressure-flow relation in the basal state and during maximal coronary vasodilation induced by intracoronary adenosine administration using Langendorff's method. Changes in basal coronary flow prompted by intracoronary infusion of CGRP or substance P and their antagonists were measured in 54 and 30 rats, respectively. Capsaicin-treated rats showed a 31.5 +/- 0.9% (mean +/- SEM) reduction (P < .01) of basal coronary flow in the range of perfusion pressures between 60 and 140 mm Hg compared with untreated control rats, but the maximal coronary flow after adenosine was similar between the two groups. Although basal coronary flow was reduced in capsaicin-treated hearts, left ventricular contractile force and myocardial oxygen consumption did not fall significantly. CGRP increased the coronary flow, but substance P did not. CGRP(8-37), a CGRP receptor antagonist, reduced basal coronary flow by 24.5 +/- 2.1% (P < .01), but FK888, a substance P antagonist, had little effect on it. Thus, capsaicin-sensitive neuropeptides in the rat heart modulate basal coronary flow, providing approximately 30% of it.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1994

Urinary trypsin inhibitor may have a protective effect on endothelial cells in preeclampsia.

Urinary trypsin inhibitor is a glycoprotein which has an inhibitory effect on many enzymes, especially neutrophil elastase. The concentration of urinary trypsin inhibitor in serum (maternal and fetal), urine and amniotic fluid was measured in 20 cases of preeclampsia and compared with levels in normal pregnancy. Urinary trypsin inhibitor levels were significantly increased in the maternal and fetal serum of preeclamptic patients compared to normal pregnancy (p < 0.0001), as well as in urine and amniotic fluid of the same patients. Relative fluorescence release of a calcium chelating agent (fura-2) from human umbilical vein endothelial cell cultures was significantly increased by preeclamptic serum compared to serum of normal pregnant women (p < 0.03). After incubation of urinary trypsin inhibitor with the cultures, significant decrease of fura-2 release was observed (p < 0.03). Urinary trypsin inhibitor has an effect on suppression of activated neutrophils, elastase production and may have a protective effect on endothelial cells.

Adult↗

PubMed1993

Coagulation in vivo microcirculation and in vitro caused by endothelin-1.

This study was designed to elucidate the participation of endothelin-1(ET-1) in vivo and in vitro coagulation. The microvascular hemodynamic changes in terms of intravascular thrombus formation in rat mesentery induced by the superfusion of ET-1 (0.5, 1 and 2 pmol) were visualized by an intravital microscope system assisted by television-video tape recorder system. In addition to vasoconstriction we observed the blockade of circulation by clumps resembling thrombus in a dose dependent fashion by ET-1. Thrombus formation could be attenuated by pretreatment with superfusion of 3.8% Na citrate solution but not by the prior superfusion of 1 to 3 ng of nitroglycerine. Thrombus formation was found after the administration of 10 microliters of CaCl2 (100 nM) solution in Na citrate (3.8%, 20 microliters) and ET-1 treated field. In vitro study, a dose dependent increase in TAT (thrombin-antithrombin complexes) and decrease in AT III (antithrombin III) (%) activity, the prolongation of PT (prothrombin time) and APTT (activated partial thromboplastin time) was found by administering ET-1 immediately in native (unanticoagulated) blood in silicon coated test tubes (p < 0.05; n = 6). However in citrated blood, TAT complexes, AT III (%) activity, PT and APTT were not significantly changed after administration of the same doses of ET-1 (p > 0.05; n = 6). Therefore, this study suggested that endothelin-1 caused intravascular thrombosis and enhanced intra test tube coagulation which could be attenuated by blocking ionic calcium.

Animals↗

PubMed1993

Effects of percutaneous transluminal mitral valvuloplasty on plasma catecholamine levels during exercise.

Elevation of plasma catecholamine levels during exercise in patients with mitral stenosis correlated with the severity of the disease. We investigated the plasma norepinephrine changes in six patients before and after percutaneous transluminal mitral valvuloplasty (PTMV) during continuously graded ergometer exercise. Peak exercise intensity was increased from 65.8 W to 87.5 W after PTMV. Plasma norepinephrine level at 60 W workload intensity was decreased from 2308 +/- 864 pg/ml to 841 +/- 233 pg/ml after PTMV (p < 0.05). We concluded that PTMV decreased the plasma norepinephrine level during exercise in the patients with mitral stenosis. Percutaneous transluminal mitral valvuloplasty is a novel procedure for the improvement of symptoms in patients with mitral stenosis.

Adult↗

PubMed1993

Magnetic resonance imaging angiography in a case of eclampsia.

We experienced a typical case of eclampsia. After the onset of eclampsia, we performed magnetic resonance imaging angiography (MRI angiography) to estimate the function of the cerebral artery. MRI angiography showed that spasm occurred in many cerebral arteries. The spasm was still observed in some arteries 13 day after the onset of eclampsia. Vasospasm of eclampsia was clearly, easily and noninvasively confirmed in this case by MRI angiography. This observation suggests that MRI angiography is very useful and informative for diagnosis and in treatment of eclampsia.

Adult↗

PubMed1993

HELLP syndrome-like biochemical parameters obtained with endothelin-1 injections in rabbits.

We studied the effects of bolus injections and infusion of endothelin-1 (ET-1) in female rabbits by measuring serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LDH), antithrombin III (AT-III), thrombin antithrombin (TAT) complexes, platelet counts and indirect bilirubin. Two successive bolus doses of 0.125 and 0.25 nmol/kg of ET-1 with an interval of 30 min were given to conscious non-pregnant female rabbits (n = 8). GOT, GPT and LDH were found to be significantly increased after injections of ET-1 (p < 0.02, p < 0.04 and p < 0.05, respectively). The percent AT-III activity decreased significantly (p < 0.005). Vasospasm of the hepatic artery was demonstrated by angiography with the same bolus doses in rabbits. There was also an increase in GOT (p < 0.003), GTP (p < 0.05), LDH (p < 0.007), indirect bilirubin (p > 0.07) and TAT complexes (p < 0.02) and a decrease in AT-III (p < 0.03) and platelet counts (p < 0.02) in rabbits (n = 10) after 24 h of continuous infusion of ET-1 (0.6 nmol/kg/h). Histological examination of rabbit liver tissues showed varying degrees of ischemic necrosis of hepatocytes. Thus this study suggests that exogenously administered ET-1 causes vasospasm and liver ischemia resulting in HELLP syndrome-like blood parameters in rabbits.

Alanine Transaminase↗