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Biomedical subjects

Y Kajiwara

Publications and source records attributed to Y Kajiwara.

At least 37 records · Page 2Linked to original sources

Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan.

Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.

Adolescent↗

Hypolumbarlordosis: a predisposing factor for preeclampsia.

OBJECTIVE: The aim of this research was to study the relationship between lumbar lordosis and preeclampsia. STUDY DESIGN: We studied lumbar lordosis of 52 primipara patients with pregnancy-induced hypertension and 59 normal primipara pregnant women. We determined the lumbar lordotic deviation (LLD) from lumbar lordosis measurement device in the lateral recumbent position and standing position. Roll-over test was performed for both groups. Resistance index (RI) of internal iliac artery was also measured by color Doppler sonography. RESULTS: The LLD was 33 +/- 6.1 degrees week 20-29 and 34 +/- 6.9 degrees week 30-40, respectively. In patients with preeclampsia, the LLD was 19.8 +/- 6.3 degrees week 20-29, 21.3 +/- 7.9 degrees week 30-40. The LLD in patients with preeclampsia was significantly lower than in the normal pregnant women. The LLD correlated to the increase diastolic pressure after roll-over test significantly. Hypolumbarlordosis was frequently associated with high resistance of peripheral vessel. CONCLUSIONS: We conclude that hypolumbarlordosis is frequently associated with preeclampsia. It is also closely related to the mechanism for positive roll-over test and increase of resistance of vessels. As lumbar lordosis does not change greatly in individuals before pregnancy, hypolumbarlordosis may be a predisposing factor for preeclampsia.

Adult↗

[Mutagenicity studies of (+/-)-4-diethylamino-1,1,-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a novel drug for urinary frequency and incontinence].

The mutagenicity of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was investigated by the reverse mutation test in bacteria, the chromosome aberration test in vitro, and the micronucleus test in mice. The reverse mutation test was performed at a dose from 31.3 to 4000 micrograms/plate, at which dose cell killing was observed, using Salmonella typhimurium TA100, TA1535, TA98, and TA1537, and Escherichia coli WP2uvrA. NS-21 did not increase revertant colonies significantly in any of the test strains with or without metabolic activation system (S9 mix). The chromosome aberration test was carried out at a dose from 3.75 to 140 micrograms/ml, at which dose more than 50% cell proliferation was inhibited, using cultured Chinese hamster lung cells (CHL/IU). No significant increases of the frequencies of cells with chromosome aberrations were observed with or without S9 mix. The micronucleus test was conducted in the bone marrow cells of Slc : ddY male mice. Mice were given NS-21 by a single oral administration at doses of 0, 43.8, 87.5, 175, and 350 mg/kg, the geometric mean dose between the maximum tolerated dose and the minimum lethal dose. There were no significant increases in the frequencies of micronucleated polychromatic erythrocytes at any dose levels. These results show that NS-21 has no mutagenic activity in vitro or in vivo.

Animals↗

[A case of infected subdural hematoma complicating chronic subdural hematoma in a healthy adult man].

The authors report a case of so-called "infected subdural hematoma" as a complication of chronic subdural hematoma. The patient was a 55-year-old man who had sustained a small laceration of the forehead in a traffic accident on March 29, 1995. No fractures were detected on skull roentgenograms, and general and neurological examinations failed to reveal any abnormal findings. In early August 1995, the patient began to experience headaches, and on August 5 he developed a fever of 38 degrees C. On August 8 he suffered a left motor seizure and was admitted to our hospital. Laboratory studies revealed a peripheral leukocyte count of 10,800/mm3 and a C-reactive protein level of 18.1 mg/dl. Computed tomography scans showed a thick right fronto-parietal subdural low density mass and a thin left frontal subdural low density mass. An emergency operation was performed via a single right fronto-parietal burr hole. A chronic subdural hematoma containing slightly yellowish, bloody, purulent fluid was found beneath an outer membrane. The hematoma was irrigated with physiological saline containing antibiotics, and a drain was inserted into the subdural space. A subdural membrane was also present on the left but it contained no pus. Aggressive antibiotic therapy was performed, and the patient was discharged without any neurological deficit. Histologically the membrane was determined to be the outer membrane of a typical chronic subdural hematoma. Enterococcus faecalis, which has rarely been reported to cause infection of the central nervous system, was detected in a bacterial culture of the pus. Systemic investigation showed no evidence of otorhinologic or other focal infection. The above clinical findings suggested that hematogenous seeding of a chronic subdural hematoma had occurred in this patient. Subdural empyema arising from hematogenous seeding to a pre-existing subdural hematoma by an infection is very rare, but this type of complication must be kept in mind not only in the elderly, infants, and compromised hosts, but in patients without complications as well.

Chronic Disease↗

Methylmercury transport across the placenta via neutral amino acid carrier.

Methylmercury (MeHg) penetrates the placental barrier to affect developing fetuses in the uterus. However, the mechanism of placental MeHg transport is not well defined. To clarify the MeHg transport system that functions in the placenta, pregnant rats were intravenously administered MeHg on day 18 of gestation. The fetal blood was collected from the umbilical cord at 30 and 60 min after the administration, and its mercury concentration was measured. MeHg was found to be rapidly transported to the fetal blood in a time- and dose-dependent manner, and predominantly distributed in the blood cells there. MeHg transport was effectively suppressed by the co-injection of neutral amino acids, i.e., L-methionine and L-phenylalanine, suggesting that MeHg is actively transported as its cysteine conjugate via the neutral amino acid carrier system. The suppression by methionine was not so marked as by phenylalanine. Since methionine administration caused a rapid increase of the cysteine, which functioned as a predominant carrier in MeHg transport, in the maternal plasma, newly synthesized cysteine seemed to accelerate the mercury uptake. Accordingly, the acceleration by the extra cysteine would compensate partly the competitive effect of methionine as a neutral amino acid.

Amino Acid Transport Systems↗

Ultrastructural observations of lymphatic vessels in lymphedema in human extremities.

Microsurgical lymphaticovenous anastomoses were done on a total of 14 patients. Six upper extremities of six female patients (average age 56.5 years) were operated on with lymphaticovenous anastomoses and were followed up for 17 months or more after surgery (average 25.5 months). Twelve legs of eight patients (average age 44.6 years) also were operated on and followed up for 12 months or more after surgery (average 23.4 months). Among these patients, 33 biopsied lymphatic trunks with lymphedema in 16 extremities of 12 patients were evaluated histologically by light and electron microscopy. Regarding the operative effect in the arms, the decreased circumference of the arms ranged from 2 to 9 cm (average 5.3 cm). The rate of preoperative versus postoperative excess circumference decreased in range from 25 to 94.7 percent (average 65.7 percent). As for the surgical effect in the legs, half the legs showed improvement. These postoperative improvements showed no correlation with the preoperative duration of edema and excess circumference in either the upper or lower extremities. Histologically, in the initial stage of lymphedema, there was destruction of both endothelial cells and smooth muscle cells in the proximal level of the lymphatic trunks. The lumen of some proximal trunks was then occluded by organization with a few small recanalizations, but the distal lymphatics remained patent with minimal destruction of both the endothelial cells and the smooth muscle cells even in the later stage of lymphedema. These results suggest that the occlusions of the lymphatic trunks and degeneration of the smooth muscle cells may start from the proximal ends of the extremities and that the timing of the occlusions and the degeneration of smooth muscle cells may not correspond to the duration of edema. It is also considered that because of the smooth muscle degeneration, the lymph-drainage capacity of the lymphatic trunks may be remarkably weakened in the proximal lymphatics of the extremities. Therefore, it is suggested that the remaining lymphatic drainage function with the smooth muscle cells may correlate with the postoperative improvement of edema. It is also suggested that the preoperative ultrastructural examination of the lymph-drainage capacity may be a suitable method for predicting the surgical effect and operative indication for lymphatic edema in the extremities.

Adult↗

[Adult-onset aqueductal stenosis caused by membranous occlusion in the aqueduct: a case report].

The authors report a case of adult-onset aqueductal stenosis caused by membranous occlusion of the aqueduct. The patient was a 35-year-old man, who suffered from progressive headache. On admission, computed tomography (CT) scan showed marked dilatations of the lateral and third ventricles. Midsagittal T1-weighted magnetic resonance imaging (MRI) scan showed a membranous occlusion at the lower end of the aqueduct, with dilatation of the proximal aqueduct and elevation of the tectum. Midsagittal cine-MRI demonstrated the cerebrospinal fluid flow in the aqueduct. The patient was diagnosed as having hydrocephalus resulting from membranous stenosis of the aqueduct by MRI. A ventriculo-peritoneal shunt operation was performed and his symptoms improved markedly. The membranous occlusion of the aqueduct is a rare cause of hydrocephalus. The etiology and therapy of aqueductal stenosis are discussed.

Adult↗

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↗

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↗

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↗

Suppression of ischemia-reperfusion injury in murine models by neopterins.

We investigated the effects of D-neopterin (NP) and its reduced form, 5,6,7,8-tetrahydro-D-neopterin (NPH4), in two models of ischemia-reperfusion injury, i.e., ischemic paw edema in mice and gastric ischemia in rats. In ischemic paw edema, iv administration of either NP or NPH4 more potently inhibited the increase of paw thickness after release from ischemia than did administration of superoxide dismutase plus catalase or allopurinol. In gastric ischemia, NP and NPH4 also significantly suppressed the formation of gastric mucosal erosions. Lipid peroxidation in the stomach was increased by ischemia-reperfusion treatment, and the increase was inhibited by the administration of NP or NPH4. The minimum dose of NPH4 required to suppress the gastric ischemic injury in this experiment was 0.3 mg/kg of body weight. These results suggest that neopterin may be effective as a protective agent against ischemia-reperfusion injury, in which active oxygen species are believed to play a major role.

Allopurinol↗

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↗

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↗

Effect of 5,6,7,8-tetrahydroneopterin on the bovine endothelial cell injury induced by cumene hydroperoxide.

Neopterin is an 2-amino-4-hydroxypteridine derivative and a precursor of biopterin, which is derived from guanosine triphosphate. Previously, we have reported that 5,6,7,8-tetrahydroneopterin (NPH4), a reduced form of neopterin, possesses an antioxidant activity in various systems. In this study, we investigated the activity in more detailed manner and discussed the possible applications of this antioxidant. Analysis by electron spin resonance spectrometry indicated that NPH4 scavenged superoxide anion radicals and hydroxyl radicals as well. Moreover, NPH4 protected the rat brain homogenate from autoxidation. Next, we examined the effect of NPH4 on the cell injury induced by cumene hydroperoxide (CHP) in cultured bovine artery endothelial cells. The activity of lactate dehydrogenase, a marker enzyme of cell injury, was elevated by CHP in a dose-dependent manner, and this elevation was dose-dependently suppressed by NPH4. The elevation of lipid peroxide content was also inhibited by NPH4 in the same fashion. These data suggest that NPH4 would be effective against various diseases whose pathogenesis is active oxygen-related.

Animals↗

Effect of aspirin and iloprost on adhesion of platelets to intact endothelium in vivo.

Aspirin has been used for the prevention of platelet thrombi, both prophylactically and therapeutically, in a wide variety of conditions. Although the dosage used has also varied, it is now suggested that lower doses are as efficacious and probably safer than higher doses. Part of the problem in determining the amount to be used is that aspirin not only inhibits the formation of the proaggregatory thromboxane A2 in the platelet, at any dose, but also that it interferes with the production of prostacyclin (antiaggregatory) by the endothelial cells in a dose-dependent manner. Previously, utilizing a hamster cheek pouch preparation, we demonstrated that platelets would adhere to intact endothelium, in vivo, after an otherwise ineffectual dose of thrombin if the glycosaminoglycans of endothelial cells that produce antithrombin activity were first neutralized by protamine. Reported here is the effect of aspirin on the platelet thrombi produced by thrombin in this manner. Aspirin was found to inhibit platelet thrombosis by thrombin in low doses (optimum dose 2.5 mg/kg body weight), but at higher doses the aspirin was less effective. Actually, the higher doses of aspirin promoted platelet thrombus formation by thrombin even in the absence of protamine. Infusion of iloprost, an analog of prostacyclin, also prevented platelet thrombus formation by protamine and thrombin with or without the administration of aspirin, and this infusion overcame the thrombogenicity of the higher doses of aspirin. The results of these experiments in the hamster suggest that the optimum dosage of aspirin in the clinical treatment of prophylaxis of thrombosis in human patients would be 160 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗