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Biomedical subjects

H Komatsu

Publications and source records attributed to H Komatsu.

At least 91 records · Page 5Linked to original sources

GBV-C/HGV infection in children with chronic hepatitis C.

The role of GB virus-C/hepatitis G virus (GBV-C/HGV), a recently identified member of the Flaviviridae family, in children with liver disease is not well understood. The aims of this study were to evaluate the prevalence of GBV-C/HGV and to clarify its pathogenic role in young patients with chronic hepatitis C. Sixty-four Japanese children and adolescents with chronic hepatitis C virus (HCV) infection, with a mean age of 9.8 years, were evaluated retrospectively. Twenty-one (32.8%) of the 64 patients were positive for serum GBV-C/HGV RNA. Only 1 (1.6%) of the 64 patients was positive for antibody against the envelope protein E2 of GBV-C/HGV (anti-E2) and GBV-C/HGV. None of them was positive for anti-E2 alone. There was no significant difference in clinical, virological, or histological characteristics between GBV-C/HGV-positive and GBV-C/HGV-negative patients, except for underlying malignant disease. There was no evidence that GBV-C/HGV might affect the response of HCV to interferon therapy in young patients with chronic hepatitis C. The prevalence of GBV-C/HGV infection in young patients with chronic hepatitis C is similar to that in adult patients with chronic hepatitis C, but E2-seroconversion is observed infrequently. Underlying malignant disease is a risk factor for GBV-C/HGV viremia. GBV-C/HGV does not seem to affect the clinical course of young patients with chronic hepatitis C.

Adolescent↗

Study of inhibition mechanisms of glycosaminoglycans on calcium oxalate monohydrate crystals by atomic force microscopy.

Atomic force microscopy (AFM) was applied to the (-101) faces of calcium oxalate monohydrate (COM) crystals grown from calcium oxalate (CaOx) solutions. Microstructures of many spiral hillocks with step height of 1 nm were observed on the faces. Then using AFM in situ, we analysed the re-growth process of the spiral steps on the face of COM seed-crystals in CaOx growth solutions that contained growth inhibitors of glycosaminoglycans and studied their inhibition mechanisms on COM crystals. The total morphology of the faces of COM seed crystals re-grown in the CaOx growth solutions was assessed by scanning electron microscopy (SEM). In the growth solution without glycosaminoglycans (control experiment) or with chondroitin sulphate (ChS), AFM images and SEM micrographs of the faces of the re-grown seed crystals showed two-dimensional (2D) nucleation although 2D nucleation was delayed in the presence of ChS. However, the addition of dermatan sulphate (DS) to the growth solution resulted in isotropic growth by a step flow mode and spiral mechanism. With regard to the main inhibition mechanisms of two glycosaminoglycans (ChS and DS) on COM crystals, it can be concluded from these results that ChS delays 2D nucleation and DS inhibits 2D nucleation.

Calcium Oxalate↗

Treatment effects of bisphosphonates on ovariectomy-induced osteopenia in rats: comparison between clodronate and etidronate.

We studied the effects of clodronate and etidronate on bone loss induced by ovariectomy (OVX) in rats. Drug administration was initiated 8 weeks after the surgery and continued for 12 weeks (twice per week, s.c.). Lumbar (L4-L5) bone mineral density (BMD) and femoral BMD in the sham-operated group were increased to 113% and 114%, respectively, whereas those in OVX group were suppressed to 98.8% and 105%. Clodronate significantly restored the suppressed BMD over the entire dose range used (4-25 mg/kg). Etidronate restored BMD only at 4 mg/kg. In a histomorphometric analysis of lumbar vertebrae, both bisphosphonates depressed the amount of labeled surface, which was increased by OVX, to 11.9%-20.1% of the OVX group value for clodronate and to 0.23%-9.7% of the OVX group value for etidronate. The osteoid area was significantly increased by etidronate treatment over the entire dose range (OS/BS, 175%-295%). On the other hand, the osteoid area in the clodronate group did not increase at any dose tested (OS/BS, 38.1%-49.9%). Urinary excretion of deoxypyridinoline and plasma level of osteocalcin were elevated in the OVX group (162%-182% and 123%, respectively), suggesting that OVX enhanced bone turnover. Both bisphosphonates suppressed the bone turnover accelerated by OVX, and the data indicated that both bisphosphonates recovered BMD by means of inhibition of bone resorption. These data suggested that clodronate and etidronate reversed osteopenia induced by ovariectomy in rats. As judged from the dose response of BMD and histomorphometric findings, clodronate showed a wider safety margin than etidronate.

Amino Acids↗

Effects of Y-24180, a receptor antagonist to platelet-activating factor, on allergic cutaneous eosinophilia in mice.

We examined the effects of Y-24180, a potent and long-acting antagonist to platelet-activating factor (PAF), on allergic cutaneous eosinophilia and cytokine production in the skin of mice. Mice sensitized actively with ovalbumin (OA) were challenged by an intradermal injection of OA solution. The number of inflammatory cells, including eosinophils and eosinophil peroxidase (EPO) activity reflecting eosinophil infiltration into the tissue increased in OA-challenged skin 12 hr after the challenge. The levels of interleukin-4 (IL-4) and IL-5 also increased significantly in the challenged skin 12 hr and 3-24 hr, respectively, but that of interferon-gamma (IFN-gamma) did not change. Then, we evaluated the effects of Y-24180, ketotifen, suplatast and prednisolone on the increase in EPO activity, IL-4 and IL-5. These drugs were orally administered once a day for 5 days beginning 4 days before the challenge. Y-24180 (10 mg/kg) and prednisolone (5 mg/kg) significantly suppressed these parameters. Suplatast did not affect EPO activity, but significantly decreased the levels of IL-4 and IL-5. Ketotifen had no effect on them. These results indicate that the inhibition of IL-4, IL-5 and PAF are required to suppress the cutaneous eosinophilia and Y-24180 contributes to the treatment of allergic cutaneous eosinophilia.

Animals↗

Inhibition of activation of human peripheral blood eosinophils by Y-24180, an antagonist to platelet-activating factor receptor.

We examined the effects of Y-24180, a potent and long-acting antagonist to platelet-activating factor (PAF) receptor, on the PAF- or leukotriene B4 (LTB4)-induced activation of eosinophils using human peripheral blood in vitro. As activation markers, CD11b expression level and soluble intercellular adhesion molecule-1 (sICAM-1)-binding activity were analyzed by flow cytometry. Y-24180 significantly inhibited PAF-induced increase in the ratio of strongly positive cells for CD11b expression and sICAM-1 binding at 0.01 microM or more. WEB 2086, another PAF receptor antagonist, also inhibited the increase significantly at 1 microM or more. LTB4-induced increases in the ratio of strongly positive cells for CD11b expression and sICAM-1 binding were inhibited by Y-24180 at 1 microM, but not WEB 2086 up to 10 microM. These results indicate that Y-24180 inhibits the PAF- or LTB4-induced activation of eosinophils in human peripheral blood more potently than WEB 2086.

Azepines↗

Inhibition of eosinophil activation in bronchoalveolar lavage fluid from atopic asthmatics by Y-24180, an antagonist to platelet-activating factor.

We examined the effects of Y-24180, a potent and long-acting antagonist to platelet-activating factor (PAF) receptor, on the expression of adhesion molecules in peripheral blood and bronchoalveolar lavage fluid (BALF) eosinophils from atopic asthmatics. Y-24180 (20 mg/day) was administered to 4 atopic asthmatics for 8 weeks. The number of eosinophils, the level of eosinophil cationic protein (ECP), the bindings of soluble intercellular adhesion molecule-1 (sICAM-1) and fibronectin (FN), and the expressions of CD11b (alpha chain of Mac-1) and CD49d (alpha chain of VLA-4) on eosinophils were evaluated in peripheral blood (n=4) and BALF (n=3) before and after the administration of Y-24180. The infiltration of eosinophils into the bronchial wall was also examined by taking biopsies. Eosinophil count, sICAM-1 and FN binding to eosinophils in BALF significantly decreased after the administration of Y-24180 (p<0.05). The level of CD11b expression also decreased remarkably after the administration (n=2). In peripheral blood, eosinophil count and ECP level did not change. The binding of sICAM-1 and FN, and expression of CD11b on eosinophils in peripheral blood showed a tendency to decrease after the administration. The level of CD49d expression on eosinophils changed neither in BALF nor in blood. Eosinophil infiltration into the bronchial wall markedly decreased in one out of 3 cases after the administration. These results suggest that Y-24180 inhibits the activation of eosinophils by antagonizing the actions of PAF in atopic asthmatics.

Adult↗

A comparison of methods for detecting bacteria in root canal exudate.

This study compared the ability of bacterial detection from intracanal exudate by two different methods. One is a conventional method (i.e. the samples were transported into anaerobic chambers immediately after sampling and then moved to an outside laboratory for identification of bacteria). Another is a preculture method (i.e. the samples were inoculated into semisolid medium immediately after sampling, incubated for 24 h under anaerobic conditions, and then moved to the laboratory for bacterial identification). In 22 cases, the preculture method detected bacteria in 18 of 22 cases, whereas the conventional method detected bacteria in 6 of 22 cases. The preculture method showed significantly higher frequency of bacterial detection (p = 0.0003). Gram-positive cocci (alpha-Streptococcus, Enterococcus, etc.) were detected in many cases. These results suggested that the preculture method could be helpful in detecting root canal bacteria and enhance antibiotic treatment of endodontic disease.

Adult↗

Outbreak of severe neurologic involvement associated with Enterovirus 71 infection.

Enterovirus 71 has been associated with several outbreaks, as well as sporadic cases, of central nervous system infection and has a worldwide distribution. Seven children with encephalitis and five with aseptic meningitis caused by Enterovirus 71 were seen at Otsu Municipal Hospital during the summer of 1997. The infections were confirmed serologically, although detection of the viral genome in cerebrospinal fluid was unsuccessful. Seven children were diagnosed as having hand-foot-and-mouth syndrome, two were diagnosed as having herpangina, and three patients younger than 12 months old developed no eruptions. The skin or mucosal manifestations of this outbreak demonstrated considerable variation. The Enterovirus 71 strain that caused the outbreak had a strong neurovirulent tendency. Among the patients with encephalitis, symptoms originating from the impairment of diencephalon were seen in four patients, and those originating from cerebellar impairment were seen in two patients. Brain magnetic resonance imaging in one patient revealed an abnormality in the pons. The neurologic manifestations associated with Enterovirus 71 infection may be characterized by involvement of the cerebellum, brainstem, and diencephalon. Enterovirus 71 is one of the pathogenic viruses that cause hand-foot-and-mouth syndrome, as well as a variety of other clinical manifestations. The most important of these is neurologic disease, especially in infants and young children.

Antibodies, Viral↗

Severe late acute allograft rejection in a child after living-related auxiliary partial orthotopic liver transplantation for ornithine transcarbamylase deficiency.

Auxiliary liver transplantation (ALT) is known to correct liver-based metabolic disorders. However, it remains unclear whether the presence of a native liver influences the long-term prognosis of ALT for metabolic diseases. We reported on a 4-yr-old girl who had undergone living-related auxiliary partial orthotopic liver transplantation (APOLT) for ornithine transcarbamylase deficiency and experienced severe late acute rejection 18 months after liver transplantation, during weaning of immunosuppressive agents. Results of histological analysis of the graft indicated very severe acute rejection (rejection activity index, 9/9), and computed tomography revealed graft liver atrophy. These observations suggest the possibility that severe rejection might occur in APOLT, especially during weaning of immunosuppression.

Acute Disease↗

Selective usage of D-type cyclins in lymphoid malignancies.

Three D-type cyclins, cyclin D1, D2 and D3, belong to the G1 cyclin, which regulates the G1/S transition of the cell cycle, and feature highly homologous amino acid sequences. The cyclin D1 gene was found to be transcriptionally activated in B-lymphoid malignancies with t(11;14), but available information is limited regarding expression of cyclin D2 and D3 in hematopoietic malignancies. We examined the expressions of three D-type cyclins to investigate how these homologous genes are differentially used. Northern blot hybridization with densitometric analyses was performed to examine 64 cell lines and 159 patients with various hematopoietic malignancies. Among lymphoid malignancies, cyclin D1 overexpression was exclusively detected in B cell malignancies accompanied by a genetic event consisting of 11q13 chromosomal translocation, consisting of 13 of 19 (68%) patients with mantle cell lymphoma, two of 11 (18%) with B-chronic lymphocytic leukemia, and one of six (17%) with multiple myeloma. The cyclin D2 expression was significantly higher in T cell malignancies than in B cell malignancies (P = 0.003 for cell lines and P < 0.0001 for patient samples, respectively). In the T cell malignancies, cyclin D2 overexpression was predominantly recognized in those with mature phenotype. Furthermore, cyclin D2 expression was upregulated by phytohemagglutinin (PHA) stimulation of normal T-lymphocytes, suggesting that this simply represents the proliferation status of mature T cells. Although cyclin D3 was ubiquitously expressed, its expression was reduced in lymphoid malignancies with cyclin D1 or D2 overexpression. In myeloid leukemias, although three D-type type cyclins were differentially expressed, no preference for particular D-type cyclins was found. This selective usage of D-type cyclins in lymphoid malignancies suggests an existence of a regulatory mechanism among three D-type cyclins.

Cell Lineage↗

Mycobacterium avium infection of the skin associated with lichen scrofulosorum: report of three cases.

We report three Japanese children with Mycobacterium avium infection of the skin who also developed lichen scrofulosorum, a previously undescribed association. They were healthy except for the presence of several noduloulcerative lesions associated with multiple asymptomatic papules on the trunk and extremities. Histology of the ulcerative lesions showed features of mixed-cell granuloma, whereas the papular lesions showed features consistent with lichen scrofulosorum. M. avium was identified by polymerase chain reaction-aided DNA-DNA hybridization analysis in specimens obtained from the noduloulcerative lesions. Both the noduloulcerative and the papular lesions responded well to combination chemotherapy consisting of antituberculous agents and antibiotics.

Anti-Bacterial Agents↗

Hepatitis B precore mutant in children with chronic hepatitis B virus infection.

BACKGROUND: In adults, hepatitis B virus (HBV) with a G to A point mutation at nucleotide 83 in the precore region (mutant HBV 83), is commonly found in HB e antibody positive HBV carriers. It has been reported that this mutant is not able to produce HB e antigen. The exact prevalence of mutant HBV 83 in patients with chronic HBV infection is not fully understood, especially in children. METHODS: To investigate the role of mutant HBV 83 in children with chronic HBV infection, sera were tested for the presence of mutant HBV 83 using a mutation site-specific assay. RESULTS: Mutant HBV 83 was detected in 15 of 22 children (68%). Seven children were followed longitudinally, of which three were asymptomatic carriers and the other four had chronic hepatitis B on entry. There was no clear relationship between the disease activity and the presence of mutant HBV 83. CONCLUSIONS: It was concluded that mutant HBV 83 is commonly present in children with chronic HBV infection and this mutant is not necessarily associated with activation of hepatitis.

Adolescent↗

Antianginal effects of ranolazine in various experimental models of angina.

The effects of ranolazine (CAS 95635-55-5, KEG-1295), a novel antianginal drug, on the ST-segment changes induced by coronary ligation, epinephrine, and vasopressin were examined following oral or intraduodenal administration. In anesthetized dogs, intraduodenal administration of KEG-1295 (10, 30, or 50 mg/kg) or atenolol (10 mg/kg) significantly attenuated the ST-T wave elevation induced by 2-min coronary ligation imposed during electrical heart pacing (200 beats/min). This antianginal effect of KEG-1295 persisted for 3 h without any changes in hemodynamic parameters, while that of atenolol was accompanied by more or less maintained decreases in diastolic blood pressure, heart rate, and the maximum first derivative of left ventricular pressure. In anesthetized rats, oral administration of KEG-1295 (10, 30, or 50 mg/kg) attenuated the ST-T wave elevation induced by epinephrine (0.3 microgram/kg i.v.) in a dose-dependent manner, although KEG-1295 (10 or 30 mg/kg p.o.) failed to attenuate the ST-segment depression induced by vasopressin (0.2 IU/kg i.v.). These findings suggest that, taken orally, KEG-1295 may exert potent protective effects against angina pectoris, except that caused by vasospasm. Further, KEG-1295 may be categorized as a new type of antianginal agent, without any primary hemodynamic effects.

Acetanilides↗

Structure and enzymatic properties of genetically truncated forms of the water-insoluble glucan-synthesizing glucosyltransferase from Streptococcus sobrinus.

Glucosyltransferase-I (GTF-I: 175 kDa) of a cariogenic bacterium, Streptococcus sobrinus 6715, mediates the conversion of water-soluble dextran (alpha-1,6-glucan) into a water-insoluble form by making numerous alpha-1,3-glucan branches along the dextran chains with sucrose as the glucosyl donor. The structures and catalytic properties were compared for two GTF-I fragments, GTF-I' (138 kDa) and GS (110 kDa). Both lack the N-terminal 84 residues of GTF-I. While GTF-I' still contains four of the six C-terminal repeats characteristic of streptococcal glucosyltransferases, GS lacks all of them. Electron microscopy of negatively stained samples indicated a double-domain structure for GTF-I', consisting of a spherical head with a smaller spherical tail, which was occasionally seen as a long extension. GS was seen just as the head portion of GTF-I'. In the absence of dextran, both fragments simply hydrolyzed sucrose with similar K(m) and k(cat) values at low concentrations (<5 mM). At higher sucrose concentrations (>10 mM), however, GTF-I' exhibited glucosyl transfer activity to form insoluble alpha-1, 3-glucans. So did GS, but less efficiently. Dextran increased the rate and efficiency of the glucosyl transfer by GTF-I'. On removal of the C-terminal repeats of GTF-I' by mild trypsin treatment, this dextran-stimulated transfer was completely lost and the dextran-independent transfer became less efficient. These results indicate that the N-terminal two-thirds of the GTF-I sequence are organized as a structurally and functionally independent domain to catalyze not only sucrose hydrolysis but also glucosyl transfer to form alpha-1,3-glucan chains, although not efficiently; the C-terminal repeat increases the efficiency of the intrinsic glucosyl transfer by the N-terminal domain as well as rendering the whole molecule primer-dependent for far more efficient insoluble glucan synthesis.

Bacterial Proteins↗

Acute cerebellar ataxia with human parvovirus B19 infection.

A 2 year old boy developed acute cerebellar ataxia in association with erythema infectiosum. During the disease, genomic DNA and antibodies against human parvovirus B19 were detected in serum but not in cerebrospinal fluid. Parvovirus B19 associated acute cerebellar ataxia might occur due to transient vascular reaction in the cerebellum during infection.

Acute Disease↗

Fibromuscular dysplasia involving coronary arteries--a case report.

The authors report a young patient with fibromuscular dysplasia involving multivessels including coronary arteries. If young patients have chest pain on effort, fibromuscular dysplasia of coronary arteries must be considered. As fibromuscular dysplasia is a chronic progressive disease and some cases progress rapidly in a few months, careful follow-up and comprehensive medical management may be necessary in such patients.

Adult↗