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Biomedical subjects

T Kurashige

Publications and source records attributed to T Kurashige.

At least 91 records · Page 5Linked to original sources

The evidence of human herpesvirus 6 infection in the lymph nodes of Hodgkin's disease.

Human herpesvirus 6 (HHV-6), the causative agent of exanthem subitum, has been implicated in other diseases. Recently HHV-6-specific sequences have been detected by Southern blot analysis and polymerase chain reaction in the lymph nodes of three patients with Hodgkin's disease. The pathological localization of HHV-6, however, is still unknown. In order to study the pathological role of HHV-6 in Hodgkin's disease, we investigated, by immunohistochemical and molecular methods, two lymph node biopsies taken from a 7-year-old boy with Hodgkin's disease during the course of disease evolution. Although the histopathological findings of the first biopsy differed from those of the second, HHV-6 antigens and sequences could be detected in both lymph nodes by immunohistochemistry and in situ hybridization, respectively. HHV-6 was localized in macrophages, predominantly in lymphoid follicles, but not in Reed-Sternberg cells. Antibody titres to HHV-6 were consistent with reactivation of latency. Neither cytomegalovirus nor Epstein-Barr virus was present. Our data suggest a role for HHV-6 in the pathogenesis of Hodgkin's disease.

Antibodies, Viral↗

Defective activity of Epstein-Barr virus (EBV) specific cytotoxic T lymphocytes in children with chronic active EBV infection and in their parents.

Antibodies of Epstein-Barr virus (EBV), EBV-specific cytotoxic T lymphocyte (EBVCTL) activity and the lymphocyte subset of CTL were examined in 13 Japanese children with chronic active EBV infection (CAEBV) and their parents (eight fathers and 10 mothers). Anti-virus-capsid antigen (VCA)-IgG antibody titers ranged from 1:640 to 1:5120 in the patients with CAEBV and from 1:40 to 1:640 in the parents. While anti-VCA-IgM antibody was detected in three patients, anti-VCA-IgA antibody in five and anti-early-antigen (EA)-IgG antibody in 11, no antibody was detected in the parents except anti-EA antibody, which was positive in the mothers of cases 5 and 13 (1:10 and 1:40). Anti-EBV-associated nuclear antigen (EBNA) antibody was < or = 1:10 in six out of 13 patients with CAEBV and in 10 out of 18 parents tested. Epstein-Barr virus activity was significantly lower (P < 0.005) both in the children with CAEBV and in their parents than in seropositive age-matched controls. Proportions of a CTL subset (CD8+ CD11- lymphocytes) in the patients with CAEBV were significantly higher (P < 0.005) than in controls, while those in the parents were at the same level as in controls. Defective EBVCTL activity and anti-EBNA-antibody responses were frequently observed both in children with CAEBV and in their parents, which may suggest that the abnormal immune response to EBV may be based on a familial disorder, though no familial involvement has been reported in Japanese children with CAEBV.

Adolescent↗

[Pharmacological studies on small peptide fraction derived from soybean. The effects of small peptide fraction derived from soybean on fatigue, obesity and glycemia in mice].

The present research was an attempt to determine the pharmacological actions as for anti-fatigue, anti-obesity and hypoglycemia of small peptide isolated from soybean in mice. Small peptide administration prevented the decrease in sporting movement induced by concussion stress for 3 h in mice. In addition, it should be noted that the recovery rate of fatigue in 60 min after small peptide administration was over one hundred percentage in comparison with that after pretreatment, while the equivalent dose administration of amino acid mixture with the same small peptide amino acid composition did not prevent the decrease in sporting movement. In gold-thioglucose (500 mg/kg (i.p.))-induced obese mouse body weight gain, liver weight and body lipid level around uterine were significantly reduced by the chronic oral administration of small peptide (200, 1000 mg/kg). Administration in 1000 mg per kg of small peptide significantly lowered hyperglycemia in 30 and 120 min after glucose (3 g/kg (p.o.)) administration, whereas the equivalent amino acid mixture showed no effect. In conclusion, it suggested that small peptide isolated from soybean might have some pharmacological effects of anti-fatigue, anti-obesity, and hypoglycemia.

Animals↗

Effect of indomethacin and aspirin on the TNF-alpha-induced priming and protein tyrosyl phosphorylation of human neutrophils.

Receptor-mediated superoxide (O2-.)-generation in human peripheral neutrophils (HPPMN) is enhanced by various priming agents, such as granulocyte colony stimulating factor (G-CSF) and tumor necrosis factor (TNF-alpha). We previously reported that this enhancement occurred in parallel with the priming agent-induced increase in protein tyrosyl phosphorylation which is sensitive to tyrosine kinase (TK) inhibitors [Akimaru K. et al. Arch. Biochem. Biophys. 298:703, 1992]. We describe here that nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and aspirin, modulate the priming and tyrosine phosphorylation of HPPMN. The enhancement by TNF-alpha of formylmethionyl-leucyl-phenylalanine (FMLP)-induced O2-. generation was not inhibited by 5 microM azide, whereas that of FMLP-induced luminol chemiluminescence (LCL) was sensitive. Enhancement of FMLP-induced O2-. generation and LCL by priming agents was inhibited by both aspirin and indomethacin in a concentration dependent manner. This inhibition by the NSAIDs was much stronger than that for FMLP-induced O2-. generation without priming. The half-inhibition dose of indomethacin and aspirin were 50 microM and 1.5 mM, respectively. The priming-induced enhancement of tyrosyl phosphorylation of some neutrophil proteins, such as that of 108 and 115 kDa, was also inhibited by aspirin and indomethacin in a dose-dependent manner. However, dose dependent inhibition of the enhanced O2-. generation by the NSAIDs was not completely similar to that of enhanced tyrosyl phosphorylation. However, PKC-mediated O2-. generation, which has little sensitivity to TNF-alpha or G-CSF, was rather stimulated by the NSAIDs. These findings suggest that aspirin and indomethacin inhibit also the early steps of neutrophil activation as reflected by their ability to inhibit priming and the related tyrosyl phosphorylation of neutrophil proteins.

Animals↗

[Clinical studies of S-1108 fine granules in pediatrics].

We have evaluated S-1108 fine granules for therapeutic effectiveness in children. The results are summarized as follows. 1. A clinical study was performed with 16 children with infections, including 8 with acute tonsillitis, 3 with acute pharyngitis, 2 with scarlet fever, 1 each with acute bronchitis, pertussis and urinary tract infection. Doses ranging from 8.8 to 10.6 mg/kg body weights were given in 3 divided portions. Durations of treatment ranged from 2 to 15 days. The therapeutic responses were considered "excellent" in 1 and "good" in 13, with an efficacy rate of 87.5%, and the bacteriological eradication rate was 91%. 2. No adverse reactions were observed. In laboratory tests, eosinophilia was observed in one patient. It was concluded the S-1108 was promising drug for the treatment of bacterial infections in children.

Administration, Oral↗

[The usefulness and limitations of the radioallergosorbent test in diagnosing food allergy in atopic dermatitis].

To clarify the diagnostic value of the radioallergosorbent test (RAST), the relationship between RAST and the oral food challenge test was evaluated. 263 children with atopic dermatitis were challenged by egg, cow's milk or soy bean after their skin manifestations had been improved by elimination diet and environmental control. Of 200 cases with negative RAST results for egg white, 108 cases (54.0%) showed no reaction in egg challenge tests. However, 65 cases (31.5%) had non-immediate reactions, while 29 cases (14.5%) had immediate reactions (within 2 hours of challenge). Of 16 cases with RAST score of 1 for egg white, 11 cases (68.8%) had non-immediate reactions and 2 cases (12.5%) had immediate reactions in egg challenge tests. Of 19 cases with RAST scores of 2 for egg white, 2 cases (10.5%) had no reaction, 6 cases (31.6%) had non-immediate reactions and 11 cases (57.9%) had immediate reactions in egg challenge tests. Of 21 cases with RAST scores of 3 for egg white, 1 case (4.8%) had no reaction, 3 cases (14.3%) had non-immediate reactions and 17 cases (81.0%) had immediate reactions in egg challenge tests. All 7 cases with RAST scores of 4 for egg white had immediate reactions in egg challenge tests. Almost the same relationship between RAST and challenge tests were found in test using cow's milk or soy bean. In conclusion, false negative results were seen in 46.0% of RAST for egg white, 51.7% of RAST for cow's milk and 26.9% of RAST for soy bean.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Identical twins with atypical benign partial epilepsy].

Female identical twins with atypical absence in waking state and partial seizures in sleep state were reported. During atypical absence the EEGs of both cases showed bursts in bilateral parietal and temporal regions during waking state and almost continuous diffuse spike-waves during sleep. Phenytoin was effective to discontinue the seizures in both cases. These findings were compatible to atypical benign partial epilepsy first reported by Aicardi et al. A possibility of genetic cause of this disorder may be considered.

Child↗

Inhibition of interferon-gamma- and phorbol ester-induced HLA-DR and interleukin-1 production by the expression of a transfected poly(ADP-ribose) synthetase gene in human leukemia THP-1 cells.

We have examined a correlation between an expression level of poly(ADP-ribose) synthetase gene and the stage of monocytic differentiation. We selected three human leukemia cell lines, U937, THP-1, and J111, whose differentiation stage was characterized by nitroblue tetrazolium reduction activity, non-specific esterase activity, phagocytic activity and a cell surface marker. Enzyme activity and mRNA level of the synthetase decreased in accompaniment with the progress of monocytic differentiation. When THP-1 cells were treated with either interferon-gamma or phorbol ester, mRNA level of the synthetase decreased and HLA-DR or interleukin-1 was induced, respectively. We transfected expression plasmid of the exogenous synthetase gene to examine whether the down-regulation of the synthetase is a necessary step to induce these proteins. An expression of the exogenous synthetase gene inhibited the interferon-gamma- and phorbol ester-dependent induction of HLA-DR and interleukin-1. The results suggest that down-regulation of the synthetase may be a signal mediator of immunological response such as HLA-DR or interleukin-1 production in monocytes.

Cell Differentiation↗

Experimental study on Reye's syndrome: inhibitory effect of interferon alfa on acetylsalicylate-induced injury to rat liver mitochondria.

Viral infection and acetylsalicylate (ASA)-induced mitochondrial aberration have been reported to play important roles in the pathogenesis of Reye's syndrome. We report that increasing amounts of ASA (0 to 250 mumol/L) resulted in increases in state 4 respiration and decreases in state 3 respiration in rat liver mitochondria in vitro when using alpha-ketoglutarate and/or beta-hydroxybutyrate as respiratory substrates, but not when using succinate as substrate. Interferon alfa (IFN-alpha) (1.5 to 5 x 10(4)IU/mL, approximately 1/100 the therapeutic dosage for humans) and interleukin-1 (IL-1) (1.5 to 2 x 10(4)IU/mL, nearly equivalent to the therapeutic dosage) decreased the severity of the above effects via interaction with mitochondrial membranes. Interferon gamma (IFN-gamma) and interleukin-2 (IL-2) had no such protective effect. Electron microscopic observation indicated that IFN-alpha prevented the induction of mitochondrial swelling by ASA. These results suggest that IFN-alpha may prove to be effective for the treatment of Reye's syndrome.

Animals↗

The longevity of the immune response to filamentous hemagglutinin and pertussis toxin in patients with pertussis in a semiclosed community.

Titers of antibodies to the filamentous hemagglutinin (FHA) and pertussis toxin (PT) of Bordetella pertussis were studied in patients from a semiclosed community after an outbreak of the disease in 1985 and in the general population. In convalescent-phase serum obtained after B. pertussis infection in patients in the semiclosed community, high anti-FHA IgG and anti-PT IgG titers were observed; these titers tended to disappear over the next 5 years. On the other hand, among the medical staff, high anti-FHA and anti-PT IgG titers persisted during the same 5-year period. It seems likely that anti-FHA and anti-PT IgG levels reflect the frequency of exposure to the bacteria and that B. pertussis is widespread in the Japanese population. Although the anti-FHA IgG antibody response decreased in patients from the semiclosed community, the cellular immune response was maintained.

Adult↗

IgG subclass imbalance in children with acute lymphoblastic leukemia receiving maintenance chemotherapy.

Serum levels of IgG subclasses were measured in 18 children with acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy and in 36 age-matched controls in order to attempt to analyse the effects of chemotherapy. The IgG subclasses were measured by enzyme linked immunosorbent assay. Serum IgG1, IgG2 and IgG4 levels in the patients were significantly (p less than 0.01, p less than 0.005, p less than 0.005) lower than in the controls, but serum IgG3 levels in patients were as high as in controls. Suppression on IgG2 and IgG4 were more profound than IgG1. In six children, the levels of the IgG subclasses were measured at diagnosis, during maintenance chemotherapy and one year after cessation of chemotherapy. The levels of the four IgG subclasses at diagnosis and after cessation of chemotherapy were as high as those in control children except for the IgG4 levels in the post-chemotherapy group. IgG2 and IgG4 may be more susceptible to suppression by chemotherapy than IgG1 and IgG3 may not be suppressed by chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

[Therapeutic effects of cefprozil in the treatment of various infectious diseases in children].

Therapeutic effects of cefprozil (CFPZ, BMY-28100), a new cephalosporin, were examined in various infectious diseases in children. Clinical efficacy rates were 50% (2/4) in acute bronchitis, 80% (4/5) in pharyngitis, 0% in laryngitis, 100% (7/7) in tonsillitis, 100% (8/8) in impetigo contagiosa, furuncle and posthitis. Hence, the overall efficacy rate was 84% (21/25). Adverse effects were observed in 1 case with slightly elevated serum GOT and GPT. Changes in serum concentrations and urinary excretion of CFPZ were examined in 4 and 2 children without infection, respectively. T 1/2 values obtained were between 1 hour to 2 hours (bioassay). Six hour recovery rates in urine were 51.8% and 77.8% (bioassay). CFPZ was considered to be a safe and useful drug in treating various infectious diseases in children.

Administration, Oral↗

Stimulatory effect of interleukin-1 beta on the interferon-gamma-dependent HLA-DR production.

Expression of major histocompatibility complex (MHC) class II genes is induced by interferon-gamma (IFN-gamma) in antigen-presenting cells. When human leukaemia THP-1 and PL-21 cells were pretreated with phorbol ester, IFN-gamma-dependent induction of MHC class II gene was markedly enhanced. To elucidate the mechanism of the phenomenon, we examined the effect of cytokines which were secreted from THP-1 cells by the treatment of phorbol ester. Among those cytokines, interleukin-1 beta (IL-1 beta) had a positive effect on IFN-gamma-dependent induction of MHC class II genes. In order to rule out the possibility that different clones of THP-1 cells respond independently to IFN-gamma or phorbol ester, we showed that all independent single clones expressed MHC class II and produced IL-1 beta by IFN-gamma or phorbol ester, respectively.

Culture Media↗

[Wyburn-Mason syndrome--a case report].

A 5-year-old girl with Wyburn-Mason syndrome was reported. A vascular nevus on the right cheek was noticed since early infancy. External strabismus and impaired vision of the right eye were noticed at 5 years of age. Fluorescein angiography showed an arteriovenous malformation on the right retina. Brain CT, MR, and right carotid angiography demonstrated an arteriovenous malformation from the orbita to the hypothalamic region along the optic nerve. This congenital vascular disorder is extremely rare.

Child, Preschool↗

Fluctuation of gene expression for poly(ADP-ribose) synthetase during hemin-induced erythroid differentiation of human leukemia K562 cells and its reversion process.

We have studied the regulation of gene expression for poly(ADP-ribose) synthetase during erythroid differentiation and its reversion process. When human leukemia K562 cells were incubated in the presence of 80 microM hemin, benzidine-positive cells appeared at day 2 and 90% of the cells became positive at day 6. However, RNA blot analysis reveals that mRNA for gamma-globin was already abundant in untreated K562 cells and the level of the message was slightly increased by hemin-treatment. Spectroscopic analysis and polyacrylamide gel electrophoresis of the induced cell extracts indicate that hemoglobin molecules were not detected in untreated cells, and increased successively up to day 6. The hemin-induced cells were thoroughly washed, and then recultured in the absence of hemin. The benzidine-positive cells mostly disappeared 3 days after the elimination of the inducer. During the hemin-induced erythroid differentiation, the activity and mRNA for poly(ADP-ribose) synthetase decreased to 50% and 20% of the initial level at day 3 and a low level of the gene expression was maintained afterwards, whereas the activity and mRNA returned to the initial value 1 day after hemin elimination. The results indicate that the hemin-induced erythroid differentiation of K562 cells is a reversible process and depression of the synthetase may be involved in the progress of differentiation.

Blotting, Northern↗

Inhibitory effect of interferon-gamma-dependent induction of major histocompatibility complex class II antigen by expressing exogenous poly(ADP-ribose) synthetase gene.

Ia antigen, one of class II major histocompatibility complexes, was induced by treatment of mouse macrophage P388D1 cells with interferon-gamma. During the process, expression of poly(ADP-ribose) synthetase gene was depressed. We examined whether or not down-regulation of the synthetase was required for the interferon-gamma-dependent induction of Ia antigen. We constructed expression plasmid harboring metallothionein promoter-regulated synthetase gene. The enzyme activity and mRNA level of the synthetase were increased in exogenous synthetase gene-transfected clones. Induction of Ia antigen gene was strongly inhibited by expressing the exogenous synthetase gene upon treatment of the transfected clones with interferon-gamma. The result suggests that interferon-gamma-dependent down-regulation of the synthetase may be involved in a step of the signal transduction to induce Ia antigen.

Animals↗

Enhanced expression of poly(ADP-ribose) synthetase gene in malignant lymphoma.

Over-expression of cellular protooncogenes has been proposed to function in the initiation and maintenance of malignancies. In order to distinguish malignant lymphoma from reactive proliferative diseases, we surveyed the expression levels of three protooncogenes(c-myc, c-fos and c-myb) in malignant lymphoma and reactive proliferative diseases. An increased level of c-myc or c-fos mRNA was observed in one case, respectively, out of three malignant lymphomata. The other cases exhibited no enhancement in protooncogenes. These oncogenes are critically regulated during differentiation, but the half-life of c-myc mRNA was very short, and the level of the mRNA decreased to the initial level very quickly. Thus, the high level of the expression of these oncogenes may not always be maintained in all malignant cells. We then examined the level of mRNA for poly(ADP-ribose) synthetase in those cases. An enhanced expression for the synthetase gene was observed in all five malignant lymphomata tested, but no increase in the level of the mRNA was observed in any reactive proliferative cases or normal lymph nodes. These results suggest that enhanced expression of poly(ADP-ribose) synthetase gene seems to be a common characteristic of protopathic malignant lymphoma. By using the characteristics of malignant lymphoma, the level of mRNA for the synthetase may be applicable for differential diagnosis of malignant lymphoma from several pathologically indistinguishable diseases.

Blotting, Northern↗

Immune responses to Bordetella pertussis infection and vaccination.

To assess antibody and cellular immune responses, 156 healthy children were immunized at approximately 18 months of age with acellular diphtheria-tetanus-pertussis vaccine. Changes in antibody responses to filamentous hemagglutinin (FHA) and to pertussis toxin (PT) were similar in pattern, and antibody titers reached values equal to those from patients with convalescent-stage pertussis. The FHA-induced DNA synthesis in peripheral blood mononuclear cells was maximum at 4 weeks after the primary series, and these levels were equal to those of patients with pertussis. High amounts of PT-induced DNA synthesis were observed in both immunized and nonimmunized children; thus, PT seemed to act mainly as a nonspecific mitogen. Almost the same responses to several mitogens that activate different subsets of lymphocytes were observed in young infants compared with older children. Furthermore, young infants who had Bordetella pertussis infection responded by FHA stimulation almost as well as older children.

Age Factors↗