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Biomedical subjects

T Kurashige

Publications and source records attributed to T Kurashige.

At least 55 records · Page 3Linked to original sources

Primary changes in liver damage by aspirin in rats.

BACKGROUND: It has been known that acetylsalicylic acid (ASA) causes liver cell damage, however, its mechanisms remain obscure. METHODS AND RESULTS: To clarify the earliest change in the course of liver cell damage induced by oral administration of ASA, rats that had received ASA at 50 mg/kg and 150 mg/kg bodyweight orally for 7 days were investigated. Mitochondria were isolated for measurements of mitochondrial respiration, and for electron microscopic observations, small pieces of liver were excised and fixed. Uncoupling of oxidative phosphorylation was observed in mitochondria isolated from ASA-treated rats. Although no histological changes were evident, lamellar structures in bile canaliculi were ultrastructurally observed in all rats treated with ASA. CONCLUSIONS: This laminar structure, which is negative for bilirubin staining, seems to be one of the most sensitive indicators of ASA-induced liver damage.

Administration, Oral↗

Periodic discharge of adrenocorticotropin and vasopressin associated with focal glomerulosclerosis.

We report the first case of the syndrome of periodic adrenocorticotropin (ACTH) and vasopressin (ADH) discharge associated with focal glomerulosclerosis. Approximately 30 cases of this syndrome have so far been reported in Japan, but no cases associated with renal dysfunction have yet been reported. The patient, a 10-year-old Japanese boy, was referred to our hospital because of recurrent attacks of vomiting. He was diagnosed as having this syndrome from clinical and laboratory findings. While various drugs were tried to manage his vomiting attacks, only valproic acid appeared to be effective in reducing the frequency of the attacks. Chronic nephritis was manifested when the patient was 12 years old, which required treatment with continuous ambulatory peritoneal dialysis. Valproic acid was proved to be effective in reducing the number of attacks over 4 months.

Adrenocorticotropic Hormone↗

Soluble thrombomodulin and antibodies to bovine glomerular endothelial cells in patients with Henoch-Schönlein purpura.

AIM: To evaluate the clinical significance of soluble thrombomodulin and antiendothelial cell antibodies (AECA) in children with Henoch-Schönlein purpura. METHODS: Binding of serum AECA to bovine glomerular endothelial cells was evaluated by enzyme linked immunosorbent assay, cytotoxicity against glomerular endothelial cells by spectrophotometric assay, and soluble thrombomodulin concentrations by sandwich enzyme immunoassay. RESULTS: IgA AECA were detected in seven of 15 patients with Henoch-Schönlein purpura and nephritis, but were not detected in patients without nephritis or in controls. Patients with Henoch-Schönlein nephritis had raised titres of IgA AECA and serum thrombomodulin; severe proteinuria and renal histological changes were associated with raised titres of IgA AECA and raised serum thrombomodulin. No subjects had complement dependent cytotoxicity against glomerular endothelial cells. CONCLUSIONS: High titres of IgA AECA and raised serum thrombomodulin may be clinically useful markers of renal involvement in patients with Henoch-Schönlein purpura.

Adolescent↗

Altered expression of CD11b and CD62L after cross-linking of CD45 isoforms on human eosinophils.

BACKGROUND: Phosphotyrosine phosphatase CD45 is exclusively found on nucleated hematopoietic cells. CD45 is an essential component of signaling of mast cel degranulation and of lymphocyte activation, but little is known about its role in eosinophils. In the present study, we have determined the expression and function of CD45 isoforms on human eosinophils. METHODS: Expression of CD45 isoforms on purified peripheral blood eosinophils was examined using indirect immunofluorescence and flow cytometry. Eosinophils were cultured with anti-CD45 isoform monoclonal antibodies (mAbs) for up to 24 h. Eosinophil activation was evaluated by measuring surface expression of CD11b or CD62L by flow cytometry. RESULTS: Fresh eosinophils express CD45, CD45RB, CD45RO epitopes but not CD45RA. Incubation with anti-CD45 isoform mAb for 30 min did not alter the expression of either CD11b or CD62L on eosinophils. In contrast, the expression of CD11b was significantly enhanced after 24 h of incubation with mAbs against CD45, CD45RB, or CD45RO. In addition, the expression of CD62L was also significantly reduced with anti-CD45RB and with anti-CD45RO mAbs. CONCLUSIONS: Cross-linking of surface CD45 isoforms for 24 h significantly induced upregulation of CD11b expression and CD62L shedding, consistent with activation of eosinophils. Our data suggest that CD45 isoforms are functionally expressed on human eosinophils, and are capable of modulating eosinophil function and might participate in allergic inflammation.

Antibodies, Monoclonal↗

Clonal lymphoproliferation following chronic active Epstein-Barr virus infection and hypersensitivity to mosquito bites.

In order to elucidate the possibility of lymphoproliferation in cases of chronic active Epstein-Barr virus infection (CAEBV), to clarify the clonality and genotype of proliferating lymphocytes, and to search for the factors that induce lymphoproliferation, we studied 11 cases of CAEBV, using genetical and immunological techniques. Epstein-Barr virus (EBV) DNA in peripheral mononuclear cells was detected in eight cases by Southern blotting. Among those eight cases, monoclonal proliferation of EBV DNA-positive cells was observed in three cases and oligoclonal proliferation in three cases. In the cases of monoclonal proliferation, one case manifested T-cell lymphoproliferation and the rest natural killer (NK) cell lymphoproliferation. The anti-EBV antibody titers in the study did not have any relativity to lymphoproliferation. On the other hand, three of the four cases of NK cell lymphoproliferation and one of the two cases of T-cell lymphoproliferation exhibited hypersensitivity to mosquito bites (HMB) in their clinical histories, while none of the three nonlymphoproliferation cases did. These facts indicate that T-cell and NK cell lymphoproliferative diseases (LPDs) could be more closely associated with EBV infection than we had previously expected. Also, the anti-EBV antibody titers may not be the indicator of EBV-associated LPD, and HMB may be one of the factors that induce EBV-associated LPD.

Animals↗

Two primary doses of diphtheria-tetanus-acellular pertussis vaccine induce immunological responses to Bordetella pertussis as strong as those induced by three primary doses.

Pertussis vaccinations are administered worldwide under various conditions and schedules with diphtheria-tetanus-pertussis (DTP). In Japan, a general vaccination with three primary doses of diphtheria-tetanus-acellular pertussis (DTaP) at 4-week intervals and one booster dose 12 months after the primary series have been used since 1981. Decreasing the number of doses of the vaccination would lessen the physical and economic costs. To compare the immunological response to two versus three primary doses, we assessed antibody and cellular immune responses in health children. The anti-filamentous hemagglutinin (anti-FHA) and anti-pertussis toxin (anti-PT) antibody responses to two primary doses of DTaP before a booster were significantly lower than the responses to three primary doses. Although these antibody levels were low in children who received two primary doses, the FHA-induced DNA synthesis was equal to that of the children who received three doses. The anti-FHA and anti-PT antibody levels 4 weeks after the booster following two doses were similar to the levels following three doses, and high antibody titers were maintained over a long period. In areas where contact with bacteria is expected, two primary doses of DTaP may be adequate to induce the necessary level of immunological responses.

Adhesins, Bacterial↗

Antibodies to endothelial cells in Kawasaki disease lyse endothelial cells without cytokine pretreatment.

Kawasaki disease (KD) is characterized by diffuse vasculitis and marked immune activation. To confirm the presence of antiendothelial cell antibodies (AECA) and cytotoxicity of AECA, we investigated the presence of AECA using ELISA and cytotoxicity of AECA in KD. Sera from patients with acute KD were assessed for binding to human umbilical vein endothelial cells (HUVEC) using a cell-based ELISA, and for cytotoxicity against HUVEC as indicated by the conversion of a tetrazolium salt (MTT) into a coloured product. IgM AECA were detected in 8/19 KD sera, IgG AECA were detected in 5/19 KD sera. Significant differences in both AECA titres existed between patients and febrile and afebrile controls. Six out of 19 patients showed complement-dependent cytotoxicity against HUVEC. Cytotoxicity was significantly enhanced by pretreating HUVEC with tumour necrosis factor (TNF), and reduced by incubation with gammaglobulin. Serum titres of IgM AECA in the KD patients were positively correlated with cytotoxicity. Findings suggest that IgM AECA mediates complement-dependent cytotoxicity against endothelial cells in patients with KD, and gammaglobulin may reduce complement-dependent cytotoxicity of AECA against endothelial cells.

Antibody-Dependent Cell Cytotoxicity↗

Viral interleukin-10 in chronic active Epstein-Barr virus infection.

Viral interleukin-10 (IL-10), a product of the Epstein-Barr virus (EBV) replication gene BCRF1, shares extensive structural and functional similarity with the human cytokine IL-10. Both viral and human IL-10 inhibit T cell growth and interferon-gamma production. With two ELISAs, one that recognized both human and viral (total) IL-10 and the other specific for viral IL-10, IL-10 was measured in serum or plasma from 34 patients with chronic active EBV infection (CAEBV) and from 15 healthy controls. Of the patients, 56% had measurable total IL-10 and 29% had measurable viral IL-10. In contrast, total IL-10 was detectable in only 2 of 15 controls and viral IL-10 was undetectable. Thus, many patients with CAEBV have abnormally high levels of circulating IL-10 that may contribute to disease pathogenesis by inhibiting host immunity.

Adolescent↗

Hypersensitivity to mosquito bites conceals clonal lymphoproliferation of Epstein-Barr viral DNA-positive natural killer cells.

In order to clarify the relationship between Epstein-Barr (EB) virus and hypersensitivity to mosquito bites (HMB), and to search for the mechanism which induces EB virus-associated lymphoproliferative diseases, we investigated patients with HMB, using hematological, immunological and virological techniques. Among 5 cases of HMB, CD56+ cells had proliferated and CD3+ cells were diminished in 4 cases. Although anti-EB virus antibody titers were not consistent with chronic active EB virus infection, EB viral DNA was detected in the peripheral blood mononuclear cells in all 5 cases. Moreover, EB viral DNA-positive cells had proliferated monoclonally in 4 cases, and biclonally in 1 case. It was proved that most of the EB viral DNA existed in natural killer (NK) cells through polymerase chain reaction analysis. These findings suggest that the basis of HMB may be clonal lymphoproliferation of EB viral DNA-positive NK cells and this hematological abnormality may induce the characteristic symptoms of HMB. In some cases, the proliferating NK cells can metamorphose into leukemic cells, and hemophagocytic syndrome, which has been assumed to be a complication of HMB, may then occur.

Adolescent↗

Reflex sympathetic dystrophy in childhood: a case report.

A case report is presented of a 15-year-old girl with reflex sympathetic dystrophy (RSD). She was referred to hospital because of left upper limb pain. Her left upper limb was cold, edematous and blue with a limited active range of movement. The serum concentration of noradrenaline was lower on the painful side than on the healthy side, and neurotropin, which has an antinociceptive effect to hyperalgesia, was clearly effective. Early diagnosis and management is essential in the treatment of RSD and administration of neurotropin is a useful and non-invasive treatment without severe adverse effects.

Adolescent↗

Pharmacological studies on Puerariae flos III: protective effects of kakkalide on ethanol-induced lethality and acute hepatic injury in mice.

Kakkalide, one of the major isoflavonoid components of Puerariae flos, has been investigated for its effect on ethanol-induced intoxication and on hepatic injury, including hyperglycaemia, in mice. Kakkalide reduced mortality associated with administration of ethanol. At doses of 100 and 200 mg kg-1 the effect of kakkalide was significant. The same dose of kakkalide prevented increased serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activity. At a dose of 200 mg kg-1 it also counteracted ethanol-induced elevation of glucose levels. These results suggest that kakkalide might be useful for counteracting the effects of alcohol and might be effective for treating hepatic injury.

Acute Disease↗

Correlation between HLA-DR expression and level of poly(ADP-ribose) synthetase in human thyroid carcinoma cells.

The expression of MHC class II molecules is normally restricted to antigen presenting cells. Aberrant expression of class II molecules, however, was detected in the thyrocytes of autoimmune thyroid diseases. We attempted to regulate the expression of HLA-DR molecules in thyroid carcinoma cells by expressing the exogenous poly(ADP-ribose) synthetase gene. We transfected a metal inducible expression plasmid capable of expressing poly(ADP-ribose) synthetase gene into thyroid carcinoma 8505C cells and the transformants, treated with metal and IFN-gamma, were separated by Magnetic Cell Separation. The activity of the synthetase was increased in the HLA-DR-enriched transformants as compared with that in control or the HLA-DR+ transformants. RNA blot analysis and flow cytometric analysis revealed that the IFN-gamma-inducible expression of HLA-DR molecules was depressed by the induction of exogenous poly(ADP-ribose) synthetase gene. This result indicates that HLA-DR expression was correlated with the level of poly(ADP-ribose) synthetase in human thyroid carcinoma cells. Furthermore we examined the level of poly(ADP-ribose) synthetase in patients with autoimmune thyroid diseases. We observed a significant decrease in poly(ADP-ribose) synthetase in the patients. Taken together with the previous observation, the decrease in poly(ADP-ribose) synthetase is closely linked to the aberrant expression of HLA-DR molecules in some autoimmune thyroid diseases.

Autoimmune Diseases↗

A deletion of five nucleotides in the L1CAM gene in a Japanese family with X-linked hydrocephalus.

X-linked hydrocephalus (HSAS) is the most common form of inherited hydrocephalus characterized by hydrocephalus due to stenosis of the aqueduct of Sylvius, mental retardation, clasped thumbs, and spastic paraparesis. MASA syndrome (mental retardation, aphasia, shuffling gait and adducted thumbs) and SPG1 (X-linked complicated spastic paraplegia) are also X-linked disorders with overlapping clinical signs. Linkage analysis studies implicated the neural cell adhesion molecule L1 (L1CAM) gene as a candidate gene for these X-linked disorders. This genetic study analyzes the L1CAM gene in a Japanese family with members suffering from HSAS, and describes a deletion of five nucleotides in exon 8. Screening by Bg1I digestion of polymerase chain reaction (PCR) products revealed that two siblings have the same mutation and a sister was identified as a heterozygous carrier. The 5 nucleotide deletion causes a shift of the reading frame and introduces a premature stop codon 72 nucleotides downstream, which might result in a truncated protein. The mutation identified herein is a novel L1CAM mutation, which triggers hydrocephalus. We report a unique L1CAM mutation that causes HSAS: the first report of such a mutation in a Japanese family.

Adult↗

[A case of Smith-Magenis syndrome].

A boy with an interstitial deletion of the short arm of chromosome 17 was reported, with special reference to radiological and electroencephalographic findings. Brain MRI showed megacisterna magna caused by cerebellar hypoplasia, and suspected cortical dysplasia. Sleep EEG showed humps, spindles, and REM sleep patterns. This case performed sleep disturbance. It seems like to tendency of awakeness in REM sleep.

Abnormalities, Multiple↗

[Pharmacokinetic and clinical evaluations of azithromycin in the pediatric field].

Azithromycin (AZM), an oral macrolide antibiotic drug, was studied for its efficacy and pharmacokinetics in the treatment of pediatric patients with respiratory tract infections. The results of the study are presented. Fifteen pediatric patients in an age range between 1 and 10 years were given 8.9 to 14.7 mg/ kg body weight of AZM once daily for 3 to 4 days. Pharmacokinetics of AZM in three patients were examined. AZM concentration in plasma was 0.037 microgram/ml at 72 hours after final dosing, while urine concentration was 10.9 micrograms/ml measured during a period between 72 and 96 hours post-dosing. Fourteen patient cases were included in analysis of drug efficacy for AZM. AZM was found "markedly effective" in all seven patients with pneumonia, and "effective" in all three patients with acute bronchitis, two patients with mycoplasmal pneumonia, and one patient with tonsillitis. In one patient with mycoplasmal bronchitis, AZM was found slightly effective. The efficacy rate was 92.9% (13/14). The study found one case of side effect, moderate diarrhea. No laboratory abnormality was documented. In conclusion, an antibiotic AZM was found useful in a treatment of pediatric respiratory tract infections.

Anti-Bacterial Agents↗

Classic steroid 11 beta-hydroxylase deficiency caused by a C-->G transversion in exon 7 of CYP11B1.

Steroid 11 beta-hydroxylase deficiency (11 beta OHD) is derived from mutations in the P45011 beta gene (CYP11B1) and inherited in an autosomal recessive manner. In the present study, we have performed a molecular genetic analysis of CYP11B1 in a Japanese patient clinically diagnosed as classic 11 beta OHD. Nucleotide sequencing of the PCR-amplified exons from the patient's genomic DNA reveals a unique C-->G transversion that converts codon 384 CGA (arginine) to GGA (glycine) in exon 7. Restriction fragment length polymorphism (RFLP) data demonstrate that the patient is homozygous for this mutation. When the full-length cDNA corresponding to CYP11B1 of the patient is transfected into COS-7 cells, no steroid 11 beta-hydroxylase activity is detectable in mitochondria of the cells. These results indicate that this point mutation completely abolishes P45011 beta activity and causes the classic 11 beta OHD.

Adolescent↗

Prevention of influenza by the intranasal administration of cold-recombinant, live-attenuated influenza virus vaccine: importance of interferon-gamma production and local IgA response.

To clarify which immunological factors were more effective in preventing influenza virus infection, we measured immunological parameters induced by vaccination and infection in vivo and in vitro. Healthy adult subjects (n = 128) were divided into vaccinated (n = 85) and untreated (n = 43) groups. Eighty-five were vaccinated intranasally with a trivalent cold-adapted recombinant influenza virus vaccine containing type A (H1N1 and H3N2) and B viruses. Subjects were mostly seropositive before vaccination. In 29 (80.6%) of the 36 examinees showing a prevaccination HI antibody titre of less than 1:128, the titre increased more than four times after vaccination. On the other hand, an increase of more than four times was found in four (8.2%) of the 49 individuals who had shown a prevaccination titre of more than 1:128. The IgA antibody was negligibly detected in the nasal wash specimens before vaccination, and was induced by vaccination in some cases. Lymphocyte proliferation and interleukin 2 (IL-2) production in cultured lymphocytes of the same subjects stimulated by H1N1 virus in vitro were correlated with the HI antibody titre. However, the interferon gamma (IFN-gamma) production was low before vaccination, regardless of the HI antibody titre, and showed a significant increase after vaccination. It was suggested that local IgA response and IFN-gamma production play important roles in the prevention of influenza. Since there was the outbreak of influenza A (H1N1) in Kochi Prefecture after completion of blood samples 6-8 weeks after the second vaccination, we examined the above hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗