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T Mitsuda

Publications and source records attributed to T Mitsuda.

53 records · Page 3Linked to original sources

The murine Sm-D autoantigen: multiple genes, genetic polymorphism, evolutionary conservation and lack of intervening sequences in the coding region.

Antibodies to the Sm nuclear antigen are diagnostic of systemic lupus erythematosus (SLE). MRL/Mp-lpr/lpr mice develop a similar illness, and a proportion also develop anti-Sm. To understand better anti-Sm reactivity in this murine model, we have cloned the murine Sm-D autoantigen. One cDNA clone was 517 bp long with an open reading frame of 357 nucleotides, encoding a 13.3 kDa protein of 119 amino acids. At the nucleotide level, the murine Sm-D cDNA was 89.8% homologous with human Sm-D (94% in the coding region), yet there was identity at the protein level, including a Gly-Arg nine-fold repeated C-terminus motif. Southern blot analysis of PstI-digested genomic DNA from seven mouse strains demonstrated a 7.8 kb band in every strain; in addition, a 2.8 kb band was seen in AKR/J, LG/J and MRL/Mp-lpr/lpr. PCR amplification of genomic DNA showed a single Sm-D gene product of 360 bp, which indicated a lack of intervening sequences. The Sm-D protein is thus highly conserved in evolution, probably owing to its essential role in the physiology of the cell.

Alleles↗

[Effect and limitation of intravenous methylprednisolone pulse therapy in the long-term follow-up of childhood systemic lupus erythematosus].

The course of 6 patients with childhood systemic lupus erythematosus was analysed with emphasis on the effect and limitation of intravenous methylprednisolone pulse therapy in the long-term follow-up. The present findings suggest that using pulse therapy within 2 months in the course of disease flares, probably before irreversible organ damage has occurred, may be more beneficial in suppressing the disease activity and maintaining long-term remission. The demonstration of low serum complement activity (CH 50), and in some cases, proteinuria, was useful to decide the time of pulse therapy. Complications of pulse methylprednisolone plus long-term oral prednisolone therapy included cushingoid appearance and low body height in addition to cataract and glaucoma, all of which were attributable not to methylprednisolone pulse therapy alone but to long-term accumulation of corticosteroids. The combination therapy including several immunosuppressants needs to be established in order to avoid these steroidal complications.

Administration, Oral↗

Perinatal hepatitis B virus infection caused by antihepatitis Be positive maternal mononuclear cells.

To investigate the infectivity of hepatitis B virus (HBV) from mothers to their newborn offspring, HBV-DNA in plasma and peripheral mononuclear cells from 28 antihepatitis Be positive, hepatitis B surface antigen positive carrier mothers was examined by a highly sensitive polymerase chain reaction/Southern hybridisation technique. HBV specific DNA was detected in three maternal mononuclear cell samples, but was absent in plasma. Two of four infants born to the three mothers with HBV-DNA positive mononuclear cells developed acute or fulminant hepatitis within three months after birth. Two infants were effectively prevented from infection with HBV by combined hepatitis B immunoglobulin/HBV vaccine administration. The 25 infants born to the HBV-DNA negative mothers were free of HBV infection within the next seven months to 3.5 years. These results suggest that latent infection with HBV in maternal mononuclear cells is responsible for perinatal HBV infection.

Alanine Transaminase↗

[Hyper IgE syndrome--a disease of imbalanced activation of helper T-cell subsets?].

Hyper-IgE syndrome is a rare immunodeficient disorder characterized by recurrent severe staphylococcal infections of the skin and sinopulmonary tract, chronic eczematoid rashes, coarse facial features, mild eosinophilia, and markedly elevated serum IgE levels. Hyperimmunoglobulinemia D, depressed DTH, and varying degrees of pathogenesis of this syndrome is unknown. The clinical manifestations and the recent research findings indicated the followings: 1) increased production of IL-4: hyperimmunoglobulinemia E, increased number of Fc epsilon R(+)-cells in peripheral blood, 2) defective production of IFN-gamma: abnormal local inflammatory responses (formation of cold abscesses), chemotactic defect in the circulating neutrophils (abnormalities in IFN-gamma/IL-8 pathway), depressed DTH, 3) T-cell immunodeficiency?-chronic dermatitis? 4) genetic factors (frequent familial occurrence, characteristic facial appearance with broad nasal bridge). These observations led us to postulate that both the increased production of IL-4 and the defective production of IFN-gamma may be the immunopathological bases of this syndrome. Recently, these cytokines were demonstrated to be secreted by different subsets of helper T-cells, designated TH1 and TH2, in murine system, suggesting that the regulatory imbalances between IL-4 and IFN-gamma in this syndrome might be due to the differential activation or inactivation of these helper T-cell subsets.

Humans↗

Demonstration of mother-to-infant transmission of hepatitis B virus by means of polymerase chain reaction.

To investigate the failure of vaccines to prevent mother-to-infant transmission of hepatitis B virus (HBV), serum, cord blood, and colostrum samples from eleven mothers, known to be carriers of hepatitis B surface antigen, and their infants were examined by means of a highly sensitive polymerase chain reaction (PCR) method. HBV-specific DNA was detected in ten maternal serum samples, eight samples of colostral whey, eight samples of colostral cells, and one cord blood sample. Four infants of mothers with HBV-DNA-positive colostrum showed low responsiveness to hepatitis B vaccine. The infant whose cord blood was positive for HBV DNA showed low responsiveness to hepatitis B vaccine and subsequently became an HBV carrier. These results suggest the need for further study to evaluate whether breastfeeding is advisable for HBV carriers.

Carrier State↗

An alternative nonradioactive method for labeling DNA using biotin.

An alternative nonradioactive labeling method and a highly sensitive technique for detecting specific DNA sequences are described. The labeling method requires the "Klenow" fragment of DNA polymerase I and random hexanucleotides (synthesized or naturally extracted) as a primer for the production of highly sensitive DNA probes. The system has three main steps: (i) labeling of DNA with biotinylated 11-dUTP; (ii) detection of biotinylated DNA by a one-step procedure with streptavidin-alkaline phosphatase complex; (iii) blocking of background with Tween 20. Twenty attograms (2 X 10(-17) g) of pBR322 plasmid DNA was detected by dot-blot hybridization. Upon Southern blot hybridization, 7.4 fg (7.4 X 10(-15) g) of pBR322 HindIII DNA was detected using the biotinylated pBR322 plasmid DNA probe; 40.8 ag and 7.4 fg of lambda HindIII DNA were detected with the biotinylated whole lambda DNA probe by dot and Southern blot hybridization, respectively. Specific bands were also detected with the biotinylated argininosuccinolyase probe upon Northern blotting of mouse poly(A+) RNA. Further applications for in situ hybridization are also described.

Animals↗

Characterization of alloreactive T cell hybridomas.

Four T cell hybridoma clones were established and characterized from 250 hybridoma cell lines and characterized. All clones were strongly positive for Thy-1 and H-2 antigens. The Lyt-1 and L3T4 determinants were weakly but significantly positive, whereas I-A antigens and surface immunoglobulin were negative. Three of the clones secreted IL-2 upon stimulation with H-2Kk cells, whereas the remaining clone did not. This IL-2 secretion was stimulated not only by macrophage-dendritic cells, but also by B cells. All clones produced significant footpad swelling following injection into the footpads of H-2k mice. The time course and histology of the footpad swelling suggested that the reaction might be a delayed type hypersensitivity (DTH)-like response.

Animals↗

Clinical features in a girl with Duchenne muscular dystrophy with an X-autosome translocation; (X;4)(p21;q26).

A female with Duchenne muscular dystrophy (DMD) and an X/4 translocation is reported. Her clinical signs, laboratory data and muscle pathology are compatible with those of typical DMD. She also has a ASD, type II, with some kind of cardiomyopathy. Detailed cytogenetic analyses by means of high resolution banding and R-banding techniques showed that the exchange point was located in band p21 of the X chromosome, suggesting the localization of the DMD gene within it. The clinical course of DMD in a female with an X/autosome translocation is variable, as in the case of heterozygous females, compared with that in male patients. The mild phenotype in female cases with an X/autosome translocation could be explained by the fact that in some cultured cells the normal X chromosomes replicate early and therefore may be active.

Child, Preschool↗