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Biomedical subjects

K Tanimoto

Publications and source records attributed to K Tanimoto.

At least 271 records · Page 15Linked to original sources

A new method for the detection of Lesch-Nyhan heterozygotes by peripheral blood T cell culture using T cell growth factor.

Thioguanine-resistant T lymphoblast populations were selectively amplified using T cell growth factor in the cultures of peripheral blood T cells from four Lesch-Nyhan heterozygotes. Although Lesch-Nyhan T lymphoblasts were all thioguanine-resistant, none of the cultures from 13 control subjects yielded the growth of such defective cell populations. These data provide direct evidence for the existence of a small percentage (5%-40%) of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficient T cells in the heterozygotes, but not in normal individuals. Conversely, culture of the T lymphoblasts with azaserine plus hypoxanthine permitted the growth of the other part of the cell population that was enzyme positive. The low percentages of HGPRT-negative cells among T cells in heterozygotes suggest that the presence of this enzyme is beneficial for differentiation of lymphocytes of T cell linkage. Considering the ease and the reliability, culture of the peripheral T cells with thioguanine and T cell growth factor is very likely of practical use for detecting Lesch-Nyhan syndrome carriers among predisposed females.

Adolescent↗

Inhibitory effect of lithium on neuroleptic and serotonin receptors in rat brain.

We investigated the effect of acute and chronic administration of lithium on neuroleptic receptors ([3H]spiroperidol binding sites) and serotonin receptors ([3H]serotonin binding sites) in rat brain. In the limbic-forebrain, both acute and chronic lithium treatment significantly reduced the density (Bmax) of neuroleptic receptors, without affecting the affinity (Kd) of those receptors. However, lithium treatment had no apparent effect on neuroleptic receptors in the caudate-putamen and frontal cortex in either acute or chronic administrations. On the other hand, acute lithium administration markedly decreased the Kd and Bmax of serotonin receptors in the hippocampus, but not in the cerebral cortex; this distinct observation was also found in animals chronically treated with lithium. These results indicate that lithium has an inhibitory effect on neuroleptic receptors in the limbic-forebrain and on serotonin receptors in the hippocampus. Therefore, it is possible to postulate that these effects of lithium in specific brain regions may be related to the therapeutic mechanism of this drug in affective disorders.

Animals↗

Transfer inhibition of RP4 by F factor.

When RP4 and F factors were brought together into one E. coli cell, the F factor reduced 500-1000-fold the frequency of transfer of RP4. However, F had almost no effect on the surface exclusion and pilus formation by RP4. In contrast, RP4 did not affect the transfer of F. Using in vitro recombinant DNA techniques, a gene of F responsible for the above-mentioned transfer inhibition of RP4 was located within the BamHI fragment (40.4-42.8 kb) of the mini-F sequence on F. From the result of product analysis using minicells, the responsible gene in the BamHI fragment was inferred to encode the 33 K protein.

Chromosome Mapping↗

Human anticentriole autoantibody in patients with scleroderma and Raynaud's phenomenon.

Unique autoantibody was found in sera from two different patients that reacted with centrioles of both cultured mammalian cells and human peripheral leukocytes as detected by the indirect immunofluorescent method. Sera from the same individuals, one with scleroderma and the other suffering from Raynaud's phenomenon, also stained the basal bodies of rat tracheal ciliated cells by the identical technique. Data from subsequent investigations have suggested that the antigen(s) involved in the reaction are water-insoluble protein(s) or polypeptide(s) associated with centrioles and are distinct from microtubular proteins or purine nucleoside phosphorylase.

Adolescent↗

Inhibition of T gamma rosette formation by the sera from patients with systemic lupus erythematosus. Relation to T gamma-specific antilymphocyte antibody.

The cytotoxic activities of lupus sera were measured against IgG Fc-receptor-bearing T lymphocytes (T gamma cells) and T lymphocytes lacking this receptor [T gamma (-) cells], and the activities were compared with the inhibitory activities of the sera for the formation of rosettes (T gamma rosettes) between T lymphocytes and ox erythrocytes sensitized with IgG antibody. The cytotoxic activities of the sera against both T gamma and T gamma (-) cells well correlated with their T gamma rosette inhibitory rates. Also, the cytotoxic activities after the removal of IgM antibodies strongly correlated with the inhibitory rates. Among them, the highest correlation was observed between IgG T gamma-specific cytotoxic antibodies and T gamma rosette inhibitory rates of the sera. Gel filtration, ultracentrifugation, pepsin digestion, and reduction and alkylation of the sera revealed that main inhibitory activities were contained in IgG fractions. These results suggested that IgG T gamma-specific antibody suppressed T gamma rosette formation and might contribute to the reduction of T gamma cell number in patients with systemic lupus erythematosus.

Antibody Specificity↗

Heterogeneity of antilymphocyte antibody in SLE and its correlation with disease activity.

The cytotoxic activities of individual lupus sera were demonstrated against T gamma cells, T gamma (-) cells and B cells. Immunoglobulin classes were also determined in these antilymphocyte antibodies (ALA) in SLE. T gamma-specific ALA and B-cell-specific ALA were almost equally distributed as regards IgG-dominant type, mixed IgG and IgM type and IgM dominant type, while IgM dominant type was predominant in T gamma (-)-specific ALA. Only the IgG type of T gamma-specific ALA among these ALA was significantly associated with clinical parameters, including hypocomplementemia, elevated immune complex levels and high anti-double-stranded (ds) DNA titres. Serial studies on ALA in a typical case of SLE were performed. Active clinical signs were associated with elevated cytotoxicities of IgG type of T gamma-specific ALA and with relatively low cytotoxicities of the IgM type, whereas after massive corticosteroid therapy, these signs disappeared in tact with the reduction in cytotoxic activities of IgG type of the ALA and the relative rise in cytotoxicities of IgM type of the ALA. These results suggested that IgG class of T gamma-specific ALA seemed to play a major role among several types of ALA in SLE.

Antibodies, Antinuclear↗

Antagonizing effect of lithium on the development of dopamine supersensitivity in the tuberoinfundibular system.

We investigated whether receptor supersensitivity occurs in the tuberoinfundibular dopaminergic system, as reported in the nigrostriatal and mesolimbic areas. Animals received either haloperidol or saline for 2 weeks. Five days after the last injection of haloperidol, animals pretreated with haloperidol showed a significantly longer lasting inhibition of prolactin (PRL) secretion by apomorphine, compared with the controls. This dopamine receptor supersensitivity was also observed on the 12th, but not the 33rd day after the cessation of haloperidol administration. The effect of lithium on this dopamine supersensitivity in PRL release was investigated. All rats were treated with haloperidol and fed either a diet containing lithium carbonate or a diet without lithium for 2 weeks. Lithium administration with haloperidol resulted in the inhibition of PRL-lowering action of apomorphine at 5 days of withdrawal from haloperidol, indicating that the supersensitivity of dopamine receptors of dopamine receptors on pituitary lactotrophs were decreased by lithium. This action of lithium may be related to the prophylactic effect of the drug on the manic-depressive disease.

Animals↗

Age-related changes in auto- and natural antibody in the Werner syndrome.

To assess the immunologic disturbance in WErner syndrome, antibodies to "intrinsic" (auto)antigens (anti-DNA antibodies and rheumatoid factors) and "natural" antibodies to "extrinsic" antigens (hemagglutinins for sheep red cells and antibodies against ABO blood type antigens) were measured in serum samples from 16 patients with Werner syndrome and compared with those from 150 healthy persons ranging in age from less than a year to 98. Employing a sensitive solid-phase radioimmunoassay, we found that the levels of both anti-double-stranded and anti-single-stranded DNA antibodies in the IgG class gradually increased with age in normal donors; a more abrupt increase with age was observed in those with Werner syndrome, although they lacked any complication of renal disease and hypocomplementemia. The titers of rheumatoid factor detected by sensitized sheep cell agglutination also gradually rose in normal persons and patients with Werner syndrome. In contrast, the titers of natural antibodies declined with age in both groups. These disturbances in antibody production suggested that Werner syndrome expresses an accelerated form of aging in immunologic aspect.

Adolescent↗

Association between HLA and Japanese patients with rheumatoid arthritis.

Japanese patients with rheumatoid arthritis (RA) were observed to have a statistical association with HLA-DR4, MT3. Strong association between the clinical severity of RA and HLA was also observed. Male patients had a stronger association with HLA than female patients. Males are more resistant to RA than females. This suggested that the threshold of liability for RA is higher in males than in females. Japanese patients with RA with systemic vasculitis were negative for HLA-Bw44 and had antilymphocytotoxic autoantibody, indicating that RA with systemic vasculitis is different in etiology from RA without systemic vasculitis.

Adult↗

Reduced natural killer cell activity of lymphocytes from patients with Werner's syndrome and recovery of its activity by purified human leucocyte interferon.

Natural killing (NK) activities were measured in peripheral blood lymphocytes (PBL) from 14 patients with Werner's syndrome (WS), and the results were compared with those of 187 normal individuals at different ages. The NK activities of healthy donors were demonstrated a characteristic and invariable manner in accordance with the age and the sex, whereas the activities of WS patients were considerably reduced irrespective of the age and the sex. When normal PBL were preincubated with WS sera containing anti-lymphocyte antibodies (ALA) plus rabbit complement, the NK activities of the surviving PBL were markedly reduced when compared with those of PBL treated with other heterologous ALA of rabbit origin in the same manner. PBL from WS patients treated with purified human leucocyte interferon augmented the NK activity even beyond the range of controls. These results suggested that NK activities in WS patients were reduced in a manner similar to that in normal old individuals. The ALA reactive to NK cells in WS patients may participate in the reduction of NK activities. The augmentative effect of interferon on NK activities in WS patients may also suggest the possible blocking of potent NK activities by an unknown mechanism rather than an intrinsic defect of their NK cells.

Adolescent↗

Isolation of human suppressor T cells by peanut agglutinin.

Peanut agglutinin (PNA) is a plant lectin which has been used for the separation of suppressor T cells in mice. The present study was carried out to determine whether PNA would be useful in the isolation of human suppressor T cells. Normal human peripheral blood mononuclear cells (PBMC) were activated by concanavalin A (Con A) and the resultant blastoid cells were then incubated with PNA-coated autologous erythrocytes to induce the rosette formation. The PNA rosette-forming cells (15-18% of Con A-activated PBMC) were separated from non-rosette-forming cells by differential centrifugation. The rosette-forming cells suppressed pokeweed mitogen-induced polyclonal immunoglobulin synthesis by 2- to 5-fold. This degree of suppression was greater than that seen with non-rosette-forming cells or with unseparated Con A-activated cells. Our data indicate that PNA rosette fractionation provides a simple and useful method for the isolation of human suppressor T cells.

Cell Separation↗

T lymphocyte interaction with immunoglobulin G antibody in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple immune disturbances whose mechanisms remain unclear. We examined the interaction of antilymphocyte antibodies with cultured normal T lymphocytes. T cells were prepared by E-rosetting after petri-dish removal of adherent cells and cultured for 2-7 d in the presence of SLE sera or normal human sera. Cultured T cells were washed and sonicated, and the amount of cell-associated IgG was quantitated by radioimmunoassay or enzyme-linked immunoassay (ELISA) methods. T cells cultured with 27 of 39 SLE sera showed marked increments of associated immunoglobulin G (IgG) although this was not observed with sera from mixed connective tissue disease patients containing high titers of ribonucleoprotein antibody or normal donors. The effective factors for IgG association in SLE sera were absorbed with normal peripheral blood lymphocytes or T cells. Anti-T cell IgG cytotoxic activity strongly correlated with T cell IgG association (P less than 0.01). T cell-associated IgG was not removed by stripping of cell membrane IgG from living cells by acid buffer treatment; indirect immunofluorescence of cells fixed after 2-4 d of culture revealed cytoplasmic IgG staining. IgG anti-T cell antibodies appeared to associate inside the cell membrane or to penetrate into the cytoplasm of cells. T cell Fc receptor blocking by heat-aggregated IgG or anti-beta 2-microglobulin antibody did not alter IgG cell association. Since pepsin-digested SLE sera showed no T cell association activity, whole IgG antibody molecules appeared to be necessary for interaction with cultured T cells. In addition, reduction and alkylation of active SLE sera completely nullified T cell reactivity. When normal T cells were cultured with SLE sera showing marked IgG T cell association, viability of cultured T cells decreased rapidly after 4 d, which suggests that IgG anti-T cell antibodies were associated with cell destruction. IgG cell-associating antilymphocyte antibodies present in SLE sera may cause T cell disturbances in vivo and may be related to the lymphocytopenia present in SLE patients.

Adult↗