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Biomedical subjects

M Homma

Publications and source records attributed to M Homma.

At least 325 records · Page 18Linked to original sources

Characterization of a high molecular weight acidic nuclear protein recognized by autoantibodies in sera from patients with polymyositis-scleroderma overlap.

Autoantibodies in the serum from a patient with connective tissue disease have been used to define a high molecule weight acidic nuclear protein antigen. The antigen tentatively termed Ku, after the first two letters of patient's name, has distinct physicochemical properties and immunological specificities that distinguish it from previously reported antigens. The Ku antigen has an apparent 300,000 mol wt as determined by gel filtration and sucrose density gradient ultracentrifugation techniques. The antigen is destroyed by trypsin, mild heating, and pH variations greater than 10 and less than 5. Treatment with ribonuclease or deoxyribonuclease did not affect the antigenic reactivity. The Ku antigen was demonstrated in the soluble extracts of human, calf, and rabbit, but not of rat tissues. Purified antibody localized the Ku antigen within the nuclei of human liver where a "reticular" pattern of immunofluorescence was seen. Of 330 patients with various connective tissue diseases, 9 had precipitating antibodies to the Ku antigen. Preliminary results of clinical analysis indicated that antibody to the Ku antigen might become a useful marker for a group of patients with clinical characteristics of both polymyositis and scleroderma with a good prognosis.

Antigens↗

Thyrotropin (TSH) receptor and adenylate cyclase activity in human thyroid tumors: absence of high affinity receptor and loss of TSH responsiveness in undifferentiated thyroid carcinoma.

TSH receptor and adenylate cyclase activity of plasma membrane fractions of human thyroid tumors were examined. The mean (+/- SD) basal adenylate cyclase activity in normal thyroid tissues was 0.35 +/- 0.33 nmole/mg protein x 10 min. The activity rose to 280% (range, 270-310%) of basal with TSH (166 mU/ml). In adenomas, the activity rose to 600% (range, 530-650), which was significantly higher than that of normal thyroid (P < 0.005). In the differentiated carcinoma, TSH responsiveness of adenylate cyclase was heterogenous (range, 110-520), but was qualitatively similar to that of the normal thyroid. On the other hand, basal adenylate cyclase activity of undifferentiated carcinoma was significantly lower than that of normal thyroid (0.018 +/- 0.007 nmol/mg protein x 10 min; P < 0.05) and was not stimulated by TSH. LH, FSH, and ACTH did not stimulate the enzyme in either kind of carcinomas. The mean (+/- SD) of the capacity of the high affinity receptor of adenomas (0.72 +/- 0.64 pmol/mg protein) and differentiated carcinomas (0.77 +/- 0.84) was not significantly different from that of normal thyroid (0.92 +/- 0.84). The affinity constants of the receptors in these three tissues were much the same (1.6-2.4 x 10(10) M-1). On the other hand, high affinity receptor could not be detected in all of the undifferentiated thyroid carcinoma. It seems likely that the failure of adenylate cyclase to respond to TSH in undifferentiated carcinoma of the thyroid is due to an alteration at the level of the receptor site. These data suggest that growth and metabolic activity of undifferentiated carcinoma may be independent of TSH, while those of adenoma and differentiated carcinoma may be affected by TSH.

Adenoma↗

Enhancement of lymphocyte response to PHA by lysosomal enzymes from polymorphonuclear leukocytes of RA joint fluid. I. Biological effect on T lymphocyte function.

The effect of polymorphonuclear leukocyte (PMN) granule lysates obtained from joint fluid of RA on the in vitro DNA synthesis of PHA-stimulated autologous lymphocytes from joint fluid was studied. Lymphocytes were cultured for 3 days with or without PMN lysates in 2 ml of RPMI-1640 supplemented with 10% heat-inactivated fetal calf serum (FCS). The lymphocytes were stimulated with phytohemagglutinin (PHA-M). The DNA synthesis was measured by counting the [3H]thymidine incorporation. Lymphocytes from RA joint fluid stimulated with PHA-M showed 19,466+/-987 cpm (mean+/-SE) per 10(6) cells in the absence of PMN lysates. Upon addition PMN lysates to the PHA-stimulated lymphocytes, the maximum in vitro DNA synthesis increased to 44,877+/-1338 cpm. The enhancing effect of PMN lysates was abolished by plasma inhibitors or by passage through a column of protease inhibitor (Trasylol). It was concluded, therefore, that the enhancing effect of PMN lysates on PHA-stimulated lymphocytes may be associated with lysosomal proteases. Based on experiments using separated T and B lymphocytes, the enhancing effect of PMN lysates was considered to result from the activation of T lymphocytes. The results obtained in the present study suggest an important role for lysosomal proteases in the perpetuation of rheumatoid synovitis.

ABO Blood-Group System↗

Trypsin action on the growth of Sendai virus in tissue culture cells. V. An activating enzyme for Sendai virus in the chorioallantoic fluid of the embryonated chicken egg.

A trypsin-like protease which is responsible for activation of Sendai virus was found in the chorioallantoic fluid (CAF) of embryonated chicken eggs. Treatment of the inactive form of Sendai virus, grown in LLC-MK2 cells, with CAF enhanced both hemolytic activity and infectivity for the cells. Soybean trypsin inhibitor restrained the enhancing activity of CAF. These results indicate that CAF contains a trypsin-like protease which activates the inactive form of Sendai virus. The activation was strongly inhibited by phenylmethylsulfonylfluoride, ethylenediaminetetraacetate, antipain, and leupeptin but not by tosyllysylchloromethylketone, suggesting that the activating enzyme in CAF is a protease similar to but not identical with trypsin. The inactive form of the virion was produced in ovo when the seed virus was inoculated along with antipain or leupeptin. In deembryonated chicken eggs in which CAF was substituted for a culture medium, multiple cycle growth occurred, but not when soybean trypsin inhibitor was present. These observations indicate that some activating enzyme, possibly the same one as found in CAF, was secreted from the chorioallantoic membrane.

Animals↗

Mode of subacute sclerosing panencephalitis (SSPE) virus infection in tissue culture cells. II. Cell-free viruses in cell cultures infected with Kitaken-1 and Biken strains of SSPE virus.

Cell-free infectious viruses were successfully recovered by the aid of freezing and thawing from cultures infected with the Kitaken-1 and Biken strains of subacute sclerosing panencephalitis (SSPE) virus. Our results including those in a previous report which dealt with the Niigata-1 strain of SSPE virus show that cell-free viruses can be detected from all of the SSPE virus-carrying cultures established in Japan. It was also found that cell-free infectious viruses can be recovered efficiently by dispersing the virus-carrying cultures with EDTA. The inclusion of trypsin in the EDTA solution, however, caused a poor recovery of the infectious viruses. Infection of cells with the cell-free viruses readily established the virus-carrying cultures that have characteristics comparable to those of their original cultures. The culture infected with the Kitaken-1 strain produced infectious viruses in about ten times the amount of the other two infected cultures. The buoyant densities of the cell-free infectious viruses were almost the same among the three strains, the values being 1.120 to 1.132, but significantly less than that of 1.164 of measles virus. The low density can be ascribed to one of the characteristics of these SSPE viruses.

Cell Line↗

Studies of anti-lymphocyte antibody in patients with active SLE. II. Effect of anti-lymphocyte antibody on autoreactive cell clones.

The effect of anti-lymphocyte antibodies of active systemic lupus erythematosus (SLE) on the immune regulation of autoantibody production was studied. The present study demonstrated that there were native DNA (nDNA)-sensitized T lymphocytes even in inactive SLE and no or few nDNA-sensitized T lymphocytes in normal individuals, and that in the inactive stages of SLE suppressor T lymphocytes might inhibit the activation of nDNA-sensitized T lymphocytes eliciting the production of anti-DNA antibodies by B lymphocytes. In the active stage of SLE, the anti-lymphocyte antibodies could eliminate the suppressor function of T lymphocytes or a subset of cells capable of either regulating their appearance or differentiating into them, which inhibited such responses. The different suppression of DNA and extractable nuclear antigen (ENA)-stimulated blastogenic response is further discussed.

Antibodies, Antinuclear↗

The cellular basis of impaired T lymphocyte functions in the elderly.

Immunologic changes associated with aging were studied by various immunologic tests in 24 aged persons (age range, 76-83) and 25 young persons (age range, 20-40). The responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were depressed in the aged subjects compared to the young ones (p less than 0.05), whereas the responses to pokeweed mitogen (PWM) were similar. The activity of adhereent and non-adherent cells was assessed in various combinations. The adherent cells of aged persons were indistinguishable from those of young persons in their ability to response to Con A. Lymphocytes from the aged synthesized larger in vitro amounts of immunoglobulin than did lymphocytes from the young, when stimulated with PWM. Con A-stimulated T lymphocytes derived from aged subjects showed a variable loss of suppressor activity. The mixed lymphocyte culture reaction with mitomycin-treated allogeneic and autologous cells was also impaired in aged subjects. Such an impaired response in the aged is related to higher incidences of malignant lesions and auto-antibodies.

Adult↗

Characteristic and functional specificity of anti-human BAT (brain associated thymocyte antigen) serum.

A rabbit antiserum to human fetal brain after multiple absorption reacted with 100% of thymocytes, 55% of peripheral blood lymphocytes and 90% of enriched T lymphocytes, but not significantly with B lymphocytes. Spontaneous SRBC rosette formation was inhibited by anti-BAT pretreatment, but EAC-rosette formation remained unaffected. The antiserum was itself highly stimulatory. However, cells treated with the antiserum and complement exhibited marked inhibition of responsiveness to Con A, little effect with PHA and no alteration with PWM. The MLC reaction was inhibited only when the responder cells were treated with the antiserum and complement. Treatment of sensitized lymphocytes with the antiserum and complement caused a dose-dependent suppression of blastogenic response to both PPD and n-DNA. No effect, however, was noted in MIF producing cells. Con A induced suppressor function of lymphocytes was abolished by treatment with the antiserum and complement. These results indicate that the anti-BAT serum obtained by us can be utilized for the isolation of T lymphocyte subsets.

Animals↗