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Biomedical subjects

I Tsuyuguchi

Publications and source records attributed to I Tsuyuguchi.

At least 37 records · Page 2Linked to original sources
PubMed1992

A raised level of soluble CD8 in bronchoalveolar lavage fluid in summer-type hypersensitivity pneumonitis in Japan.

We used ELISA to measure soluble CD8 (sCD8) in the bronchoalveolar lavage fluid (BALF) and serum of patients with summer-type hypersensitivity pneumonitis (HP). The sCD8 levels in BALF were significantly higher in the patients with summer-type HP, surpassing those found in sarcoidosis and the other pulmonary diseases studied; however, the sCD8 levels in the serum of patients with summer-type HP did not differ from the levels of the healthy controls. The numbers of CD8+ T cells were increased in the BALF of the patients with summer-type HP, and there was a correlation between the sCD8 levels and the concentrations of CD8+ T cells. Gel filtration and polyacrylamide gel electrophoresis of the fluid revealed that the anti-CD8 monoclonal antibody-reactive components in the BALF of patients with pneumonitis corresponded to a protein with a molecular weight of between 52 and 54 kDa. Soluble CD8-rich fraction purified from the BALF of patients with summer-type HP augmented in vitro lymphocytes' proliferative responses stimulated with Cryptococcus neoformans, one of the causative agents for summer-type HP. Our result suggests that soluble CD8 in the BALF may play an important role in the pathogenesis of summer-type HP.

Adult↗
PubMed1992

[Prediction formulas for pulmonary function tests expressed in linear and exponential form for healthy Japanese adults].

We studied 21 parameters of pulmonary function in 172 healthy Japanese adult smokers and non-smokers ranging from 18 to 83 years of age. Prediction formulas for each parameter were calculated in both linear and exponential form using multiple regression analysis with regard to sex, age, height and weight. The exponential form was superior to the linear form for V25, V50, PEF, FVC, VC, FEV1.0, FEV1.0%, TLC, DLCo and DL/VA, namely, the parameters whose predictive value decreases with aging. In particular for V25, only the exponential form of the predictive formula could be applied for subjects with advanced age. For PMI, LCI, IDI, pulmonary N2 clearance delay, and single breath delta N2, indices for unevenness of intrapulmonary gas distribution, there has been no previous report about their predictive formulas and ours is the first. These predictive formulas all showed increasing values with aging, and showed higher predictive values in females than in males, except for delta N2. These parameters require further study with respect to their normal value ranges and differences between males and females.

Adolescent↗
PubMed1991

Increase of T-cell receptor gamma/delta-bearing T cells in cord blood of newborn babies obtained by in vitro stimulation with mycobacterial cord factor.

Cord blood T lymphocytes proliferated in vitro in response to mycobacterial organisms but did not proliferate in the presence of tuberculin purified protein derivative. Components recognized by cord blood T cells were resistant to protease digestion. In contrast, T lymphocytes derived from tuberculin-positive adult peripheral blood proliferated when stimulated by the protease-sensitive component of mycobacterial organisms or purified protein derivative, confirming that adult T cells respond to protein components whereas cord blood T cells respond to the nonpeptide component of mycobacteria. In vitro culture of cord blood lymphocytes stimulated by either mycobacterial lysates or the lipid fraction showed increases in the numbers of T-cell receptor (TcR) gamma/delta T lymphocytes with no changes in the numbers of TcR alpha/beta T lymphocytes in contrast to the in vitro cultures of adult blood lymphocytes stimulated with mycobacterial ligands in which no increase of TcR gamma/delta cells was observed. Interleukin-2 receptor (CD25) and Ia antigen (HLA-DR) analyses evidenced the activation of a large proportion of cord blood gamma/delta T cells which had increased after stimulation with mycobacteria in vitro. Further characterization of mycobacterial ligand suggested that the lipid fraction of mycobacterial lysate or trehalose dimycolate-cord factor was the most plausible cause for T-cell proliferation in cord blood. These results suggest that when the gamma/delta T cells in a newborn infant not yet sensitized to any pathogenic organisms are confronted by a mycobacterium, they respond nonspecifically to the mycobacterial organism or its lipid component (cord factor). gamma/delta T cells may therefore play a distinct role in forming the first line of the host defense system against certain microorganisms.

Cord Factors↗
PubMed1991

Release of a suppressor cell-inducing factor by monocytes from patients with pulmonary tuberculosis.

We observed that blood monocytes from tuberculous patients secreted a factor which induced suppressor cells. Monocyte-enriched adherent cells were prepared from peripheral blood mononuclear cells (PBMC) of 14 patients with active pulmonary tuberculosis or nine healthy tuberculin skin reactors and were cultured without any stimulus for 5 days. For induction of suppressor cells, PBMC from a healthy tuberculin reactor were cultured with the monocyte culture supernatants (MN SUP). After 2 days, those cells were washed and irradiated, then tested for their ability to suppress blastogenesis in autologous PBMC stimulated with purified protein derivative (PPD). Mean activity of suppressor cell induction in MN SUP of patients with pulmonary tuberculosis was significantly greater than that of healthy controls. In contrast, PPD-induced blastogenic responses in PBMC from tuberculous patients were lower than in controls. When we divided those tuberculous patients into high and low secretor groups on the basis of the magnitude of suppressor cell induction by MN SUP, PBMC from the high secretors had lower direct blastogenic responses to PPD than those of the low secretors. The blastogenic responses of PBMC from the high secretors, but not the low secretors, were significantly lower than those of healthy subjects. MN SUP which contained high suppressor cell-inducing activity had no effect on PPD-induced blastogenesis of PBMC from a healthy donor. These data suggest that monocytes from some tuberculous patients indirectly depress lymphocyte blastogenesis through a suppressor cell-inducing factor.

Adult↗
PubMed1990

Basophil histamine release by platelet-activating factor in aspirin-sensitive subjects with asthma.

Histamine release induced by platelet-activating factor (PAF) from leukocytes of aspirin-sensitive subjects with asthma was higher than that from normal control subjects, despite the similarity of anti-IgE-induced histamine release. Moreover, basophils of some aspirin-sensitive subjects with asthma released histamine by PAF stimulation in the absence of cytochalasin B that affects histamine release and is required in PAF-induced histamine release from leukocytes of atopic subjects with asthma and normal control subjects. In addition to temperature dependency and inhibition by ethylenediaminetetraacetic acid reported previously, PAF-induced histamine release was enhanced by cytochalasin B and indomethacin and inhibited by dexamethasone. These features are common with IgE-mediated histamine release and suggest the existence of the common pathway to PAF-induced histamine release and IgE-mediated histamine release. The results in the present study indicate the pathophysiologic significance of PAF-induced histamine release and that activation of basophils by PAF may be relevant to the pathogenesis in some aspirin-sensitive subjects with asthma.

Adult↗
PubMed1990

Production of tumor necrosis factor alpha by monocytes from patients with pulmonary tuberculosis.

We studied the production of tumor necrosis factor alpha (TNF-alpha) by peripheral blood monocytes taken from patients with pulmonary tuberculosis and from healthy controls. It was found that the monocytes from patients with newly diagnosed tuberculosis released significantly greater amounts of TNF-alpha in vitro in response to lipopolysaccharide than did those from healthy controls (P less than 0.05). However, the monocytes from patients with chronic refractory tuberculosis released significantly lower amounts of TNF-alpha than did those from patients with newly diagnosed tuberculosis (P less than 0.005). Even when the cells were primed for 24 h with 500 U of recombinant interferon gamma per ml, the same pattern of results was observed. The depressed TNF-alpha production by the monocytes from patients with chronic refractory tuberculosis was also shown in response to Mycobacterium bovis BCG. This depressed TNF-alpha production did not recover, even when cultured for 1 to 7 days in the sera of healthy individuals. The sera from patients with chronic refractory tuberculosis did not have any suppressive effect on the lipopolysaccharide-induced TNF-alpha production. Thus, it was demonstrated that the levels of TNF-alpha produced by monocytes were related to the disease states of pulmonary tuberculosis and that the depressed TNF-alpha production by monocytes in patients with chronic refractory tuberculosis might not be acquired.

Adult↗
PubMed1990

Mycobacterium avium-Mycobacterium intracellular complex-induced suppression of T-cell proliferation in vitro by regulation of monocyte accessory cell activity.

Heat-killed whole Mycobacterium avium-Mycobacterium intracellulare complex (MAC) and its lipid component impaired the capacity of human peripheral blood mononuclear cells to proliferate in vitro in response to concanavalin A (ConA), purified protein derivative of tuberculin (PPD), and to a lesser degree, phytohemagglutinin stimulation. Inhibition by MAC was not contingent upon prior exposure of the donor to MAC or other mycobacteria and occurred with lymphocytes from tuberculin-negative as well as -positive subjects. The suppression was not due to the toxicity of MAC. The suppression by MAC was not blocked by indomethacin. Adherent cell depletion and cell mixing experiments with T cells indicated that monocytes and not T cells were a major contributor to the immunosuppression observed. However, neither interleukin-1 production nor the expression of HLA-DR (Ia antigen) by monocytes was suppressed by MAC treatment. On the other hand, treatment of monocytes with MAC or MAC-derived lipid resulted in significant decreases in CD11b, a member of the leukocyte function-associated molecule-1 and LeuM3 (CD14) molecule. Anti-CD18 (beta-chain of the leukocyte function-associated molecule-1 family) monoclonal antibody had suppressive effects on ConA- and PPD- but not phytohemagglutinin-induced in vitro lymphocyte blastogenesis. We suggest that MAC and MAC-derived lipid suppress the ConA- and PPD-induced T-cell proliferations by blocking the expression of accessory molecules on the surfaces of monocytes which might be involved in nonspecific monocyte-T-cell interactions and not by inhibiting either monocyte Ia antigen expression or interleukin-1 production by monocytes.

Antigen-Presenting Cells↗
PubMed1990

[Clinical immunology of tuberculosis].

The standard tuberculin skin test has been known as the prototype of delayed type hypersensitivity testing which is mediated by T cells and macrophages and plays an important role in the pathogenesis of tuberculosis. Tuberculosis is indeed a chronic infectious disease, but variation in the host immune responses to tubercle bacilli results in the various clinical manifestations of the disease ranging from an immunologically hyperreactive state observed in pleural fluid lymphocytes in tuberculous pleurisy to an almost totally unresponsive state observed in those severely ill with refractory tuberculosis. In tuberculous pleurisy, T cells in pleural fluid respond remarkably in vitro to PPD tuberculin whereas T cells in peripheral blood responded poorly to PPD stimulation. Compartmentalization of PPD-reactive T cells in the pleural fluid and immunosuppression by T cells and/or macrophages in the peripheral blood were responsible for this immunological difference observed between the lymphocytes in pleural fluid and those in peripheral blood of tuberculous pleurisy. In advanced, drug-resistant tuberculosis as well as in nontuberculous mycobacterial infection, the proliferative responses of T cells in vitro to PPD stimulation were impaired. This depressed T cell response was due to depressed interleukin-2 (IL-2) production and not due to depressed IL-2 responsiveness. Therefore, the addition of exogenous IL-2, returned the depressed PPD-induced lymphocyte proliferation in vitro in these patients to the level of the response observed in lymphocytes from patients with newly-diagnosed tuberculosis. Our results suggest that recombinant IL-2 offers a novel approach to the therapy of advanced, drug-resistant tuberculosis and nontuberculous mycobacterial infection. Preliminary clinical trials of immunotherapy with recombinant IL-2 reveals the effectiveness of this therapy and encourages us to extend the trial to a larger scale. Tubercle bacilli have various biological activities. Research on tuberculosis and tubercle bacilli have contributed much to the progress of biochemistry, pathology and immunology. Mycobacterium is a fascinating organism, which now presents another big appeal to those studying immunology: Study of immunological interaction between gamma delta T cells and the highly conserved protein in mycobacteria, HSP, heat shock protein will contribute to the elucidation of the mechanism of immunological surveillance and the mechanism of autoimmune diseases. In addition, it will also contribute to the development of a new mycobacterial vaccine which will give direct, protective immunity against tuberculosis.

Humans↗
PubMed1988

Histamine release from human leukocytes by platelet-activating factor.

Platelet-activating factor (PAF) was found to induce histamine release from human basophils in mixed leukocytes in the presence of cytochalasin B. The reaction was rapid and dependent on temperature. The release was lower at a high concentration of PAF and was inhibited by EDTA, suggesting a noncytolytic mechanism. CV-3988, a PAF antagonist, inhibited the reaction dose-dependently. PAF acted as an IgE-independent stimulus, but PAF-induced histamine release from leukocytes of allergic asthmatics, who had elevated serum IgE levels, was significantly higher than that from leukocytes of controls. These results suggest that PAF-induced histamine release is useful for studying the role of PAF in the pathogenesis of allergic disorders including bronchial asthma.

Adult↗
PubMed1988

An analysis of in vitro T cell responsiveness in nontuberculous mycobacterial infection.

In vitro cell-mediated immunity was examined in patients infected with nontuberculous mycobacteria, Mycobacterium avium-intracellulare complex in Japan. Peripheral blood lymphocytes of patients, as compared with those of tuberculous patients or tuberculin-positive healthy donors, showed depressed in vitro blastogenic responses to purified protein derivative of tuberculin (PPD), not only to PPDs of Mycobacterium tuberculosis but also to PPD-B and PPD-Y of M intracellulare and M kansasii, respectively. Nonspecific lymphocyte blastogenic responses to concanavalin A, phytohemagglutinin and pokeweed mitogen were normal. Analysis of defective in vitro PPD-induced lymphocyte blastogenic responses in these patients revealed that PPD-induced interleukin 2 (IL-2) production was impaired whereas PPD-induced IL-2 responsiveness was normally developed after PPD stimulation. Therefore, addition of exogenous recombinant human IL 2 substantially recovered the in vitro depressed PPD-induced blastogenic responses in these patients with nontuberculous mycobacterial infection.

Cells, Cultured↗
PubMed1987

Recombinant human interleukin-2 reverses in vitro-deficient cell-mediated immune responses to tuberculin purified protein derivative by lymphocytes of tuberculous patients.

In vitro lymphocyte proliferative response to purified protein derivative of tuberculin (PPD) was investigated in patients with tuberculosis. Peripheral blood lymphocytes (PBL) from patients with advanced, refractory tuberculosis showed a significantly depressed response compared with the response of PBL from patients with newly diagnosed tuberculosis (P less than 0.01). A further characterization of this low responsiveness to PPD revealed that PBL from these advanced tuberculous patients failed to generate interleukin-2 (IL-2) in response to PPD stimulation. IL-2 receptor (Tac antigen) expression on the surface of T cells after PPD stimulation was also impaired, although to a lesser extent, in the patients with advanced, refractory tuberculosis. We attempted to overcome the depressed in vitro response observed in PBL from patients with advanced, refractory tuberculosis and found that the addition of exogenous, recombinant IL-2 returned the depressed PPD-induced PBL proliferation in these patients to the level of response observed in PBL from patients with newly diagnosed tuberculosis. The addition of recombinant IL-2 also had a restorative effect (up regulation) in vitro on the partly impaired PPD-induced IL-2 receptor expression by PBL from the patients with advanced, refractory tuberculosis. Our results suggest that recombinant IL-2 may offer a novel approach to the therapy of advanced, drug-resistant tuberculosis.

Humans↗
PubMed1987

T-lymphocyte subsets in primary lung cancer.

T-cell subsets in the peripheral blood of 63 primary lung cancer patients (23 with adenocarcinoma, 23 with squamous cell carcinoma and 17 with small cell carcinoma) and 24 normal healthy controls were determined by indirect immunofluorescence, using the monoclonal antibody reagents OKT3, OKT4 and OKT8. Correlations between T-lymphocyte subset values and stages or cell types of disease were sought. Total lymphocytes in the patient group were decreased. However, no significant difference from controls was seen in the percentage of OKT3-positive cells (Pan T-cells) in the cancer patients. The percentage of OKT8-positive cells (cytotoxic/suppressor) was increased in the early stage of disease whereas the percentage of OKT4 positive cells (inducer/helper) remained at the control level throughout all stages. The ratio of OKT4-positive to OKT8-positive T-cells (OKT4/OKT8), reflecting the balance of immunoregulatory T-cells, was, therefore, significantly decreased in patients with stage I-II lung cancer (P less than 0.05), especially in squamous cell lung cancer (P less than 0.05), whereas in stages III or IV, this T4/T8 ratio returned to the control level. In small cell carcinoma, the T4/T8 ratio was significantly decreased in stage III (P less than 0.01) and returned to the control level in stage IV.

Adult↗
PubMed1986

Frequency of tuberculin-reactive T-lymphocytes in pleural fluid and blood from patients with tuberculous pleurisy.

A limiting dilution assay was used to determine the frequency of T-lymphocytes reactive to purified protein derivative of tuberculin (PPD). Pleural fluid from patients with tuberculous pleurisy showed higher frequencies of PPD-reactive T-lymphocytes than peripheral blood from the same patients or tuberculin-positive healthy control subjects. The mean frequencies were 1/2,204 T cells in pleural fluid from tuberculous pleurisy, 1/14,970 T cells in peripheral blood from the same patients, and 1/13,130 T cells in peripheral blood from healthy controls. The concentration of tuberculin-reactive lymphocytes in tuberculous pleural fluid could represent selective accumulation or in situ expansion of this population of cell.

Adult↗
PubMed1986

Increased circulating activated T-cells in lung cancer.

T-cell activation (Tac) antigens, which are closely associated with the receptors for interleukin 2 (IL 2) and expressed on activated human T-lymphocytes, are found on a small percentage of normal peripheral T-cells. Elevated levels of Tac antigen-positive (Tac+) cells were observed in a high proportion of patients with untreated primary lung cancer assessed by using monoclonal anti-Tac antibody. The mean percentage of Tac+ cells in peripheral blood lymphocytes was 13.1 +/- 6.4 percent in patients with primary lung cancer (n = 67), as compared with 4.3 +/- 1.9 percent in normal controls (n = 30) (p less than 0.001). No significant differences were observed among the cell types of lung cancer examined (adenocarcinoma and squamous and small cell carcinoma). The stages of the disease also showed no significant differences in the development of Tac+ cells. Our results suggest that T-cell-mediated active immune mechanisms against malignant cancer cells are operative in patients with lung cancer, resulting in an increase in activated T-cells in the peripheral blood, although it remains to be elucidated whether these activated T-cells exert a favorable or unfavorable effect on their host.

Adenocarcinoma↗
PubMed1984

Analysis of T cell subsets by monoclonal antibodies in patients with tuberculosis after in vitro stimulation with purified protein derivative of tuberculin.

By using OKT monoclonal antibodies; OKT3(pan T), OKT4(inducer/helper), OKT8 (suppressor/cytotoxic) and OKIa1, T lymphocyte subsets were examined in lymphocytes of patients with tuberculosis both before and after in vitro stimulation with purified protein derivative of tuberculin (PPD). In freshly obtained lymphocytes samples before culture, a significantly high T4/T8 ratio in pleural fluid lymphocytes (PFL) from patients with tuberculous pleurisy was observed as compared with either their PBL, or the PBL from healthy controls. In addition, PFL from patients with tuberculous pleurisy showed increased numbers of E rosetting (E-RFC), OKT3+ and OKT4+ cells as compared with their PBL. A low T4/T8 ratio was also observed in PBL of patients with advanced, refractory tuberculosis. After stimulation with PPD in vitro, the T4/T8 ratio increased further in PFL as well as in PBL from patients with newly diagnosed, fresh tuberculosis. Investigation of fractionated T lymphocyte subsets revealed that PPD-induced proliferating lymphocytes belonged to T4+ and not T8+ lymphocytes. Ia antigen bearing T lymphocytes (Ia-T) were increased in all lymphocyte groups studied after in vitro stimulation with PPD. In particular, a remarkable increase was observed when PFL were stimulated in vitro with PPD. Our results suggest that the clinical features of tuberculosis reflect the immunological activity of T lymphocyte subsets in this disease.

Adolescent↗