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Biomedical subjects

T Sakane

Publications and source records attributed to T Sakane.

214 records · Page 12Linked to original sources
PubMed1977

Human suppressor T cells induced by concanavalin A: suppressor T cells belong to distinctive T cell subclasses.

Human peripheral blood lymphocytes were stimulated by concanavalin A (Con A) and then evaluated by their suppressive activity for thymus-derived (T) cell- and bone marrow-derived (B) cell-proliferative responses to mitogen and allogeneic cells. Con A-activated T cells markedly suppressed these responses, but Con A-activated B cells failed to demonstrate suppressor activity. Discontinuous bovine serum albumin (BSA) density gradient separation of T cells which had been activated by Con A demonstrated that a fraction containing blast cells as well as fractions containing unproliferated cells manifest the same degree of suppressor capabilities. However, when density gradient separation of T cells followed by subsequent incubation with Con A was performed, fractions of proliferating cells of low density exhibited no suppression; a fraction containing high density T cells produced marked suppression, but this fraction incorporated only little thymidine in response to Con A. Thus, these studies indicate that Con A-induced suppressor T cells belong to a distinctive subpopulation which has already been programmed to express this function before exposure to Con A and that cell proliferation may not be a prerequisite for the development of such suppressor T cells.

B-Lymphocytes↗
PubMed1975

Unscheduled DNA synthesis in human lymphocytes treated with neocarzinostatin.

In an attempt to quantitate DNA repair induced by Neocarzinostatin, the incorporation of labeled thymidine into the human peripheral lymphocytes after exposure to the agent was studied by autoradiography. The exposure of lymphocytes to Neocarzinostatin for 60 min at the concentrations as low as 0.05 mug/ml caused a significant increase in the number of grains per cell within 2 hr of incubation with 10 muCi/ml of 3H-thymidine in the presence of 2mM of hydroxyurea. The number of grains increased with the increasing dose of the agent up to the concentration of around 2.5 mug/ml and then fell at higher concentrations. The extent of maximum incorporation induced by Neocarzinostatin was found to be almost comparable to that induced by 100 erg/mm2 of UV irradiation. Hydroxyurea or caffeine in the labeling medium showed little or no effect on the grain count, but acriflavine at 0.1 mM reduced the grain count by a factor of about 6. These results indicate that relatively high level of repair synthesis occurred in human lymphocytes after exposure to Neocarzinostatin and provide further evidence for the direct damage of cellular DNA induced by the antibiotic.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Studies of immune functions of patients with systemic lupus erythematosus. I. Dysfunction of suppressor T-cell activity related to impaired generation of, rather than response to, suppressor cells.

T cell suppressor function in patients with systemic lupus erythematosus (SLE) was evaluated by studying the ability of concanavalin A- (Con A) activated T cells to suppress proliferative responses by responder cells autologous with the Con A-activated T cells. Impaired suppressor T-cell activity in patients with SLE was observed with regard to three effector functions: 1) the allogeneic response of T cells, 2) the Con A response of T cells, and 3) the B cell response to pokeweed mitogen (PWM). No defect was found with regard to suppression of the T-cell response to phytohemagglutinin (PHA). Mixing experiments between SLE and normal cells were carried out to further define the nature of the SLE suppressor defect. When responder cells from SLE patients were cultured with Con A-activated T cells from normal controls, the normal suppressor T cells caused suppression of SLE responder cells. In contrast, Con A-activated T cells from SLE patients were incapable of exerting suppressor effects on normal responder cells. These observations indicate that the impaired suppressor activity in SLE patients resides in the generation of suppressor T cells, rather than in the response to suppressor T cell signals.

B-Lymphocytes↗
PubMedDate not supplied

Sublingual nifedipine in elderly patients: even a low dose induces myocardial ischaemia.

1. Low doses of sublingual nifedipine are still used for the treatment of hypertensive crises, although recent studies have raised concerns that sublingual nifedipine may cause serious dose-dependent adverse effects. The present study was performed to test the safety of low-dose sublingual nifedipine administered to elderly hypertensive patients. 2. Systemic blood pressure measurements and electrocardiographic (ECG) examinations were performed before and 45-60 min after a 5 mg dose of sublingual nifedipine in 93 consecutive hypertensive patients, 65 years of age or older, who were without coronary artery disease. In 33 patients, the effects of nifedipine on myocardial lactate metabolism were studied during cardiac catheterization. 3. In all patients, following nifedipine administration, blood pressure (BP) decreased significantly, while heart rate (HR) increased, and symptoms associated with elevated BP disappeared. However, changes consistent with myocardial ischaemia appeared on the ECG in six of 55 patients with left ventricular hypertrophy (LVH) and in one of 38 patients without LVH, although only two of these seven patients experienced angina-like precordial tightness. Sublingual nifedipine decreased myocardial lactate extraction from 52 +/- 13 to 38 +/- 19% in 20 patients with LVH (P = 0.02), but myocardial lactate extraction remained stable in 13 patients without LVH (49 +/- 7 to 50 +/- 5%; NS). The change in lactate extraction was significantly correlated with the percentage change in diastolic arterial pressure (r = 0.77, P < 0.001). 4. These results suggest that sublingual nifedipine, even at the low dose of 5 mg, may cause myocardial ischaemia in some elderly patients with LVH that is associated with a marked reduction in coronary perfusion pressure.

Administration, Sublingual↗
PubMedDate not supplied

Troponin T in the coronary sinus and percutaneous transluminal coronary angioplasty related myocardial injury.

1. Myocardial injury has been shown to be associated with successful percutaneous transluminal coronary angioplasty (PTCA). The present study was designed to determine whether uncomplicated successful PTCA results in myocardial injury by measuring coronary sinus (CS) cardiac troponin T (cTnT). 2. We measured cTnT in the CS and the femoral vein (FV) in 16 patients with stable angina pectoris who underwent uncomplicated PTCA for stenotic lesions of the left anterior descending artery. Blood samples were drawn from both the CS and FV before and immediately after PTCA and every 4 h for the next 12 h. 3. All patients had chest pain and electrocardiographic ST segment elevation or depression during balloon inflation and higher peak elevation of cTnT in the CS than in the FV (0.054 +/- 0.059 vs 0.036 +/- 0.022 ng/mL; P < 0.05). However, all CS cTnT levels were within the normal range over the 12 h period. 4. The fact that CS cTnT measurements showed no evidence of uncomplicated PTCA-related myocardial injury led us to conclude that uncomplicated successful PTCA does not cause myocardial injury.

Aged↗
PubMedDate not supplied

Involvement of cAMP responsive element binding protein (CREB) in the synovial cell hyperfunction in patients with rheumatoid arthritis.

OBJECTIVE: To elucidate a possible role of cAMP responsive element binding protein (CREB) in rheumatoid arthritis (RA) synovial cell function, we have studied CREB expression of synovial cells and the effects of an inhibitor of the cAMP/CREB signal pathway on synovial cell function in patients with RA. METHODS: We examined CREB expression by immunohistochemical staining, immunocytochemical staining, and gel shift assays. Effects of cAMP/CREB inhibitor on the proliferation of RA synovial cells were assessed by [3H]-TdR incorporation, and those on proinflammatory cytokine and matrix metalloproteinase (MMP) production by reverse transcription PCR and ELISAs. RESULTS: Immunohistochemical staining of synovial tissue revealed that CREB is expressed mainly in the lining and sublining layers of synovium in patients with RA. DNA binding activity of CREB was ascertained by a gel shift assay. We also confirmed nuclear translocation and phosphorylation of CREB in TNF-alpha stimulated RA fibroblast-like synovial cells by immunocytochemical staining. Modulators of cAMP/CREB signaling pathway, such as Rp-cAMP, had an inhibitory potential on RA synovial cell proliferation in vitro. Rp-cAMP also inhibited the proinflammatory cytokine and MMP production. CONCLUSION: CREB is involved in the synovial cell activity in patients with RA. Inhibition of CREB activity by its inhibitor brings about the correction of aberrant synovial cell functions in patients with RA, thus suggesting a possible clinical application of cAMP/CREB inhibitors.

Aged↗
PubMedDate not supplied

Aberrant expression of Fas ligand on anti-DNA autoantibody secreting B lymphocytes in patients with systemic lupus erythematosus: "immune privilege"-like state of the autoreactive B cells.

BACKGROUND: Fas/Fas ligand (FasL) system has been assigned a pivotal role in the development and maintenance of peripheral tolerance, and mice with defects in their Fas/FasL system develop lupus-like symptoms. In this study we examined FasL expression of peripheral blood lymphocytes in patients with systemic lupus erythematosus (SLE). METHODS: We assessed FasL mRNA and protein expression by reverse transcription (RT)-PCR and immunoblotting and immunocytochemical staining, respectively, in patients with SLE. Anti-DNA antibody secreting B cells were purified using biotin labeled DNA and streptavidin-bead. RESULTS: Expression of FasL protein was not or very weakly detected in freshly isolated PBMC in normal individuals. In contrast, freshly isolated SLE PBMC exhibited the enhanced expression of FasL protein without in vitro stimulation. Not only purified T cells but also purified B cells expressed FasL on their cell surface spontaneously. In addition, freshly isolated anti-DNA autoantibody secreting B cells express FasL without in vitro stimulation. CONCLUSION: The results suggest that autoreactive B lymphocytes which aberrantly express FasL may kill Fas+ immunoregulatory T lymphocytes. Thus aberrantly expressed FasL may facilitate escape of the autoreactive B cells from the immune tolerance system, and may contribute to the sustained secretion of autoantibodies in patients with SLE.

Adolescent↗
PubMedDate not supplied

Preferential expression of B7.2 (CD86), but not B7.1 (CD80), on B cells induced by CD40/CD40L interaction is essential for anti-DNA autoantibody production in patients with systemic lupus erythematosus.

OBJECTIVE: B7 (CD80/CD86) molecules are over-expressed in patients with SLE. However, it is not clear whether CD80/CD86 molecules are involved in the pathogenic autoantibody production specifically or in the polyclonal antibody production in human SLE. The present study was carried out to characterize B7 molecules on B cells in autoantibody production. METHODS: Expression of costimulatory molecules was analyzed by RT-PCR and two-color immunofluorescence staining. Purified B cells were co-cultured with T cells in the presence of anti-costimulatory molecule antibody. RESULTS: Excessive expression of CD86 and CD80 molecules was evident on freshly isolated B cells in patients with SLE. Normal B cells did not express CD86 molecules spontaneously and expressed it after co-culture with activated T cells. CD86 expression on normal and SLE B cells induced by the activated T cells was inhibited by the addition of anti-CD40L into the cell culture. Furthermore, CD40L expression on T cells upon activation was enhanced in SLE patients. Anti-DNA antibody production by SLE B cells in the presence of activated T cells was markedly inhibited by anti-CD86, but not anti-CD80. Anti-CD86 treatment inhibited polyclonal Ig and anti-SS-A antibody production of SLE B cells, suggesting the preferential involvement of CD86 in polyclonal antibody production. CONCLUSION: SLET T cells express CD40L excessively, and the CD40/CD40L pathway is involved in the CD86 over-expression of SLE B cells; thus T cell abnormality is at least partially involved in B cell hyperactivity. Enhanced CD86 expression of B cells by CD40L is essential for polyclonal antibody production.

Adolescent↗
PubMedDate not supplied

Selective suppression of resting B cell function in patients with systemic lupus erythematosus treated with cyclophosphamide.

The immunological function of patients with inactive systemic lupus erythematosus (SLE) receiving chronically administered, low-dose cyclophosphamide (CY) together with prednisolone (PSL) was compared with that of inactive patients receiving PSL alone. A striking selective suppression of "genuine" resting, but not "partially" or "fully" activated, B cell function was noted in the patients receiving PSL + CY as measured by Staphylococcus aureus Cowan I (SAC)-induced proliferative responses by Percoll-separated small resting B cells of high density; the small resting B cells sedimenting in a high density fraction were more responsive to SAC in patients treated with PSL alone than those in normal controls. However, the spontaneous proliferation and spontaneous secretion of immunoglobulins by peripheral blood B cells were elevated in both the patient groups. The proliferative responses to phytohaemagglutinin and concanavalin A by T cells were not significantly different between both patient groups. The data indicate that the genuine resting B cells may be the major target for the CY effect in SLE, and thus such selective suppression may help explain the efficacy of CY and PSL together in treating SLE.

Adult↗
PubMedDate not supplied

The role of somatostatin in the pathophysiology of rheumatoid arthritis.

Involvement of neuro-endocrineimmune interactions in the development of pathologic responses has been suggested in patients with rheumatoid arthritis (RA). Recently we studied the production of an inhibitory neuropeptide-somatostatin (SOM)--and somatostatin receptor (SOMR) expression in RA synovium and its function in patients with RA. We found that physiologic concentrations of SOM inhibited the proliferation of RA synovial cells. Proinflammatory cytokine and matrix metalloproteinase (MMP) production by RA synovial cells were also inhibited by SOM. Subtype 1 and subtype 2 SOMR were expressed on fibroblast-like synovial cells, and the expression of subtype 2 SOMR was up-regulated with the proinflammatory cytokine treatment of the synovial cells in RA patients. RA fibroblast-like cells synthesized SOM by themselves, suggesting that SOM may act as an autocrine regulator of synovial cell functions in RA patients. SOM and SOM analogues have also been reported to be effective in the treatment of patients with RA. In summary, SOM inhibited aberrant synovial cell functions in patients with RA, suggesting a possible clinical application of this neuropeptide.

Arthritis, Rheumatoid↗