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Biomedical subjects

T Sakane

Publications and source records attributed to T Sakane.

At least 145 records · Page 8Linked to original sources
PubMed1987

The ratio of lipidperoxides to superoxide dismutase activity in the skin lesions of patients with severe skin diseases: an accurate prognostic indicator.

We studied 35 patients with active inflammatory skin diseases, measuring the levels of lipidperoxides and of the oxygen radical scavenging enzyme superoxide dismutase (SOD) in biopsy specimens of skin lesions. Lipidperoxide levels were markedly elevated in all patients. In fifteen patients with disease that was severe and highly resistant to therapy, SOD activity was only slightly increased, in comparison with normal controls. In contrast, in the twenty patients with mild disease that responded well to therapy, SOD activity was markedly elevated. The ratio of lipidperoxide levels to SOD activity was thus an accurate prognostic indicator, being elevated only in the group not responding to treatment. These findings suggest that the severity of allergic inflammatory skin disease and/or the response to treatment may in part be governed by the degree to which the patient's SOD activity is up-regulated in response to the generation of tissue-damaging substances such as lipidperoxides. Interestingly, our studies revealed the SOD activities of both normal and inflamed skin to be unexpectedly high; our data suggest that SOD plays a critical role in protecting the skin from the effects of oxygen radicals and ultraviolet light.

Adolescent↗
PubMed1987

Luminol-independent chemiluminescence by phagocytes is markedly enhanced by dexamethasone, not by other glucocorticosteroids.

The effect of several glucocorticosteroids on the generation of reactive oxygen species (ROS) was examined. The ROS assessed were O-2, H2O2, OH., and chemiluminescence (CL) (determined in the presence or absence of luminol), generated by both opsonized zymosan-stimulated neutrophils or monocytes and by the xanthine-xanthine oxidase system. Except for luminol-independent CL, only high concentrations (10(-4) M) of steroids could decrease each ROS. In contrast, luminol-independent CL generation in the phagocyte system was increased in a dose-dependent manner by the addition of dexamethasone, but not by any other steroid. Further, in lymphocyte cultures stimulated with Con A for four days, luminol-independent CL generation was demonstrated and enhanced by the addition of dexamethasone, although CL generation was not detected in the absence of dexamethasone. These findings provide evidence that CL does not always represent light specific to ROS, and they suggest the possibility that dexamethasone induces emission of light at sites of inflammation.

Adrenal Cortex Hormones↗
PubMed1987

Enhanced gastrointestinal absorption of drugs in rats pretreated with the synthetic immunomodulator, levamisole.

The effect of levamisole on drug absorption from the rat small intestine has been investigated by means of an in-situ recirculation technique. The absorption of salicylic acid, sulphanilamide and aminopyrine was significantly increased by the intraperitoneal administration of levamisole (2 mg) 1 day before the absorption studies, but there was no significant effect on absorption from the small intestine of indomethacin, bromthymol blue, sulphafurazole (sulfisoxazole), quinine, sulphanilic acid, phenol red (phenolsulfonphthalein), L-tryptophan and fluorescein isothiocyanate-dextrans. The effect of levamisole on the absorption from the small intestine of salicylic acid was marginally dose- and time-dependent, the maximal effect being observed after pretreatment with 2 mg of levamisole 1 day before the absorption studies. Sulphanilamide, similarly, was better sorbed from the small intestine and also from the stomach in the presence of levamisole. The intraperitoneal administration of levamisole may influence the absorption of some low molecular weight drugs from the gastrointestinal tract.

Animals↗
PubMed1987

Phospholipid base exchange activity in the leukocyte membranes of patients with inflammatory disorders.

Phospholipid base exchange and cholinephosphotransferase (CPT) and ethanolaminephosphotransferase (EPT) activities were assessed in the membranes of neutrophils or lymphocytes from patients with various inflammatory disorders. Ethanolamine exchange activity was significantly enhanced in both neutrophils and lymphocytes from patients with active Behçet's disease, active systemic lupus erythematosus (SLE), and severe bacterial infections and slightly enhanced in those from patients with active rheumatoid arthritis (RA), compared with healthy controls. No abnormal findings were found in CPT, EPT, or serine or choline base exchange activities in the leukocytes from any of the diseased groups tested or in the ethanolamine exchange activity of patients with severe viral infections and inactive SLE, RA, and Behçet's disease. The authors have recently demonstrated the enhancement of transmethylation and phospholipase A2 activity in human leukocyte membranes at the height of inflammatory disease states, as well as the activation of leukocyte ethanolamine exchange by bioactive stimulants. These data postulate that phosphatidylethanolamine synthesis by the base exchange reaction may be the precursor of transmethylation and its subsequent activation of phospholipase A2, leading to the induction of arachidonic acid cascade.

Adolescent↗
PubMed1986

Deficiencies in suppressor T cell activity seen in patients with active systemic lupus erythematosus are due to the dilution of normally functioning suppressor T cells by nonsuppressor T cells.

Concanavalin A (Con A)-activated T lymphocytes from patients with active, but not inactive, systemic lupus erythematosus (SLE) failed to express normal suppressor activity, regardless of the phenotype of CD4+ or CD8+. Con A-activated CD4+ or CD8+ T lymphocytes from the SLE patients and from normal controls were further separated into two populations, using the autologous erythrocyte rosette technique. One population very rich in cells capable of forming rosettes with autologous erythrocytes from the active patients showed the same degree of suppressor activity, as did that from normal controls; the CD4+ or CD8+ population poor in autorosetting cells derived from Con A-activated T lymphocytes from both the controls and patients did not express suppressor activity. Moreover, when autorosetting T cells from the active patients and nonrosetting cells from the same patients were mixed at a normal ratio (4:6), normal suppressor activity could be restored. It was notable that the frequency of autorosette-forming cells was markedly reduced in the Con A-activated T lymphocytes from the active, but not inactive, SLE patients, regardless of the phenotype of CD4+ or CD8+. These findings indicate the presence of a normally functioning suppressor T cell population in patients with active SLE. It seems that the lack of suppressor T cell function in patients with active SLE is due to the dilution of a few normal suppressor T cells by large numbers of nonsuppressor T lymphocytes.

Adult↗
PubMed1986

Effect of cyclosporin A on the membrane-associated events in human leukocytes with special reference to the similarity with dexamethasone.

The effect of an immunosuppressive drug, cyclosporin A, and dexamethasone was assessed on the enzymatic reactions of membrane phospholipid in normal human lymphocytes and neutrophils. Incubation for 20 min with cyclosporin A markedly suppressed, in a dose dependent manner, phospholipase A2 activity and the release of prostaglandin E2 in lymphocytes, and slightly those in neutrophils, while no inhibition of phosphatidylethanolamine (PE)-N methyltransferase activity was observed. Choline phosphotransferase (CPT) activity was not inhibited by the drug, either. These inhibitory effects on enzyme activities of membrane phospholipid are similar to those of dexamethasone, although different incubation time of the drug was required to induce inhibitory effects. These findings suggest that cyclosporin A acts upon early membrane events in the activation of cells involved in inflammatory reactions; they further suggest that suppression of immune response by cyclosporin A is at least partly due to inhibition of phospholipase A2 in the plasma membrane of inflammatory cells. This inhibition reduces the production of cell membrane lyso-phosphatidylcholine (PC) and arachidonic acid from PC, which is produced by transmethylation of PE and cytidine diphosphate (CDP) choline pathway of which the last reaction to PC is mediated by CPT.

Cell Membrane↗
PubMed1986

Abnormal B cell function in patients with Behçet's disease.

We evaluated B lymphocyte function in 23 patients with Behçet's disease at various stages. The patients with active disease, but not those with inactive disease, were found to have elevated numbers of cells spontaneously secreting immunoglobulin and a decreased B cell response to the T cell-independent B cell mitogen, Staphylococcus aureus Cowan 1. Moreover, B cells from almost all patients with Behçet's disease were unresponsive to the T cell-dependent polyclonal activator, pokeweed mitogen. These results indicate that B cell abnormalities, including some which are associated with disease activity, could be involved in the pathogenesis of Behçet's disease.

Adult↗
PubMed1986

Analysis of interleukin-2 activity in patients with Behçet's disease. Ability of T cells to produce and respond to interleukin-2.

We examined interleukin-2 (IL-2) activity in patients with Behçet's disease. T cells from all patients with Behçet's disease were able to produce normal levels of IL-2 in response to phytohemagglutinin; however, responsiveness to IL-2 was impaired in their concanavalin A-activated lymphoblasts. This defect was due to decreased numbers of cells bearing IL-2 receptors in patients with early active disease; in patients with chronic active or with inactive disease, there was a decrease in density of IL-2 receptors on T cells bearing these receptors. Unresponsiveness of T cells to IL-2 may thus contribute to immunologic aberrations in Behçet's disease.

Adult↗
PubMed1986

Phospholipid transmethylation and choline phosphotransferase in microsomal fraction of human diseased liver.

The activities of three enzymes catalyzing the production or degradation of phosphatidylcholine, a major structural phospholipid of cell membranes, were assessed in hepatocyte membrane microsomal preparation from patients with various types of liver disease. Choline phosphotransferase activity of preparation from patients with chronic aggressive, chronic active, chronic persistent, alcoholic hepatitis and cirrhosis accompanied by marked necrosis and relatively slight fibrosis was markedly decreased, compared with normal liver; the activity from patients with fatty liver and chronic inactive hepatitis was slightly decreased. Specimens from patients with acute transient hepatitis were not significantly different from normal. Methyltransferase and phospholipase A2 activities tended to parallel that of choline phosphotransferase, although the degree of changes was generally less marked. Our studies indicate that enzyme activities that are critical for hepatic cell membrane integrity and activity are attenuated in liver specimens from patients with disease in which there is marked hepatic cell necrosis.

Adult↗
PubMed1986

Immunological control of drug absorption from the gastrointestinal tract: the mechanism whereby intestinal anaphylaxis interferes with the intestinal absorption of bromthymol blue in the rat.

Rats were immunized intraperitoneally with ovalbumin and the disappearance of bromthymol blue (BTB) from the intestinal lumen, its accumulation in the tissue, and its net absorption were examined by means of an in-situ recirculation technique during local anaphylaxis. The disappearance of BTB from the intestinal lumen and its net absorption were significantly reduced, but there was no significant effect on its accumulation in the tissue. The pH value of the luminal solution and the perfusate volume were not influenced by intraluminal challenge with the antigen in ovalbumin-immunized rats. In addition, no significant effect was observed on intestinal permeability to BTB in the in-vitro everted sac technique. The intestinal blood flow, measured by a hydrogen clearance method, was not reduced significantly by the intraluminal exposure to antigen. There was enhanced Evans Blue leakage and mucus release in the perfusate after intraluminal challenge with ovalbumin in ovalbumin-immunized rats, but not in non-immunized rats. A significant increase of BTB binding with macromolecular substances in the perfusate was observed during the local anaphylaxis. These findings suggest that the decreased absorption of BTB is due to the interaction with the macromolecular substances in the perfusate during local anaphylaxis.

Anaphylaxis↗
PubMed1986

Implications for the role of cognate interactions in in vitro human B cell activation by Staphylococcus aureus Cowan I and pokeweed mitogen.

Human B cell-triggering mechanisms were investigated using the polyclonal activators Staphylococcus aureus Cowan I (SAC) and pokeweed mitogen (PWM). When the cultures of B cells, T cells, and monocytes were stimulated for 5 d by SAC or PWM, B cells could be activated by both mitogens to proliferate and secrete Ig. Even when T cells were substituted by T cell-derived soluble factors, SAC-stimulated B cells could differentiate into Ig-secreting cells. In contrast, interactions of B and T cells for at least the first 6 h of culture were necessary for the B cell triggering by PWM. Experiments that allow a more precise delineation of the B cell-triggering mechanisms by PWM demonstrated that interactions of B cells with T4+ but not T8+ cells are required for the B cell triggering; anti-Ia or anti-T4 antibody can block this triggering; in contrast, anti-T3 or anti-T8 antibody do not exert any effects on the B cell triggering. However, all these monoclonal antibodies could not modulate the ability of B cells that had been already activated by PWM to respond to T cell-derived factors. These data suggest that SAC can directly activate B cells, while cognate interactions between Ia-like antigens on B cells and T4+ cells are essential for B cell triggering by PWM. Furthermore, once B cells are triggered, they will proliferate, differentiate, and secrete Ig in response to T cell-derived factors; Ia-like antigens or T cell differentiation antigens may not be involved in the processes in this cascade.

Antibodies, Monoclonal↗
PubMed1985

Abnormalities in autologous mixed lymphocyte reaction-activated immunologic processes in systemic lupus erythematosus and their possible correction by interleukin 2.

The autologous mixed lymphocyte reaction (AMLR) represents the activation, proliferation and differentiation of T cells in response to signals from autologous non-T cells. Upon stimulation by autologous non-T cells, OKT4+ cells produce interleukin 2 (IL2); cells contained within both OKT4+ and OKT8+ cell populations can also be activated by autologous non-T cells to become sensitive to IL2. Once these activated OKT4+ and OKT8+ cells are exposed to IL2 produced by OKT4+ cells, they will proliferate and go on to differentiate into effector cells. Patients with systemic lupus erythematosus (SLE) have a defect in the AMLR. The ability of OKT4+ cells to produce IL2 in the AMLR is impaired. Upon triggering with autologous non-T cells, their OKT8+ cells become sensitive to proliferative signals of IL2; however, their OKT4+ cells fail to express IL2 receptors. These defects are a consistent feature in patients with SLE. AMLR-induced immunologic processes which require cell interactions between OKT4+ cell subpopulations are not correctable even by the addition of normal IL2. However, the immunologic processes mediated through OKT4+-OKT8+ cell interactions can be corrected with normal IL2. The latter finding suggests that the partial correction of the AMLR-induced immunologic processes with IL2 might lead to suppressed B cell hyperactivity of patients with SLE.

Adult↗
PubMed1985

Methyltransferase and phospholipase A2 activity in membranes of neutrophils and lymphocytes from patients with bacterial and viral infections.

Phospholipid methylation and phospholipase A2 activation in the cell membrane are necessary for the induction of cell function in neutrophils and lymphocytes. We assessed the activity of membrane-associated methyltransferase and phospholipase A2 in neutrophils and lymphocytes from patients with acute and severe bacterial and viral infections. In bacterial patients, methyltransferase and phospholipase A2 activities of neutrophils were significantly enhanced, and [3H]methyl incorporation of lymphocytes was slightly increased. In viral infections, only phospholipase A2 activity of the lymphocytes was increased. These enhanced enzyme activities paralleled disease activity of the two disorders. The methylated products detected by two-dimensional thin-layer chromatogram were confined to methylated phospholipids, indicating that our assay system measures specifically the activity of methyltransferase which mediates the translocation of membrane phosphatidylethanolamine (PE) to phosphatidylcholine (PC) and lyso-PC(LPC). The two enzymatic activities of both neutrophils and lymphocytes in bacterial infections and phospholipase A2 of lymphocytes may, in part, have some correlation to the defense mechanism in these two disorders.

Adult↗
PubMed1985

Role of stimulated neutrophils from patients with systemic lupus erythematosus in tissue injury, with special reference to serum factors and increased active oxygen species generated by neutrophils.

To examine the possible correlation between tissue injury and neutrophil-produced active oxygen (AO) species in patients with systemic lupus erythematosus (SLE), we studied the capacity of the serum from six patients with untreated, active SLE to generate AO and release lysosomal enzymes by normal neutrophils. Cultured endothelial cells from human umbilical cord vein were incubated with serum-stimulated neutrophils to assess AO-induced tissue injury. Serum from patients with bacterial infections and healthy individuals served as controls. AO production was highest in the neutrophils stimulated with SLE patient-derived serum, while lysosomal enzyme release was only slightly increased. SLE neutrophils with or without stimulation and SLE serum-stimulated normal neutrophils produced significantly high levels of cytotoxicity upon coincubation with 51Cr-labeled human endothelial cells. These excessive cytotoxicities were reversed by the presence of superoxide dismutase and catalase, indicating the specificity of the AO effect on endothelial cell damage. These findings suggest that tissue damage in SLE may be partially due to excessive production of AO and that both neutrophils themselves and a serum factor which activates neutrophils are involved in the mechanism for vascular injury.

Adolescent↗
PubMed1985

Reverse relationship between lysosomal-enzyme release and active-oxygen generation in stimulated human neutrophils.

The relationship between the generation of active species of oxygen (O-2, H2O2 and OH.), chemiluminescence, and the release of lysosomal enzymes (lysozyme, alpha-mannosidase and beta-glucuronidase) was examined in human neutrophils stimulated with opsonized zymosan in the presence or absence of active-oxygen scavengers. In the absence of scavengers, increasing zymosan concn stimulated a marked increase in active-oxygen production in a concn-dependent manner and a less rigorously dose-dependent increase in enzyme secretion. Addition of OH. and/or 1O2 scavengers (benzoate, 1,4-diazo-bicyclo-2,2,2-octane or xanthine) caused a marked increase in enzyme release and a decrease in the generation of active-oxygen species except O-2 and H2O2. These findings suggest that exocytosis of lysosomal enzymes by stimulated neutrophils might be attenuated by the active generation of OH. and chemiluminescence. Superoxide dismutase (SOD) at low concns inhibited lysosomal enzyme release while promoting OH formation; and SOD at high concns decreased OH. and O-2 formation and chemiluminescence, accompanied by higher levels of lysosomal enzyme release. Catalase showed an effect similar to that of SOD. Our data suggest that the reduction by scavengers of active-oxygen levels, particularly of the species detected in the OH. and chemiluminescence assays, results in an increase in lysosomal enzyme release.

Dose-Response Relationship, Drug↗
PubMed1985

Decreased oxygen radical generation by neutrophils from patients with measles presumably owing to activation of suppressor T lymphocytes.

The capacity for the generation of oxygen radicals by polymorphonuclear leukocytes (PMNs) was assessed in 29 patients with measles and in control groups. Patients with secondary bacterial infections showed a significantly decreased generation of oxygen radicals; this abnormality did not persist for more than 2 months after disease onset. Normal PMNs incubated with T lymphocytes from these measles patients generated significantly fewer oxygen radicals than those incubated with T cells from either control group. However, normal PMNs incubated with non-T lymphocytes from these measles patients produced normal oxygen radical levels. In addition, irradiation above 1,500 rads of T lymphocytes abrogated the suppressive effect of T cells on PMNs. On the other hand, these abnormal findings were not observed in patients with measles but without secondary bacterial infections. The secondary bacterial infections sometimes seen in measles patients may result from a decrease in oxygen radical generation, presumably induced by the suppressive activity of the T lymphocytes of the patients.

Adolescent↗