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Factors of delayed hypersensitity in pulmonary tuberculosis.

In a study of delayed hypersensitivity in 54 patients with pulmonary tuberculosis who were on specific treatment, 33 patients could not be sensitized to dinitrochlorobenzene (DNCB) although 25 of these were tuberculin (PPD) positive. The majority of the patients also had positive skin reactions to another recall antigen, streptokinase-streptodornase. To exclude a drug effect on DNCB reactivity, 40 untreated patients were studied. Twenty-six (65 per cent) of these did not show DNCB reactivity. The cause for nonsensitization to DNCB was not clear. There was no abnormality in the number of T lymphocytes in the peripheral blood of 28 patients.

Adolescent↗

The effect of in vivo hydrocortisone on subpopulations of human lymphocytes.

This study was designed to determine the effect of in vivo hydrocortisone on subpopulations of lymphoid cells in normal humans. Subjects received a single intravenous dose of either 100 mg or 400 mg of hydrocortisone, and blood was drawn at hourly intervals for 6 h, and then again at 10 and 24 h after injection. Profound decreases in absolute numbers of circulating lymphocytes and monocytes occurred at 4-6 h after both 100 mg and 400 mg of hydrocortisone. Counts returned to normal by 24 h. The relative proportion of circulating thymus-derived lymphocytes as measured by the sheep red blood cell rosette assay decreased maximally by 4 h and returned to base line 24 h after hydrocortisone. There was a selective depletion of functional subpopulations of lymphocytes as represented by differential effects on in vitro stimulation with various mitogens and antigens. Phytohaemagglutinin response was relatively unaffected, while responses to concanavalin A were significantly diminished. Responses to pokeweed mitogen were unaffected by 100 mg of hydrocortisone, but greatly diminished by 400 mg of hydrocortisone. In vitro responses to the antigens streptokinase-streptodornase and tetanus toxoid were markedly diminished by in vivo hydrocortisone. Reconstitution of monocyte-depleted cultures with autologous monocytes partially corrected the diminished response to antigens. This transient selective depletion of monocytes and subsets of human lymphocytes by a single dose of hydrocortisone is most compatible with a redistribution of these cells out of the circulation into other body compartments.

Adult↗

Depression of the lymphocyte transformation response to microbial antigens and to phytohemagglutinin during pregnancy.

Lymphocyte transformation (LT) responses to Chlamydia trachomatis, to four other microbial antigens, and to phytohemagglutinin (PHA) were studied in 201 women during pregnancy and/or 3-18 wk postpartum. The LT responses to all stimulants tested were significantly depressed during pregnancy when compared with postpartum LT responses. This difference occurred whether LT assays were performed in autologous or pooled heterologous plasma collected from nonpregnant donors. Among women studied in the third trimester and again postpartum, the autologous LT stimulation index (LTSI) rose from 1.7 to 3.4 (P less than 0.001) with C. trachomatis elementary body antigen, from 3.7 to 7.9 (P less than 0.001) with Candida albicans cell wall extract, from 4.5 to 7.8 (P = 0.008) with streptokinase-streptodornase, from 1.7 to 3.0 (P = 0.007) with fluid tetanus toxoid, from 1.7 to 2.8 (P = 0.046) with mumps virus skin test antigen, from 35.5 to 87.0 (P less than 0.001) with PHA (2 micrograms/ml), and from 107.2 to 181.9 (P = 0.007) with PHA (10 micrograms/ml). LT responses to C. trachomatis were compared in 52 pregnant women and 58 nonpregnant women; all the women had C. trachomatis isolated at the time of LT assay. Using either plasma supplement, the mean LTSI with C. trachomatis antigen was significantly higher in nonpregnant women than in pregnant women, regardless of trimester (P less than 0.001). Among 12 women who were serially tested and remained culture positive for C. trachomatis throughout pregnancy and the postpartum period, the mean autologous LTSI rose from 1.9 in the third trimester to 7.8 postpartum (P = 0.0004). These data are the first to show that the immune response to an ongoing bacterial infection is depressed during pregnancy and to definitively document the depressed LT responses during human pregnancy.

Antigens, Bacterial↗

[Evaluation of cell-mediated immunity in the course of primary malignant tumors of the ovary. Cutaneous reactivity. (author's transl)].

The present possibilities of clinically evaluating cell-mediated immune potential using skin reactivity to microbial protein antigens (streptokinase-streptodornase; tuberculin; formalin-killed parotitis virus) together with a contact sensitized such as dinitrochlorobenzene are examined. A single evaluation index for the set of cutireactions is proposed and, as a practical example, the delayed hypersensitivity data based on intradermal and patch tests in 41 cases of primary malignant tumor of the ovary are reported. There is a definite correlation between immune impairment and cancer spread, with a survival prognosis value even in initial cases.

Dinitrochlorobenzene↗

Skin reactivity and phagocytic function of neutrophil leucocytes in Crohn's disease and ulcerative colitis.

A decreased capacity of the leucocytes to phagocyte yeast particles was found in patients with Crohn's disease of the ileum. Patients with lesions only in the colon showed normal phagocytic activity as did patients with ulcerative colitis (U.C.). Intradermal injection of killed Strep. pyogenes produced an increased erythrmatous reaction after 48 hours in patients with U.C., and the reaction was pustular in half of them. None of the controls or the patients with Crohn's disease of the ileum had such a reaction. An increased erythematous reaction to streptokinase-streptodornase was also more common in patients with U.C. than in those with Crohn's disease and a control group. No such difference was seen to other bacterial antigens. The reactivity to kallikrein, prostaglandin E1, histamine or bradykinin did not differ from that of normal subjects.

Adolescent↗

Topical treatment of pressure ulcers. A randomized comparative trial of Varidase and zinc oxide.

In a single-blind, randomized trial, the efficacy of topical streptokinase-streptodornase (Varidase) solution was compared with that of zinc oxide on necrotic pressure ulcers in 28 patients. The effectiveness was determined by measuring the necrosis removal within 8 weeks. This occurred in 6 patients (43%) treated with Varidase and in 7 (50%) treated with zinc oxide. The statistical tests applied showed no significant difference between the two treatments despite the use of a high power (1-beta = 0.95). The data suggest that the two regimens are about equally effective in the treatment of necrotic tissue.

Aged↗

Cell-mediated immunity in the rheumatoid diseases. I. Skin testing and mitogenic responses in sero-negative arthritides.

Cellular immunity has been investigated in patients with various kinds of sero-negative arthritis. The incidence of cutaneous response to recall antigen streptokinase-streptodornase (SK-SD), and the ability to mount a primary cutaneous response to dinitrochlorobenzene (DNCB) have been examined in patients with ankylosing spondylitis and psoriatic arthritis. The results were not significantly different from normal. In vitro lymphocyte transformation in the presence of phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) has been measured using peripheral blood lymphocytes from patients with ankylosing spondylitis, psoriatic arthritis and Reiter's disease. In comparison with a control group, significantly reduced responses were found to a low dose of PHA in the ankylosing spondylitis and Reiter disease patients. Significant increase in response occurred to a high dose of PHA, in patients with psoriatic arthritis and Reiter's disease, and to PWM in Reiter's disease patients. The in vitro results in the ankylosing spondylitis, psoriatic arthritis and Reiter's disease patients suggest some abnormality in the T-cell population in sero-negative arthritis.

Adult↗

Stimulation of lymphocytes by antigen in microplate cultures; absence of an effect of transfer factor in vitro.

The best conditions for the optimum stimulation of human leucocytes by antigens, including protein purified derivative (PPD), streptokinase-streptodornase varidase (SKSD) and tetanus toxoid have been studied in microplate cultures. The leucocytes of each donor have their own characteristic response to antigen which depends on the culturing conditions such as antigen concentrations, cell concentrations and the time of measuring the rate of DNA synthesis. Thus, no conditions provide a universal optimum for antigen stimulation in vitro. Leucocyte dialysates, i.e. potential transfer factors, have been prepared from donors, who between them are strongly positive to the antigens PPD, SKSD, tetanus toxoid, diphtheria toxoid and Keyhole limpet haemocyanin. In contrast to some previous reports these leucocyte dialysates had no effect on the thymidine incorporation by leucocytes grown in the presence of these antigens. It is suggested that the selection of optimal conditions for the response to antigen may have obscured the effect of any non-specific enhancement of reactivity b lyeucocyte dialysates.

Adult↗

Diagnosis and prognosis in colon cancer based on a profile in immune reactivity.

An immunologic profile consisting of measurements of circulating carcinoembryonic antigen (CEA), tumor antigen-induced inhibition of monomuclear cell migration (IMM) and skin reactivity to purified protein derivative, streptokinase-streptodornase, and mumps was assessed as a diagnostic and prognostic tool in 16 patients with colon cancer. Preoperatively, 10 of 14 patients tested had elevated CEA, 12 of 12 showed tumor antigen-induced IMM, and 10 of 11 failed to react to 2 or more recall antigens. Potential surgical cure (7 patients) was accompanied by normal CEA in 4, absent tumor antigen-induced IMM in all 7, and increased skin-test reactivity in 6. Disseminated cancer (9 patients) was associated with elevated CEA in all 9, with absent IMM in all 7 and with suppressed skin-test reactivity in 6 of 9.

Adult↗

Immunodeficiency in patients with non-Hodgkin lymphomas.

Seventy-one previously untreated patients with non-Hodgkin lymphomas were studied with several readilyvailable tests of immune function: number of peripheral blood lymphocytes, serum immunoglobulins, and delayed hypersensitivity to six recall antigens. The results were correlated to histology (Rappaport classification), stage (Ann Arbor classification), the presence of symptoms, and survival. As a group, 38 patients with diffuse lymphomas exhibited marked impairment in reactivity to five of six antigens (p less than 0.03 to p less than 0.001). In addition, lymphopenia and reduced levels of serum IgA were found in association with diffuse histiocytic lymphoma. Among patients with diffuse lymphoma, lymphocyte number and skin test reactivity tended to be greater in those with localized disease or without constitutional symptoms, and survival was superior for patients free of symptoms (p less than 0.01). As a group, 33 patients with nodular lymphoma had normal numbers of lymphocytes, lower levels of serum IgG and IgA, and significant impairment of reactivity to two antigens (streptokinase-streptodornase and mumps; p less than 0.01); reactivity to three other antigens (Candida albicans, coccidiodin, and tuberculin) was normal. Survival for patients with nodular lymphoma was superior (p less than 0.01) compared to those with diffuse lymphomas. In summary, severe immunodeficiency was found in patients with diffuse lymphoma (particularly diffuse histiocytic lymphoma), and definite but much less severe immunodeficiency was characteristic of patients with nodular lymphoma.

Adult↗

Effect of human monocytes and macrophages on Trypanosoma cruzi.

Studies were undertaken to determine whether Trypanosoma cruzi can invade and multiply within human monocytes and macrophages cultured in vitro and, if so, whether macrophages can be activated to inhibit the multiplication. A reticulotropic strain of T. cruzi was capable of infecting human monocytes and monocyte-derived macrophages. Intracellular multiplication was observed in both cell types when they were examined microscopically. An increase in the number of trypanosomes occurred in the supernatants as well, providing additional evidence of intracellular multiplication and cell disruption by the parasite. Activation of monocyte-derived macrophages was accomplished by incubating the monolayers in the presence of lymphocytes and streptokinase-streptodornase. These activated macrophages inhibited intracellular multiplication of T. cruzi and the number of T. cruzi in the supernatants of these monolayers was markedly decreased as well.

Adult↗

Delayed cutaneous hypersensitivity and lymphocyte transformation: dissociation in atopic dermatitis.

Studies of cell mediated immunity (CMI) in atopic dermatitis have demonstrated various defects and frequently contradictory results. The true nature of immune dysfunction remains uncertain. We approached this question by concurrently examining two aspects of CMI: delayed cutaneous hypersensitivity and in vitro lymphocyte transformation. Responses were tested using the antigens Candida albicans and streptokinase-streptodornase (SKSD). Mean lymphocyte transformation was equal in atopic patients and controls, although a subgroup of severely dermatitic patients showed depressed responses. Cutaneous anergy was the rule in atopic patients (96% to candidin and 84% to SKSD). Although normal subjects showed good correlation between in vitro and cutaneous responses, atopic patients showed a significant lack of correlation. Many patients manifested cutaneous anergy in the face of normal lymphocyte transformation re sponses.

Adolescent↗

Effect of extracellular products of Streptococcus on macrophage Fc receptors for IgG.

The effect of the extracellular products of Streptococcus (EPS) on the receptors for Fc of IgG of dog alveolar macrophage (AM) was evaluated by the rosette test. The AM controls produced 80 per cent rosettes; those treated with EPS, a reduced number of rosettes, which was directly related with the concentration of EPS. The adhesion of EPS treated AM to glass was less than that of the AM controls. Incubation of AM with streptokinase-streptodornase did not modify the amount of rosettes. The data support the possibility that streptolysin-O is the substance which modifies, or destroys the Fc receptors, or the integrity of the cell membrane. Ouabain did not alter the capacity of the dog alveolar macrophages to form rosettes, suggesting that cellular energy is not required for the interaction between the Fc receptor and the IgG.

Animals↗

Random monocyte migration: an in vitro correlation with the delayed hypersensitivity skin reaction.

The in vitro random migration and chemotactic activity of peripheral blood monocytes and neutrophils was compared with the delayed hypersensitivity skin test to streptokinase-streptodornase in fourteen normal subjects. A significant positive correlation (P less than 0.001) was observed between the random migration of monocytes and the size of the skin test reaction. No significant correlation was found with random neutrophil migration or monocyte and neutrophil chemotactic responses. These results indicate that the in vitro random mobility of monocytes is related to the in vivo expression of a delayed-type hypersensitivity skin reaction.

Adult↗

A basophil-activating factor from human T lymphocytes.

Human T lymphocytes stimulated with phytohaemagglutinin (PHA) or streptokinase-streptodornase (SK-SD) generate an activity which elicits non-cytotoxic histamine release from human basophils. Filtration of the T lymphocyte-derived activity on columns of Sephadex G-100 and Fractogel 55F sequentially revealed one predominant basophil-activating factor of mol. wt. 70,000-90,000, that was designated BAF-T. BAF-T was composed of two acidic proteins of approximate pI 4.4 and 5.2-5.5, as assessed by isoelectric focusing. The distinction of BAF-T from IgE was confirmed by the failure of BAF-T to bind to an anti-IgE affinity column and the capacity of BAF-T to release histamine maximally from basophils desensitized to IgE-dependent stimuli. The inability of BAF-T to release histamine from human lung mast cells and dog cutaneous mastocytoma cells suggests target cell specificity. The source and activity of BAF-T are consistent with a specific contribution of this mediator to human cellular immune and hypersensitivity responses involving T lymphocytes and basophils.

Basophils↗

Characterization of human macrophage activation factor (MAF) prepared from antigen-stimulated lymphocytes.

Macrophage activation factor (MAF) and migration inhibitory factor (MIF) obtained from sensitized human lymphocytes stimulated by streptokinase-streptodornase (SK-SD) were characterized by gel filtration and isoelectric focusing (IEF) techniques. Twenty-four and 48 hr supernatants were chromatographed on Sephadex G-100 columns and the eluate pooled into 5 fractions: the void volume (Fr. I), the eluate containing molecules with a molecular weight ranging from 55-70,000 (Fr. II), 30-55,000 (Fr. III), 20-30,000 (Fr. IV) and 10-20,000 (Fr. V). The 24 hr supernatants contained MIF activity in Fraction IV and maximal MAF activity in Fractions I and II whereas the 48 hr supernatants contained MIF activity in Fractions II and IV and maximal MAF activity in Fractions II and III. When the supernatants were purified by IEF, the eluant was pooled into 5 fractions: Fraction I (pI 3.5-4), Fraction II (pI 4-4.5), Fraction III (pI 4.5-5), Fraction IV (pI 5-5.5) and Fraction V (pI 5.5-6). The 24 hr supernatants contained maximal MIF activity in Fractions III and IV and maximal MAF activity in Fraction III whereas the 48 hr supernatants contained both maximal MIF and MAF activity in Fractions I and IV. Thus, it appears that although human MAF can be differentiated from MIF in the 24 hr supernatants, MAF and MIF activity in the 48 hr supernatants are generally found in the same fractions when examined either by IEF or gel filtration techniques.

Chromatography, Gel↗

[Skin tests as immunologic parameters in cervical cancer].

Immunological skin-tests in 158 patients admitted at the 1st Department of Gynaecology and Obstetrics, University of Vienna, and in 25 healthy controls were done in a long-term prospective study. 123 examined patients were suffering from invasive cervical cancer stage I or Ii (group 1), 17 patients were suffering from preinvasive lesions of the cervix (group 2) and 18 patients were admitted for treatment of benign disorders (group 3). Recall-antigens--streptokinase-streptodornase (SKSD), purified protein derivate (PPD) and candida (CAND)--and a primary antigen (DNCB) were used testing cutaneous delayed hypersensitivity reactions. Preoperative total reactivity to recall-antigens calculated by a score was significantly reduced in cancer patients in comparison to other groups. Subdividing the cancer patients according to histological criteria of the malignancy we could find significantly differences in particular tests (SKSD and CAND) but not in total reactivity score. Comparing the preoperative reactivity of cancer patients with or without recurrence of malignancy within two years less pronounced differences were found. Reactivity to recall-antigens in all tests and in all patient groups were better three weeks after surgical treatment than preoperatively. The prior found differences between the groups remained significant (p less than 0,05). In contrast, cancer patients demonstrated severe anergy in postoperative DNCB sensitization test as only 1 of 33 patients exhibited normal hypersensitivity reaction. 113 out of 24 patients of group 2 and 3 (54%) demonstrated delayed hypersensitivity to DNCB in operative sensitization test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Differential responses to mitogen stimulation in lymphocytes from normal individuals and Lesch-Nyhan patients: influence of the bicarbonate buffer system.

Three patients affected with the Lesch-Nyhan syndrome were found to have normal levels of immunoglobulins, normal numbers of circulating B and T cells and normal IgG secretion in vitro in response to polyclonal activators. However, when cultures were performed in the absence of a bicarbonate buffer system, the proliferative response to several T cell stimulants (phytohaemagglutinin, concanavalin A and streptokinase-streptodornase) was impaired in Lesch-Nyhan cells as judged from the incorporation of labelled thymidine, uridine and leucine. This situation could be abolished by incubation in a 5% CO2 atmosphere and even reversed by supplementation of bicarbonate to the culture medium. Blocking the de novo purine synthesis by Methotrexate resulted in a more pronounced inhibition of the mitogenic response in Lesch-Nyhan lymphocytes than in normal cells. The differences in proliferative response between normal and Lesch-Nyhan lymphocytes with regard to culture conditions point to the critical role of the de novo pathway in lymphocyte stimulation.

Adolescent↗