In vitro lymphocyte responsiveness of human subjects receiving azathioprine.
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Antigens↗
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Cell-mediated hypersensitivity in pigeon breeders.
This investigation was carried out to study possible differences in cell-mediated hypersensitivity between symptomatic and asymptomatic pigeon breeders. A variety of pigeon antigens were investigated using the indirect migration inhibition test. Cell-mediated hypersensitivity to pigeon antigens was detected in 6 of 8 symptomatic pigeon breeders, and in only 2 of 12 asymptomatic pigeon breeders. The results suggest that cellular mechanisms may be important in the pathogenesis of pigeon breeder's disease.
Animals↗
A method for eliciting indurated DTH reactions to soluble protein antigens in the flank skin of mice: correlation of visual measurements with 125I-UdR uptake indices.
A new technique for eliciting specific indurated delayed type hypersensitivity (DTH) reactions to soluble protein antigens in the flank skin of mice is reported here. We show that immunization with soluble antigens emulsified in complete Freund's adjuvant emulsion allows elicitation of indurated reactions upon intracutaneous test of sensitized mice with antigen on alum precipitates. With this method it is possible to measure simultaneously the gross induration of the cutaneous DTH reactions and correlate it with the degree of mononuclear cell infiltration as quantitated by the cPM of 125I-UdR uptake in mononuclear cells at biopsied reaction sites and confirmed by histological examination.
Alum Compounds↗
Counter inhibitor: a low molecular weight cytokine derived from human leukocyte dialysates reverses antigen dependent PMN and macrophage migration inhibition.
A low molecular weight component, termed counter inhibitor (CI), has been partially purified from human dialyzable leukocyte extracts. Addition of CI to either a direct leukocyte or macrophage migration inhibition system results in reversal of antigen-induced migration inhibition. CI activity requires the presence of antigen for expression, but does not require that the donor of the CI be immune to the antigen used in the migration inhibition assay. Reversal of migration inhibition by CI appears to be a consequence of its ability to prevent PMNs or macrophages from responding to lymphokines which induce migration inhibition.
Antigens↗
[A rapid method for determination of actual urinary fibrinolytic activity].
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Fibrin↗
Human alveolar macrophage support of lymphocyte responses to mitogens and antigens. Analysis and comparison with autologous peripheral-blood-derived monocytes and macrophages.
Observations from animal studies and investigations using human peripheral-blood-derived macrophages may not be representative of human alveolar macrophage functions. Thus, we extensively examined and compared accessory cell functions of autologous human alveolar macrophages and peripheral-blood-derived monocytes and macrophages obtained from healthy, nonsmoking volunteer subjects. The alveolar and peripheral-blood-derived cells differed in ability to enhance mitogen- and antigen-stimulated transformation responses of purified autologous lymphocytes. Peripheral-blood-derived cells supported greater lymphocyte responses to optimal concentrations of several mitogens, but alveolar macrophages supported much greater responses to suboptimal concentrations of the mitogen phytohemagglutinin. Peripheral-blood-derived macrophages supported, but alveolar macrophages did not support, lymphocyte responses to streptococcal and influenza virus antigens. Such relative accessory cell functions of the different macrophages and monocytes were not due to different kinetics of response, nor were they due to differences in the proportion of macrophages required to support the lymphocyte responses. These data indicate that human alveolar macrophages have functional characteristics different from autologous peripheral-blood-derived monocytes and macrophages. Such differences may be important in both pulmonary immune homeostasis and in the pathogenesis of pulmonary disease.
Adult↗
Impaired lymphocyte transformation in intestinal lymphangiectasia: evidence for at least two functionally distinct lymphocyte populations in man.
Intestinal lymphangiectasia is a disease characterized by hypoproteinemia and edema resulting from protein-losing gastroenteropathy secondary to abnormal intestinal lymphatics. Immunologic abnormalities associated with this disease include hypogammaglobulinemia, lymphocytopenia, skin anergy, and impaired allograft rejection. In the present study, the in vitro blastogenic transformation of lymphocytes from 12 patients with intestinal lymphangiectasia was assessed in order to gain insight into the mechanism of the cellular immune defect in this disease. Peripheral blood lymphocytes from patients with intestinal lymphagiectasia showed impaired in vitro transformation to nonspecific mitogens, specific antigens, and allogeneic cells when compared to equal numbers of cells from normal individuals. Patients with the most deficient in vitro reactivity tended to have the lowest serum albumin concentration and the lowest absolute lymphocyte count. Lymphocytes obtained from chylous effusions in each of the four patients studied transformed more vigorously than peripheral blood cells from the same patients. These results may be explained by the loss of recirculating, long-lived lymphocytes into the gastrointestinal tract, resulting in a relative depletion of the population of lymphocytes necessary for in vitro blast transformation. This disease thus represents a clinical analogue of animals with experimental thoracic duct drainage, and provides evidence for the existence, in man, of two functionally distinct lymphocyte populations. In addition, these findings establish a new mechanism of impaired delayed hypersensitivity and defective in vitro lymphocyte transformation, i.e. the gastrointestinal loss and consequent depletion of the long-lived, recirculating population of lymphocytes from the peripheral lymphocyte pool.
Adolescent↗
Degradation of human fibrinogen by plasms alpha2-macroglobulin-enzyme complexes.
This study demonstrates that human plasma alpha(2)-macroglobulin preparations possess an enzymic activity that degrades fibrinogen, resulting in the formation of products whose structure resembles that of circulating fibrinogen catabolites. The sequence of degradation is similar to that observed in plasmin-catalyzed digests, in that Aalpha-chain fragmentation precedes that of Bbeta-chain. The addition of plasminogen activators to plasma induced an increase in the N-alpha-tosyl-l-arginine methyl ester HCl esterase and fibrinogenolytic activity associated with alpha(2)-macroglobulin purified from this plasma, indicating that the enzymic activity of the complex was preserved and could be increased in the presence of other plasma enzyme inhibitors. Immunochemical studies demonstrated that an alpha(2)-macroglobulin-plasmin complex had formed in urokinase-treated plasma. This alpha(2)-macroglobulin preparation manifested an esterolytic profile like that of a complex prepared from plasmin and purified alpha(2)-macroglobulin. After complex formation with alpha(2)-macroglobulin in plasma, plasmin retained less than 0.1% of its fibrinogenolytic activity. That plasmin expressed its activity while bound to alpha(2)-macroglobulin was suggested by immunoprecipitation of this activity with alpha(2)-macroglobulin antibody and by the demonstration that pancreatic trypsin inhibitor did not effectively inhibit its fibrinogenolytic or esterolytic activity. These results raise the possibility that, in addition to its activity as a major plasma proteolytic enzyme inhibitor, alpha(2)-macroglobulin may modulate enzyme-substrate interactions, such as those resulting in the formation of circulating fibrinogen catabolites, by providing a mechanism for the preservation and protection of a portion of the enzymic activity in the presence of other circulating inhibitors.
Acetates↗
Interaction of leukocyte chemotactic factors with the cell surface. I. Chemotactic factor-induced changes in human granulocyte surface charge.
The negative surface charge of human granulocytes was diminished after incubation with the chemotactic factors C5a, dialyzable transfer factor, and the enzymes kallikrein and plasminogen activator. No such change was observed after incubation with human IgG, albumin, horeseradish peroxidase, or a mixture of prekallikrein and plaminogen proactivator. Hydrocortisone inhibited the effect of C5a upon granulocyte surface charge and inhibited its chemotactic activity, suggesting that steroids act at the cell surface. The chemotactic inhibitors cholchicine and cytochalsin B had no effect upon granulocyte surface charge, consistent with their presumed effect upon microtubules and microfilaments, respectively. The data suggest that the decrease in cell surface charge may be a preerequiste for normal cell movement.
Chemotaxis↗
Suppressor function of peripheral blood mononuclear cells in normal individuals and in patients with systemic lupus erythematosus.
Normal peripheral blood mononuclear cells demonstrated increased DNA synthesis and secretion of newly synthesized protein when suboptimal concentrations of Concanavalin A (Con A) were added to the cultures after 24-h incubation in vitro. Cells stimulated by Con A, 1 mug/ml, after 24-h incubation demonstrated 3.0 times more tritiated thymidine incorporation, and 4.4 times more 14C-amino acid incorporation into newly synthesized secreted protein, than cells stimulated at 0 h (P less than 0.001). The acquisition of increased responsiveness was not abrogated by washing and resuspending the cells in fresh medium. Since the increased responsiveness could be inhibited by the addition to the cultures of small numbers of cells previously activated by Con A it is suggested that the enhanced reactivity acquired in culture represents the loss of a subpopulation of suppressor cells that modulate the T-lymphocyte response. Cells from nine patients with active, untreated systemic lupus erythematosus demonstrated normal responses to optimal concentrations of Con A added at 0 h, but an impaired response to Con A, 1 mug/ml. When these cells were incubated for 24 h, a significant increased response to Con A was not observed. This observation suggests that patients with active SLE lack circulating suppressor cells. When seven SLE patients were again studied after corticosteroid therapy had led to clinical improvement, the response to Con A, 1 mug/ml, added after 24-h incubation was similar to that observed in normal controls, suggesting that suppressor function in SLE returns as disease activity declines.
Adolescent↗
Cytotoxicity of human macrophages for tumor cells. Enhancement by human lymphocyte mediators.
Human macrophages, derived from peripheral blood monocytes, acquire enhanced cytotoxicity for human target cells after incubation in mediator-rich supernates from antigen-stimulated lymphocytes. Maximum cytotoxicity was observed after 24-h incubation in mediators. In comparison to normal macrophages, mediator-activated macrophages were cytotoxic to five of the six malignant cell lines tested but had no effect on five nonmalignant cell lines. In 20 experiments with one target (SK-BR-3), mean cytotoxicity was 23 +/- 2.7% and with another target (MA-160), was 29 +/- 3.4%. Macrophages became cytotoxic after 8-h incubation with mediators and the enhanced cytotoxicity persisted for at least 40 h after the lymphocyte mediators were removed. These findings are consistent with the hypothesis that macrophages, activated by antigen-induced lymphocyte mediators, can contribute to the host resistance to tumor growth in man.
Cell Division↗
Purification and further characterization of human mononuclear cell histamine-releasing factor.
We have purified and further characterized a histamine releasing factor (HRF) derived from human mononuclear cells using gel-filtration HPLC, reverse-phase HPLC, anion exchange chromatography, and elution from SDS gels after electrophoresis. Considerable heterogeneity is seen, far exceeding that published in prior reports. Gel filtration HPLC yielded a major peak at molecular weight 30,000 and minor peaks at 50,000 and 12,000. Reverse-phase HPLC gave one major fraction in the void volume and an eluted peak at 50-60% acetonitrile. Accell QMA anion exchange HPLC revealed three peaks of activity; one in the void volume similar to that published previously using QAE-Sephadex, and peaks that eluted at 0.5 and 0.8 M ammonium acetate, respectively. Electroelution following SDS-PAGE yielded peaks at MW 12,000 and 15-17,000 plus variable peaks at 25-27,000, 31-34,000, and 80-90,000 D. Using a combination of the aforementioned procedures, we have purified molecular species of HRF at 41,000 and 17,000 D to apparent homogeneity, as judged by SDS PAGE and autoradiography. Since human interleukin 3 and granulocyte-macrophage colony-stimulating factor possess histamine-releasing capability, it is clear that multiple cytokines can share this activity. However, the major HRF we isolate from human mononuclear cells appears, thus far, to be unique.
Biomarkers, Tumor↗
A new approach in the treatment of peripheral arterial occlusions: defibrination with arvin.
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Arterial Occlusive Diseases↗
Thrombectomy and thrombolysis--therapeutic alternatives?
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Anticoagulants↗
Immune monitoring protocol for patients with carcinoma of the head and neck. Preliminary report.
Numerous investigators have observed a depression of cell-mediated immunity in patients with carcinoma of the head and neck using a variety of in vitro and in vivo assays. This report presents the data obtained when a group of head and neck cancer patients were evaluated for reactivity in an in vitro lymphocyte blastogenesis assay using polyclonal mitogens and specific antigens, numbers of peripheral blood T-lymphocytes, and levels of circulating immune complexes. Such an immunological monitoring protocol revealed a depressed reactivity of the cancer patients in the lymphocyte blastogenesis assay when compared to normal age-matched controls. We also observed that 75% of these patients had circulating soluble immune complexes in their sera before and after therapy. These preliminary data indicate that further research is needed to examine the potential role of soluble immune complexes in modulating the host's immune response.
Adult↗
Reduced in vivo cell-mediated immune responses to mumps, tuberculin, and streptokinase/streptodornase but not to Candida albicans in oral lichen planus.
Oral lichen planus is considered to be a T-cell-mediated disease. The purpose of this study was to investigate the capacity of T-lymphocytes in oral lichen planus patients to respond to a number of commonly encountered environmental antigens in vivo. To do this, we assessed dermal delayed-type hypersensitivity responses to mumps, streptokinase/streptodornase, Candida albicans, and purified protein derivative of tuberculin (PPD) in 17 oral lichen planus patients and in matched controls. Reduced induration in response toward mumps, PPD, and streptokinase/streptodornase was demonstrated in oral lichen planus patients compared with controls. In addition, the total sum of induration diameters was decreased in the patients. However, C. albicans stimulation resulted in similar levels of response in both groups. The differences in induration size between matched patients and controls for mumps and PPD were thus significantly greater than the corresponding differences for the C. albicans antigen. This suggests that a selective difference in the response to these antigens exists in oral lichen planus patients. The results may point to a loss of memory T-helper function to infrequently encountered environmental antigens, represented by mumps, PPD, and streptokinase/streptodornase, contrarily to memory function to common antigens (C. albicans), which seem to be unaffected.
Aged↗
A case of coagulated haemothorax treated by intrapleural varidase.
Haemothorax can occur as a result of thoracic trauma or following diagnostic or therapeutic pleural aspiration. Early removal of blood from the thoracic cavity is essential to prevent coagulation and fibrin deposition within the pleural cavity. The case described is one in which a large coagulated haemothorax was drained via a standard pleural drain following liquefaction by the use of a proprietary fibrinolytic agent more commonly used in the desloughing of wounds.
Adult↗
A double-blind randomized comparison of the effect and tolerance of Varidase versus saline when instilled in the urinary bladder in patients with catheter problems.
Thirty-eight patients with problems with their urinary catheters were randomly treated with Varidase or normal saline solution once a day for 10 days. Photographs were taken by using a cystoscope before treatment, at day 10 and day 24 after the commencement of treatment. The photographs were evaluated according to the occurrence of pus, debris, coagula and rubor. In the Varidase group the improvements from baseline to day 10 and day 24 were statistically significant (p less than 0.05) in all parameters while there were no statistically significant improvements in the saline group. Comparing the two treatment groups, regarding the changes from baseline to day 10 and day 24, it was statistically demonstrated that Varidase was significantly more effective than saline in all parameters (p less than 0.05). In conclusion, this study shows that Varidase effectively cleans the urinary bladder from pus, fibrin, necrotic tissue and blood clots.
Aged↗