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Biomedical subjects

C H Kirkpatrick

Publications and source records attributed to C H Kirkpatrick.

At least 37 records · Page 2Linked to original sources
PubMed1991

Allergic histories and reactions of patients treated with digoxin immune Fab (ovine) antibody. The Digibind Study Advisory Panel.

Seven hundred seventeen adult patients with life-threatening digitalis intoxication were treated with Fab fragments of ovine antidigoxin immunoglobulin G (IgG). Results of the efficacy of treatment and adverse effects were collected with standard report forms. Eighty-two (11%) of the patients were recorded as having histories of allergy (71 patients) and/or asthma (11 patients). Of the "allergic" subjects, 35 described reactions to antibiotics, 19 to other medications, 3 to foods, and 2 to pollens; in 12 subjects the etiologic agent was not specified. Six subjects had adverse reactions that were probably or possibly due to allergy to components of the antibody preparation. Of these 4 (5%; 95% confidence interval (Cl) 1.8% to 12%) occurred in the 82 subjects with histories of allergy or asthma and 3 (9%; 95% Cl 1.8% to 23%) of these occurred in the 35 persons with histories of allergy to an antibiotic. In contrast, only 2 (0.3%; 95% Cl 0.04% to 1.1%) similar reactions occurred in the 635 subjects with no histories of allergy or asthma. All reactions responded to symptomatic treatment. The authors conclude that treatment of digitalis intoxication with ovine antidigoxin IgG-Fab (Digibind) is generally well tolerated and allergic reactions are rare. However, there is a significantly increased risk of reactions in patients with histories of allergy or asthma.

Aged↗
PubMed1989

Chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis can be defined as a group of syndromes that have as a common feature infections of the skin, nails and mucous membranes with Candida albicans. A variety of disorders including endocrine dysfunctions, alopecia, vitiligo, malabsorption syndromes, neoplasms and other infections may also occur in patients with chronic mucocutaneous candidiasis, but these vary considerably from patient to patient. In most patients with chronic mucocutaneous candidiasis, there are abnormalities of cell-mediated immunity. These may be limited to antigens of Candida albicans, but in some patients they are more extensive and involve the T-lymphocyte-mediated responses to all antigens. These immunologic defects are the factors that predispose patients to infections with opportunistic organisms such as Candida spp. Fungal infections in patients with chronic mucocutaneous candidiasis usually respond to treatment with conventional antifungal agents, but often relapse shortly after treatment is stopped unless the defects in the cell-mediated immune system have been corrected.

Candidiasis↗
PubMed1989

Phenotypes of infiltrating cells in trehalose dimycolate-induced interstitial pneumonitis.

Trehalose dimycolate is a glycolipid component of the cell walls of mycobacteria, nocardia, and corynebacteria. When trehalose dimycolate is injected into certain strains of mice, they develop interstitial pneumonitis that is characterized by mononuclear cell infiltration of the alveolar walls, intra-alveolar hemorrhages, and in some animals, granuloma formation. The disorder is seldom fatal, and in approximately 4 weeks, the lungs are normal. There is strong evidence that T lymphocytes are essential for production of interstitial pneumonitis by trehalose dimycolate, but little is known about the mechanisms of lung injury in this model. The experiments described in this report were conducted to identify the roles of the various cells that accumulate in the lungs of mice with this form of interstitial pneumonitis. We found that Mac3+ macrophages were the first cells to appear in the alveolar walls. Increases in the number of L3T4+ T lymphocytes, Lyt2+ T lymphocytes, and surface-immunoglobulin-positive lymphocytes followed, but significant increases in the number of lymphoid cells were not observed until day 7, when the pulmonary lesions were well developed. Treatment of the mice with cyclophosphamide or anti-T-cell sera significantly reduced the number of lymphoid cells in the alveolar walls but did not affect the number of Mac3+ cells and did not affect development of intra-alveolar hemorrhages. Treatment with poly(I.C) significantly decreased the number of Mac3+ cells in the lungs, and these mice did not develop pulmonary hemorrhages. We conclude that although development of pulmonary lesions in trehalose dimycolate-treated mice is a T-cell-dependent process, macrophages are also essential and are more directly involved in production of the lung injury. We postulate that the lung lesions are the direct effect of macrophage-produced cytokines, such as tumor necrosis factor.

Animals↗
PubMed1989

Biological response modifiers. Interferons, interleukins, and transfer factor.

Natural consequences of knowledge of the mechanisms that regulate immune responses are the attempts to modify the immune system in order to increase resistance to infectious diseases and to enhance activity against tumor cells. This review describes the roles of interferons and interleukins in immune responses and reviews the experience with transfer factor in treatment of certain diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Methionine-enkephalin as immunomodulator therapy in human immunodeficiency virus infections: clinical and immunological effects.

Enkephalins have been shown to enhance T cell-mediated immune responses and natural killer-cell activity in vitro. We have studied the effects of infusions of methionine-enkephalin on immune functions and clinical courses in seven patients with various stages of infection with human immunodeficiency virus (HIV). All patients were clinically stable at the time of entry into the study. Each received 10 micrograms/kg of methionine-enkephalin in an intravenous infusion three times weekly for up to 12 weeks. Evaluation of cellular immunity (T-cell subsets, in vitro interleukin-2 production and interleukin-2 receptor expression, T-cell responses to mitogens and antigens, and delayed-hypersensitivity skin tests) as well as clinical and toxicity monitoring was performed prior to treatment, at 2-week intervals during treatment, and after the cessation of treatment. Increases in interleukin-2 receptor expression were seen on lymphocytes collected on one occasion from each of two patients 30 min postinfusion. Studies done 24 hr after infusions revealed increases in interleukin-2 production in one patient, but when pre- and posttreatment values were compared there were no significant changes in numbers of circulating T cells of any phenotype or in T-cell responses to mitogens or antigens. None of the patients with Kaposi's sarcoma had regression of tumor; one patient dropped out of the study at week 5 because of deteriorating clinical status and progression of tumor. There were no adverse reactions or evidence of toxicity. We conclude that methionine-enkephalin appears to enhance temporarily selected immune responses in patients with HIV infection, however, in the schedule used in this study it was not clinically efficacious.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Murine transfer factor. IV. Studies with genetically regulated immune responses.

Transfer factor-containing dialysates from mice that were either high or low responders to GAT10, GLA5, or ovalbumin were assayed for their ability to transfer delayed hypersensitivity to murine recipients of either high or low responder phenotype. Dialysates from high responder strains contained transfer factor that would transfer delayed hypersensitivity to both high and low responder recipients. These transfers were not restricted by disparities at the MHC or Igh loci. Identically prepared materials from low responder donors contained little or no transfer factor activity and would not transfer delayed hypersensitivity to either high or low responder recipients. Thus, administration of transfer factor transfers the high responder phenotype to low responder recipients. The data also suggest that production of transfer factor is regulated by Ir genes but that the immunologic activities of transfer factor are not.

Animals↗
PubMed1988

Human tonsillar IgE biosynthesis in vitro. II. Analysis of T cell regulation with monoclonal antibodies.

Phenotypes of T cells regulating human tonsillar IgE biosynthesis in vitro were studied by use of Leu 2a and Leu 3a monoclonal antibodies that recognize T cell subsets. B cells cultured with Leu 3a+-enriched populations (B cells plus T3a) produced significantly more IgE and IgG in the presence of pokeweed mitogen than B cells with the Leu 2a+-enriched populations (B cells plus T2a) (p less than 0.001 for IgE and p less than 0.001 for IgG). No significant differences were observed in IgE and IgG synthesis between the cultures of B cells alone and B cells plus T2a. T2a, but not T3a cells, significantly suppressed IgE synthesis (p less than 0.05 for geometric means and p less than 0.001 for percent suppression) when the cells were added to cultures of B cells plus T3a. Suppression of IgG synthesis was not observed under conditions that suppressed IgE synthesis, suggesting qualitative and quantitative differences in regulation of production of these isotypes. When T2a cells were irradiated, the suppressor activity disappeared. When graded numbers of T3a cells were added to B cells, it was noted that IgE synthesis first increased and then decreased as the numbers of T3a were increased. When the T3a cells were irradiated, IgE biosynthesis was suppressed at lower T/B ratios (less than 1 in four of five experiments) and was enhanced at higher T/B ratios (greater than 1 in all five experiments). Similar results were observed in experiments with OKT4 and OKT8 monoclonal antibodies. It is concluded that phenotypes of helper T cells for IgE synthesis are Leu 3a+ or OKT4+ and that IgE suppressors are predominantly Leu 2a+ or OKT8+ and are radiosensitive, as reported for regulation of other isotypes. However, it is suggested that Leu 3a+ and OKT4+ cells consist of radioresistant and radiosensitive helper cells and, presumably, a minor population of suppressor cells.

Antibodies, Monoclonal↗
PubMed1988

Transfer factor.

It has been more than 30 years since Dr. H. S. Lawrence first reported that it was possible to transfer delayed-type hypersensitivity from sensitized donors to unsensitized recipients with lysates of blood leukocytes. During recent years, research from several laboratories has demonstrated that this effect is immunologically specific. Although the molecules that possess this activity have not been completely characterized, there is a significant body of evidence that they are small polypeptides and that they can interact with antigen molecules in an immunologically specific manner. Studies with immune responses that are under genetic control have demonstrated that the ability of an animal to produce transfer factor is genetically regulated but that transfer of delayed hypersensitivity with transfer factor is not genetically restricted. In fact, when mice of low-responder phenotypes are administered transfer factor from high-responder donors, they express delayed hypersensitivity responses that are comparable to the high responders. Clinical studies have demonstrated that transfer factor is an efficacious method for immunotherapy of certain viral and fungal infections.

Animals↗
PubMed1988

Pathogenesis of trehalose dimycolate-induced interstitial pneumonitis. IV. Evidence against roles for immunoglobulins and the complement system.

We showed previously that trehalose dimycolate (TDM) in oil administered intraperitoneally into susceptible mice produced interstitial and hemorrhagic pneumonitis by the seventh day after injection and that mature T cells are necessary for the production of these lesions. TDM has been reported to activate complement and to be chemotactic for macrophages in vitro. Accordingly, we looked for involvement of humoral mechanisms in the pathogenesis of TDM-induced pneumonitis. Genetically C5-deficient B10D2/oSn mice developed pulmonary lesions just as well as C5-sufficient mice. No activation of C3 occurred in the plasma of TDM-treated mice as determined by crossed immunoelectrophoresis. Some splitting of C3 occurred in bronchoalveolar lavage fluids, but this was similar in control and experimental mice. By immunofluorescence microscopy, there was no deposition of C3 or immunoglobulins (Ig) along the alveolar membranes. These findings and our published data provide additional evidence that TDM-induced interstitial inflammation in mice is exclusively a T-lymphocyte-dependent process.

Animals↗
PubMed1987

Lymphokines and platelets promote human monocyte adherence to fibrinogen and fibronectin in vitro.

Monocytes must accumulate in areas of tissue injury and inflammation to effect phagocytosis, antigen presentation, and monokine production. Fibrinogen/fibronectin matrices have been demonstrated in healing wounds and in delayed-type hypersensitivity skin reactions. We have developed an in vitro system for investigation of the ability of fibrinogen and fibronectin matrices to serve as substrata for human peripheral blood monocyte adherence. Monocyte adherence was greatest on matrices of both fibrinogen and fibronectin, less to fibrinogen alone, and least to fibronectin alone. Lymphokines increased adherence of monocytes to all three surfaces but not to albumin-coated surfaces. Addition of platelets also caused a dose-dependent increase in monocyte adherence to all three surfaces. This increased adherence was not a simple function of arachidonic acid metabolites, stable platelet products, nor monocyte binding sites on the platelet membrane. The effect of platelets was not additive to the effect of lymphokines. We conclude that fibrinogen and fibronectin provide a framework for monocyte adherence and that factors present in areas of inflammation and wound healing, such as lymphokines and platelets, can augment this adherence. Such adherence facilitates the transformation of monocytes into macrophages in vitro and may also foster such transformation in vivo.

Blood Platelets↗
PubMed1987

The significance of antilymphocyte antibodies in patients with acquired immune deficiency syndrome (AIDS) and their sexual partners.

Antilymphocyte antibodies have been demonstrated in autoimmune diseases, acute viral infections, and acquired immune deficiency syndrome (AIDS) by using either the conventional microlymphocytotoxicity or the double fluorescence technique. In the present study, we used both methods to detect the antilymphocyte antibodies and to characterize further their immunologic significance in patients with AIDS and their sexual partners. The results using the conventional microlymphocytotoxicity method demonstrated that 8 of 10 patients with AIDS and 6 of 10 partners had significant levels of antilymphocyte antibodies which were reactive with B and T cells at cold and warm temperatures. A significant loss in antibody activity following absorption with B, T, and Daudi cells and Staphylococcus aureus, but not platelets or red cells, indicated that these antibodies are not directed to HLA class I antigens but, rather, to antigens that are common to both groups of lymphocytes. There is a close association between antilymphocyte antibodies and lymphopenia in patients but not in partners. Antibodies against lymphocyte subclasses [helper (T4) and suppressor (T8)] were detected by the double fluorescence staining technique, which employs C6-deficient serum as a nonlytic source of complement, and demonstrated the binding of antibodies to target cells, in contrast to lysing of the target cells as in the microlymphocytotoxicity method. The results of this assay showed that antibodies were directed to both populations, and there was no correlation or association between the absolute numbers of peripheral T4 and T8 cells and the percentage of antibody binding. Taken together, there appear to be at least two kinds of antilymphocyte antibodies: lymphocytotoxic antibodies detected by the conventional microlymphocytotoxicity assay and noncytotoxic antibodies detected by the double fluorescence staining technique. The former may be responsible in part for the lymphopenia. The latter may alter lymphocyte function. The patients and partners who had antilymphocyte antibodies also had anti-HTLV-III antibodies, although there was not any close correlation between titers. These findings support the possibility that both types of antibodies occur as part of a generalized immune response, possibly stimulated by the same viral agent.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Correlation of absent inner dynein arms and mucociliary clearance in a patient with Kartagener's syndrome.

Recent experimental studies have demonstrated extensive biochemical differences between the outer and inner dynein arms of cilia. The inner dynein arms are now emerging as the "prime movers" for ciliary clearance. We studied ciliary motility as evidenced by radioisotope mucociliary clearance, and the ultrastructure of respiratory cilia in a patient with Kartagener's syndrome. Cilia exhibited complete absence of only the inner dynein arms, while retaining outer arms, and mucociliary clearance was totally absent. We also studied neutrophil chemotaxis and other immunologic functions in our patient and found them to be normal. Our findings demonstrate an association between the structural abnormality of absent inner dynein arms alone and ciliary immotility in Kartagener's syndrome. The neutrophil migration abnormalities may have a different mechanism which needs further study.

Adenosine Triphosphatases↗