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Biomedical subjects

R D deShazo

Publications and source records attributed to R D deShazo.

At least 55 records · Page 3Linked to original sources

Human immunodeficiency virus infection in hemophiliac patients. A three-year prospective evaluation.

Thirty-seven heterosexual hemophiliac patients underwent prospective evaluation with clinical examinations, serologic studies for antibody to human immunodeficiency virus (HIV), and tests of immune function for an average of 37 months. At the time of entry into the study in 1982 to 1983, 18 subjects (49 percent) were already seropositive for HIV and 11 (30 percent) had persistent generalized lymphadenopathy. Seventy percent of the total population were clinically asymptomatic. In nine subjects, seroconversion occurred during the study such that 81 percent of the population was seropositive at the conclusion. During the same period, lymphadenopathy developed in six subjects, there was progression to AIDS-related complex (ARC) in four, and acquired immunodeficiency syndrome (AIDS) developed in one patient. Thus, at the end of the study, 54 percent were clinically asymptomatic, 32 percent had persistent lymphadenopathy, and 11 percent had ARC. Subjects who remained seronegative had received less factor concentrate than seropositive subjects, remained asymptomatic, and had normal results on tests of immune function. In those who had experienced seroconversion, there were decreased absolute numbers of CD4+ lymphocytes prior to seroconversion, and abnormalities of lymphocyte function developed after seroconversion. The development of persistent generalized lymphadenopathy was associated temporally with seroconversion. The presence of persistent generalized lymphadenopathy did not appear to be associated with an increased risk for AIDS in seropositive persons, since the condition of most hemophiliac patients with persistent generalized lymphadenopathy at the time of initial evaluation remained clinically and immunologically stable. In contrast to patients with persistent generalized lymphadenopathy, asymptomatic seropositive subjects had progressive abnormalities of lymphocyte function over time that were independent of the numbers of CD4+ cells in the peripheral blood.

AIDS-Related Complex↗

RAST-inhibition studies of the imported fire ant Solenopsis invicta with whole body extracts and venom preparations.

Whole body extracts of imported fire ants (IFAWBE) are the only reagents currently available for diagnosis and immunotherapy of patients with anaphylaxis to these Hymenoptera. To characterize better IFAWBE of the species Solenopsis invicta, we evaluated the sera of 29 patients with systemic or large local reactions to imported fire ant (IFA) stings. Forty-eight percent (14/29) of these sting-sensitive patients were IFAWBE RAST positive (greater than or equal to 6% binding of total radioactivity added). With a pool of sera with an initial IFAWBE-RAST value of 16.2% binding, we evaluated RAST inhibition by IFA venom (IFAV), IFAWBE, and the venom component, transpiperidine. Maximum RAST inhibition obtained was 84% with 300 micrograms/ml of IFAV, 95% with 5 mg/ml of protein IFAWBE, and insignificant with undiluted transpiperdine. We conclude that IFAWBE contains large quantities of immunoreactive venom components other than transpiperidine and that the allergenicity of IFAWBE and venom resides in the small amount of protein present in IFAV.

Adult↗

Drug allergy.

Adverse reaction to drugs is a common problem in the pediatric population. This article discusses the different types of adverse drug reactions and their mechanisms. Also included are representative clinical syndromes of drug hypersensitivity reactions, as well as certain organ systems syndromes. Finally, diagnosis and management of allergic reactions to particular drugs such as penicillin, iodinated contrast dye, insulin, and others are discussed.

Anaphylaxis↗

Superiority of Solenopsis invicta venom to whole-body extract in RAST for diagnosis of imported fire ant allergy.

RAST determinations using imported fire ant (IFA) whole-body extract (IFAWBE) and venom (IFAV) were performed with the sera of 29 sting-sensitive patients. Only 48% (14/29) of sera were positive (percent binding greater than or equal to 6%) in RAST to IFAWBE compared with 79% (23/29) positive to IFAV, and there was significantly greater binding to IFAV than to IFAWBE (p less than or equal to 0.0002). Thus, RAST with IFAV identified 31% more sting-sensitive individuals than RAST with IFAWBE, a finding similar to that noted in studies using IFAV and IFAWBE for skin testing. We conclude that IFAV is the more appropriate allergen for use in in vitro tests to detect IFA-specific IgE antibody in allergic patients.

Animals↗

Natural killer cell activity in asbestos workers. Interactive effects of smoking and asbestos exposure.

Both the numbers and function of natural killer (NK) cells in 60 were evaluated in asbestos cement workers grouped by smoking history and chest roentgenogram findings (ILO profusion scores less than 1/0 or greater than or equal to 1/0, or isolated pleural plaques). Worker and control subjects who smoked had smoking histories of less than 27 pack-years, a level of smoking lower than that previously determined to adversely affect NK function. Asbestos workers who did not smoke had percentages and total numbers of NK cells and NK function not different from that of nonsmoker control subjects. Workers who smoked and had evidence of asbestosis (ILO profusion category greater than or equal to 1/0) had significantly lower total numbers of NK cells and mononuclear cell NK activity than did smoker control subjects or smokers with pleural plaques only (p less than or equal to 0.05). Numbers of NK cells and NK cell function were not decreased in either of the asbestos-exposed smoking groups without asbestosis when compared to nonsmoker controls. We conclude that smoking and asbestos exposure interact to decrease mononuclear cell NK function in workers with levels of asbestos exposure sufficient to induce asbestosis. This finding may explain in part the previously reported synergistic effect of smoking and asbestos exposure on the risk of lung cancer. Furthermore, the data presented here clarify previous conflicting reports on NK function where asbestos exposed groups have not been stratified for analysis of data.

Adult↗

Spontaneous suppressor cell activity in patients with the acquired immune deficiency syndrome and associated conditions.

Patients with the acquired immune deficiency syndrome (AIDS) have depressed cell-mediated immunity partially explained by a depletion of helper-inducer T-lymphocytes. We questioned if the remaining elements of the mononuclear cell (MNC) population also played a part in the immunologic abnormalities noted. We therefore evaluated the ability of MNC populations from homosexuals with AIDS and AIDS-associated conditions to suppress the mitogenic responses of control MNCs in an assay of "spontaneous suppressor" cell activity (SSCA). Asymptomatic homosexuals and homosexuals with chronic lymphadenopathy, Kaposi's sarcoma, or opportunistic infections (OIs) had levels of SSCA equal to or greater than that of control subjects. Levels were significantly higher in patients with lymphadenopathy (p less than or equal to 0.1) and in patients with OI (p less than or equal to 0.05). Although percentages of Ia+ cells were increased in all homosexual groups and highest in patients with OIs (p less than or equal to 0.05), percentages of either monocytes or suppressor/cytotoxic T-lymphocytes, potential mediators of SSCA function, did not correlate with levels of SSCA observed. Therefore, patients with AIDS and AIDS-associated conditions have MNC populations that appear to interact in producing normal or augmented down regulation of residual T-lymphocyte function, even in the face of helper/inducer T-lymphocyte depletion.

AIDS-Related Complex↗

Anaphylaxis. Why it happens and what to do about it.

Anaphylaxis is an often severe, potentially life-threatening symptom complex. Urticaria, airway edema, vascular collapse, asthma, abdominal pain, and diarrhea are common clinical signs. Recently recognized syndromes of anaphylaxis include reactions due to exercise, food preservatives, aspirin, steroids, dialysis, various serums, and human seminal fluid. Initial therapy is directed at maintaining an effective airway and circulatory system. Administration of aqueous epinephrine is always indicated. Other measures may include oxygen delivery by controlled flow, administration of an aerosolized beta agonist, slow infusion of aminophylline, and rapid infusion of intravenous fluid. Patients with severe acute reactions should be monitored in-hospital.

Adrenergic beta-Agonists↗

Diminished natural killer-cell activity of interstitial pulmonary cell populations from patients with carcinoma of the lung.

Natural killer-cell activity of fresh interstitial pulmonary cell populations from patients with squamous cell and adenocarcinoma of the lung and carcinoma metastatic to the lung was assessed and compared to that of apparently normal lung. No increase in the percentage of lymphoid cell populations was noted in the interstitium of lung contiguous with tumor, and the cytotoxic capacity of the cells present was depressed as compared to that of normal lung. Natural killer-cell function appears to be down regulated in lung cancer and may be amenable to therapies which activate such cytotoxicity in vivo.

Adenocarcinoma↗

Cytotoxic cell function in bronchogenic carcinoma.

Biologic response modifiers (BRM) such as interleukin-2 (Il-2) and gamma-interferon (gamma IFN) can augment preexisting or initiate new cytotoxic capacity of human lymphocytes against tumor cells. Although in vivo therapy with BRM or adoptive immunotherapy with BRM-treated cells seems logical in the treatment of bronchogenic carcinoma, recent studies have shown that lymphocytes from the lung and tumor tissues of patients with bronchogenic carcinoma have defective cytotoxic function. We sought to determine if defects in lung cytotoxic cell function are primary or secondary to local tumor effects, and if peripheral blood lymphocyte populations from patients can serve as a source for BRM-stimulated cytotoxic cells. We evaluated the natural killer (NK) cell and lymphokine (Il-2) activated killer cell activity (LAK) activity of mononuclear cell populations from 11 patients with newly diagnosed bronchogenic carcinoma and three control groups. Cultured human squamous cell and adenocarcinoma cell lines proved useful in evaluating LAK activity in these studies. Levels of NK and LAK activity in patients compared favorably with both those of non-smokers in two different age ranges and with smokers. Peripheral blood cytotoxic cell function remains intact and responsive to augmentation by BRM in patients with recently diagnosed bronchogenic carcinoma. Reported defects in patient lung cell cytotoxic function appear to be local tumor-related defects not present in peripheral blood lymphocytes.

Adult↗

Pulmonary immunologic features of alveolar septal amyloidosis associated with multiple myeloma.

A 74-year-old man presented with interstitial pulmonary disease which was proven to be alveolar septal amyloidosis by transbronchial biopsy. Multiple myeloma was diagnosed on the basis of monoclonal IgG-lambda protein in serum, monoclonal lambda light chains in urine, a bone marrow plasmacytosis of 22 percent, and serum IgA and IgM levels less than 100 mg/dl and 50 mg/dl, respectively. Appropriate investigations failed to show additional sites of deposition of amyloid. Analysis of fluid from bronchoalveolar lavage showed an increase in total cells recovered, a lymphocytosis with a ratio of T helper over T suppressor cells greater than that in peripheral blood, the presence of an IgG-lambda paraprotein, and an IgG/albumin ratio greater than that in serum. While plasma cells could not be identified in the recovered cell population, cultured cells from bronchoalveolar lavage fluid showed increased production of IgG. These findings provide evidence of an ongoing pulmonary immune response resulting in excess IgG-lambda protein in the pulmonary compartment, a factor which may contribute to the development of amyloidosis.

Aged↗

Analytical and functional assessment of lymphoid cells within murine lung.

In this study we sought to characterize the tissue leukocytes in murine lung which (when derived from peripheral lymphoid organs) have been associated with host defense against tumors and certain microbial agents. Numerical and functional properties of lung lymphoid populations obtained by collagenase digestion were evaluated in inbred mice. Flow cytometric analysis of monoclonal and polyclonal antibody labelled preparations revealed that lung cells so derived were 47% T-lymphocytes (helper-suppressor ratio 4.25), 23% B-cells (surface immunoglobulin+) and 26% asialo GM1 (natural killer) cells. Lung T-cells responded well to mitogen stimulation after partial depletion of adherent macrophages, but the magnitude of this response was less than that of autologous spleen cells. Natural killer cell (NK) activity against chromium labelled tumor target cells was also manifested by lung cells and was similar to that of peripheral spleen cells. This lung NK activity could be boosted in vitro by incubation with interferon and in vivo by treatment with poly I:C. Together, these data indicate that normal murine lung contains a large number of functional T-cell and NK cell mononuclear populations. The characterization of the cell populations presented here should facilitate future studies of their role(s) in host defense against infection and neoplasia.

Animals↗

Modulation of natural killer cell function by human alveolar macrophages.

Lymphocyte natural killer (NK) activity appears to be important in resistance against viral infection and malignancy. Since pulmonary alveolar macrophages (PAM) derived from nonsmokers suppress NK activity in vitro, we asked if PAM derived from smokers modulated NK activity in a similar fashion. Bronchoalveolar lavage cells (BLC) were obtained from healthy nonsmokers and healthy smokers by bronchoalveolar lavage. Increasing numbers of BLC were cocultured with a fixed ratio of monocyte-depleted peripheral blood lymphocytes (PBL) and Cr51-labeled K562 tumor target cells (PBL:K562, ratio 25:1; BLC:PBL ratios ranging from 0.02:1 to 1:1). Increasing numbers of BLC progressively suppressed the ability of either autologous or homologous PBL to lyse tumor targets. Smoker and nonsmoker BLC inhibited NK activity of homologous lymphocytes with similar potency. Suppression of NK activity by BLC was not reversed by the addition of indomethacin or catalase to cell cultures. Furthermore, suppression could not be reproduced by performing cytotoxicity assays in the presence of BLC culture supernatants. Lymphocytes boosted to high levels of NK activity by preincubation with alpha-interferon or interleukin-2 were still susceptible to suppression by BLC. Thus, PAM derived from smokers efficiently suppress lymphocyte NK activity, and the degree of suppression increases as the ratio of PAM to lymphocytes increases. Since smoking causes a bronchoalveolar accumulation of PAM, these inhibitory cells may result in profound local suppression of NK activity in smoker's lungs.

Adult↗

Immunologic studies in homosexual and hemophiliac subjects with persistent generalized lymphadenopathy: a comparative analysis.

Hemophiliac patients receiving factor VIII replacement therapy and homosexual subjects are at risk for the acquired immune deficiency syndrome. Immunologic abnormalities, especially depletion of helper T cell populations, have been noted in members of these groups and may parallel their clinical state. We have evaluated the peripheral blood immunologic status of a group of hemophiliac and homosexual subjects with and without persistent generalized lymphadenopathy (PGL). Although individuals with PGL had more abnormal T-lymphocyte parameters, including lower helper/suppressor ratios, than group members without lymphadenopathy, there were no significant differences noted within each respective risk group. However, differences between hemophiliac and homosexual patient groups were noted. T-lymphocyte subpopulations of hemophiliac patients with lymphadenopathy were significantly more abnormal than the corresponding homosexual groups. All groups had decreased lymphocyte proliferative responses to mitogen. Homosexual subjects with lymphadenopathy exhibited the most profoundly depressed lymphocyte mitogenic responses. We conclude that, although abnormalities of T-lymphocyte subpopulation and lymphocyte mitogenic responses exist within each risk group, homosexual subjects (both asymptomatic and with PGL) had lower mitogenic responses than would be expected for their T-lymphocyte helper/suppressor ratios as compared to either control subjects or hemophiliac patients. These findings suggest that additional factors are operative in the mononuclear cell populations of homosexual subjects that depress lymphocyte function. An analysis of these factors may help explain the higher incidence of AIDS in homosexual subjects as compared to hemophiliac patients.

Acquired Immunodeficiency Syndrome↗

Immunomodulation by bronchial lavage cells in normal individuals and patients with bronchogenic carcinoma.

The ability of bronchoalveolar lavage cells to facilitate lymphoproliferation to mitogen in a system which allows assessment of pulmonary alveolar macrophage accessory cell function was investigated. Bronchoalveolar lavage cells were obtained from healthy non-smokers and smokers and from patients undergoing diagnostic bronchoscopy. Lavaged cells were cultured with monocyte-depleted homologous blood lymphocytes obtained from healthy, young volunteers and stimulated with suboptimal (2 micrograms/ml) or optimal (20 micrograms/ml) concentrations of phytohemagglutinin. Mitogen responses of lymphocytes in all groups were related to the number of lavage cells added, increasing with 1:100 and 1:10 bronchoalveolar lavage cell to lymphocyte ratios and decreasing with 1:2 and 1:1 ratios. Lymphoproliferative responses observed in smoker and nonsmoker cultures were not different. In contrast, maximal proliferative responses of cell cultures from patients with epidermoid and small cell carcinoma were decreased compared with cultures from patients with adenocarcinoma or controls. These data show that pulmonary bronchial lavage cells from smokers and nonsmokers provide similar dose related augmentation and suppression of lymphocyte mitogenic responses. Furthermore, accessory cell function of lavage cell populations is normal in patients with adenocarcinoma, but depressed in patients with epidermoid or small cell carcinoma.

Adenocarcinoma↗