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Biomedical subjects

K R Mueller

Publications and source records attributed to K R Mueller.

8 recordsLinked to original sources
PubMed1990

T- and B-cell dysregulation of IgE synthesis in cystic fibrosis patients with allergic bronchopulmonary aspergillosis.

Since Aspergillus fumigatus (Af)-specific and polyclonal serum IgE levels are characteristically elevated in patients with allergic bronchopulmonary aspergillosis (ABPA), we evaluated in vitro regulation of IgE synthesis in cystic fibrosis (CF) patients with ABPA. We studied 11 CF patients with ABPA, 37 patients with positive Af prick skin tests and/or IgG precipitating antibodies (ST/PPT+), and 35 patients with no humoral or skin responses to Aspergillus (ST/PPT-). Mean serum IgE concentration was significantly elevated in CF subjects with ABPA compared to ST/PPT+ and ST/PPT- patients, 2866 vs 303 and 61 IU/ml, respectively (P less than 0.01). In vitro studies demonstrated that ABPA patients' B cells spontaneously synthesized significantly increased amounts of IgE compared to ST/PPT positive and negative subjects, 1980 vs 220 and 13 pg/ml, respectively (P less than 0.01). In addition, preformed B-cell-associated IgE was also significantly elevated in ABPA subjects (P less than 0.01), indicating prior in vivo activation. Supernatant cultures of Af-stimulated T cells from ABPA subjects significantly induced allogeneic B-cell IgE synthesis compared to ST/PPT positive and negative CF subjects, 206 vs 13 and 4 pg/ml, respectively (P less than 0.01). Thus T cells stimulated with Aspergillus antigens secrete cytokines that induce B-cell IgE synthesis in ABPA subjects. B-cell IgE hyperactivity is manifested by in vivo and in vitro increased IgE concentrations. Analyses of T-cell regulation and B-cell IgE synthesis distinguish CF subjects with ABPA from Aspergillus sensitive non-ABPA subjects.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed1990

T cell cytotoxicity in cystic fibrosis: relationship to pulmonary status.

T cell cytotoxicity (CTL) to an allogeneic lymphocyte target was evaluated in patients with cystic fibrosis (CF) before and during pulmonary exacerbations (group 1) compared to another group of CF patients who had stable pulmonary disease activity during their two study periods (group 2). CTL activity was significantly decreased in group 1 subjects studied prior to their pulmonary flares and in group 2 CF patients compared to normal controls at effector:target ratios of 12.5:1 and 6.25:1 (p less than 0.05 and p less than 0.05, respectively). Furthermore, in group 1, CTL lysis was significantly decreased during pulmonary flares compared to before flares at the 25:1 and 12.5:1, effector:target, (p less than 0.05 and p less than 0.05, respectively). T suppressor cell activity as measured by effect on in vitro control B cell IgM synthesis was significantly increased during pulmonary flares (p less than 0.05). Diminished CTL may be partially responsible for persistent colonization of Pseudomonas aeruginosa in CF.

Cystic Fibrosis↗
PubMed1990

Serum immunoglobulins E and G anti-Aspergillus fumigatus antibody in patients with cystic fibrosis who have allergic bronchopulmonary aspergillosis.

Patients with cystic fibrosis frequently have pulmonary colonization with Aspergillus fumigatus (Af) and develop anti-Af immunoglobulin E (IgE) and IgG antibodies. The diagnosis of allergic bronchopulmonary aspergillosis in subjects with cystic fibrosis is difficult because of the high incidence of Af colonization, with development of humoral antibody responses. In this study, we sequentially measured serum anti-Af IgE (Af-E) and IgG (Af-G) antibodies by ELISA in subjects with cystic fibrosis. In subjects with cystic fibrosis who have allergic bronchopulmonary aspergillosis, Af-E and Af-G antibodies were significantly increased when compared with other groups of patients with cystic fibrosis who had positive skin tests or precipitins to Af (or both) (p less than 0.01, p less than 0.01, respectively). In addition, increased Af-E and Af-G levels were sometimes seen in other groups, especially subjects with cystic fibrosis who had positive Af skin tests or precipitin tests, two of whom later developed criteria diagnostic of allergic bronchopulmonary aspergillosis. Thus, serum Af-E and Af-G levels were quantitatively increased in subjects with cystic fibrosis who had allergic bronchopulmonary aspergillosis and thus adjunctive data in diagnosis. However, it also suggested that subclinical pulmonary inflammation may also occur.

Adolescent↗
PubMed1989

Decrease of CD4 cell number and function in HIV-seropositive hemophiliacs in a longitudinal study.

The Regional Hemophilia Center in St. Louis initiated a prospective study beginning in 1982 to measure sequentially T-cell subpopulations and in vitro lymphoproliferative responses in hemophilia A patients. In a cohort of 106 hemophiliacs, the prevalence of HIV-seropositivity increased from 46.7% in 1982 to 74.5% by 1987. There was a persistent gradual decline over time of T helper/inducer (CD4) cells in HIV-seropositive hemophiliacs (P less than .01). This was reflected by an increasing percentage of hemophiliacs with abnormally low CD4 cells (less than 2 standard deviations below the mean of normal individuals) from 6.7% in 1983 to 52.4% in 1987. Function of CD4 cells, as estimated by in vitro lymphoproliferative responses to phytohemagglutinin (PHA) and tetanus toxoid stimulations also demonstrated a decline over the same years. Lymphoproliferative responses to PHA by HIV-seropositive hemophiliacs' mononuclear cells (MNC) declined from a 90.2% normal response in 1983 to a 71.7% normal response in 1987 (P less than .05). Decreased responses to stimulation with the soluble antigen tetanus toxoid were also seen from 1983 compared with 1987 (P less than .05). This was due to an increased percentage of HIV-seropositive hemophiliacs' MNC, which were unresponsive to stimulation to tetanus toxoid (stimulation index less than 3.0) from 20.8% in 1983 to 41.0% in 1987. These findings indicate that HIV-infection was associated over time with a decline of CD4 number and function in a substantial portion of hemophiliacs.

Adolescent↗
PubMed1988

Decreased T helper cell function in patients with cystic fibrosis.

T cell immune function was further evaluated in cystic fibrosis (CF) patients. CF patients, regardless of severity of pulmonary disease or colonization with Pseudomonas aeruginosa, had lower percentages of T helper cells (p less than 0.01) and decreased T helper function as demonstrated by diminished T help for control B cell pokeweed mitogen-stimulated IgG (p less than 0.01) and IgM (p less than 0.01) synthesis. Increased T suppressor function, measured by co-culture with control B and T cells, was noted in only 25% of CF patients. CF patients' T cells exhibited decreased allogeneic T cell cytotoxicity compared to normal controls (p less than 0.01). This study extends previous studies demonstrating decreased T cell functions in CF patients and indicates a specific decrease in T helper function.

Adolescent↗
PubMed1986

Time relationship of immune changes to HTLV-III/LAV seroconversion in patients with hemophilia.

Longitudinal immune studies of patients with hemophilia A were begun in 1982 by the Regional Hemophilia Center in St. Louis, Missouri. Serum samples collected from 74 participants between 1982 and 1985 were analyzed for antibody to human T-lymphotropic virus type III (HTLV-III)/lymphadenopathy-associated virus (LAV). The incidence of antibody to HTLV-III/LAV has increased significantly in this population of patients with hemophilia. Only one of eight hemophiliacs had detectable antibody before July 1982, whereas 88.7% (55/62) were positive in 1985. T-cell surface markers were markedly abnormal in seropositive hemophilia patients with decreased percentage and number of OKT4-positive cells compared with seronegative hemophiliacs and controls. Lymphoproliferative responses to mitogens and antigens were normal in seronegative hemophilia patients. Seropositive hemophiliacs, compared with seronegative hemophiliacs, had significantly decreased lymphoproliferative responses, especially to pokeweed mitogen, tetanus, and Candida stimulations. Immune studies of seven HTLV-III/LAV seropositive hemophiliacs revealed antigen unresponsiveness and decreased T4 cells 2 to 32 months prior to development of full-blown AIDS. Longitudinal immune studies from 1983-85 revealed increasing number of seropositive hemophiliacs with antigen unresponsiveness and decreased T4 cells.

Acquired Immunodeficiency Syndrome↗