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Biomedical subjects

A Saxon

Publications and source records attributed to A Saxon.

At least 127 records · Page 7Linked to original sources
PubMed1986

Identification and partial purification of species-specific allergens from Triatoma protracta (Heteroptera:Reduviidae).

This article describes the immunochemical characterization of allergens from Triatoma protracta, a hematophagous insect that causes IgE-mediated anaphylactic reactions when it bites sensitized allergic persons. Comparison of the allergenic potency of T. protracta salivary gland extract, thoracic and abdominal hemolymph, and a whole body extract by RAST inhibition demonstrated that salivary glands were the main source of T. protracta allergens. Concentrated salivary gland extracts were purified by gel filtration and isoelectric focusing. Fractions were tested for allergenic activity by RAST inhibition and for protein purity by polyacrylamide gel electrophoresis and immunoelectrophoresis. Two protein peaks were obtained on gel filtration. The high-molecular-weight peak contained a 70,000 MW protein/glycoprotein that had little allergenic activity. The low-molecular-weight peak comprised six proteins, molecular weight 17,000 to 25,000, and T. protracta allergen(s) eluted in parallel with this peak. These proteins were resolved by isoelectric focusing, and two fractions, pI 6.7 to 7.3 and pI 8.2, contained most of the allergenic activity. By RAST, 25/28 sera from T. protracta-allergic patients contained IgE antibody to these fractions, suggesting that they were major allergens. Each fraction demonstrated a single precipitin arc on immunoelectrophoresis and two bands, molecular weight 18,000 to 20,000, on gel electrophoresis. Cross-inhibition radioimmunoassays demonstrated that each fraction completely inhibited binding of the other fraction to IgE antibody, suggesting that they contained different isoelectric forms of the same allergen.

Allergens↗
PubMed1986

Regulation of ongoing IgE synthesis by human T-cell supernatants derived from atopic and nonatopic donors.

Supernatants derived from T cells of donors with and without atopic disease were assessed to determine whether they could regulate ongoing IgE, IgG, or IgA synthesis of three different human B-cell lines. The results were compared with the ability of T-cell supernatants from the atopic donors to specifically induce IgE synthesis of nonatopic peripheral blood B lymphocytes (PBL-B cells). We found that, when tested on the B-cell lines, the T-cell supernatants from atopic donors doubled the IgE as well as the IgG and IgA synthesis. Although the T-cell supernatants from nonatopic donors had no effect on Ig synthesis of PBL-B cells or on the IgG of the IgG-secreting cell line, the supernatants doubled the IgE and moderately enhanced IgA synthesis of the IgE- and IgG-secreting cell lines. These results demonstrate that T-cell supernatants derived from atopic and nonatopic donors differ in their regulatory effects, not only on PBL-B cells, as had been shown previously by others, but also in their effects on ongoing Ig production.

B-Lymphocytes↗
PubMed1986

Designed transfer of specific immune responses with bone marrow transplantation.

Bone marrow transplant donors were immunized with tetanus/diphtheria toxoids 6-7 d before bone marrow donation to investigate the role of B cell subpopulations in reconstitution of humoral immunity. Lymphoblastoid B cells spontaneously producing IgG antitetanus and/or antidiphtheria toxoid were detected in the donor marrows at the time of transplantation. Recipients rapidly demonstrated 3-90-fold increases in serum IgG antitetanus and antidiphtheria toxoid levels. Antidiphtheria fragment A antibody in three donor/recipient pairs demonstrated spectrotypic identity indicating transfer of the donors' response. Reimmunization of three recipients 64-154 d after transplant revealed an IgG antibody response associated with reappearance of spontaneous antibody-producing B cells and an antidiphtheria fragment A response characteristics of the donor's immune response. These observations extend the understanding of the role of B cell subpopulations and provide a basis for specific modulation of immunity in the setting of bone marrow transplantation.

Adult↗
PubMed1985

Investigation into the immunologic cross-reactivity of aztreonam with other beta-lactam antibiotics.

The cross-reactivity between the monobactam antibiotic aztreonam and the commonly used beta-lactam antibiotics, penicillins, and cephalosporins was investigated. Antibodies to aztreonam, penicillin, and cephalothin were raised in rabbits. The ability of the homologous or heterologous drug or drug conjugates to inhibit antibody binding was assessed in a solid-phase radioimmunoassay. Aztreonam demonstrated very little ability to interact with anti-penicillin or anti-cephalothin antibodies as it required 10,000-fold higher concentrations than other beta-lactams to achieve equivalent blocking. Similarly, penicillin and cephalothin conjugates did not cross-react, to any significant degree, with anti-aztreonam rabbit antiserums. Interestingly, free aztreonam was as effective as conjugated aztreonam in reacting with antibodies raised against conjugated aztreonam. This result suggested that, in contrast to the other beta-lactams, antibodies to aztreonam recognize the side chain rather than the nuclear structures. Studies with other beta-lactam analogs confirmed that the IgG rabbit anti-aztreonam binding was indeed side chain-specific. Thirty-six volunteers were given a seven-day course of therapeutic doses of aztreonam and in none did any detectable IgE anti-aztreonam antibodies develop. Four of these subjects had evidence of preexisting IgG antibodies cross-reactive with aztreonam, but the levels rose in only one patient following drug exposure. This human IgG anti-aztreonam was also directed to the side chain and did not cross-react with cephalothin or penicillin. The ability of aztreonam to cross-react with human IgE to various penicillin determinants was also investigated. Aztreonam determinants analogous to the penicillin determinants (penicillin, penicilloyl, and penicilloate) were constructed and the maximal concentration that did not evoke false-positive skin test results was determined to be 6 X 10(-3) mol/liter. None of 41 patients with documented IgE-reactive skin tests to various penicillin determinants concurrently demonstrated reproducible reactivity to any aztreonam reagents. IgE anti-penicilloyl antibodies from three persons were also tested in vitro for their ability to cross-react with conjugated or free aztreonam. Minimal, if any, reactivity was observed between the IgE anti-penicilloyl and any of the aztreonam materials. These results indicate that there is very little cross-reactivity between the monobactam aztreonam and other beta-lactam antibiotics.

Adult↗
PubMed1985

Fc epsilon receptors on human cell lines and peripheral blood lymphocytes detected by binding of IgE immune complexes.

To identify Fc epsilon receptors on human cell lines and peripheral blood lymphocytes, we developed a new method which relies on the binding of constructed immune complexes to Fc epsilon receptor-positive cells. Cell suspensions from either cell lines or peripheral blood lymphocytes were incubated with complexes of human myeloma IgE and murine monoclonal anti-human IgE at various ratios prior to cytocentrifugation. The complexes bound to the cells were subsequently visualized by immunoperoxidase staining. The specificity of this assay to detect cell surface Fc epsilon receptors was shown by the ability of human myeloma IgE to block the binding of the IgE complexes, resulting in unstained cells, whereas IgM, IgG, and IgA were unable to block the binding of the complexes (stained cells). This method is reproducible, allows quantification of a single sample at different times, and provides a record of the results. It can also be adapted to identify any cell surface receptor for which the ligand is known.

Antibodies, Monoclonal↗
PubMed1985

Recurrent respiratory disease, azoospermia, and nasal polyposis. A syndrome that mimics cystic fibrosis and immotile cilia syndrome.

Three adult men with chronic sinopulmonary disease, nasal polyposis, and azoospermia were studied. All had normal sweat chloride values and pancreatic function. The azoospermia was due to a block in the epididymis that was distinguishable from the defect in the vas deferens seen in cystic fibrosis. Cilia structure was normal in sperm tails from testicular biopsy specimens and in cilia from tracheal biopsy specimens. These cases represent a clinical entity distinct from cystic fibrosis and known immotile cilia disorders.

Adult↗
PubMed1984

Comparison of high-dose and low-dose intravenous immunoglobulin therapy in patients with primary immunodeficiency diseases.

To assess safety and efficacy of high-dose intravenous immunoglobulin therapy in patients with primary immunodeficiency syndromes we treated a group of 19 patients with a monthly dose of 400 mg/kg of reduced and alkylated, maltose-containing immunoglobulin (Gamimune, Cutter Biological, Berkeley, California) and compared their responses with a group of 16 patients receiving 100 mg/kg per month intravenously. Side effects observed were mild to moderately severe and similar in both groups. In one adult patient receiving the high dose a severe enough reaction developed during the first infusion to exclude her from the study. Serum IgG levels of patients receiving high-dose immunoglobulin showed a stepwise increase in both trough and peak values until a new plateau was reached after four to six infusions. None of the patients receiving the low dose showed such a stepwise increase. On average, serum IgG levels rose by approximately 250 mg/dl for each 100 mg/kg immunoglobulin infused. The mean catabolic rate of the infused IgG was estimated to be 26 days in patients receiving high-dose immunoglobulin infusions. We demonstrated that 400 mg/kg immunoglobulin given intravenously every four weeks to patients with immunodeficiency results in a substantial increase in serum IgG during the postinfusion period, suggesting persistence of specific antibody throughout the interval between infusions.

Adult↗
PubMed1984

Successful immunotherapy for Triatoma protracta-induced anaphylaxis.

A successful program of immunotherapy for Triatoma protracta-induced anaphylaxis was developed. This program included a new passive extract-antigen preparation standardized by RAST inhibition. This antigen facilitated the development of a reliable skin test protocol for in vivo diagnosis of Triatoma protracta allergy. Five patients with T. protracta-induced anaphylaxis underwent a rapidly increasing dosage schedule of immunotherapy. The IgE- and IgG-antibody responses during immunotherapy were followed with solid-phase RIA. Protection against anaphylaxis was confirmed in all patients with a "bite challenge" by T. protracta. This is the first report of completely successful T. protracta immunotherapy.

Adult↗
PubMed1984

Lack of cross-reactivity between aztreonam , a monobactam antibiotic, and penicillin in penicillin-allergic subjects.

Monobactam antibiotics are a new class of beta-lactam antibiotics. In contrast to penicillins or cephalosporins, monobactams possess a monocyclic beta-lactam structure. IgE or immediate hypersensitivity cross-reactivity between aztreonam (a monobactam) and penicillin was investigated, since this will be an important consideration when therapy is chosen. The maximum concentration of aztreonam reagents not giving false-positive skin tests was determined in normal subjects who were not allergic to penicillin. Subsequently, 41 subjects with IgE antibody to one or more penicillin moieties, as determined by positive skin reactions, were tested with the aztreonam reagents. Thirty-seven of these persons showed no reactivity while four showed equivocal tests. Repeat tests in those four persons were negative to the aztreonam reagents, while their penicillin tests remained unchanged. These in vivo data suggest that there is no cross-reactivity between IgE antibodies to penicillin and aztreonam and provide a basis for investigating the therapeutic use of monobactams in patients who are allergic to penicillin.

Adult↗
PubMed1984

Human auto-antiidiotypes regulating T cell-mediated reactivity to tetanus toxoid.

While investigating the effect on B cells of repetitive in vivo immunization with tetanus toxoid (TT), we observed the subsequent development of specific anergy for T cell delayed hypersensitivity (DTH) to TT. This appeared approximately 35 d after a series of five booster immunizations. Concurrently, in vitro T cell blastogenic responses were preserved. Serum obtained when the skin tests were nonreactive demonstrated a profound inhibitory activity on T cell reactivity. This activity was shown to be anti-antibody activity that was both anti-F(ab)'2 and, specifically, anti-TT F(ab)'2. It blocked binding of TT to a pool of allogeneic antibodies and also inhibited allogeneic antigen-specific T cell blastogenesis. Thus, we could identify activity in the serum of hyperimmunized individuals that appeared auto-anti-idiotypic (anti-id) and represented a single or family of major crossreacting idiotypes (id) for TT. The expression of the auto-anti-id correlated with the loss of T cell reactivity in vivo and in vitro. Subsequent examinations revealed persistent, specific cutaneous anergy beyond six months, which was then associated with a failure of T cells to react with antigen in vitro. Mixing experiments with cells from these later times and cryopreserved autologous cells obtained prior to hyperimmunization revealed there had been the development of antigen-specific T suppressor cells. Thus, in vivo DTH tolerance following hyperimmunization was associated with an inhibitory serum activity that appeared to be anti-id. Persistence of tolerance (greater than 6 mo) occurred with the development of T suppressor cells.

Adult↗
PubMed1984

Antibody synthesis by bone marrow cells in vitro following primary and booster tetanus toxoid immunization in humans.

Normal volunteers received either initial or booster immunization with tetanus toxoid. Bone marrow and peripheral blood mononuclear cells were obtained for up to 28 d after immunization and were analyzed for synthesis of total Ig and specific antibodies to tetanus toxoid. Cells were cultured in vitro for 3 or 7 d with or without pokeweed mitogen (PWM). Synthesis of IgG and IgM antibodies to tetanus (IgG-Tet and IgM-Tet) and total IgG and IgM was determined by radioimmunoassay. Four functional B cell subpopulations were detected in the bone marrow after booster tetanus immunization: (a) B cells that spontaneously synthesized IgG-Tet appeared on day 7 after immunization but were undetectable by day 21; (b) B cells that synthesized IgG-Tet after stimulation with PWM appeared after day 21 and persisted for greater than 1 mo; (c) B cells that synthesized IgM-Tet in the presence of PWM were detectable before and after immunization; and (d) B cells that spontaneously synthesized IgM-Tet appeared on day 7 and were undetectable by day 21. In contrast to the other three types of bone marrow B cells described, this fourth subpopulation of PWM-independent IgM-Tet-synthesizing B cells was not detected in the peripheral blood. After primary immunization, no spontaneous antibody-producing cells were detected in the blood or bone marrow, although there was a small rise in IgM-Tet in two of three subjects. In the bone marrow, only IgM-Tet PWM-inducible cells were seen, although mitogen-responsive IgM and IgG-Tet cells were detected in the circulation. The IgM-Tet PWM-reactive cells were present even before primary antigen exposure and appear to represent the initial B cells involved in the antibody response. These data indicate that there are specific times after immunization when different functional classes of anti-Tet-synthesizing B cells and memory B cells appear in human bone marrow. Knowledge of these data may be important in developing a strategy for the transfer of immune memory from donors to recipients in the setting of bone marrow transplantation.

Adult↗
PubMed1984

Isotype-specific human suppressor T cells for IgE synthesis activated by IgE-anti-IgE immune complexes.

The ability of human IgE-anti-IgE (mouse hybridoma anti-Fc) immune complexes (IC) to generate suppressor T cells for human myeloma IgE synthesis in vitro was tested. T cells incubated with 0.1 micrograms/ml of IC that had an IgE to anti-IgE ratio of 1:1 inhibited myeloma IgE synthesis by 16% more than the control (p less than 0.01). Inhibition was also seen with IC in which the IgE to anti-IgE ratio was higher (2:1 and 4:1), but these differences in synthesis were smaller and were not statistically significant (8 and 3%, respectively, p greater than 0.05). Thymidine incorporation by T cells incubated 3 days with 0.1 microgram/ml of IC at the 1:1 or 2:1 ratio was consistently greater (p less than 0.0025 and less than 0.0125, respectively) than by controls. The IC lost their ability to generate suppressor T cells when the cytophilic site on the IgE molecule was destroyed with heat treatment (0% inhibition with IC at 1:1 and 4% inhibition with IC at 2:1). The activation of T cells with IC showed isotype specificity because the activated T cells failed to suppress IgG and IgA synthesis by the lymphoblastoid cell lines GM-1500 and GM-1056, respectively. T cells were fractionated by incubation with IC and then were panned on plates coated with goat anti-mouse IgG. The adherent cells spontaneously suppressed IgE by 25% when compared to controls (p less than 0.005). These cells failed to suppress IgG and IgA. The activation of the T cells was not due to the panning process itself because activation did not occur with cells that adhered to plates coated with bovine serum albumin (p greater than 0.05) when compared to untreated T cell controls or the IC nonadherent population. These experiments extend previous findings that isotype-specific suppressor T cells for IgE synthesis can be generated in vitro.

Adult↗
PubMed1983

Effect of midbrain stimulus-induced analgesia on immune function in humans.

Electrical stimulation of midbrain structures produces significant and clinically useful analgesia in humans. However, it has been suggested to have immunosuppressive effects in animals. We evaluated immune function in two women who were utilizing implanted midbrain electrodes for pain control. An elevated B cell percentage was observed in one patient after a 72-h control rest period and this was followed by a reproducible fall in B cells after acute stimulation. However, midbrain electrical stimulation did not appear to have any other acute or chronic effects on these persons' immune functions.

Analgesia↗
PubMed1983

Ecto-5'-nucleotidase activity in human T cell subsets. Decreased numbers of ecto-5'-nucleotidase positive cells from both OKT4+ and OKT8+ cells in patients with hypogammaglobulinemia.

T lymphocytes from control subjects were separated into subsets using monoclonal antibodies of the OKT series and complement lysis and analyzed for ecto-5'-nucleotidase activity both by quantitative radiochemical assay and a histochemical stain. T cells from 15 control subjects contained 54+/-4% OKT4(+) (helper/inducer) cells and 32+/-3% OKT8(+) (cytotoxic/suppressor) cells. Total T cell ecto-5'-nucleotidase activity was 10.9+/-2.1 nmol/h per 10(6) cells with 25+/-7% positive by histochemical stain. Ecto-5'-nucleotidase activity in OKT4-enriched populations was 5.43+/-1.8 nmol/h per 10(6) cells with 14+/-2% positive by histochemical stain; that in OKT8-enriched populations was 17.1+/-5.9 nmol/h per 10(6) cells with 35+/-8% positive by histochemical stain. Two of four patients with congenital agammaglobulinemia and four of seven patients with common variable immunodeficiency had decreased proportions of OKT4(+) T cells with corresponding increases in the proportions of OKT8(+) T cells (OKT4/OKT8 = 0.60 to 1.0 as compared with 1.7+/-0.2 for control subjects). All four patients with congenital agammaglobulinemia, and three of seven patients with common variable immunodeficiency also had low T cell ecto-5'-nucleotidase activity (<5.5 nmol/h per 10(6) cells). Ecto-5'-nucleotidase activity in OKT4- enriched populations isolated from four patients with low total T cell activity was 2.85+/-0.90 nmol/h per 10(6) cells with 10+/-4% positive by histochemical stain; that in OKT8-enriched populations was 6.82+/-1.7 nmol/h per 10(6) cells with 7.5+/-3% positive by histochemical stain. Thus, the number of ecto-5'-nucleotidase positive cells is decreased, especially in the OKT8(+) subpopulation, and the low total T cell ecto-5'-nucleotidase activity seen in these patients is due to fewer positive cells rather than to substantially less activity per cell. Our data indicate that ecto-5'-nucleotidase activity defines two subpopulations of T lymphocytes (ecto-5'-nucleotidase positive and negative), the proportions of which are markedly altered in many patients with hypogammaglobulinemia. In preliminary studies with seven patients, increased numbers of ecto-5'-nucleotidase negative T cells appeared to correlate with increased suppressor T cell activity toward in vitro immunoglobulin synthesis. Therefore, ecto-5'-nucleotidase may be a useful cell surface marker in the study of imbalances of regulatory T cell subsets in patients with antibody synthesis disorders.

Adenosine Deaminase↗
PubMed1983

Inhibition of ongoing myeloma IgE synthesis in vitro by activated human T cells.

The ability of activated T cells to suppress ongoing IgE synthesis in vitro was assessed using U266--a human myeloma cell line spontaneously producing IgE. T cells were able to inhibit U266 IgE synthesis in the presence of 10 micrograms/ml of Con A by 41.8% (p less than 0.01). T cells preincubated with 10 or 50 micrograms/ml of Con A and washed extensively were still able to inhibit U266 IgE synthesis in the absence of Con A by 41 and 46% (p less than 0.05 and p less than 0.02, respectively). The decrease in IgE measured was due to inhibition of newly formed IgE by U266, as shown by control experiments with cycloheximide. The inhibition was not due to the simple depletion of nutrient growth factors by the activated T cells, as it did not occur with MOLT-4, T cells that are very active metabolically; nor could it be reversed with medium containing IL 2 and B cell growth factors. Culture supernatants of Con A-activated T cells were also able to suppress IgE synthesis by U266 (21%; p less than 0.01), which suggests that upon appropriate activation, T cells secrete material(s) with inhibitory properties for IgE synthesis. Activation of T cells by mixed lymphocyte culture using puromycin-treated lymphoblastoid cell lines as stimulators also generated T cells that had suppressive activity for IgE synthesis. T cells activated with Con A and subsequently incubated with IgE demonstrated a diminished ability to suppress IgE synthesis. This observation is in agreement with the finding that patients with high levels of IgE may lack isotype-specific suppressor T cells for spontaneous IgE secretion. However, T cells from such patients have so far shown variable loss of IgE suppressive function. These results suggest that human IgE synthesis is susceptible to inhibition at a very differentiated stage, and this may be important in expression of allergic diseases.

Adult↗
PubMed1983

Human-human B cell hybridomas from in vitro stimulated lymphocytes of patients with common variable immunodeficiency.

Human-human B cell hybridomas have been established from the peripheral blood lymphocytes of patients with common variable immunodeficiency (CVI) by fusion with an HGPRT-negative B lymphoblastoid cell line. IgM-secreting hybridomas were successfully obtained from CVI lymphocytes after stimulation for 5 days in vitro with a combination of PWM and Staphylococcus aureus strain Cowan I. Fusion of peripheral blood lymphocytes that were stimulated for 5 days in vitro with a single mitogen resulted in no viable hybrids from a total of 600 X 10(6) CVI lymphocytes. The combination of PWM and Cowan I did not induce appreciable Ig secretion from the CVI lymphocytes during the 5-day course, although it did so in normal lymphocytes. After the 5-day stimulation with this mitogen combination, however, a large percentage of the original number of peripheral blood cells were recovered, and these had a fusion frequency of approximately 1 to 2 per 10(6) with the B lymphoblastoid line. Fifteen cloned IgM-secreting hybridomas have been isolated from five different CVI patients. These hybridomas are tetraploid and have been stable in culture for 6 to 12 mo. All of the hybridoma lines that were examined contain a functionally rearranged IgM heavy chain gene from the B cell parent of the CVI patients. These human-human B cell hybridoma lines will enable a more thorough characterization of the B cell defects involved in CVI at the cellular and molecular levels.

Adult↗
PubMed1983

Rhinopharyngoscopy for the evaluation of allergic-immunologic disorders.

We have developed fiberoptic rhinopharyngoscopy as an important procedure for the evaluation of allergic and immunologic disorders. The procedure is useful for office practice, well tolerated and without serious complications. This paper outlines the technique for fiberoptic rhinopharyngoscopy, the pathology which can be identified, instruments available and our experience in nearly 100 patients.

Candidiasis↗