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Biomedical subjects

A Saxon

Publications and source records attributed to A Saxon.

At least 145 records · Page 8Linked to original sources
PubMed1982

Production of anti-basement membrane-zone antibody by peripheral blood leukocytes of pemphigoid patients.

Peripheral blood leukocytes (PBL) from patients with bullous pemphigoid stimulated by pokeweed mitogen (PWM) produce an anti-basement membrane-zone(BMZ) antibody. the antibody produced in vitro was biosynthetically radiolabeled, and its binding to the BMZ was histologically demonstrated by autoradiography. The IgG nature of the antibody was evidence by the fact that it was absorbed by rabbit anti-human IgG antiserum immunoabsorbents. The peak antibody production in vitro occurred after 6 days of culture. Antibody produced in vitro did not bind to the BMZ of human skin, but it did bind to the BMZ of the monkey esophagus. Normal human volunteers and control patients did not produce such an antibody. In other experiments the effects of adding serum containing anti-BMZ antibody to the synthesis of Ig by cells of patients and normal subjects were studied. Although serum from patients with bullous pemphigoid stimulated Ig production with either normal or BP-patient PBL, the difference was not statistically significant. The availability of the assay system allows for studying the immunoregulatory mechanism of autoantibody production in bullous pemphigoid.

Aged↗
PubMed1982

In vitro depression of human lymphocyte mitogen response (phytohaemagglutinin) by asbestos fibres.

Asbestosis is a fibrotic lung disease associated with chronic inhalation of asbestos dust. The response of peripheral blood mononuclear cells (PBM) to phytohaemagglutinin (PHA) in asbestosis patients has been reported to be impaired, suggesting a disturbance in the cell-mediated response of chronically exposed individuals. We demonstrated that PHA responses of normal PBM are also depressed when exposed to various forms of asbestos fibres in vitro. Furthermore, we showed the primary effect of the fibres to be on lymphoid (non-adherent) populations rather than monocytes (adherent cells). Exposure as brief as 1 hr affected the subsequent PHA response of the cells. This effect did not appear to involve suppressor cell activation nor was it mediated by soluble factors. Our findings therefore offer an explanation for the alterations in the cellular immune response observed in humans as a result of lymphoid cells coming into transient contact with inhaled asbestos fibres residing in the lung.

Adult↗
PubMed1981

Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency.

Four previously healthy homosexual men contracted Pneumocystis carinii pneumonia, extensive mucosal candidiasis, and multiple viral infections. In three of the patients these infections followed prolonged fevers of unknown origin. In all four cytomegalovirus was recovered from secretions. Kaposi's sarcoma developed in one patient eight months after he presented with esophageal candidiasis. All patients were anergic and lymphopenic; they had no lymphocyte proliferative responses to soluble antigens, and their responses to phytohemagglutinin were markedly reduced. Monoclonal-antibody analysis of peripheral-blood T-cell subpopulations revealed virtual elimination of the Leu-3 / helper/inducer subset, an increased percentage of the Leu-2 + suppressor/cytoxic subset, and an increased percentage of cells bearing the thymocyte-associated antigen T10. The inversion of the T/ helper to suppressor/cytotoxic ratio suggested that cytomegalovirus infection was an important factor in the pathogenesis of the immunodeficient state. A high level of exposure of male homosexuals to cytomegalovirus-infected secretions may account for the occurrence of this immune deficiency.

Adult↗
PubMed1981

Management of pancreatic abscesses.

The records of twenty-one patients treated for pancreatic abscesses were reviewed. Pancreatitis developed following alcohol ingestion, operative procedures, biliary tract disease, ulcers, and undetermined causes. The clinical findings included abdominal pain in 19 patients (90%); fever in 18 (86%); tenderness in 18 (86%); and leukocytosis in 18 (86%). Ultrasonographic examination aided the diagnosis in seven of 11 patients. Computerized tomography was useful in diagnosing eight of ten cases. There were twenty-nine hospital admissions, with a mean length of hospitalization of 76 days per patient. The operative findings varied with extent and duration of underlying pancreatitis. The surgical approach depended on clinical presentation and prior localization of the abscess. Eleven additional operations were performed. Complications included respiratory failure (three patients); fistula formation (five patients); hemorrhage (two patients); renal failure (one patient); and splenic vein thrombosis (one patient). Thirteen patients were treated with hyperalimentation and nine patients had gastrostomy and jejunostomy placed for decompression and feeding. Of 15 patients in whom microbial studies were reviewed, nine patients had polymicrobial infections. Three patients had Candida albicans. There was one death.

Abscess↗
PubMed1981

Lymphoid interstitial pneumonitis and hypogammaglobulinemia in children.

Lymphoid interstitial pneumonitis is an uncommon process, and an association with hypogammaglobulinemia in children is rare. Three patients, a 10-yr-old boy (Patient 1), a 17-yr-old girl (Patient 2), and a 13-yr-old boy (Patient 3) were evaluated for progressive interstitial pneumonitis and hypogammaglobulinemia. At presentation, symptoms or signs of lung disease had been present for 9, 6, and 1.5 yr and consisted of severe exertional dyspnea asymptomatic pneumonitis on roentgenogram, and mild exertional dyspnea, respectively. Serum immunoglobulin deficiencies were variable with IgG and IgA being depressed in all patients and IgM being within normal limits in Patient 2. In vitro neutrophil function and T lymphocyte number and mitogen responses were normal. Measurement of in vitro immunoglobulin production suggested a primary B lymphocyte dysfunction. Pulmonary function testing revealed restrictive lung disease in Patient 1, arterial hypoxemia in Patients 1 and 2, and increased alveolar-arterial oxygen differences in all patients. Microscopic examination of lung specimens from each patient revealed diffuse lymphoid parenchymal infiltration with formation of follicles with occasional germinal centers, varying degrees of fibrosis, and negative examinations for viruses, bacteria, and fungi. The factors responsible for the cessation of antibody production and for the striking lympho-proliferative process seen in these patients remain to be identified.

Adolescent↗
PubMed1981

Lymphocyte dysfunction in chronic graft-versus-host disease.

Three recipients of HLA-identical bone marrow transplants developed chronic graft-versus-host disease (cGVHD) and hypergammaglobulinemia. All three had evidence of abnormal B-lymphocyte function, including a polyclonal increase in immunoglobulins (Ig), antinuclear antibodies, rheumatoid factor, lymphocytotoxins, and increased immune complexes. T-lymphocyte function was also abnormal, including decreased mitogen reactivity and delayed cutaneous hypersensitivity. The cellular basis of these immune abnormalities was studied in an in vitro system in which we analyzed spontaneous pokeweed mitogen (PWM) driven Ig synthesis. Multiple defects in both T- and B-lymphocyte function were detected. In contrast to normal B cells, circulating B cells from all three patients with cGVHD spontaneously synthesized in vitro greater than 200 ng of IgG and in two of the three greater than 175 ng of IgM. This increase in spontaneous Ig synthesis was not due to a deficiency of regulatory cells, since T cells from the three patients suppressed spontaneous Ig synthesis in a normal fashion. In contrast to this increased spontaneous Ig synthesis, the response of the patients' B cells to PWM-driven Ig synthesis was normal. Using the PWM system we demonstrated several defects in these patients' T cells, including increased suppressor activity and decreased helper cell activity. These data indicate that some patients with cGVHD have multiple defects in both T- and B-cell function that may contribute to their profound immune deficiency.

Adolescent↗
PubMed1980

Isotype-specific human B lymphocytes that produce immunoglobulin E in vitro when stimulated by pokeweed mitogen.

Normal human peripheral blood lymphocytes can be stimulated by PWM and T cells to produce IgE in vitro. Between 4% and 10% of circulating B lymphocytes were found to bear noncytophilic membrane IgE. In contrast, limiting diluton analysis of active B cell precursor frequency revealed that only about 1 in 50,000 B cells was responsible for the synthesis of IgE in vitro. Variation inthe precursor frequency was primarily responsible for differences in the amount of IgE produced in vitro by different individuals while the amount of IgE produced per precursor cell was relatively constant. B lymphocytes with surface IgM, IgG, or IgE were depleted. Depletion of IgE-bearing cells decreased IgE production 70% to 83% while IgM-bearing-cell removal lowered IgE synthesis by 59% to 72%. Dual removal of IgM- and IgE-bearing cells did not give an additive effect. IgE- and IgM-positive B cells showed enhanced IgE synthesis of 327% and 182%, respectively. The consequences of crosslinking different surface isotypes on subsequent IgE production were also assessed. Anti-epsilon treatment inhibited IgE production up to 68% while anti-mu treatment decreased it by up to 38%. Thus only a very limited subset of B lymphocytes is responsible for PWM and T cell-dependent IgE synthesis in vitro and those cells probably bear both surface IgE and IgM.

Adult↗
PubMed1980

Profile of multiple lymphocyte functional defects in acquired hypogrammaglobulinemia, derived from in vitro cell recombination analysis.

Immunoregulatory defects in patients can be assigned to B cells, T helper cells, or T suppressor cells by means of a modification of the in vitro PWM-stimulated Ig biosynthesis assay. When lymphocyte subpopulations from patient and normal are recombined, multiple internal comparisons within a single experiment reveal the functional activity of each subpopulation. By this technique we studied nine adult patients with acquired panhypogammaglobulinemia and one with isolated IgG deficiency. Low total Ig production by the B cell fraction was demonstrated in seven of the nine panhypogammaglobulinemic patients. In four of these seven, IgG and IgA secretion was markedly reduced compared with IgM. In the two patients with normal total Ig production, elevated IgM compensated for lower IgA and IgG. The one patient with no surface Ig+ cells had a B cell defect, but no T cell defect. Reduced T help and excessive T suppression characterized two of the four patients with the most severe B cell defects. Three patients were anergic by delayed hypersensitivity skin testing and failed to sensitize to DNCB, but the patient with the most severe T cell defects in vitro was not among them. One of these three patients showed a mild T cell help defect and suppressor excess and the other two had pure B cell defects. Thus, anergy and T regulator function were not correlated. In three instances where hypersuppression was more evident by adding patient unfractionated cells than by adding patient T cells, suppression by the T depleted fraction could be demonstrated. No cases of radiation-resistant T suppression were revealed among the seven patients tested. Subnormal total protein synthesis, noted in six of seven patients with low Ig production, was invariably less marked than the Ig defect and often affected both T and B cells. One additional patient with pure IgG deficiency of 2 yr duration was essentially normal in her in vitro lymphocyte function. The general applicability of this experimental design for analysis of positive or negative immunoregulatory abnormalities is emphasized.

Adult↗