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Biomedical subjects

A J Ammann

Publications and source records attributed to A J Ammann.

At least 91 records · Page 5Linked to original sources

T-lymphocyte subsets in lymph nodes from homosexual men.

To evaluate further the immunodeficiency of homosexual men, blood and lymph node specimens were obtained from five homosexual men with lymphadenopathy and from seven homosexual men with Kaposi's sarcoma. Monoclonal antibodies were used to identify T-lymphocyte subsets in blood by cytofluorometry and in frozen sections of nodes by immunoperoxidase techniques. The homosexuals with Kaposi's sarcoma had a T-helper/suppressor ratio in blood of 0.7; the homosexuals with lymphadenopathy had a ratio of 0.6, compared with controls of 2.1. Control lymphoid tissue had a ratio of 3.0 in the interfollicular areas compared with the reactive lymph nodes in the homosexuals with lymphadenopathy, which was 0.7, and nodes from patients with Kaposi's sarcoma, 0.9. The nodes from homosexual men had evident numerous suppressor cells in the follicular center and mantle regions, locations in normal lymphoid tissue where suppressor cells were uncommon.

Flow Cytometry↗

Acquired immunodeficiency in an infant: possible transmission by means of blood products.

An infant who received multiple transfusions during the first few days of life for rhesus disease became ill with recurrent infections when 6 months old. Hepatitis, thrush, Candida dermatitis, otitis media, and disseminated Mycobacterium avium intracellulare infection occurred by 14 months of age. Immunological studies showed raised immunoglobulin levels, decreased mononuclear-cell responses to allogeneic cells and mitogen, and a decreased helper/suppressor cell ratio. It was determined that one of the blood donors, who was well at the time of blood donation, had died 17 months after with multiple opportunistic infections and acquired immunodeficiency. The clinical and laboratory findings in our patient suggest that he acquired a transmissible infectious agent from a blood transfusion, resulting in acquired immunodeficiency, and that this agent was not cytomegalovirus, Epstein-Barr virus, or hepatitis B virus.

Acquired Immunodeficiency Syndrome↗

Significance of a positive antinuclear antibody test in a pediatric population.

Clinical and laboratory findings in 138 children seen during a ten-year period with a positive antinuclear antibody (ANA) test were reviewed. Two thirds (91 of 138) of the patients had specific autoimmune or rheumatic diseases, including systemic lupus erythematosus (n = 37), juvenile rheumatoid arthritis (n = 33), Sjögren's syndrome (n = 9), mixed connective tissue disease (n = 7), dermatomyositis (n = 3), and discoid lupus (n = 2). Another 27 patients had symptoms of autoimmune disease but did not fit criteria for specific disorders. Nine patients with IgA deficiency had a positive ANA test but did not have symptomatic autoimmune disease. Ten children had a positive ANA test in association with infections, mainly viral, and one had leukemia. Because most children with a positive ANA test had readily diagnosable autoimmune disorders, pediatric patients with a positive ANA on repeated testing should undergo clinical and laboratory studies for autoimmune or rheumatic disease.

Adolescent↗

Changes in purine nucleoside phosphorylase activity during thymosin-induced human null cell differentiation.

Purine nucleoside phosphorylase (PNP) is a purine salvage pathway enzyme which we have found to be 8-10 times more active (per cell) in human peripheral blood null lymphocytes than in T lymphocytes. To test the hypothesis that null cells are, in part, pre-T lymphocytes we have defined an in vitro system for null cell differentiation into T cells and examined PNP activity during this differentiation process. We found that about 10% of human null cells could be driven to differentiate into T cells using thymosin fraction 5 (TF5) an extract of bovine thymus glands. The response to TF5 was dose related to up to 250 micrograms/ml with a maximum response occurring by 42-46 hr incubation. Exposure to TF5 was necessary for more than 4 hr but no more than 8 hr in order to obtain a maximum response. Both OKT4 and OKT8 positive cells were present in the newly differentiated T cell population but OKT8 positive cells appeared to predominate (OKT4/OKT8 = 0.698 +/- 0.30, mean +/- 1 SD). The differentiation process did not involve DNA synthesis but was inhibited at 4 degrees C. In the newly differentiated T cells PNP activity per cell was 8- to 10-fold lower (36 +/- 23 nm/hr/106 cells) than in null cells (311 +/- 136), and was at a level similar to mature T cells (56 +/- 7). Thus, human peripheral blood null cells can be induced to differentiate into T lymphocytes which can be characterized by both surface markers and biochemical parameters. Future studies will look at the function of TF5-induced T cells and the regulation of PNP activity during the differentiation process.

Adult↗

Acquired immune dysfunction in homosexual men: immunologic profiles.

Homosexual men with Kaposi sarcoma, lymphadenopathy syndrome, opportunistic infection, and nonhomosexual traditional Kaposi sarcoma were evaluated for B cell, T cell, and complement immunity and compared to normal controls and homosexual controls. No significant immunologic abnormalities were found in the traditional Kaposi group. All homosexual groups, including the homosexual controls, had a significant decrease in the helper/suppressor cell ratio. Functional abnormalities of T-cell immunity were observed in the homosexual Kaposi sarcoma, lymphadenopathy syndrome, and opportunistic infection groups. Significant elevations of IgG, IgM, IgA, and IgE were found in the lymphadenopathy group, while only IgG and IgA were elevated in the Kaposi sarcoma group. C3, C4, and immune complexes were normal, while total hemolytic complement activity was increased in the Kaposi sarcoma and lymphadenopathy syndrome groups.

Acquired Immunodeficiency Syndrome↗

Patients with abnormal proportions of T-lymphocyte subsets have reduced in vitro cellular immunity.

Monoclonal antibodies which identify helper/inducer (OKT4) and cytotoxic/suppressor (OKT8) subsets of human T lymphocytes have recently been used to investigate immunoregulation in isolated cell populations, as well as in human disease states. However, the relationship between relative proportions of OKT4- and OKT8-positive blood lymphocytes and in vitro cellular immune function in patients with immunodeficiencies has not been studied extensively. We enumerated T-lymphocyte subsets with OKT4 and OKT8 antibodies, and measured proliferative responses to allogeneic cells in mixed lymphocyte culture (MLC) and to phytohemagglutinin (PHA), in peripheral blood mononuclear cells (PBMCs) from 60 patients with varying degrees of immunodeficiency and 20 healthy controls. Controls had 56.0 +/- 5.3% (mean +/- 1SD) OKT4-positive lymphocytes, 28.6 +/- 5.9% OKT8-positive lymphocytes, and an OKT4/8 ratio of 2.05 +/- 0.55. We defined as abnormal values of less than 40% OKT4-positive or greater than 45% OKT8-positive lymphocytes (3 SD below and above mean values, respectively), or an OKT4/8 ratio of less than 1.2. Patients with these abnormal percentages of T-lymphocyte subsets had significantly lower mean MLC and PHA responses (P less than 0.001), and higher incidences of abnormal MLC and PHA responses (P less than 0.01). Abnormal proportions of T-lymphocyte subsets correlated with low MLC and PHA responses in most immunodeficient patients, although some patients with low MLC and PHA responses had normal subset distributions. T-Cell subset proportions were heterogeneous among patients with the same diagnosis.

Adult↗

Clinical and laboratory findings in childhood mixed connective tissue disease: presence of antibody to ribonucleoprotein containing the small nuclear ribonucleic acid U1.

Seven children and adolescents are described with mixed connective tissue disease. The patients had varying clinical features, commonly characterized by Raynaud phenomenon, arthritis, abnormal pulmonary function, and esophageal dysmotility. All patients had speckled antinuclear antibodies and high titers (greater than 1:100,000) of antibodies to ribonuclease-sensitive extractable nuclear antigen. We prepared extractable nuclear material from radioactively labeled HeLa cells, analogous to classic extractable nuclear antigen. Sera from all seven patients precipitated ribonucleoprotein containing the small nuclear ribonucleic acid species U1 from the HeLa cell extract. Antibody to U1 ribonucleoprotein was not found in sera from 51 of 53 children and adults having a variety of autoimmune and other diseases, nor in sera from nine normal individuals. The U1 ribonucleoprotein appears to be the component of extractable nuclear antigen characteristically reacting with sera from patients with mixed connective tissue disease. The finding of a distinct molecular marker in all children studied with mixed connective tissue disease indicates that this is a distinct disease entity and not a heterogeneous population of immune disorders.

Adolescent↗

Increased serum opsonic activity and antibody concentration in patients with sickle cell disease after pneumococcal polysaccharide immunization.

Opsonic defects have been reported in unimmunized patients with sickle cell disease. We found significant increases (P less than 0.001) in serum opsonic activity, measured by a radiolabeled bacterial uptake assay, and in type 7 pneumococcal polysaccharide antibody concentration in 17 such patients 2 years of age or older after pneumococcal polysaccharide immunization. All 17 patients and six healthy controls achieved a type 7 antibody concentration of more than 300 ng antibody nitrogen per milliliter, believed to be the protective level of antibody in vivo. Six patients with sickle cell disease less than 2 years of age did not have a significant increase in type 7 antibody concentration after immunization. Only three of these six patients achieved a postimmunization type 7 antibody concentration exceeding 300 ng Ab N/ml. Overall, 16 of 23 patients with sickle cell disease (70%) had a twofold or greater increase in type 7 antibody concentration, and 13 of these (81%) had a corresponding increase in opsonic activity (P less than 0.001). Thus most patients who responded to pneumococcal polysaccharide immunization had a concurrent increase in opsonic activity in vitro.

Adolescent↗

Response of agranulocytosis to prolonged antithymocyte globulin therapy.

A girl with a history of autoimmune disease developed life-threatening agranulocytosis. A bone marrow biopsy demonstrated selective granulocytic hypoplasia. No antineutrophil antibodies were found. In vitro bone marrow culture of granulocytic progenitor cells suggested T cell-mediated inhibition of colony formation, which was reduced by in vitro treatment of marrow cells with either hydrocortisone or an antibody directed against T-lymphocytes and complement. The patient responded to treatment with antithymocyte globulin after administration of corticosteroids and other immunosuppressants failed to increase her neutrophil count significantly. Attempts to stop ATG treatment resulted in precipitous drops in her neutrophil counts, which reversed with readministration of ATG. She then received weekly ATG infusions for over 24 months until she was able to maintain a normal neutrophil count. A trial of ATG therapy may be indicated in severe neutropenia when in vitro culture results indicate a possible autoimmune basis.

Agranulocytosis↗

Immunologic abnormalities in patients with hemophilia A.

To assess the immunologic status of healthy persons with hemophilia A, we performed studies of T cell immunity in 21 patients, 10 given only cryoprecipitate and 11 given factor VIII concentrate. Patients in the factor VIII group had significantly decreased helper/suppressor T cell ratios. Both groups had diminished mononuclear cell response to phytohemagglutinin and normal mixed lymphocyte culture, compared with controls. Abnormalities in T cell number or function did not correlate with the presence of antibody to cytomegalovirus, Epstein-Barr virus, or hepatitis B. Physicians caring for patients with hemophilia A should realize that asymptomatic individuals may have early evidence of immunodeficiency.

Acquired Immunodeficiency Syndrome↗

Effect of antibody concentration on opsonic requirements for phagocytosis in vitro of Streptococcus pneumoniae types 7 and 19.

We investigated the effect of the concentration of type-specific antibody to pneumococcal polysaccharide (PPS) on opsonic requirements for phagocytosis in vitro of Streptococcus pneumonia types 7 and 19. We measured the uptake by human neutrophils of radiolabeled S. pneumoniae opsonized with either complement-intact, complement-depleted (by heat inactivation), or alternative complement pathway-activated (by magnesium dichloride-ethylene glycol tetraacetic acid (MgEGTA) chelation) immune sera with varying concentrations of antibody from individuals immunized with polyvalent PPS vaccine. Increased opsonization was found with increasing concentrations of type-specific antibody in the sera. Higher concentrations of antibody were required to opsonize type 7 than type 19 bacteria, both in the presence and absence of complement activity. Type 19 bacteria were more efficiently opsonized via the alternative complement pathway than type 7. For both types, antibody and the alternative complement pathway provided most of the opsonic activity in sera with lower concentrations of type-specific antibody. At high antibody concentrations, effective opsonization occurred in heat-activated sera, indicating the requirement for complement could be overcome with sufficient amounts of antibody alone.

Antibodies, Bacterial↗

The DiGeorge syndrome and the fetal alcohol syndrome.

Four patients with clinical and laboratory features of the DiGeorge syndrome had a definite history of maternal alcoholism. Certain clinical abnormalities in the patients were characteristic of the DiGeorge syndrome as well as the fetal alcohol syndrome, including abnormalities of the eyes, ears, mouth, face, cardiovascular system, CNS, and immune system. Maternal alcoholism may result in the DiGeorge syndrome either as the single causative factor or in conjunction with other as yet unknown teratogens.

Alcoholism↗

Aspergillus pneumonia in chronic granulomatous disease: recurrence and long-term outcome.

Four of 13 patients followed with chronic granulomatous disease (CGD) developed biopsy-proven Aspergillus pneumonia. Two patients died of disseminated aspergillosis despite intensive treatment; delays in diagnosis appear to have been a major contributing cause. Two patients survived two episodes each of Aspergillus pneumonia, three and six years apart. At 12 and 18 years of age, both are well and active, although their chest X-rays show residual scarring and pulmonary function tests indicate obstructive lung disease. These cases demonstrate that in patients with CGD, 1) multiple episodes of Aspergillus pneumonia can occur; 2) effective immunity to the organism does not develop after infection; and 3) some survivors of Aspergillus pneumonia experience only minimal morbidity.

Aspergillosis↗