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Biomedical subjects

A J Ammann

Publications and source records attributed to A J Ammann.

At least 55 records · Page 3Linked to original sources
PubMed1988

Production of lymphotoxin and tumor necrosis factor by human neonatal mononuclear cells.

Lymphotoxin (LT) and tumor necrosis factor (TNF) are cytokines with many common biologic effects including antiviral activity and induction of fever and the acute phase response; despite common effects, they are molecularly distinct. Because neonates are unduly susceptible to viral infection and frequently fail to mount a febrile response to infection, we hypothesized that neonatal cells would produce less LT and TNF than adult cells. We analyzed LT and TNF production by blood mononuclear cells and purified T cells using Northern blot analysis to detect specific messenger ribonucleic acid and specific assays to detect LT and TNF protein in culture supernatants. Compared to LT, TNF messenger ribonucleic acid and protein were produced more rapidly both by total mononuclear cells and by T cells in response to mitogen stimulation. Although there was intersubject variability, adult and neonatal mononuclear cells and T cells (n = 6) produced similar amounts of LT and TNF messenger ribonucleic acid and protein with similar kinetics. In experiments with phytohemagglutinin-stimulated mononuclear cells from ten additional subjects, supernatant LT was somewhat greater in neonatal cultures (neonatal = 62.8 +/- 60.5, adult = 13.2 +/- 10.7 units/ml, p less than 0.05), and TNF was somewhat greater in adult cultures (neonatal = 708 +/- 429, adult = 1987 +/- 392 pg/ml, p less than 0.01) at 24 h; results at 48 h and 72 h were similar. Thus, neonatal MC produced as much or more LT than did adult MC. Although the decreased production of TNF by neonatal MC was statistically significant, these cells did produce substantial amounts of this cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Immunopathogenesis of pediatric acquired immunodeficiency syndrome.

Pediatric acquired immunodeficiency syndrome (PAIDS) results from infection with human immunodeficiency virus (HIV). The majority of infants with AIDS are infected in utero. In most instances, mothers are infected from intravenous drug abuse or bisexual partners. Infected individuals, both mothers and infants, may be asymptomatic for prolonged periods of time. Initially viral replication may be limited and the virus integrated into immune cells. Activation of the virus may result from several factors including infection with other viral agents, such as cytomegalovirus and Epstein-Barr virus. Variable progression of disease may be related to dose of virus, the degree of pre-existing immunodeficiency, and the presence of other infectious agents. Recent evidence suggests that individual HIV isolates vary in their capacity to infect cells. This may explain differences in clinical presentation and progression. A diagnosis of HIV infection may be difficult in infants who have persistence of maternal antibody. Viral isolation is often difficult and unreliable, even in infants who have clinical features of AIDS. Currently only azidothymidine has been shown to reduce viral replication and improve prognosis. However, azidothymidine does not eradicate HIV and patients require repeated or chronic therapy. The drug is not yet approved for use in children, although studies are being performed at several medical centers. Prevention of HIV infection is the single most important approach to controlling its rapid spread in infants. Screening of all blood products by using HIV antibody testing is essential. Increased effort in preventing drug abuse and in reducing pregnancy rates among infected women should be a priority of health care workers.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Tumor necrosis factors alpha and beta in acquired immunodeficiency syndrome (AIDS) and aids-related complex.

Human immunodeficiency virus (HIV) infection is associated with abnormalities of both T-cell and B-cell immunity in patients with acquired immunodeficiency syndrome (AIDS). Previous studies demonstrated deficient production of the cytokines interleukin-1 (IL-1), interleukin-2 (IL-2), and gamma interferon (IFN-gamma). Tumor necrosis factor alpha and tumor necrosis factor beta have not been previously investigated in AIDS. In this study we demonstrate that peripheral blood mononuclear cells from patients with HIV infection who have either AIDS-related complex or acquired immunodeficiency syndrome are deficient in the production of tumor necrosis factor alpha and tumor necrosis factor beta. These cytokines, derived predominantly from monocytes or lymphocytes, respectively, function as immunoregulatory, antitumor, and antiinfective proteins. A deficiency in their production may therefore be responsible for many of the complications associated with HIV infection in patients with AIDS-related complex or acquired immunodeficiency syndrome.

AIDS-Related Complex↗
PubMed1987

The effects of human immunodeficiency virus recombinant envelope glycoprotein on immune cell functions in vitro.

The effect of human immunodeficiency virus (HIV) recombinant envelope glycoprotein 120 (rgp 120) on the functions of peripheral blood mononuclear cells (PBMC) in vitro was investigated. The results demonstrate that rgp 120 used at concentrations less than 1 microgram/ml has no significant effects on PBMC function in vitro. However, the addition of 1-20 micrograms/ml of rgp 120 significantly inhibits the tetanus toxoid-induced PBMC proliferative response in a dose-related manner as determined by [3H]thymidine incorporation. The data also show that rgp 120 (5 micrograms/ml) causes up to 70% reduction in the number of immunoglobulin G-secreting cells in pokeweed mitogen-stimulated PBMC cultures. Further, rgp 120 can selectively interact with the CD4a epitope of the CD4 helper cell membrane receptor. These results indicate that microgram per milliliter levels of rgp 120 can depress certain immune functions in vitro. The significance of these findings to the pathogenesis of immunodeficiency in HIV infection remains to be determined.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Lymphocyte abnormalities in infants born to drug-abusing mothers.

To evaluate the possible effects of maternal intravenous drug use on infant immunity, we measured the in vitro peripheral blood mononuclear cell proliferative responses to phytohemagglutinin (PHA) and pokeweed mitogen, T cell subset numbers, immunoglobulin levels, and titers of antibodies to cytomegalovirus (CMV) and human immunodeficiency virus (HIV) in a group of drug-abusing mothers and their infants. Infants of drug abusers had a lower proliferative response to mitogen, associated with altered kinetics of the maximum response to PHA. The OKT4/OKT8 ratio decreased with age in the drug-exposed infants compared with control infants (P less than 0.005). There was no evidence of CMV infection in either group. One mother and her infant had antibody to HIV. Our data demonstrate that infants of intravenous drug-using mothers have distinct immunologic differences at birth compared with non-drug-exposed infants and that these persist throughout the first year of life. The cause appears unrelated to intrauterine viral infection, suggesting a direct toxic effect of the drugs on fetal immunologic development.

Antibodies, Viral↗
PubMed1986

Impaired monocyte-to-macrophage maturation in patients with lymphadenopathy syndrome.

The in vitro maturation of monocytes from patients with lymphadenopathy syndrome (LAS) was studied by means of enzymatic activity performed during a 7-day incubation period. Monocytes from LAS patients, healthy homosexuals, and healthy heterosexuals were assayed for beta-galactosidase and beta-N-acetylglucosaminidase activity on days 3, 5, and 7 of culture. The LAS monocytes had significantly lower (P less than 0.01) absolute levels of both enzymes compared with controls or healthy homosexual subjects. All three groups showed a linear increase in enzyme activity over time. There was no statistical difference between the slopes of the curves of enzyme activity vs time for the three groups, indicating that the rate of increase in enzyme activity was similar for the groups. These results suggest that monocyte-to-macrophage maturation is impaired in LAS. LAS monocytes are initially less mature than those of healthy homosexuals or heterosexuals but retain their capacity to mature during incubation in vitro.

AIDS-Related Complex↗
PubMed1986

Laboratory investigation of pediatric acquired immunodeficiency syndrome.

Unique laboratory abnormalities, found in pediatric patients with clinical features of immunodeficiency, led to the original observation that a syndrome of acquired immunodeficiency (AIDS) was also occurring in pediatric populations. Initial observations which demonstrated the nonspecific findings of polyclonal hypergammaglobulinemia and T-cell deficiency were followed by confirmatory findings when testing for the AIDS retrovirus became available. In the pediatric population availability of antibody testing and viral isolation became critical in differentiating primary immunodeficiency disorders which involved both the B- and T-cell systems from AIDS associated with retrovirus infection. At this time based upon clinical, epidemiologic, immunologic, and serologic studies, the syndrome of pediatric AIDS can be distinguished from other primary and secondary pediatric immunodeficiency disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Antibodies to AIDS-associated retrovirus distinguish between pediatric primary and acquired immunodeficiency diseases.

Antibody to acquired immunodeficiency syndrome (AIDS)-associated retroviruses (ARVs) was investigated in 68 pediatric patients with abnormalities of T-cell and/or B-cell immunity. All except seven patients conformed to a specific World Health Organization classification for immunodeficiency disease. These seven patients had polyclonal hypergammaglobulinemia and T-cell immunodeficiency. Six of the seven patients had antibody to ARV and had risk factors associated with AIDS. The one patient without antiviral antibody had no AIDS risk factors. No antibody was detected in 61 patients with other primary immunodeficiency disorders. We conclude that ARV first appeared in our population of immunodeficient pediatric patients prior to 1978, is associated with a distinctive immunologic phenotype consisting of polyclonal hypergammaglobulinemia and T-cell immunodeficiency, and does not appear as an opportunistic infection in other immunodeficiency disorders. Detection of the retrovirus associated with AIDS is of value in identifying infants and children who may have unique medical and social problems that occur with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Growth retardation in sickle-cell disease treated by nutritional support.

The effect of increased nutritional intake was evaluated in 5 growth-retarded children with sickle-cell disease. Growth on recommended daily calorie and protein intakes had been inadequate in all 5. Fat absorption and intestinal mucosal morphology were normal in all 5. 2 children were given nutritional supplementation by nasogastric intubation, 1 received nightly oral formula supplements, and 2 were supplemented with zinc, iron, folate, and vitamin E only. Nutritional supplementation by the nasogastric route produced a rapid sustained increase in growth rate, associated with striking reductions in pain crises and infections which had previously necessitated many hospital admissions. Oral supplementation improved the clinical course but had no effect on growth rate. Mineral and vitamin supplements influenced neither the growth rate nor the clinical course. The observations indicate that nasogastric nutritional supplementation may accelerate growth and reduce the incidence and severity of complications in growth-retarded children with sickle-cell disease.

Adolescent↗
PubMed1985

Maternal-fetal transfer of pneumococcal capsular polysaccharide antibodies.

Maternal-fetal transfer of IgG antibodies is an important host defense for newborns, who have an increased incidence of bacterial infections. To study the transfer of specific pneumococcal capsular polysaccharide (PPS) antibodies, we measured the concentrations, in 30 paired maternal and cord serum samples, of IgG and IgM by radial immunodiffusion, of serotype 7F Streptococcus pneumoniae PPS antibodies by radioimmunoassay and enzyme immunoassay, and of opsonic activity to that organism by a radiolabeled bacterial uptake assay. Cord serum had significantly greater total IgG, yet significantly less type 7F PPS IgG antibodies and opsonic activity than maternal serum. Cord serum had low concentrations of total IgM and no IgM type 7F-specific antibodies. Reduced transport of specific IgG antibodies and absent transfer of IgM may contribute to the susceptibility of newborns to bacterial infection.

Antibodies, Bacterial↗
PubMed1985

Haploidentical bone marrow transplantation for severe combined immunodeficiency disease using soybean agglutinin-negative, T-depleted marrow cells.

The major limitation of mismatched bone marrow transplantation is fatal graft versus host disease (GVHD). We processed haplotype-identical parental marrow with soybean agglutinin (SBA), sheep erythrocytes (SRBC), and neuraminidase-treated SRBC (N-SRBC) to enrich for marrow stem cells and remove mature T cells. Nine patients with severe combined immunodeficiency disease (SCID) who lacked histocompatible donors received these SBA-negative, SRBC-negative, N-SRBC-negative marrow transplants (0.5-5.0 X 10(8) cells/kg). Seven of the nine patients (78%) had documented T-lymphocyte engraftment based on HLA typing and/or chromosomal analysis. Six patients showed evidence of B-cell immunity on the basis of increased immunoglobulin levels, isohemagglutinins, and/or HLA-DR typing of non-T cells. Three patients received marrow ablative chemotherapy pretransplant for maternal-fetal GVHD; neutrophil engraftment occurred between 9 and 17 days posttransplantation, erythrocytes engrafted within 3-4 weeks of transplantation, and platelet recovery was seen between day 17 and day 49 following the transplants. No immunosuppression was given prophylactically posttransplant. Three patients had no GVHD, two had transient rash and/or fever, and two developed mild focal (stage I) chronic cutaneous GVHD. Of the seven who engrafted, five (71%) are alive and clinically well without GVHD 18-35 months posttransplant. These data demonstrate that SBA- and SRBC/N-SRBC-treated haploidentical marrow transplantation results in functional lymphocyte engraftment in SCID without significant GVHD, and can be used for some patients who otherwise would have no hope for survival.

Adolescent↗
PubMed1985

Impaired mononuclear-cell proliferation in patients with the acquired immune deficiency syndrome results from abnormalities of both T lymphocytes and adherent mononuclear cells.

Peripheral blood mononuclear cells from patients with acquired immune deficiency syndrome proliferate poorly after stimulation with soluble mitogens. The present study was undertaken to assess the relative contributions of T lymphocytes and of plastic adherent mononuclear cells to the impaired mononuclear cell responses. We employed a four-step separation procedure including terminal depletion using a monocyte-specific monoclonal antibody (61D3) to derive populations of highly purified T cells from patients and from normal subjects. Highly purified T cells proliferated poorly in response to phytohemagglutinin and pokeweed mitogen. The addition of autologous adherent cells to highly purified T cells markedly improved mitogen-driven proliferation in all subjects; however, mononuclear cells from patients with AIDS responded less well than normals (P less than or equal to 0.01) for both phytohemagglutinin and pokeweed. Allogeneic normal adherent cells fully restored both phytohemagglutinin and pokeweed responses in normal highly purified T cells. Adherent cells from patients were comparable to normal adherent cells in phytohemagglutinin-driven proliferation but performed significantly less well when pokeweed was used to stimulate normal highly purified T-cell responders (4308 cpm after coculture with patients' adherent cells vs 8244 cpm after coculture with allogeneic normal adherent cells; P = 0.05). Similarly, when patient's highly purified T cells were stimulated with pokeweed mitogen, control adherent cells functioned substantially better than patient adherent cells (1198 cpm for allogeneic patient adherent cells vs 2324 cpm for normal adherent cells; P = 0.05). Although the addition of normal adherent cells to patients' highly purified T cells significantly improved pokeweed mitogen responses, these values did not reach normal. Suppression by patients adherent cells was not demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗