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Biomedical subjects

S Cunningham-Rundles

Publications and source records attributed to S Cunningham-Rundles.

17 recordsLinked to original sources
PubMed1991

Acute shift in immune response to microbial activators in very-low-birth-weight infants.

Investigation of lymphocyte activation in vitro to microbial pathogens was undertaken in very-low-birth-weight infants during the first 2 weeks of life. Twenty-three infants with birth weights less than 1500 g were studied on day 1. Normal adults (n = 23) and cord blood from seven full-term infants were used as controls. Longitudinal studies were also carried out on seven of the 23 infants 2 weeks following delivery. Results indicated that lymphocyte responses of very-low-birth-weight infants on day 1 of life were significantly greater than those of both adult controls and full-term infants, particularly to Haemophilus influenzae, Staphylococcus epidermidis and Staphylococcal protein A. In contrast, response to the T cell mitogen phytohaemagglutinin (PHA) was significantly less in very-low-birth-weight infants than in adult controls and full-term infants. The seven very-low-birth-weight infants studied showed a down-regulation of immune response in the 2 weeks following birth, such that responses on day 14 were significantly less than those on day 1 for the same activators. This shift in immune response appears to have important implications for the immune development and host defence in the post-natal period.

Bacteria↗
PubMed1991

Deferoxamine-induced bone dysplasia in patients with thalassemia major.

Metaphyseal irregularity and abnormal vertebral bodies resembling a bone dysplasia were seen in two of five children with thalassemia major who were begun on a regimen of hypertransfusion and chelation with deferoxamine before the age of 3 years. Similar changes were not seen in 22 other children in whom chelation was started after the age of 3. Whether the dysplastic bone growth was related to drug dose or age of onset of chelation could not be determined, as deferoxamine dosages differed in the two groups. Findings on radiographs included flattening of the thoracic and lumbar vertebral bodies, circumferential metaphyseal osseous defects, sharp zones of provisional calcification, and widened growth plates. Healing was noted in one of the patients after the dose of deferoxamine was decreased. Zinc levels in both affected patients did not differ from those in the 25 other chelated patients.

Adolescent↗
PubMed1990

Experimental approach to the study of immune function in children with possible human immunodeficiency virus infection.

The clinical immunology laboratory is often called on to assess risk in pediatric patients with clinical evidence of immunodeficiency and possible human immunodeficiency virus (HIV) exposure while antibody tests are being considered or are underway. Since non-HIV-related conditions including neoplasia, certain viruses, and primary immunodeficiency can potentially produce lymphocyte subset imbalance and functional impairment, there is need for a laboratory approach to differential analysis of pediatric immunodeficiency. In addition, laboratory methods may also influence the results obtained. In order to investigate these issues, we screened pediatric patients with and without HIV exposure. Altered lymphocyte subset expression and function were found among non-HIV-infected pediatric patients. The use of percentage and absolute lymphocyte numbers was found to affect the results obtained in a significant manner. Some patients who were chronic blood transfusion recipients were found to have blocking factors, presumably alloantibodies, in serum, which affected detection of lymphocyte surface antigens. In this population, age at seroconversion was a factor influencing subsequent levels of CD4+ T lymphocytes. Significant differences in CD4+ T lymphocyte percentages were also observed in children congenitally exposed to HIV compared with controls, even among those children with CD4/CD8 ratios greater than 1.0, who therefore had possibly escaped infection. Immune changes in children should be interpreted with caution.

Adolescent↗
PubMed1990

ImuVert activation of natural killer cytotoxicity and interferon gamma production via CD16 triggering.

The effect and mechanism of action of ImuVert, a new biological response modifier consisting of ribosomes and natural membrane vesicles of Serratia marcescens, on endogenous natural killer (NK) cells and activated NK activity has been analyzed. The studies showed that endogenous NK activity of peripheral blood mononuclear cells (PBMC) from normal cell donors was significantly increased (P less than 0.03) against K562, U937, and Molt-4 target cells. PBMC from cord blood of newborn infants lacking NK activity were upregulated (1.5-4 fold over endogenous NK activity) by ImuVert. Other studies showed that the abnormal NK activity of PBMC from patients with the human immunodeficiency virus (HIV) infection was significantly augmented in vitro (P less than 0.01) by ImuVert. ImuVert strongly stimulated interferon gamma production and in combination with interleukin 2 produced synergistically enhanced interferon gamma production and greater cytotoxicity than that induced by either alone. Studies on lymphocyte differentiation antigen expression following treatment with ImuVert indicated that ImuVert triggers interferon gamma production through binding the low affinity IgG Fc receptor, type III, CD16. The studies suggest that ImuVert may trigger interferon gamma production by binding to the Fc receptor and that the amplitude of the ensuing reaction and the ability of ImuVert to induce cytotoxicity in a setting where this activity has been down regulated is based on the absence of suppressor activation or direct contra suppressor activity.

Antigens, Differentiation↗
PubMed1986

Correlation of in vitro antibody synthesis with the outcome of intravenous gamma-globulin treatment of chronic idiopathic thrombocytopenic purpura.

Intravenous gamma-globulin (IVGG) effectively elevates the platelet count of most patients with chronic idiopathic thrombocytopenic purpura (ITP). This study examined whether this effect was related to changes in in vitro immunoglobulin secretion and suppression in coculture. Before treatment, patient in vitro immunoglobulin secretion was less than 50% of the concurrent control in all eight cases and the patients suppressed antibody synthesis in coculture an average of 39%. After treatment, increases in in vitro immunoglobulin secretion and decreases in suppression were closely related to a good response to IVGG therapy as measured both by acute increases in the platelet count (P less than 0.05) and by the long-term outcome from therapy (P less than 0.05). Decreases in platelet-associated IgG correlated with increases in in vitro immunoglobulin secretion (P less than 0.05). Data consistent with the lack of inhibition of in vitro immunoglobulin secretion following IVGG included long-term increases in both serum IgM and IgG (independent of transfused IgG) and maintenance of the percentage of total IgG that was IgG3. T-cell numbers and subsets and lymphocyte proliferation were unaffected by IVGG. IVGG tends to normalize in vitro immunoglobulin secretion and its suppression in those ITP patients with good clinical responses in conjunction with decreased levels of autoantibody. This evidence suggests that good responders to IVGG may have inhibition of antiplatelet antibody production. IVGG does not appear to interfere with normal antibody production.

Adolescent↗
PubMed1986

Immunological variables as predictors of prognosis in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome.

Multivariate analysis was used to identify which of a large number of pretreatment immunological parameters correlated with therapeutic response, subsequent development of opportunistic infection, and survival from the time of diagnosis in a group of 70 patients with Kaposi's sarcoma and acquired immunodeficiency syndrome treated with recombinant leukocyte A interferon. In a logistic regression model, delayed type hypersensitivity response to one or more recall antigens and high proliferative response to Escherichia coli were significant predictors for response to recombinant leukocyte A interferon (for the model, P = 0.01). For prediction of the development of opportunistic infection, the model selected low proliferative responses to phytohemagglutinin and E. coli (P less than 0.001). Favorable factors predicting survival in the Cox regression model were the absence of endogenous serum interferon activity and a high proliferative response to E. coli (P less than 0.001). The estimated median survival for the group with endogenous serum interferon activity and low E. coli response was 12 months; the median has not yet been reached for the group with no serum interferon and a high E. coli response. We conclude that immunological parameters may be useful in predicting prognosis in patients with Kaposi's sarcoma and acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1977

In vitro lymphocyte transformation of MS patients to paramyxovirus antigens.

The immune response of 21 MS patients and 21 healthy volunteers was tested in vitro lymphocyte transformation assay. The stimulating antigens were measles, mumps, parainfluenza, E. coli, S. aureus and C. albicans. MS patients were found to respond similarly to the normal controls to all antigens tested with the exception of mumps antigen. The maximum responses of the MS patients to this antigen were significantly lower than those observed for the normals. However, since 95 per cent of the MS lower maximum responses were still within the positive range, the immunological significance of this phenomenon will require further clarification.

Antigens, Viral↗
PubMed1976

The use of cryopreserved lymphocytes for longitudinal studies of immune function and enumeration of subpopulations.

The responses of fresh and frozen lymphocytes to mitogens and antigens have been compared using samples collected on five separate occasions from one normal donor. The day-to-day variation seen with the fresh cells was eliminated by the use of frozen cells. Thawed cells from one donor collected on one occasion but studied on five separate occasions and compared to fresh cells on the same days, showed fluctuations from day to day as well, confirming that the day-to-day variation seen is due to technical and not biological phenomena. Cryopreserved cells showed a decrease in responses to specific microbial antigens, a slight shift in the PHA dose-response curve, but no significant difference in responses to Con A or PWM. The relative proportion of lymphocyte subpopulations changed with freezing and thawing. The proportion of T cells increased slightly and the proportion of B cells decreased.

Antigens, Bacterial↗
PubMed1975

Isolation, characterization, and mapping of Escherichia coli mutants blocked in the synthesis of ornithine decarboxylase.

Several Escherichia coli K-12 mutants blocked in the synthesis of ornithine decarboxylase (OD) were isolated after transduction for serA+ in a strain (MA197) blocked in agmatine ureohydrolase (AUH) with a mutagenized phage lysate of P1. The new double-polyamine mutants were characterized by an unconditional polyamine dependence; either putrescine or spermidine was required for normal growth. The mutational block was varified by the demonstration of a virtual absence of OD activity in cellular extracts. The mutation, designated speC, was mapped by P1 transduction in several strains and was shown to have a cotransduction frequency of 17.2% with serA. Map order was established as serA speB speC metK. A derivative of one of the OD mutants having wild-type levels of AUH and blocked in OD was utilized along with an OD AUH mutant and an OD+ AUH strain to explore the phenomenon of "pathway selection" using growth rate as a parameter. Polyamine pool studies were carried out simultaneously. The results presented here support the hypothesis of pathway selection, implying a preferential utilization of exogenous arginine rather than endogenously produced arginine in polyamine biosynthesis.

Agmatine↗
PubMed1975

Ribosomal distribution in a polyamine auxotroph of Escherichia coli.

The distribution of ribosomal particles has been studied in a polyamine-deficient mutant of Escherichia coli by sucrose gradient centrifugation analysis. Lysates from starved cells contained less 70S monomers and 30S subunits but more 50S particles than those prepared from bacteria supplemented with putrescine. The addition of the polyamine to putrescine-depleted cells induced a rapid change of the ribosomal profile. A similar effect could be obtained in vitro by equilibrium dialysis against a polyamine-containing solution. The ribosomal pattern obtained from starved bacteria was specific for polyamine deficiency. We conclude that the changes in ribosomal profiles upon restoration of putrescine levels in previously starved cells denote a shift of the equilibrium between 30S-50S couples and ribosomal subunits.

Escherichia coli↗