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Biomedical subjects

D J Barrett

Publications and source records attributed to D J Barrett.

At least 55 records · Page 3Linked to original sources
PubMed1985

Human immune responses to polysaccharide antigens: an analysis of bacterial polysaccharide vaccines in infants.

Mechanisms of human immunity to polysaccharide encapsulated bacteria and the development and testing of the currently available purified polysaccharide bacterial vaccines are reviewed. These vaccines appear to be poorly immunogenic in infants under the age of two years--those at greatest risk for infection. In an effort to understand the poor responses of infants, the human immune response to polysaccharide antigens was characterized in more detail. Using pneumococcal polysaccharide type 3 as an example, it appears that human polysaccharide antibody responses are analogous to the type 2 T cell independent responses defined in the murine system. These studies suggest that the deficient polysaccharide response of human infants is due to a deficiency in maturation of distinct B lymphocyte subpopulations, as well as imbalanced T regulatory influences. The development of vaccines containing the purified capsular polysaccharides of S. pneumoniae, H.influenzae, and N. meningitidis during the past decade offered promise for the prevention of the major causes of bacterial sepsis and meningitis during childhood. The fulfillment of that promise was thwarted by the unrecognized complexities of human antibody responses to polysaccharide antigens. Continued vigorous research in this area has led us to a better understanding of the cellular requirements and immunoregulation of human polysaccharide antibody responses and has given us a clear direction for the pursuit of an effective means for immunization of infants.

Adult↗
PubMed1984

Prevalence of T-lymphocyte abnormalities in infants with congenital heart disease.

Thirty-two infants younger than 6 months with catheterization-proved congenital heart disease were prospectively examined for T-lymphocyte immunodeficiency (compared with adult and normal newborn controls). Cardiac lesions were separated into two groups: (1) "high-risk" lesions previously associated with T-cell abnormalities in DiGeorge's syndrome, and (2) the remaining "low-risk" lesions. Cardiac patients as a whole did not have significant abnormalities in T-cell rosette (TCR) percentages (mean +/- SE, 50.0% +/- 22%) or response to phytohemagglutinin (PHA) (72,243 +/- 38,388 counts per minute). However, a greater percentage of patients with high-risk cardiac lesions had abnormal TCR and PHA results than either the control or low-risk group, due to the inclusion of three infants with DiGeorge's syndrome. These findings suggest that newborn infants without evidence of DiGeorge's syndrome have normal T-lymphocyte function. Infants with high-risk cardiac lesions deserve a careful immunologic evaluation to avoid significant morbidity and mortality.

Cardiac Catheterization↗
PubMed1984

Characterization of the acquired immune deficiency syndrome at the cellular and molecular level.

The acquired immunodeficiency syndrome (AIDS) is a new disease characterized by severe dysfunction of both the T cell and B cell systems, occurring in previously healthy individuals. Affected individuals may have recurrent and chronic opportunistic infections and/or Kaposi's sarcoma or other malignancy. Analysis of the cellular and subcellular components of immunity demonstrates a profound depression in the number and function of helper/inducer T cells bearing the OKT4 (Leu 3) differentiation antigen and a concomitant defect in the synthesis of the immuno-enhancing soluble growth factor, interleukin 2 (IL-2). Hypotheses to explain the etiology of the immunological dysfunction and implications for future therapy of AIDS are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Familial DiGeorge syndrome with tetralogy of Fallot and prolonged survival.

Two brothers with DiGeorge syndrome had tetralogy of Fallot with pulmonary valve atresia, illustrating similarity of the type of congenital heart disease (CHD) within affected families; the specific type of CHD differs between families. The late recognition of hypocalcemia in the older brother and his survival to age 21 years emphasizes the need to consider. DiGeorge syndrome in patients of all ages with hypocalcemia and congenital heart disease.

Adult↗
PubMed1984

Changes in heart rate during progressive hyperoxia in the dogfish Scyliorhinus canicula L.: evidence for a venous oxygen receptor.

Progressive hyperoxia caused a gradual increase in arterial blood oxygen tension (PaO2). Initially there was no change in venous O2 tension (PvO2) but in extreme hyperoxia (PO2 650 mmHg) it increased to 2.5 times the normoxic (PO2 150 mmHg) level (Table 1). Ventilation frequency gradually decreased down to 73% of the normoxic value as PO2 rose towards a maximum at 700 mmHg (Fig. 1). In moderately hyperoxic water (mean PO2 233 mmHg) heart rate (fH) increased significantly above the normoxic level. Further increases in ambient PO2 caused a progressive reduction in fH to a level significantly below the normoxic rate in extreme hyperoxia (Fig. 2). Injection of atropine abolished these changes, and the atropinized fH was similar to that measured during moderate hyperoxia. The initial increase in fH during progressive hyperoxia is attributed to release of vagal tone, due to removal of normoxic stimulation of peripheral oxygen receptors; whereas, the secondary bradycardia is attributed to the stimulation of oxygen receptors located in the venous system. Injection of 5 ml of hyperoxaemic blood into the venous system of normoxic fish caused a transient bradycardia (Fig. 3), lasting a mean of 73 sec, which is the approximate time for passage of the blood volume of the venous system through the heart. This bradycardia was neither pH dependent nor a pressor response and provides supporting evidence for the existence of a venous oxygen receptor.

Animals↗
PubMed1984

Restoration of complement function in vivo by plasma infusion in factor I (C3b inactivator) deficiency.

The serum complement activities of a 1-year-old infant with recurrent life-threatening bacterial infections and persistent C3-Coombs-positive red blood cells were investigated. The patient's serum had a depressed serum level of CH50, C3, factor B, and factor H as well as undetectable antigenic or functional factor I. The complement profile of the parents was normal, with the exception of factor I, which was approximately 50% of normal in each parent. The Coombs positivity of the patient's red blood cells could be reversed in vitro by incubation with normal serum containing factor I. Infusion of normal plasma into the patient resulted in increased levels of CH50, with concomitant increases in serum C3, factor B, and factor H levels. The patient's red blood cells became transiently Coombs negative. At no time after plasma infusion was factor I detectable in the patient's serum. All complement functions and the C3 Coombs reactivity of the patient's red blood cells returned to preinfusion levels within 14 days. These findings are consistent with an inherited deficiency of factor I and emphasize the critical role this protein plays in the regulation of the alternative complement pathway. Plasma therapy may be an adjunct to the management of acute infection in patients with factor I deficiency.

Afibrinogenemia↗
PubMed1984

IgG and IgM pneumococcal polysaccharide antibody responses in infants.

The ontogeny of human antibody responses to pneumococcal polysaccharide antigens was studied by determining whether the age at immunization affects the level and/or immunoglobulin isotype of antibody produced. Twenty-nine healthy infants between 2 and 18 months of age and 13 normal adults were studied. Responses were found to vary markedly with the age at the time of immunization and with the pneumococcal serotype tested. Three general patterns of isotype-specific antibody response were observed in the infants: a high response in IgG antibody occurred as early as 2 months of age following immunization with type 3 pneumococcal polysaccharide; little or no response was noted in either IgG or IgM antibody with types 6, 18, and 19; and intermediate responses with IgM antibody increases greater than IgG increases were found for type 23. These data suggest that different factors control the immunologic response of infants to various pneumococcal polysaccharide serotypes following immunization at various ages.

Age Factors↗
PubMed1983

Inhibition of human lymphocyte activation by wheat germ agglutinin: a model for saccharide-specific suppressor factors.

The suppressive effect of wheat germ agglutinin (WGA) on lectin-stimulated blastogenesis and immunoglobulin production was studied. Addition of WGA at 10 micrograms/ml inhibited phytohemagglutinin (PHA)-, concanavalin-A (Con-A)-, and pokeweed mitogen (PWM)-induced mitogenic responses by 70-80%. PWM-driven immunoglobulin synthesis was suppressed by 45% with WGA. The inhibitory effects of WGA were not due to cell death or to interference with lectin binding at the cell surface. Inhibition was dependent on the presence of WGA in the cell culture during the first 24 hr of mitogen exposure and was observed in cultures of both monocyte-depleted peripheral blood mononuclear cells as well as T-cell-enriched populations. WGA-induced inhibition of blastogenesis was blocked by the addition of N-acetylglucosamine (GluNAc) which prevents WGA binding to the cell surface. WGA was found to mimic the suppressive effect of a soluble immune suppressor supernatant (SISS) derived from Con-A-activated mononuclear cell cultures. PHA responses were inhibited by 80 and 95% with SISS and WGA, respectively. The inhibition by both WGA and SISS was totally reversed with addition of GluNAc. Furthermore, WGA and SISS demonstrated competition for the same cell surface receptor site. WGA may therefore be useful as an in vitro model of a saccharide-specific, biologically relevant, soluble mediator for the investigation of mechanisms of immunologic suppression.

Cells, Cultured↗
PubMed1983

Assay of antibody to group A streptococcal carbohydrate by enzyme-linked immunosorbent assay.

An indirect enzyme-linked immunosorbent assay system for determination of antibody levels to the group A streptococcal cell wall carbohydrate antigen is described. Optimal conditions for antigen preparation, purification, and conjugation to poly-L-lysine for adequate adsorption to the solid phase are presented. Antibody titers of unknown sera were determined by comparison to known reference standard pool sera. A highly significant correlation (p less than 0.0001) was found between enzyme-linked immunosorbent assay antibody titers and antigen-binding capacity in a previously described radioimmunoassay. Utilizing an isotype-specific anti-immunoglobulin reagent and immunoabsorbent-purified antibody to group A streptococcal cell wall carbohydrate antigen, we were able to detect nanogram quantities of antibody by the enzyme-linked immunosorbent assay technique. This system will provide for more generalized use of group A streptococcal cell wall carbohydrate antigen antibody determinations for the study of immune responses after streptococcal infections and their complications.

Alkaline Phosphatase↗
PubMed1982

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↗
PubMed1981

Spectrum of Sjögren syndrome in children.

Sjögren syndrome, consisting of keratoconjunctivitis sicca and xerostomia with or without another autoimmune disease, is uncommon in children. We describe our retrospective experience with eight pediatric patients with SS. All had recurrent parotid enlargement and abnormal salivary gland biopsies, six had keratoconjunctivitis sicca, and five had other autoimmune manifestations, although only two of these had other clearly defined autoimmune disorders (mixed connective tissue disease and hypergammaglobulinemic purpura). Our patients had a higher incidence of primary SS, parotid enlargement, and hematologic abnormalities than did children previously reported with SS. Children with SS demonstrate a clinical heterogeneity comparable to that seen in adults.

Adolescent↗
PubMed1981

Clinical and immunologic spectrum of the DiGeorge syndrome.

This report summarizes the spectrum of clinical and immunologic findings gathered prospectively in 13 patients with the DiGeorge syndrome. Our patients demonstrated marked variability in both the clinical manifestations and the degree of immunodeficiency, confirming the findings of earlier individual case reports and retrospective autopsy reviews. Ages at the time of presentation ranged from one day to 4 months. Congenital heart defects including truncus arteriosus, ventricular septal defect, interrupted aortic arch, and tetralogy of Fallot commonly brought these infants to medical attention within the first two weeks of life. Abnormal calcium homeostasis was found in all patients. Those patients presenting after the first month of life often had hypocalcemic seizures as the initial clinical manifestation. Parathyroid hormone levels and the number and location of parathyroid glands varied considerably. Immunologic evaluation revealed that total lymphocyte counts, percent T-cells, total T-cells, and T-lymphocyte function ranged from normal to severely depressed. The most consistent immunologic abnormality, found in 11 of the 13 patients, was a decrease in total T-cells. Sequential studies in five patients demonstrate that spontaneous resolution of immunodeficiency may occur in some, yet progressive loss of immune function may be observed in others. Complete immunologic evaluation and careful followup is mandatory in infants with persistent hypocalcemia and congenital heart disease who are suspected to have DiGeorge syndrome.

B-Lymphocytes↗
PubMed1980

Thymosin therapy in the DiGeorge syndrome.

Reconstruction of the T-cell immune defect in patients with the DiGeorge syndrome has been accomplished in the past by fetal thymus transplantation. Because of the risk of fatal graft-versus-host reaction with fetal thymus transplantation in patients with abnormal T-cell immunity, we have examined the effects of a thymus tissue extract, thymosin fraction 5, on the in vitro and in vivo immune function in children with the DiGeorge syndrome. T-cell numbers were increased with thymosin F5 in vitro in three of five patients. T-cell number and function was improved in three of four patients treated with thymosin F5 in vivo. Spontaneous improvement in the immune function of these patients cannot be excluded. These results suggest, however, that further trials with thymosin F5 therapy may be indicated in patients with the DiGeorge syndrome.

DiGeorge Syndrome↗
PubMed1980

Immunoglobulin G and M antibodies to pneumococcal polysaccharides detected by enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay has been developed to detect serum immunoglobulin G and M antibodies against pneumococcal polysaccharide antigens. Parameters affecting the specificity and sensitivity of the assay are described. A vigorous antibody response involving both the immunoglobulin G and M classes was demonstrated after pneumococcal polysaccharide immunization in normal adults. Studies with this enzyme-linked immunosorbent assay technique will allow further understanding of the biology of the primary and secondary immune response to Streptococcus pneumoniae in normals as well as in those persons most susceptible to infection with that organism.

Adult↗