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Biomedical subjects

L J Beard

Publications and source records attributed to L J Beard.

At least 19 recordsLinked to original sources
PubMed1993

Low IgG4 concentrations in infants with Haemophilus influenzae type b infections.

Haemophilus influenzae type b causes considerable morbidity and mortality in infants and young children. Immunity to this organism has been attributed in part to the formation, and increase with age, of antibodies to the capsular polysaccharide of the bacteria. A degree of immunodeficiency could explain why some infants and young children develop invasive haemophilus disease. In this study we investigated immunocompetence in ten infants with invasive haemophilus disease. We found normal lymphocyte mitogen responses, neutrophil iodination and bactericidal and fungicidal capacities in this group. While we found no deficiencies of any of the immunoglobulin classes, three patients had low concentrations of IgG4 and two of them had low concentrations of IgG2 as well. These findings suggest that in some infants who develop haemophilus infections, the measurement of IgG subclasses may reveal immune defects that would not otherwise be apparent.

Haemophilus Infections↗
PubMed1991

Early bone marrow transplantation in an infant with Wiskott-Aldrich syndrome.

The Wiskott-Aldrich Syndrome (WAS) is a rare X-linked immunohematological disorder characterized by eczema, profound thrombocytopenia, and progressive immunodeficiency. Severe hemorrhage, overwhelming sepsis, or lymphoreticular malignancy usually cause death in childhood. Recently, bone marrow transplantation (BMT) has been curative in some well-established cases, but there is no general agreement about the place of BMT in infants with WAS before the development of significant immunological abnormalities. We describe the successful use of early histocompatible BMT in a 10-month-old infant in whom WAS was diagnosed on the basis of eczema, thrombocytopenia, small platelets, and raised serum immunoglobulin A (Ig) and IgE, but before the development of immunodeficiency as evidenced clinically by recurrent infections, or immunologically by low serum IgM or consistently abnormal lymphocyte responses to mitogens. After an unstable period for several weeks posttransplantation when he developed marked hepatomegaly and severe interstitial pneumonitis, he made a good recovery. His eczema and thrombocytopenia resolved and he has shown no clinical or laboratory evidence of immunodeficiency. It is now over 2 years since his BMT. Because of the poor prognosis of WAS, where a histocompatible donor is available, BMT at the earliest opportunity, despite the inherent risks of such a procedure, may be the best option for an infant with WAS.

Age Factors↗
PubMed1991

Characterization of the major neutrophil-stimulating activity present in culture medium conditioned by Staphylococcus aureus-stimulated mononuclear leucocytes.

Culture medium conditioned by stimulating human mononuclear leucocytes (MNL) with killed Staphylococcus aureus (Scm) was found to contain a substantial amount of tumour necrosis factor-alpha (TNF-alpha) but no detectable tumour necrosis factor-beta (TNF-beta). Culture medium conditioned by MNL in the absence of bacteria contained no TNF-alpha activity. When Scm was fractionated by high-performance liquid chromatography (HPLC) on Bio-Sil TSK 250, TNF-alpha co-eluted with neutrophil-stimulating activity measured by chemiluminescence. Similarly, the ability of neutrophils to kill opsonized S. aureus was enhanced in fractions that contained this neutrophil-stimulating activity. The stimulating activity could be almost completely removed by pretreatment of the Scm with a TNF-alpha-specific monoclonal antibody (mAb). The ability of neutrophils to kill S. aureus in response to Scm was also substantially reduced by mAb to TNF-alpha. These results demonstrate that bacterial interaction with MNL leads to the release of neutrophil-stimulating activity that consists predominantly of TNF-alpha.

Antigens, Bacterial↗
PubMed1990

Aspects of immunoglobulin replacement therapy.

Immunoglobulin replacement therapy appears to benefit some patients who have IgG subclass deficiencies. Because some patients with subnormal trough concentrations of IgG subclasses remain well, because other patients who have borderline/low normal concentrations of an IgG subclass are abnormally infection-prone and helped by immunoglobulin therapy and because infection proneness in individual patients does not always appear to parallel their IgG subclass concentrations, it is evident that IgG subclass concentrations, while a helpful guide, are not an absolute determinant of the need for immunoglobulin replacement therapy in infection-prone patients. Low IgG subclass concentrations may indicate impaired ability to produce certain "specific" antibodies and antibody replacement is likely to be the crucial factor in treatment rather than merely maintaining concentrations of IgG subclasses at particular levels.

Adolescent↗
PubMed1989

IgG4 deficiency in IgA-deficient patients.

IgG subclass deficiency may be an important factor in the infection proneness of some IgA-deficient subjects. Although several studies on IgG subclass deficiency in IgA-deficient subjects have been reported, most have been unable to assess the incidence of IgG4 deficiency because the limitations of the assay methods used have often made a distinction between low normal and subnormal concentrations impossible. Having developed an enzyme-linked immunosorbent assay capable of measuring concentrations of all the IgG subclasses in healthy subjects of all ages and having established age-normal ranges for IgG subclasses using this assay, we measured IgG subclass concentrations in 73 IgA-deficient patients, the majority of whom were children with recurrent respiratory infections. The results showed that IgG4 deficiency occurred in 26% of the patients and was the most common IgG subclass deficiency found. IgG1, IgG2 and IgG3 deficiencies occurred, respectively, in 10, 12 and 8% of the patients. IgA-IgG4 deficiency occurred in 16% of the patients; IgA-IgG2-IgG4 in 4%; and IgG1-IgG2-IgG4, IgA-IgG1 and IgA-IgG2-IgG3 each occurred in 3%. Other subclass deficiencies or combinations of deficiencies were less frequent. Our results suggest that IgG4 deficiency even in the absence of IgG2 deficiency may be an important but hitherto largely unrecognized factor in infection proneness in some IgA-deficient patients.

Adolescent↗
PubMed1989

Alterations in function and subpopulations of peripheral blood mononuclear leukocytes in children with portal hypertension. Leukocyte subtypes and function in portal hypertension.

Children with advanced portal hypertension usually have splenomegaly (often associated with hypersplenism) which may lead to a decreased life span of circulating blood leukocytes. In a group of 6 children (age range 4-15 years; mean age 8.5 years) with portal hypertension, we examined peripheral blood mononuclear leukocytes for possible changes in their proportions, numbers and function. Compared to normal subjects, children with portal hypertension had a marked reduction in the percentages and absolute numbers of T lymphocytes (CD3+), T 'helper/inducer' (CD4+) and T 'suppressor/cytotoxic' (CD8+) cells. However, the percentages of B lymphocytes (FMC1+), natural killer cells (Leu 11+) and monocytes (morphological) were increased, and the absolute numbers of B cells were significantly increased in these patients. Lymphocyte responsiveness to phytohemagglutinin, pokeweed mitogen and concanavalin A were depressed in the patients, while the natural killer cell cytotoxicity was slightly increased. Thus, children with portal hypertension show changes in the relative proportions and absolute numbers of peripheral blood mononuclear blood leukocyte subpopulations as well as changes in mononuclear leukocyte function.

Adolescent↗
PubMed1988

Tumour necrosis factor beta (lymphotoxin) inhibits locomotion and stimulates the respiratory burst and degranulation of neutrophils.

The data presented here demonstrate that recombinant human tumour necrosis factor beta (rHuTNF beta; lymphotoxin) is a neutrophil modulator. The lymphokine inhibited the locomotion of neutrophils and augmented the neutrophil oxygen-dependent respiratory burst in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) and phorbol myristate acetate (PMA), as measured by their capacity to produce chemiluminescence, H2O2 and superoxide. The effects on the respiratory burst occurred at a tenth of the concentration of TNF beta required to inhibit locomotion. After incubation with TNF beta, the neutrophils could be washed without any reduction in their capacity to show augmented responses. The TNF beta enhanced granule enzyme (lysozyme and beta-glucuronidase) release of neutrophils stimulated with cytochalasin B-FMLP.

Cell Movement↗
PubMed1986

An enzyme-linked immunosorbent assay for the quantitation of human IgG subclasses using monoclonal antibodies.

An enzyme-linked immunosorbent assay was established for the quantitation of human IgG1, IgG2, IgG3 and IgG4 using IgG subclass-specific monoclonal antibodies. The method could detect 1-10 ng/ml of the Ig subclasses. The technique is suitable for measuring IgG subclass concentration in sera of healthy adults and in supernatants from human lymphocytes cultured in the presence of pokeweed mitogen.

Adult↗
PubMed1986

IgG subclass deficiency in children with IgA deficiency presenting with recurrent or severe respiratory infections.

A group of 22 children presenting with recurrent or severe respiratory tract infections who had low IgA levels (more than 2 SD below the mean for age) were examined for IgG subclass deficiency. Patients were screened for possible defects in neutrophil chemotaxis, bactericidal, fungicidal, and quantitative iodination activity, as well as for complement function. The majority of the patients showed IgG subclass levels below the mean for age. Nine of the children showed definite IgG subclass deficiency and at least two showed definite deficiency of more than one IgG subclass. The predominant subclass deficiency was found to be IgG1. While nine children showed IgG4 levels below the level detectable by the technique used, it is not possible to assess whether these patients are deficient in this isotype since some healthy subjects also give values below the level of detection. Most of the patients who had very low (1-6 mg/dl) or undetectable (less than 1 mg/dl) levels of serum IgA did not show IgG subclass deficiencies, while IgG subclass deficiencies were common among those with borderline low IgA levels (slightly more than 2 SD below the mean for age). Nine children showed total IgG levels close to 2 SD below mean for age, and at least six of these showed IgG subclass deficiency. The result suggests that patients with recurrent and/or severe respiratory infections who have borderline IgA and IgG levels may have IgG subclass deficiencies and if they do could benefit from immunoglobulin therapy.

Blood Bactericidal Activity↗
PubMed1981

Immunological competence of children with pyogenic meningitis.

A broad range of immunological tests was performed on 9 consecutive children with pyrogenic meningitis. Two were found to have combined IgG and IgA deficiency. One had a combination of IgG deficiency and impaired neutrophil chemotaxis. Primary immunodeficiency disorders as a predisposing cause of pyogenic meningitis may be more common than previously suspected.

Chemotaxis, Leukocyte↗
PubMed1981

The immunological status of children with atopic dermatitis.

We studied 16 children during the quiescent phase of atopic dermatitis with a broad range of in vitro immunological tests. Subnormal levels of IgA were present in 2 children, and subnormal IgG in 1. IgE levels were elevated in 6 children. T cell percentages were significantly but slightly reduced. Normal results were obtained for lymphocyte transformation to 3 mitogens, neutrophil chemotaxis, quantitative iodination and microbicidal activity, and for the serum levels of CH50, C3 and C4. Thus most of the abnormal immunological findings in atopic dermatitis nay be secondary to the disease process itself.

Adolescent↗
PubMed1981

Immunocompetence of children with frequent respiratory infections.

119 children with recurrent respiratory infections were investigated for immunocompetence. They were divided into two groups. The first, group A, comprised children who had had predominantly upper respiratory infections. Group B comprised those who had had repeated pneumonia in addition. The groups were comparable for gender and age (mean 4.2 years). All the children had reduced neutrophil chemotaxis, reduced neutrophil fungicidal capacity, and perhaps reduced T-cell percentages. Group B children had, in addition to the above, decreased neutrophil bactericidal capacity and a more marked depression of neutrophil chemotaxis. In both groups, some children had reduced immunoglobulin concentrations while others had either normal or increased concentrations. Serum complement, neutrophil iodination, and mitogen-induced lymphocyte transformation were comparable with adult controls in both groups.

Adolescent↗
PubMed1980

Para-influenza pneumonia in DiGeorge syndrome two years after thymic epithelial transplantation.

A patient with DiGeorge syndrome developed pneumonia caused by para-influenza virus type 3 two years after immunological reconstitution with foetal thymic eptihelium. There was a transient reduction of mitogen-induced lymphocyte transformation at the time of the pneumonia. Although she recovered from the pneumonia, brochitis persisted and the virus could still be isolated from her pharyngeal secretions 3 1/2 months later.

Antibodies, Viral↗