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Biomedical subjects

D Goldblatt

Publications and source records attributed to D Goldblatt.

At least 73 records · Page 4Linked to original sources
PubMed1996

Persistence of antibody responses to Haemophilus influenzae type b polysaccharide conjugate vaccine in children with vertically acquired human immunodeficiency virus infection.

BACKGROUND: Recurrent bacterial sepsis is common in pediatric HIV infection and immunization against Haemophilus influenzae type b (Hib) is recommended. Long term persistence of anti-Hib antibody and the need for, or timing of, a booster dose has not been adequately studied. METHODS: Immunogenicity during a 12-month period following immunization with Hib-tetanus conjugate vaccine (ACT-HIB; Merieux) was evaluated in 48 vertically HIV-infected children and 36 uninfected children, born to HIV-positive mothers. A titer of anti-Hib polysaccharide antibody of > or = 0.15 microgram/ml was considered to indicate short term and > or = 1 microgram/ml long term protection. RESULTS: At 1 month postvaccination 36 (100%) uninfected and 42 (88%) HIV-infected children achieved titers of > or = 1 microgram/ml. However, by 1 year titers had dropped below this value in 18 (43%) infected compared with only 4 (11%) uninfected children (chi square, 9.7; P = 0.002). Although the rate of fall of antibody titer was greater in uninfected than in infected children, this was no longer the case after adjustment for the 1-month postimmunization titer. The rate of antibody titer decline was not significantly related to HIV disease status or to either the age-related CD4 count at the time of immunization or the change in age-adjusted CD4 count during the 12 months after immunization. CONCLUSIONS: Not only was the initial antibody response to Hib conjugate vaccine decreased in children with HIV infection and AIDS but also 1 year later only 57% of the initial responders had persisting titers above the level associated with long term protection. The need for reimmunization of children with HIV infection against Hib requires further evaluation.

AIDS-Related Opportunistic Infections↗
PubMed1996

Human constant regions influence the antibody binding characteristics of mouse-human chimeric IgG subclasses.

Although antibody affinity is primarily determined by immunoglobulin variable region structure human IgG antibodies of the four subclasses specific for the same antigen have been shown to differ in their affinity. To explore the influence of the immunoglobulin constant region on functional antibody affinity, a set of V region identical mouse-human chimeric IgG subclasses specific for TAG72 (tumour-associated glycoprotein) were studied. Biomolecular interaction analysis (BIA) was used to determine the binding kinetics of whole IgG subclasses and F(ab')2 fragments. Despite identical V regions, binding kinetics differed for the four subclasses. The apparent dissociation rate constants of the intact immunoglobulins ranked IgG4 < IgG3 < IgG2 < IgG1. In contrast, analysis of the binding characteriztics of the F(ab')2 fragments derived from IgG1, IgG2 and IgG4 revealed identical binding kinetics. The structure of the constant regions of the humanized IgG subclass antibodies clearly influenced functional antibody affinity, as has been described for the murine IgG subclasses. The exact mechanism for this phenomenon remains obscure but such differences should be taken into account when designing or choosing antibodies for therapeutic use.

Animals↗
PubMed1996

Antibody responses to Haemophilus influenzae type b conjugate vaccine in sickle cell disease.

OBJECTIVE: To investigate the immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccines in children with sickle cell disease. DESIGN: Open study. SETTING: Haemoglobinopathy clinic. SUBJECTS: Children with homozygous haemoglobin SS disease (HbSS), sickle haemoglobin C disease (HbSC), and sickle-beta thalassaemia disease (HbS-beta Thal). INTERVENTIONS: Children over the age of 2 years received a single dose of Hib-tetanus toxoid conjugate vaccine (PRP-T). MAIN OUTCOME MEASURES: Antibody response to Hib polysaccharide (PRP) approximately one month after vaccination. RESULTS: 77 children over the age of 2 years were studied,, 55 with HbSS, 16 with HbSC, and six with HbS-beta Thal. Before vaccination, 44% had anti-PRP IgG titres less than the level associated with long term protection (1.0 microgram/ml). After a single dose of PRP-T all children mounted an antibody titre > 1 microgram/ml. Geometric mean anti-PRP IgG titre achieved postvaccination (45.2 micrograms/ml 95% confidence interval (CI) 31.6 to 64.8) was comparable to that of a healthy population. Children with HbSC, however, had a significantly higher antibody titre postvaccination (91.1 micrograms/ml; 95% CI 32.7 to 254.4) than the children with HbSS (36.7 micrograms/ml; 95% CI 25.1 to 52.9). CONCLUSIONS: Children with a diagnosis of sickle cell disease who are over the age of 2 years make a vigorous antibody response to a single dose of PRP-T vaccine and hence we suggest unimmunised individuals in this group should receive a single dose of a Hib conjugate vaccine.

Adolescent↗
PubMed1995

Undine's course.

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Eponyms↗
PubMed1995

Lightening.

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History, 18th Century↗
PubMed1994

Association of Gm allotypes with the antibody response to the outer membrane proteins of a common upper respiratory tract organism, Moraxella catarrhalis.

Previously, Gm allotypes have been shown to influence human serum Ig subclass levels as well as the Ab levels achieved after Ag stimulation. The majority of the latter studies have focused on Ab responses to polysaccharide Ags. In this study, we have investigated the relationship between Gm allotypes and naturally occurring serum Ab levels to a bacterial protein Ag, the outer membrane proteins of a common microorganism, Moraxella catarrhalis. In the sera of 160 patients having chronic/recurrent sinusitis, there was a highly significant correlation between the level of specific anti-M. catarrhalis IgG3 level and certain Gm phenotypes. After additional investigation, we found that the presence of G3m(21) homozygosity correlated significantly with lower levels of Ag-specific IgG3. Specific anti-M. catarrhalis IgG3 levels were found to be independent of total serum IgG3 concentrations, and there was no correlation between the serum level of IgG3 and any Gm phenotype. Total IgG and IgG2 that were specific for pneumococcal cell wall polysaccharide also were measured in this group of patients, and no correlation was found between the naturally occurring IgG2 subclass levels to pneumococcal cell wall polysaccharide and the interactive effect of G2m(23) (syn: G2m(n)) and Km(1). Gm allotypes may influence Ab responses other than the anti-carbohydrate responses and, therefore, should be taken into account when investigating IgG subclass responses to protein Ags.

Adolescent↗
PubMed1994

An autoantibody derived from mice with experimental systemic lupus erythematosus is directed against the essential splicing factor SF53/4--a possible role for large nuclear ribonucleoprotein particles in autoimmune disorders.

We have previously shown that nuclear transcripts of several pre-mRNAs can be released from nuclei of mammalian cells in a form of large nuclear ribonucleoprotein (InRNP) particles. These particles, which invariably sediment at the 200S region in sucrose gradient, contain all U small nuclear RNPs required for pre-mRNA splicing and a multitude of heterogeneous nuclear RNP proteins. From a panel of mAbs raised against the InRNP particles, a specific mAb (53/4) identified a nuclear protein of 88 kDa as an essential splicing factor (SF53/4). In a parallel independent study, mAbs were established in mice with experimental systemic lupus erythematosus (SLE), that had been induced by immunization with a murine mAb against a human anti-DNA mAb bearing the common 16/6 idiotype. One of the produced mAbs (2C5/3) recognized an 88 kDa RNP protein. In the present study we have used the following criteria to demonstrate that mAb 2C5/3 and mAb 53/4 recognize the same protein. First, mAb 2C5/3 inhibited splicing by direct addition. Second, the 88 kDa polypeptide that had been immunodepleted from HeLa cells nuclear extract by mAb 2C5/3 was recognized by mAb 53/4 in protein blots. Third, the HeLa nuclear extract depleted by mAb 2C5/3 was devoid of splicing activity and could not assemble into splicing complexes with exogenous pre-mRNA; however, splicing and spliceosome assembly activities were restored to such a defective extract by adding back the 88 kDa protein that had been purified by immunoaffinity binding to immobilized mAb 53/4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The role of pH in modified ELISA procedures used for the estimation of functional antibody affinity.

Solid phase assays for the measurement of functional antibody affinity are increasingly being used in both clinical and research settings. The majority of such assays employ a chemical reagent to disturb antibody binding but relatively little is known about the properties of such reagents and the basis of their effect on antigen-antibody binding. We have evaluated the diethylamine (DEA) ELISA procedure for the measurement of functional antibody affinity in two independent assays, one for functional human IgG subclass affinity to an organism, Moraxella catarrhalis, and the other for measuring functional affinity of mouse monoclonals specific for the cat allergen Fel d I. DEA was shown to increase the pH of the buffering solution and it was this rise in pH that affected antibody binding. Alkaline buffer and DEA were equally efficient in the inhibition of binding of both the human IgG subclasses and the two mouse monoclonal antibodies to the solid phase. In contrast, pH was shown to have no role in the chaotropic effect of the ion, thiocyanate.

Animals↗