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Biomedical subjects

C I Smith

Publications and source records attributed to C I Smith.

At least 181 records · Page 10Linked to original sources
PubMed1990

Effects of beta-D-xyloside on differentiation of the respiratory epithelium in the fetal mouse lung.

Differentiation of respiratory endings in the fetal lung appears to be controlled by its surrounding mesodermal capsule. The capsule may exert its influence by controlling the composition of the epithelial basal lamina or of the extended extracellular matrix that is deposited during the period when alveolar sacs are formed. As a first step in testing this hypothesis, the effects of the drug, rho-nitrophenyl-beta-D- xylopyranoside (beta-xyloside), an inhibitor of proteoglycan synthesis, and its inactive alpha anomer (alpha-xyloside) were examined. Lung primordia from mice at 16 days of gestation were tested for inhibition of morphological and functional differentiation as a result of drug treatment. Pseudoglandular lung epithelium did not form respiratory endings, contained fewer specialized cells, and accumulated little additional surfactant when treated with beta-xyloside but developed normally when treated with alpha-xyloside or grown in control medium. The results are interpreted to suggest that deposition of an extracellular matrix rich in proteoglycan is required to support maturation of the respiratory epithelium.

Animals↗
PubMed1990

Development of IgA deficiency after bone marrow transplantation. The influence of acute and chronic graft-versus-host disease.

Serum IgA levels were monitored at 3, 6, 12, and 24 months after BMT in 131 allogeneic and 3 syngeneic bone marrow transplant recipients. In general, IgA levels were low during the first 6 months and did not return to normal levels until 1-2 years after transplantation. Children (less than 15 years) had lower IgA levels at 3 and 6 months post-BMT compared to the adults (P less than 0.05), but donor age had no influence on the recipient IgA levels after BMT. Patients receiving either methotrexate or cyclosporine alone for GVHD prophylaxis had markedly lower IgA levels compared to those given a combination of these two drugs or patients transplanted with T-cell-depleted marrow (P less than 0.001). Mean IgA levels in patients without or with grade I acute GVHD were within the normal range at 3, 6, 12, and 24 months after BMT (greater than 0.3 g/L), although approximately 20% of the patients in each group showed low IgA levels (less than or equal to 0.3 g/L) early after transplantation. Patients with grade II or III acute GVHD had significantly lower values from 3 months up to 2 years after transplantation (P less than 0.01). Patients with chronic GVHD had significantly lower IgA levels 1 and 2 years after BMT compared to patients without chronic GVHD (P less than 0.005). Severe acute GVHD, particularly when followed by chronic GVHD, seems to be the main reason for low IgA levels, while other factors such as CMV infection or donor status may also contribute to the development of IgA deficiency after BMT.

Acute Disease↗
PubMed1990

Aberrant IgG subclass distribution to measles in healthy seropositive individuals, in patients with SSPE and in immunoglobulin-deficient patients.

Sera from healthy seropositive donors, patients with acute measles, subacute sclerosing panencephalitis, common variable immunodeficiency, and CH gene deletions were analysed for anti-measles IgG1-4. Compared with other anti-viral immune responses of IgG1 and IgG3, an unusual predominance of specific IgG1 prevailed; only four out of a total of 68 patients showed anti-measles IgG3. Of the 17 healthy, measles seropositive serum donors, all showed specific IgG1, none showed IgG3 and six had IgG4. Eight out of 10 patients with SSPE showed an anti-measles IgG1 and IgG4 response while IgG3 was not seen. The IgG1 and IgG4 subclass patterns had some exceptions. Anti-measles IgG3 was found in five out of five patients with deletion of the gamma-1 encoding gene segments and in four out of 15 patients with recent measles antigen stimulation. The subclass pattern was suggested to reflect the immunological compromise associated with measles infections.

Adolescent↗
PubMed1990

Frequencies of interleukin-5 mRNA-producing cells in healthy individuals and in immunoglobulin-deficient patients, measured by in situ hybridization.

Interleukin-5 (IL-5) has previously been demonstrated to enhance immunoglobulin synthesis, especially IgA. Thus, it could be hypothesized that a defect production of IL-5 may cause immunoglobulin deficiency. We have analysed the frequency of IL-5 mRNA-producing cells in healthy adults and in patients with common variable immunodeficiency or selective IgA deficiency. Unstimulated lymphocytes were rarely found to synthesize IL-5 as measured by in situ hybridization. However, pokeweed mitogen and several other activating ligands induced the synthesis of IL-5 mRNA in peripheral blood and spleen lymphocyte cultures. After pokeweed mitogen activation, the number of IL-5 mRNA-producing cells most often peaked on day 3 with a maximal frequency of around 1-2% of mononuclear cells. In a kinetic study we were unable to detect any peak frequency differences between healthy controls (mean 0.44%) and 20 patients (mean 0.58%). Thus, although IL-5 has been reported to be an important regulator of IgA synthesis, a defect production does not seem to be the underlying mechanism in human immunoglobulin deficiency.

Adult↗
PubMed1990

Early antibody responses in human schistosomiasis.

Early diagnosis is important when handling patients with acute schistosomiasis. This state is usually more severe in travellers and tourists than in the immune, resident patients. With increased travelling to areas endemic for schistosomiasis, a tool is needed to solve the problem of differential diagnosis due to the non-specific symptoms of the early stages of the disease. Early appearance of antibodies against excretory/secretory antigens of the intestinal tract in the adult worm was seen in six individuals recently infected with Schistosoma mansoni, using an indirect immunofluorescence technique. The antibodies were of IgM, IgG and IgA classes, and of the IgG1, IgG3 and IgA1 subclasses as detected by ELISA using an antigen preparation of adult worm. On immunoblots, using a freeze-dried adult worm antigen, IgG1 and IgG3 antibodies recognized antigens of 32-35 kD. Antibodies against these antigens could thus be a marker of early infection in previously non exposed visitors to endemic areas.

Adult↗
PubMed1990

RFLP of human immunoglobulin genes.

Human immunoglobulin chains are encoded by variable, diversity, joining and constant gene segments localized on chromosomes 2, 22 (light chains) and 14 (heavy chains). An extensive genetic polymorphism exists as revealed by restriction fragment length polymorphism of the different genes. These new markers allow a more precise delineation of the evolution of the immune system and of genes linked to disease susceptibility.

Genes, Immunoglobulin↗
PubMed1989

Molecular and serologic analysis of IgG1 deficiency caused by new forms of the constant region of the Ig H chain gene deletions.

Selective IgG1 deficiency is a rare disease. We report a familial form of IgG1 deficiency, in which IgG1 was undetectable in a 5-yr-old girl with a history of asthma and respiratory tract infections. Her father had an IgG1 level that was one-third of the mean amount found in normal healthy controls. The defect in the proband was caused by a homozygous deletion of the structural gene for C gamma 1. A Southern blot analysis demonstrated that the maternal haplotype contained a deletion encompassing C gamma 1, C psi epsilon 1, C alpha 1, C psi gamma, and C gamma 2, whereas the deletion on the paternal haplotype was confined to the C gamma 1 gene. Neither of these deletions has previously been reported. IgG1 normally constitutes the dominant isotype for antibodies directed against protein Ag, including viral proteins. We have analyzed the immune response to a number of different protein and polysaccharide Ag in the patient and her parents. In the proband, antiviral antibodies were restricted to the IgG3 and IgG4 subclasses. However, the total amount of IgG directed against several viruses was below the concentration found in normal seropositive individuals. The father and the paternal grandfather, both with low serum IgG1 levels, also had asthma, thus indicating a possible causal relationship.

Adult↗
PubMed1989

Interleukin 4 induces synthesis of IgE and IgG4 in human B cells.

Interleukin (IL)4 has been shown to regulate the IgG subclasses and induce IgE production in splenic mouse B cells. Here we show that IL4 and phorbol 12-myristate 13-acetate (PMA) induce, on a per cell basis, very high IgE secretion in purified human B cells by using a mouse thymoma (EL4) co-culture method. In addition, a marked increase in the number of IgG4-producing cells was also observed. Furthermore, IL2 could synergize with IL4 and PMA in the production of IgE. By using limiting dilution analysis, a considerable increase in the precursor frequency for IgE was found when IL4 and PMA were added to cultures as compared to cultures with PMA only. This indicates that IL4 induces an isotype switch in human B cells.

Antibody Formation↗
PubMed1989

Immunoglobulin levels in saliva in individuals with selective IgA deficiency: compensatory IgM secretion and its correlation with HLA and susceptibility to infections.

Total levels of IgA, IgM, and IgG were measured in unstimulated whole saliva and serum from 63 individuals with selective IgA deficiency. Values were compared with the incidence of upper respiratory tract infections, antibiotic treatments (necessitated by upper respiratory tract infection), and HLA antigens. A statistically significant increase in salivary IgM and IgG levels was noted in individuals with selective IgA deficiency compared to healthy normal individuals. Healthy individuals with selective IgA deficiency did not have increased concentrations of salivary IgM compared to infectious-prone patients. Nor was there any correlation found between proneness to infections and HLA antigens or between salivary IgM or IgG levels and HLA antigens in this patient material.

Disease Susceptibility↗
PubMed1989

Recombinant protein A of non-staphylococcal origin is not mitogenic for human peripheral lymphocytes. Mitogenicity of natural protein A is caused by a contaminant.

Recombinant protein A(SpA) produced in Escherichia coli or Bacillus subtilis bacteria did not induce activation of human peripheral mononuclear cells, whereas SpA preparations obtained from naturally occurring Staphylococcus aureus bacteria as well as recombinant SpA from Staphylococcus xylosus were potent mitogens. Further purification of SpA from S. aureus showed that the mitogenic material was concentrated in the side fractions containing more basic molecules. Some staphylococcal enterotoxins are mitogenic for human cells and in order to test whether contaminating enterotoxins would be responsible for the mitogenic effect of SpA preparations, rabbit antibodies were produced against enterotoxin A and B. These antibodies inhibited activation of human cells induced by the enterotoxins used for immunization but did not affect the activation induced by SpA preparation. The addition of selected human sera to in vitro cultures resulted in an inhibition of the response induced by low doses of SpA. There was no clear relationship between these effects and the content of IgG antibodies against staphylococcal enterotoxins A, B, and Cl in the sera. Thus, we conclude that the mitogenicity of SpA preparations is caused by contaminating molecules, probably not enterotoxins A, B, or Cl.

Blood Physiological Phenomena↗
PubMed1989

Type-specific anti-pneumococcal antibody subclass response to vaccination after splenectomy with special reference to lymphoma patients.

The IgG and IgA antibody subclass responses to pneumococcal polysaccharide antigens type 6A and 19F were studied after immunization with a 14-valent vaccine (Pneumovax, MSD), in 53 splenectomized patients (11 Hodgkin's disease, 13 nonHodgkin's lymphoma (NHL), 9 immune haemolytic anaemia or idiopathic thrombocytopenia purpura and 20 posttraumatic splenectomized patients) and 18 non-splenectomized controls. The antibodies were mainly restricted to the IgG2 and IgA2 subclasses. NHL patients had lower pre-vaccination values to the studied antigens and lower antibody response to vaccination than the other patient groups in which the antibody responses did not differ from those of controls. 1 vaccinated NHL patient experienced two episodes of pneumococcal septicaemia, both occurring after chemotherapy which abolished the previously normal IgG2 antibody levels to the pneumococcal antigens. It is concluded that the antibody response to 6A and 19F antigens after pneumococcal vaccination is not reduced in splenectomized patients but is impaired in immunodeficiency states associated with B-cell lymphoma and treatment with cytostatic drugs.

Adolescent↗
PubMed1989

Autoantibody formation after bone marrow transplantation. Comparison between acetylcholine receptor antibodies and other autoantibodies and analysis of HLA and Gm markers.

Clinical myasthenia gravis has been reported in an increased frequency after bone marrow grafting. The number of bone marrow transplanted patients making IgG autoantibodies directed against the autoantigens cardiolipin, SS-B (La) and thyroglobulin was found to be significantly lower as compared to the autoantigen acetylcholine receptor protein. The occurrence of antibodies to single-stranded DNA was found in a lower frequency than acetylcholine receptor antibodies but the difference was not statistically significant. Antibodies to cardiolipin were frequently observed prior to grafting. The G1m1,2 and G3m5 phenotype frequency did not differ in individuals who developed receptor antibodies from that found in the normal population. Analysis of HLA antigens in this patient group revealed no association to HLA B8/DR3 or B35/DR1. This may indicate that the etiology of myasthenia gravis induced by bone marrow grafting differs as compared with the spontaneous form of myasthenia gravis and the penicillamine-induced disease.

Antibody Formation↗
PubMed1989

Restriction fragment length polymorphism analysis of T-cell receptor genes in inflammatory bowel disease.

The etiology of inflammatory bowel disease is still unknown, but autoimmune phenomena are thought to play an important role. However, only a weak association between HLA or immunoglobulin allotypes and inflammatory bowel diseases has been noted. Recently, DNA markers (restriction fragment length polymorphism (RFLP) pattern) of T-cell receptor gene allotypes have been reported and shown to be linked to susceptibility to autoimmune disease. We investigated the T-cell receptor RFLP pattern in inflammatory bowel diseases. No linkage to the constant region alpha- and beta-chain markers was observed, and no differences in the frequencies of 'genoallotypes' was found between patients and normal blood donors.

Colitis, Ulcerative↗
PubMed1989

No influence of conversions affecting allotype expression on the IgG subclass restriction of specific antibodies.

Antibodies against any given antigen are usually restricted to a particular class or subclass, a finding which has been suggested to be due to a preferential association between particular VH and CH genes. The DNA sequences regulating this process are as yet entirely unknown. It is likely however that some of these regulatory sequences are located within or in the immediate vicinity of the immunoglobulin genes themselves. We therefore analyzed the IgG subclass pattern of specific antibodies in sera from individuals displaying mutations, duplications, deletions or gene conversions event (replacing parts of the constant region genes of one subclass with that of another) affecting the allotype expression of immunoglobulin heavy chain constant region genes. Marked influences on antibody levels were noted in sera from individuals displaying duplication or deletions of constant region genes. However, in no case of gene conversion or mutation was there any measurable influence on the antibody pattern, clearly suggesting a lack of VH gene regulation by sequences within and possibly also immediately downstream of the constant region genes.

Antibody Specificity↗
PubMed1989

Clonal immunoglobulin gene rearrangements in primary mediastinal clear cell lymphomas.

Cells from two patients with primary mediastinal tumors of clear cell type were characterized by immunological and molecular biological techniques. In both cases a B cell immunophenotype was suggested by the positive staining for the B1 (CD20), B4 (CD19), Leu 14 (CD22), as well as staining with other B monoclonal antibodies by immunohistochemistry. However, no definitive evidence for the expression of Ig light or heavy chains at the protein level was found. Southern blot analysis of Ig heavy and light chain gene rearrangements revealed clonal B cell populations in both cases. There was no indication of a somatic joining of T cell receptor (TCR) genes using probes for TCR beta and or TCR gamma genes. Thus, our results suggest a clonal B cell origin of clear cell lymphomas in the mediastinum.

Antigens, Differentiation↗
PubMed1988

An enzyme-linked immunosorbent assay for the determination of the IgA subclass distribution of antigen-specific antibodies.

An ELISA for the determination of the IgA subclass distribution of antigen-specific antibodies was developed using commercially available monoclonal anti-IgA1 anti-IgA2 subclass antibodies. Furthermore an anti-A2m allotype-specific antibody was included in the study. The specificity and sensitivity of the monoclonal anti-immunoglobulin antibodies used was analyzed using sera from normal and IgA class- or subclass-deficient individuals (with or without homozygous C alpha 1 subclass gene deletions). Human IgA1 and IgA2 hybridoma antibodies were also used. In this particular assay, only two out of four tested anti-IgA1 and two out of three tested anti-IgA2 antibodies proved to be specific for their corresponding IgA subclass. The anti-A2m(2) monoclonal antibody was shown to be specific for the corresponding allotype. These ELISA methods may facilitate further work on the regulation of IgA subclass production in man.

Agammaglobulinemia↗
PubMed1988

IgG subclass-associated affinity differences of specific antibodies in humans.

Human IgG subclasses differ in their biologic functions and are restricted as specific antibodies to certain Ag. The basis for this restriction is unknown but in order to characterize it further, we obtained serum preparations containing one single subclass by using subclass-specific mAb in affinity chromatography. Subsequently we determined the affinity of antibodies in the four IgG subclasses for gp30/p25, a hepatitis B surface Ag (HBsAg) complex, for a nine-amino acid cyclical peptide representing residues 139 to 147 of HBsAg, and for a peptide representing residues 126 to 140 of the hepatitis B virus pre-S2 region and the relative avidity of IgG1 and IgG2 antibodies for purified pneumococcal polysaccharide type 3. Affinities to the HBsAg showed a clear pattern of decreasing affinity in the order IgG1 greater than IgG2 greater than IgG3 greater than IgG4 both in sera from vaccinated and from naturally infected individuals. The relative avidities of antibodies to the polysaccharide Ag had a reverse pattern, IgG2 greater than IgG1. In individuals with or without Ig H chain gene deletions where the anti-HBsAg response was restricted to one subclass, the affinity was similar to that observed for the same subclass in sera from individuals who in addition possessed high or low affinity antibodies of other subclasses.

Adult↗