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B J Underdown

Publications and source records attributed to B J Underdown.

At least 55 records · Page 3Linked to original sources
PubMed1983

Estimation of polymeric IgA in human serum: an assay based on binding of radiolabeled human secretory component with applications in the study of IgA nephropathy, IgA monoclonal gammopathy, and liver disease.

Binding of 125I-human secretory component (SC) to human polymeric immunoglobulin A (pIgA) was employed to measure quantitatively the pIgA present in human sera. Interference by IgM in some sera was prevented by removal of IgM with glutaraldehyde polymerized anti-IgM antibodies. 125I-SC complexed to pIgA was measured by precipitation with anti-IgA antibodies and the quantity of pIgA in human serum was estimated by comparing the quantity of 125I-SC bound by several dilutions of human serum to that bound by standard quantities of human monoclonal pIgA proteins. The assay was specific for pIgA because heat-aggregated monomeric IgA or hypogammaglobulinemic serum did not bind 125I-SC greater than a precipitate formed with human monoclonal IgG and anti-IgG. Moreover, analysis of a series of IgA myeloma sera indicated no correlation between the IgA content of the serum and the quantity of pIgA measured. The quantity of pIgA found in 30 normal human sera was 0.13 +/- 0.08 mg/ml (1S.D.), which consisted of 11.3 +/- 5.3% (1 SD) of the total IgA. Patients with IgA monoclonal gammopathy were most often found to have predominantly monomeric IgA. Patients with IgA nephropathy also showed an elevation of pIgA, but this appeared to be a consequence of an overt IgA elevation. IgA nephropathy patients with elevated serum IgA in fact showed a significant elevation of monomeric IgA. Selective elevation of pIgA was observed in patients with primary biliary cirrhosis and alcoholic liver disease. A comparison of this assay with other assays to measure pIgA is discussed.

Aged↗
PubMed1983

Steroid hormone regulation of free secretory component in the rat uterus.

The present studies analysed the uterine free secretory component (SC) response to steroid hormones, and correlated effects on SC with those on IgA. Administration of oestradiol for 3 days to ovariectomized rats significantly increased the levels of SC in uterine secretions, when compared to those in saline-injected controls. This response was dose-dependent and specific for oestrogens, since progesterone, testosterone and glucocorticoids had no effect. The oestradiol-induced elevation in SC levels occurred in parallel with that of IgA. Time course studies of SC and IgA in uterine secretions indicated that both proteins accumulated in nearly identical patterns following oestradiol administration. The oestradiol-stimulated accumulation of SC, however, appears to be independent of IgA since dexamethasone treatment with oestradiol decreased IgA but not SC levels in uterine secretions. In contrast to dexamethasone, progesterone antagonized the oestradiol effect on both uterine IgA and SC. The uterine SC response to oestradiol was also observed in vitro. Incubation of uterine tissue following oestradiol exposure in vivo resulted in a significant accumulation of SC in the culture medium, when compared to levels from control uteri. Addition of either cycloheximide or colchicine to uterine incubation media significantly decreased the effect of oestradiol on SC accumulation. These results suggest that oestrogen regulation of uterine SC may involve stimulation of its synthesis. In addition, our findings indicate that oestradiol control of SC in uterine secretions may be responsible for the movement of IgA from uterine tissues to lumen.

Animals↗
PubMed1981

Secretory component-dependent hepatic transport of IgA antibody-antigen complexes.

The ability of the liver to transport antigen-antibody complexes containing polymeric IgA was tested in a model system using the isolated perfused rat liver and soluble complexes formed between trinitrophenylated (TNP) antigens and MOPC 315, a polymeric mouse IgA protein with anti-TNP activity. A double-label strategy (125I and 131I) was used to separately follow antigen and antibody during isolation and transport by the isolated perfused liver. Complexes formed in antigen excess and isolated by gel filtration were added to the perfusate. The quantity of antigen or antibody transported was determined by counting the radioactivity in collected bile fractions. TNP-human albumin (TNP-HSA) complexed to polymeric IgA antibody was transported from blood to bile while the same antigen complexed to IgG antibody was not. The transport of IgA-(TNP-HSA) complexes was inhibited by preincubation with human secretory component (SC), which indicated that transport of such complexes proceeds though an SC-dependent mechanism previously described for uncomplexed polymeric IgA antibody. Complexes (m.w. congruent to 970,000) of trinitrophenylated bovine thyroglobulin (TNP-TG) and polymeric IgA were transported less well than IgA-(TNP-HSA) complexes (m.w. less than or equal to 460,000), even though both types of complexes bound SC. The possibility that the poor transport of IgA-(TNP-TG) complexes reflected a size restriction on hepatic transport from blood to bile is discussed.

Animals↗
PubMed1981

Giardiasis in mice: studies on the characteristics of chronic infection in C3h/He mice.

When C3H/He mice are dosed orally with fecal cysts or trophozoites of the intestinal parasite, Giardia muris, they become chronically infected, whereas BALB/c (or DBA/2) mice rapidly eliminate their infection. The ability to eliminate a primary infection or resist a challenge infection was not related to levels of serum IgA antibody directed against a crude extract of trophozoites. The possibility that the development of host-protective immunity may either be delayed or absent in C3H/He mice was investigated by 2 types of experiment: 1) BALB/c and C3H/He mice were drug-cured at various times after a primary infection and assessed for their ability to resist reinfection, and 2) the ability of infected female mice to protect their suckling young was assessed. Under these experimental conditions, no significant difference in the kinetics of development of resistance to a challenge infection was noted. Thus, mice of both strains were capable of resisting a challenge infection after drug-cured and infected mothers were able to protect their suckling young from a challenge infection. Drug-cured long-term infected mice were resistant to a challenge of either cysts or trophozoites obtained from either 1-wk infected nude mice or long-term infected C2H/He mice. Thus, it is unlikely that the explanation for chronic infection oif C3H/He mice is that variants or a modified population of G. muris trophozoites arise to which C3H/He mice have a defective response. The possibility that G. muris is able to suppress host-protective responses in chronically-infected C3H/He mice but not in BALB/c mice is discussed.

Animals↗
PubMed1980

Evidence for a vesicular transport mechanism in hepatocytes for biliary secretion of immunoglobulin A.

Quantitative electron microscopic autoradiography and diaminobenzidine cytochemistry provide evidence for an uptake and vesicular transport mechanism for iodine-125-labeled immunoglobulin A from plasma to bile by hepatocytes in vivo. The data confirm the existence of a hepatobiliary pathway for secretion of immunoglobulin A into the intestine and are consistent with a vesicular transport mechanism for biliary proteins within liver parenchymal cells.

Animals↗
PubMed1980

Short and long latency skin sensitizing antibody in passive cutaneous anaphylaxis in the monkey.

In some allergic sera, 2-hr PCA responses can be due to IgE class antibody. In other sera where 2-hr PCA responses are not seen, removal of the IgG fracton allows expression of this 2-hr latency PCA response, suggesting an initial competition for binding sites between IgG and IgE, or that IgG can act as a blocking antibody, preventing antigen from reaching the cell-bound IgE.

Absorption↗
PubMed1979

Identification of secretory component as an IgA receptor on rat hepatocytes.

Secretory component (SC) was found to be synthesized by isolated rat hepatocytes. SC was detected by radioimmunoassay and cultured hepatocytes were found to synthesize 0.078 microgram SC/10(6) hepatocytes in a 48-h period. SC was also present on the surface of hepatocytes as detected by the specific binding of radiolabeled anti-SC antibodies as well as by the detection of specific membrane staining in indirect immunofluorescence tests using specifically purified anti-SC antibodies. Rat SC was detected on hepatocytes and intestinal epithelial cells but not on peripheral blood lymphocytes, unfractionated spleen cells, or erythrocytes. Specific binding of radiolabeled rat dimeric IgA to rat hepatocytes was also observed and evidence was obtained to indicate that such binding was mediated by SC. Thus, prior incubation of hepatocytes with anti-SC prevented binding of radiolabeled IgA. Moreover, prior incubation of radiolabeled IgA with rat SC prevented binding of the IgA to isolated hepatocytes. Cells treated with 0.25% trypsin lost their ability to bind to radiolabeled dimeric IgA.

Animals↗
PubMed1979

Biliary transport of IgA: role of secretory component.

Biliary transport of rat immunoglobulin was studied by perfusion of isolated rat liver with blood containing radiolabeled immunoglobulin. Transport to bile was selective for polymeric IgA. Between 15 and 27% of polymeric IgA was transported from blood to bile during a 210-min perfusion period, and approximately 60% of the IgA transported to bile bore secretory component. Small quantities of IgM (0.12%) were transported; transport of IgG2 alpha, IgE, or monomeric IgA was not detected. Purification of radiolabeled polymeric IgA by affinity chromatography on human secretory component-Sepharose yielded a fraction that was transported more efficiently (i.e., up to 40% transported). In contrast, secretory IgA (colostral or biliary) was transported 1/25th to 1/12th as well as polymeric IgA myeloma protein. Complexes of 125I-labeled secretory component and polymeric IgA formed in vitro were transported poorly (0.1%) compared to polymeric IgA (26%). It was concluded that biliary transport of polymeric IgA requires combination of it with secretory component in the liver. In support of this hypothesis, rabbit IgG anti-rat secretory component antibodies were also transported to bile but normal rabbit IgG was not.

Animals↗
PubMed1979

Immunological parameters in perennial rhinitis.

As part of a study of the effectiveness of beclomethasone dipropionate in perennial rhinitis five immunologically related parameters were measured. These included skin tests, total IgE, specific IgE, nasal and peripheral blood eosinophil counts. In addition, nasal biopsies were obtained in twenty out of sixty patients. It was apparent that patients with perennial rhinitis formed a heterogeneous group who could be divided into three groups based on the extent of immunological abnormality detected. Group 1 consisted of twenty patients who displayed no abnormality in any of the five parameters studied. Group 2 consisted of twenty-six patients in whom specific IgE was not detected but who had varying degrees of abnormal findings in the other laboratory parameters. The remaining fourteen patients formed a third group in whom specific IgE was detected in addition to abnormalities in other parameters. In general, patients with detectable specific IgE had a higher frequency of abnormal parameters, including abnormal histology of their nasal biopsy, than patients in whom no specific IgE was detected. The heterogeneous nature of perennial rhinitis is discussed. Despite the heterogeneous nature of the total patient group, the majority of patients (80%) treated with beclomethasone dipropionate improved compared to 20% improved in the placebo group. There was no difference in the drug effect between the three groups of patients.

Adolescent↗
PubMed1978

A comparison of secretory component - immunoglobulin interactions amongst different species.

1) SC from many species may be isolated by affinity chromatography to human IgA-Sepharose. 2) In some species SC may exist in two molecular forms. 3) The SC-binding sites on polymeric IgA and IgM are not identical. 4) In some species SC binds to IgM with higher affinity than to polymeric IgA while in other species SC binds best to polymeric IgA. This difference may influence the relative concentrations of these two immunoglobulin classes in the secretions of different species. 5) The SC-binding site is present on high molecular weight immunoglobulin in species as primitive as the nurse shark.

Animals↗
PubMed1977

Disulfide bonding of secretory component to a single monomer subunit in human secretory IgA.

The arrangement of disulfide bonds joining secretory component (SC) to the alpha chains in secretory IgA was studied by determining the molecular size of the principal fragments resulting from CNBr digestion of secretory dimeric Fc fragments from IgA (Fc)2alpha fragments). In vitro complexes formed by incubating 125I-free SC and myeloma 131I-(Fc)2alpha fragments were isolated by gel filtration and subsequently digested with cyanogen bromide. The CNBr digests of SC-(Fc)2alpha fragments were analyzed by gel filtration in 5 M guanidine. Two principal fragments were obtained, one containing a monomeric Fc fragment from IgA (Fcalpha) associated with SC (m.w. congruent to 110,000) and a second containing the second Fcalpha monomer (m.w. congruent to 50,000) from the dimeric SC-(Fc)2alpha. Similar results were obtained when secretory (Fc)2alpha fragments isolated from native secretory IgA dimer were subjected to CNBr digestion. The data indicate that SC is disulfide bonded to a single monomer subunit in secretory IgA dimer.

Chemical Phenomena↗
PubMed1976

Glomerulonephritis with mesangial deposits of IgA unassociated with systemic disease.

Typical features of IgA-associated nephritis were found in renal biopsies from 16 of 355 consecutive patients. Generalized segmental mesangial proliferation was noted in biopsies from most patients, and dense deposits were detected by electron microscopy in mesangial regions of approximately 50% of biopsies. Immunofluorescent studies showed IgA to be the predominant immunoglobulin in glomueruli; IgG was present in less than 50% of biopsies and IgM in only 12%. The serum IgA value was significantly increased (P les than 0.001) in 50% of patients and the mean IgA/IgG ratio was significantly increase (P less than 0.001) for the patient group as a whole, which suggests a selective increase in IgA. Mesangial deposits of C3 were present in 15 of 16 biopsies and properdin was noted in all biopsies tested; C4 was not demonstrated in any biopsy. This suggests activation of the alternative complement pathway. The results of this study support the concept that IgA-associated nephritis is a unique condition that in some patients gives rise to idiopathic recurrent hematuria. Although the prognosis is good in the majority of patients, the renal disease may progress.

Adolescent↗
PubMed1976

Disodium cromoglycate in ragweed-allergic rhinitis.

This study was designed to test the effectiveness of disodium cromoglycate when compared to placebo in a double-blind study in patients with ragweed allergic rhinitis. Patients were selected on the basis of a clinical history and a 4+ reaction to the intradermal injection of water-soluble ragweed, 0.02 c.c. of 500 PNU/c.c. Active agent/placebo groups were selected at random and were on the drug for approximately 8 wk, commencing 1 wk prior to the onset of the ragweed pollen season. Patient response was evaluated using patient diary cards, number of antihistamine tablets taken, and patient interviews. In the Toronto study, of 17 patients on the active drug, 15 were graded as improved, compared to only 6 of 21 placebo-treated patients who were improved. However, in the Hamilton study, results were less impressive. Nonetheless, it appears that intranasal insufflation of disodium cromoglycate was more effective in reducing ragweed hay fever symptoms than placebo.

Clinical Trials as Topic↗