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Biomedical subjects

M W Russell

Publications and source records attributed to M W Russell.

At least 109 records · Page 6Linked to original sources
PubMed1989

Complement-fixing properties of human IgA antibodies. Alternative pathway complement activation by plastic-bound, but not specific antigen-bound, IgA.

The complement-fixing properties of human IgA antibodies bound to specific antigen, or coated directly on plastic surfaces, were examined in comparison with those of IgG antibodies. Use was made of antigen-binding (anti-staphylococcal alpha-toxin) IgA and IgG monoclonal antibodies and normal polyclonal IgA and IgG, purified greater than 99.9% by avoidance of denaturing processes. Complement-fixation ELISA was used, with a high density of biotin-conjugated staphylococcal alpha-toxin bound to avidin-coated plates for the efficient capture of antibodies, and conditions were adjusted for the assessment of classical and alternative pathways of complement activation. Although IgA coated directly on plastic surfaces activated the alternative complement pathway in a dose-dependent manner, IgA antibodies bound to antigen failed to fix complement by either classical or alternative pathways. In contrast, IgG antibodies, either bound to antigen or coated directly on plastic, activated complement mainly by the classical pathway. It was concluded that the complexation of IgA antibodies with antigen is insufficient to elicit complement activation: rather a degree of denaturation seems to play a part in the expression of alternative complement pathway-activating properties by IgA.

Complement Activation↗
PubMed1989

Interaction between surface protein antigens of Streptococcus mutans and human salivary components.

The potential involvement of surface antigens (Ags) I/II and III of Streptococcus mutans in its adherence to salivary pellicle-coated tooth surfaces was investigated. The binding of radiolabelled Ag I/II to hydroxyapatite was increased by pretreating the mineral with human parotid saliva, and binding was maintained in the continuous presence of saliva. Binding of Ag III to hydroxyapatite was inhibited by pretreatment with, or in the presence of, saliva. Various aminohexoses, and also tris, inhibited the binding of Ag I/II. When Ags I/II and III were tested for their ability to bind to salivary components separated by SDS gel electrophoresis, several proteins capable of binding Ag I/II were identified, notably 2 proteins of apparent relative molecular mass 28,000 and 38,000. Analysis of these proteins, isolated by micro-preparative electrophoresis, indicated high proportions of proline, glycine, and glutamic acid, and overall compositions similar to basic proline-rich salivary proteins.

Antigens, Bacterial↗
PubMed1989

Influence of blood storage time and plasma histamine levels on the pattern of transfusion reactions.

The data from 359 transfusion reactions reported over a 3-year period have been compared with those obtained from 359 matched units given at the same time as the former but not implicated in a reaction. It was found that patients who developed reactions which were not accompanied by a change in body temperature received units with a longer storage time than patients experiencing febrile reactions. In addition it was noted that reactions which included a skin rash also tended to be associated with units stored for longer. In a further prospective assessment plasma histamine levels were measured in a group of 71 patients experiencing 'anaphylactoid', febrile and mixed transfusion reactions as well as in individuals in whom blood transfusions did not cause a reaction. The 'anaphylactoid' reaction group demonstrated a mean plasma histamine level in excess of 1 ng/ml, whereas mean concentrations below 0.50 ng/ml were recorded in the other 3 groups. Our data also suggested that in general, more and 'older' blood was given to the 'anaphylactoid' reactors. The high plasma histamine concentrations could readily contribute to the rash, wheeze and flushing recorded in these individuals. Thus, if a long shelf-life for stored blood is required, strategies which remove histamine from the unit may be worth considering.

Blood Preservation↗
PubMed1989

Oral administration of a streptococcal antigen coupled to cholera toxin B subunit evokes strong antibody responses in salivary glands and extramucosal tissues.

Generation of local and systemic immune responses by the oral administration of antigens is frequently inefficient, requiring large quantities of immunogens and yielding only modest antibody responses. In this study, we have demonstrated that oral administration of microgram amounts of Streptococcus mutans protein antigen I/II covalently coupled to the B subunit of cholera toxin elicits vigorous mucosal as well as extramucosal immunoglobulin A and G antistreptococcal antibody responses in mice. These responses were manifested by the presence of large numbers of antibody-secreting cells in salivary glands, mesenteric lymph nodes, and spleens and by the development of high levels of circulating antibodies. This novel immunization strategy may find broad application in the construction of oral vaccines for the control of infectious diseases caused by pathogens encountered at mucosal and extramucosal sites.

Administration, Oral↗
PubMed1988

Role of hepatocytes in the uptake of IgA and IgA-containing immune complexes in mice.

The role of parenchymal and nonparenchymal mouse liver cells in the uptake of polymeric IgA (pIgA) and pIgA-containing immune complexes (IC) of low mol. wt (less than 1 x 10(6)) was studied. As detected by immunofluorescence and immunoelectron microscopy, pIgA were bound on the surface of isolated hepatocytes. Following the injection of radiolabeled pIgA or pIgA-IC into mice, the total radioactivity recovered from isolated liver cells was preferentially associated with parenchymal cells. The ability to inhibit the transport of pIgA and pIgA-IC by pIgA of an irrelevant specificity suggests that pIgA-IC and pIgA are bound and transported by the same mechanism. These results indicate that mouse hepatocytes are involved in the uptake and hepatobiliary transport of pIgA and pIgA-IC of low mol. wt.

Animals↗
PubMed1987

Striking elevation of serum IgA, IgA-containing immune complexes, and IgA rheumatoid factor in clinically silent dermatitis herpetiformis.

We describe a patient with dermatitis herpetiformis with immunoglobulin A (IgA)-containing circulating immune complexes and IgA rheumatoid factor who presented with acute renal insufficiency; a renal biopsy specimen showed IgA nephropathy. The renal function and proteinuria spontaneously returned to normal despite markedly elevated levels of IgA-containing circulating immune complexes, IgA rheumatoid factor, and IgA antibodies to some environmental antigens. IgA1 was the predominant subclass. IgA2-containing immune complexes and IgM rheumatoid factor were not detected. Cultures of peripheral blood mononuclear cells produced increased quantities of IgA and IgA rheumatoid factor spontaneously and after pokeweed mitogen stimulation. These data indicate that renal function can improve and remain normal despite the presence of increased levels of IgA-containing circulating immune complexes and IgA rheumatoid factor.

Acute Kidney Injury↗
PubMed1987

IgA antibody-producing cells in peripheral blood after antigen ingestion: evidence for a common mucosal immune system in humans.

The finding that ingestion of antigens results in the selection induction of IgA antibodies in external secretions suggests that antigen sensitizes Peyer's patch lymphoid cells, which migrate to mucosal sites and generate local secretory IgA (S-IgA) antibody responses. Evidence for a common mucosal immune system in humans has been scanty because of the difficulty in demonstrating migratory behavior of Peyer's patch cells. In the present study, peripheral blood mononuclear cells (PBMC) from human volunteers who had ingested capsules containing killed Streptococcus mutans were assayed for spontaneous antibody-producing cells. Four of five volunteers exhibited circulating IgA-producing cells within 7 days and reached maximum responses by days 10-12. One IgA-deficient subject exhibited IgM responses with identical kinetics. Pokeweed-mitogen-stimulated PBMC produced anti-S. mutans antibodies predominantly of the IgA isotype. Significant S-IgA anti-S. mutans antibodies were detected in saliva and tears by day 14, and the antibodies reached maximum titers by 3 weeks. No changes in serum anti-S. mutans antibodies were noted. The IgA-deficient subject produced salivary secretory IgM antibodies. These results suggest that, after antigen ingestion, peripheral blood contains antigen-specific precursors of IgA plasma cells and that their presence precedes the appearance of S-IgA antibodies in external secretions. Therefore, these experiments provide further support for the existence of a common mucosal immune system in humans.

Adult↗
PubMed1987

Analysis of heart-reactive antibodies induced in rabbits by immunization with Streptococcus mutans.

The induction of antibodies that react with human heart muscle in rabbits immunized with Streptococcus mutans and related organisms has been investigated in order to re-examine the reported antigenic cross-reactivity between the major cell wall protein antigen I/II of S. mutans and heart tissue. Serum from 2 of 8 rabbits hyperimmunized with whole cells of S. mutans, S. sobrinus, S. rattus, or S. mitis, assayed by immunofluorescence and radioimmunoassay, revealed antibodies reactive with sarcolemma that could be attributed to immunization. Antisera raised against several crude and purified antigens of S. mutans did not reveal heart-reactive antibodies, that could be attributed to antigenic similarity between heart and these antigens. An assay designed to detect antibodies that could simultaneously bind to both heart and antigen I/II of S. mutans failed to reveal cross-reactivity due to this antigen, although antibodies separately expressing these binding activities were demonstrable. IgM rheumatoid factor was elevated in several antisera to S. mutans, and could have contributed to some previous observations ascribed to antigenic cross-reactivity between S. mutans and human heart muscle.

Animals↗
PubMed1987

Accident- and injury-related health-care utilization among benzodiazepine users and nonusers.

Benzodiazepine tranquilizers have been found to cause psychomotor and cognitive impairment, and there is evidence of an increased rate of automobile accidents among users of these drugs. To determine whether benzodiazepine users are more likely than nonusers to experience accidental injury requiring medical attention, we examined health-care utilization among 7,271 such users and an age- and sex-matched sample of 65,439 nonusers, all of whom were enrolled in an "HMO-like" health insurance plan. Benzodiazepine users and nonusers were identified through a review of 4 months' prescription drug claims. Six months' health-care claims for each user and nonuser subsequent to the first observed claim for a benzodiazepine or nonbenzodiazepine agent, respectively, were compiled. Claims related to accidents were identified on the basis of physician-recorded diagnoses. Our results indicate that benzodiazepine users were significantly (p less than .01) more likely than nonusers to experience (1) at least one accident-related episode of care; (2) a greater number of accident-related hospital admissions; and (3) a greater number of accident-related inpatient days. Accident-related utilization was also significantly higher when users had recently filled a prescription for a benzodiazepine agent. Benzodiazepine users, however, also utilized significantly more non-accident-related health-care services than nonusers. The nature of the association between benzodiazepine use and a higher accident-related utilization is thus unclear. A pretest-posttest study is now being undertaken to ascertain the significance of these findings.

Accidents↗
PubMed1987

Epsilon-aminocaproic acid for treatment of fibrinolysis during liver transplantation.

In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; aPTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F less than 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with epsilon-aminocaproic acid (0.09%) and an untreated sample. Blood treated with epsilon-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of epsilon-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, epsilon-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with epsilon-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 +/- 29.5% to 94.8 +/- 7.4% (mean +/- SD, P less than 0.001). None of the treated patients had hemorrhagic or thrombotic complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Induction and molecular properties of secretory and serum IgA antibodies specific for environmental antigens.

A generalized secretory IgA response can be induced by ingestion of various antigens due to dissemination of sensitized precursors of IgA plasma cells from gut-associated lymphoid tissue to various secretory glands. Oral ingestion of a bacterial antigen by volunteers led to the parallel appearance of secretory IgA antibodies in several external secretions that was preceded by a transitory detection of IgA antibody-secreting cells in the peripheral blood. Naturally occurring secretory and serum IgA antibodies as well as secretory and serum antibodies induced by mucosal immunization belong predominantly to the IgA1 subclass; however, in external secretions IgA2 is the predominant subclass of natural antibodies to endotoxin and lipoteichoic acid. Although in external secretions specific IgA antibodies are of polymeric form, serum IgA antibodies to different antigens display considerable variability with respect to their distribution in polymeric and monomeric forms. However, after experimental infection, serum IgA antibodies to the influenza virus hemagglutinin are almost exclusively polymeric.

Administration, Oral↗
PubMed1986

Assay of human IgA subclass antibodies in serum and secretions by means of monoclonal antibodies.

Solid-phase radioimmunoassays have been developed for the detection and quantification of human serum and secretory IgA antibodies to a variety of food, bacterial and viral antigens. Monoclonal antibodies specific for IgA1 and IgA2 and capable of binding to serum and secretory IgA were used. The assays were calibrated by reference to standard serum or purified myeloma proteins bound to solid-phase anti-immunoglobulin reagents, and sigmoid calibration curves were constructed by means of computer programs using 4-parameter logistic or weighted logit-log principles. Polymeric and monomeric forms of IgA antibodies were assayed in fractions separated by high performance size exclusion chromatography. These techniques have demonstrated the expected predominance of IgA1 antibodies in serum, and these included polymeric forms. Saliva contained both IgA1 and IgA2 antibodies, and increased proportions of IgA2 antibodies to lipopolysaccharides and lipoteichoic acid were observed.

Antibodies, Anti-Idiotypic↗
PubMed1986

IgA-associated renal diseases: antibodies to environmental antigens in sera and deposition of immunoglobulins and antigens in glomeruli.

Levels of IgA1, IgA2, IgM, and IgG antibodies specific for 10 ubiquitous food and bacterial antigens were examined by radioimmunoassay in the sera of 29 patients with IgA-associated renal diseases and 22 normal individuals. No significant differences were observed between patient and normal groups in the levels of IgA1 antibodies, and IgA2 antibodies were detected in only a few individuals in either group. Minor differences in IgM or IgG antibodies were seen against some antigens. Significant positive correlations between IgA1 and IgG and between IgA1 and IgM antibodies to casein were found in the patient group. Analysis of the molecular form of serum IgA1 antibodies revealed that although the pattern of polymeric and monomeric forms varied between individuals and between antibody specificities, there was no preponderance of one form in either patient or normal groups. Examination of kidney biopsies from 50 patients with IgA-associated renal diseases revealed that IgA1 represented the predominant subclass deposited in the glomerular mesangium; glomeruli from three patients contained both IgA1 and IgA2. Seventy-eight percent of the patients also had deposits of IgM, although IgA and IgM deposits did not always coincide. When IgG was present in glomeruli (45% of patients), the IgG1 subclass predominated. J chain was detectable in glomeruli of only four patients. C3 was detected in glomeruli of 95% of the patients, although the distribution of C3 did not always coincide with that of IgA. Indirect immunofluorescence staining with rabbit antisera to various environmental antigens showed that milk protein antigens could be deposited in association with IgA in the glomerular mesangium.

Adolescent↗
PubMed1986

The human IgA system: a reassessment.

In healthy adults the total daily production of secretory and serum IgA exceeds that of other immunoglobulin classes. Secretory and serum IgA display features of mutual independence: they are represented by molecules with different physiochemical and immunochemical properties and antibody activities and are produced by cells with different organ distributions. Secretory and serum IgA also exhibit different effector functions: interaction of secretory IgA with environmental antigens results in prevention of the penetration of such antigens by a variety of mechanisms. Although the function of polymeric serum IgA antibodies in certain animal species involves elimination of antigenic substances by noninflammatory means, the primary function of serum IgA remains unknown. It is proposed that in humans monomeric serum IgA (which prevents activation of the complement systems, inhibits phagocytosis and antibody-dependent cellular cytotoxicity) may protect endogenous antigens expressed on various cells and tissues by preventing their interaction with humoral and cellular immune mechanisms that may lead to tissue damage.

Antibody Specificity↗