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Biomedical subjects

D B Young

Publications and source records attributed to D B Young.

At least 127 records · Page 7Linked to original sources
PubMed1991

Stimulation of renin release by hyperkalemia in the nonfiltering kidney.

This study was designed to analyze the acute effects of hyperkalemia on renin release in the normal filtering kidney and the nonfiltering kidney. Plasma K was increased by acute intravenous KCl infusion. In the normal filtering kidney experiment plasma K was 5.7 vs. 3.5 meq/l. Hyperkalemia resulted in a 45% increase in renal blood flow (RBF) and a 35% increase in glomerular filtration rate (GFR) at the 120-mmHg pressure level. Renin release was significantly greater in the hyperkalemic group than in the control group (P less than 0.01) with the greatest effect over the lower pressure range. In the nonfiltering kidney experiment plasma K was 6.09 vs. 3.5 meq/l. RBF was 33% greater in the hyperkalemic than in the normokalemic group at the 130-mmHg pressure level. Renin release was also greater in the hyperkalemic group than in the normokalemic group (P less than 0.01). However, unlike the normal filtering kidney experiments, in the nonfiltering kidneys the difference in renin release was most prominent at the highest level of renal perfusion pressure. These experiments demonstrate that acute hyperkalemia can cause renal vasodilation and stimulate renin release in both filtering and nonfiltering kidney preparations and that potassium may affect renin release both through a direct effect on the juxtaglomerular cells and indirectly by affecting delivery of fluid and/or NaCl to the macula densa.

Animals↗
PubMed1990

Agalactosyl IgG, antibodies to heat shock proteins, and acute rheumatic fever.

In rheumatoid arthritis an increased proportion of the N-linked oligosaccharides on serum IgG terminate with N-acetylglucosamine (agalactosyl IgG). It has recently been shown that group A streptococcal cell wall peptidoglycan/polysaccharide complex may be used to raise monoclonal antibodies which bind to this glycoform of IgG. Patients with rheumatoid arthritis also have increased levels of antibody to the 65 kD and 70 kD families of heat shock proteins, particularly to a bacterial (Mycobacterium bovis) homologue of heat shock protein hsp65. Streptococci must contain similar heat shock proteins. Acute rheumatic fever follows infection with group A streptococci, and these organisms might theoretically evoke antibody to heat shock proteins or changes in the levels of agalactosyl IgG, which is antigenically cross reactive with their cell walls. It is shown here that serum samples from patients with acute rheumatic fever do not differ from those from normal children by these criteria.

Acetylglucosamine↗
PubMed1990

Regulation of renin release and renal hemodynamics during acute and chronic verapamil administration.

The effects of short- and long-term administration of the calcium-entry blocker verapamil on regulation of renal hemodynamics and renin release were analyzed in anesthetized dogs at controlled levels of renal perfusion pressure between 110 and 60 mmHg. The following three groups of dogs were studied: a control group, an acutely treated verapamil group (initial dose of 150 micrograms/kg followed by 4 micrograms.kg-1.min-1), and a chronically treated verapamil group (240 mg per os twice each day). At 110 mmHg the renal blood flow (RBF) in the acutely and chronically treated groups was 53% greater than (P less than 0.03) and 79% greater than (P less than 0.01) that of the control group. Glomerular filtration rate (GFR) in the acutely and chronically treated groups was 64 and 92%, respectively, greater than (P less than 0.01 for both) that of the control group. Autoregulation of RBF and GFR was extremely effective in the control group, whereas it was severely impaired by acute and long-term treatment with verapamil. Renin release at 110 mmHg in the control and the acutely treated groups were similar, 3.36 +/- 0.96 and 4.46 +/- 0.64 U.min-1.g-1, respectively, although in the chronically treated group the rate of release was 8.89 +/- 2.60 U.min-1.g-1 (P less than 0.03). As perfusion pressure was reduced, the rate of release from the acutely treated group rose to higher levels than that of the control group; at 70 mmHg release from the acutely treated group was 88% greater than that of the control group (P less than 0.01). Verapamil profoundly alters regulation of renal hemodynamics and renin release and the effect is prominent during both short- and long-term administration.

Animals↗
PubMed1990

The immune response to mycobacterial heat shock proteins.

Several prominent protein antigens involved in antibody and T cell responses to mycobacteria have been identified as members of highly conserved heat shock protein families. The immunogenicity of heat shock proteins in a broad range of infections, along with the extensive sequence identity between corresponding host and pathogen homologues, and the potential for localized accumulation in response to stress stimuli, makes these antigens attractive candidates for theories of autoimmunity based on "molecular mimicry". The 65 kilodalton (kD) heat shock protein of mycobacteria has indeed been shown to modulate the course of autoimmune disease in experimental animals, and immune responses to this and other heat shock proteins have been demonstrated in association with human autoimmune diseases. This paper provides a brief review of the immune response to mycobacterial heat shock proteins during infection and autoimmunity.

Animals↗
PubMed1990

T cell recognition of stress proteins. A link between infectious and autoimmune disease.

Exposure of any living cell to a change in environmental conditions such as increased growth temperature results in the induction of stress, or "heat shock", proteins. Proteins identified in such experiments have subsequently been shown to be ubiquitous components of all cells and to perform essential functions during normal cell growth in addition to their role during stress. It has recently been recognized that members of stress protein families play an important role in the immune response to a wide variety of infections, and the highly conserved nature of such proteins has led to the suggestion that they may also be immune targets in autoreactive responses. In this article we review the role of stress proteins in the immune response to infection and discuss the evidence which suggests that lymphocytes recognizing conserved determinants on such antigens may be associated with autoimmune diseases.

Amino Acid Sequence↗
PubMed1990

Chaperonins and the immune response.

Chaperonins are a major target of the immune response to bacteria. Infection, or immunization, with bacteria induces a strong antibody response to chaperonins, and the same proteins also provide a focus for activation of T lymphocyte subsets--including CD4, CD8 and gamma-delta T cells. The high degree of sequence conservation between prokaryotic and eukaryotic chaperonins makes them candidate antigens for models of autoimmunity based on molecular mimicry, and it is possible that the immune response to chaperonins has both protective and pathogenic potential. The interactions between chaperonins and the immune response are reviewed in this article, primarily from the perspective of intracellular bacterial infection.

Amino Acid Sequence↗
PubMed1989

The mycobacterial GroEL stress protein: a common target of T-cell recognition in infection and autoimmunity.

The 65 kD protein of mycobacteria is an immunodominant antigen for both T and B lymphocytes. Sequence analysis has revealed that this protein belongs to the highly conserved family of stress proteins, related to the GroEL gene product of E. coli, that are present in all cells from bacteria to man. We demonstrate here that human T cells from healthy individuals and disease sites are able to recognize determinants within the 65 kD protein that are either specific for M. tuberculosis or are conserved between GroEL of mycobacterial, E. coli or human origin. The induction of T cells that recognize with cross-reactive sequences of GroEL may provide an explanation for the autoimmune phenomena often associated with infection by microbial pathogens. However, both the magnitude and the biological significance of this component of the T-cell repertoire reactive with self stress proteins will be influenced by local environmental factors as well as the MHC haplotype of the individual.

Amino Acid Sequence↗
PubMed1989

Stress proteins may provide a link between the immune response to infection and autoimmunity.

Stress proteins are frequently the target of humoral and cell-mediated immune responses to infection. These proteins belong to highly conserved gene families and there is substantial sequence homology between antigens produced by pathogenic organisms and the corresponding proteins from mammalian cells. Human T cells from sites of infectious and autoimmune lesions proliferate in response to stress proteins, and mapping of antigenic determinants on a mycobacterial stress protein shows that both species specific and highly conserved, 'self-like', regions of the molecule can take part in immune recognition. It is proposed that the lymphocyte population induced in response to stress proteins of pathogens during infection includes cells capable of autoimmune recognition of the corresponding self protein. Local accumulation of self stress proteins--in response to viral infection, for example--may subsequently provide a stimulus for proliferation of such autoreactive lymphocytes, thereby triggering a cycle of events which may contribute to the pathological damage associated with autoimmune disease.

Amino Acid Sequence↗
PubMed1989

Use of an antigen-capture assay for characterisation of monoclonal antibodies to mycobacterial lipoarabinomannan.

Monoclonal antibodies directed to six separate antigen molecules of Mycobacterium leprae have been tested in an antigen-capture assay based on combined use of polyclonal ("capture") and monoclonal ("detector") antibody reagents. This approach provides a potentially versatile, sensitive and specific assay for detection and relative quantitation of M. leprae antigens. Characterisation of monoclonal antibodies to mycobacterial lipoarabinomannan (LAM-B) by the antigen-capture assay indicates that some of the antigenic determinants present on LAM-B from M. leprae may be either absent altogether or present at much lower concentrations on the corresponding LAM-B structure form M. tuberculosis.

Antibodies, Monoclonal↗
PubMed1989

Biochemical and antigenic characterization of the Mycobacterium tuberculosis 71kD antigen, a member of the 70kD heat-shock protein family.

A 71 kiloDalton antigen from Mycobacterium tuberculosis is recognized by antibodies and by T lymphocytes during infection (Britton et al., 1986a). Partial sequence analysis indicates a relationship between this antigen and the highly conserved family of 70-kiloDalton heat shock proteins (hsp70) (Young et al., 1988). Biochemical and serological characterization of the protein confirms its membership of the hsp70 gene family, and metabolic labelling demonstrates that it is a major component of the mycobacterial response to heat stress. The role of stress proteins as antigens during infection is discussed.

Adenosine Triphosphate↗
PubMed1989

Elevated IgG antibody levels to the mycobacterial 65-kDa heat shock protein are characteristic of patients with rheumatoid arthritis.

We have previously demonstrated raised levels of IgG and IgA antibody to the mycobacterial 65-kDa heat shock protein (hsp) in the sera of patients with rheumatoid arthritis (RA). We have now attempted to determine whether this phenomenon is specific for RA, and whether it is seen only with the mycobacterial homologue of this particular hsp gene family. We therefore screened antibody levels to the mycobacterial and Escherichia coli hsp 65, and the mycobacterial, E. coli, and human hsp70, in sera from RA, systemic lupus erythematosus (SLE), tuberculosis (TB), ankylosing spondylitis (AS), Crohn's disease, and control donors. RA sera show the greatest increase in IgA binding to the mycobacterial hsp65, but no increase in IgA binding to the E. coli homologue. Similarly, only RA and TB sera show increased IgG binding to the mycobacterial hsp65, and we have shown previously that the titre is greater in RA. In contrast, the use of mycobacterial and E. coli hsp70 preparations as control bacterial hsp gene products has shown that RA patients do not differ from TB or SLE patients in their antibody binding to these proteins. Moreover, neither IgA nor IgG antibody to the human hsp70 in RA sera were higher than in TB, and the IgA binding was not higher than in SLE. These findings suggest that elevated IgG antibody levels to the mycobacterial hsp65 shows some disease specificity, and further studies with the human homologue and at the T-cell level are required.

Adult↗
PubMed1989

Raised serum IgG and IgA antibodies to mycobacterial antigens in rheumatoid arthritis.

Autoantigens cross reactive with mycobacteria are implicated in the pathogenesis of adjuvant arthritis in the rat, and there are reports of changes in the immune response to mycobacteria in human rheumatoid arthritis (RA). We have therefore examined the IgM, IgG, and IgA antibody levels to crude mycobacterial antigens and to two recombinant mycobacterial heat shock/stress proteins (65 kD and 71 kD) in sera from patients with RA, systemic lupus erythematosus (SLE), and Crohn's disease, and from healthy controls. IgA binding to the crude mycobacterial antigens was significantly raised in RA sera, though IgG and IgM binding tended to be lower than in controls. Both IgA and IgG binding to the heat shock proteins were significantly raised in the RA sera. Smaller significant rises in both classes were seen in sera from patients with SLE, and in the IgA class only to the 65 kD protein in Crohn's disease. The rises in IgG and IgA antibodies to the 65 kD protein in RA were significantly higher than in the other diseases, however. It is interesting that this protein is the one responsible for adjuvant arthritis in the rat.

Adult↗
PubMed1989

Blood pressure responses to cyclic blood volume changes in awake and anesthetized dogs.

A dynamic analysis of blood pressure regulation was performed in conscious and anesthetized dogs. The mean arterial pressure (MAP) responses to 5 and 10% sinusoidal changes in total blood volume with cycle lengths of 1, 4, and 8 min were measured in anesthetized 1) control dogs, 2) carotid and vagal baroreflex (CVB)-denervated animals, and 3) spinal-ablated dogs; in addition, the MAP responses to 10% sinusoidal blood volume changes with cycle lengths ranging from 0.25 to 8 min were measured in conscious control and CVB-denervated dogs. The presence of the baroreflexes in both the conscious and anesthetized control dogs essentially eliminated MAP excursions during the cyclic volume changes. The MAP changes in both the conscious and anesthetized denervated dogs were large. However, the responses in the anesthetized denervated dogs were linear, stationary, and cycle-length insensitive with respect to the sinusoidal forcing function, whereas the responses in the conscious CVB-denervated dogs were nonlinear, nonstationary, and cycle-length dependent. These results indicate that the cardiovascular system in the anesthetized CVB-denervated and spinal-ablated dogs is passive or "hydraulic" in nature; conversely, factors other than the carotid and vagal baroreflexes appear to exist that alter the arterial pressure responses to cyclic blood volume perturbations in the conscious CVB-denervated dogs.

Anesthesia, General↗
PubMed1988

The use of nitrocellulose immunoblots for the analysis of antigen recognition by T lymphocytes.

Antigen insolubilised on nitrocellulose is able to activate T lymphocytes following presentation by appropriate accessory cells. Furthermore, complex mixtures of antigens can be fractionated by polyacrylamide gel electrophoresis under denaturing conditions (SDS-PAGE), transferred to nitrocellulose membranes and then added to T cell proliferation assays. This allows a direct screening for recognition of individual polypeptides by monoclonal and polyclonal T cell populations, without a requirement for extensive biochemical purification and in the absence of initial serological preselection of antigen. The potential use of this technique for screening of recombinant DNA libraries for expression of antigens recognised by T cells is also illustrated. The technical aspects of T cell recognition of solid-phase antigen and its application to the identification of immunodominant epitopes with the potential to modulate T cell-mediated immunity is reviewed.

Antigens↗
PubMed1988

Specificity of proliferative response of human CD8 clones to mycobacterial antigens.

Human CD8 T lymphocyte clones (TLC) were generated from the pleural effusion of patients with tuberculosis using a protocol that required, in addition to antigen, coculture of purified CD8+ T cells, accessory cells, interleukin 2 (IL2) and anti-CD3-Sepharose. The TLC obtained were stimulated by mycobacterial soluble extracts in an IL2-dependent and MHC class I-restricted manner. When antigen-responsive TLC were screened with extracts from the recombinant mycobacterial library they were found to respond to either the Y3125 (100-kDa) or the Y3111 (71-kDa) lambda gt11 clones. Polyacrylamide gel immunoblot analysis demonstrated that the CD8 TLC responded to fractions with the molecular mass range 27-45 kDa in the Y3125 lysogen and 60-90 kDa in the mycobacterial soluble extract. The specificity of TLC reactive with the Y3111 clone was confirmed using the 71-kDa antigen purified from the same lysogen. These TLC recognized sequences common to the 71-kDa protein derived from mycobacteria, E. coli or a human cell line. Studies of three TLC using antigen-presenting cells of known genetic haplotype indicated that stimulation with both the Y3125 and the 71-kDa antigens were restricted by determinants encoded by HLA-B8.

Antigens, Bacterial↗