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Biomedical subjects

D B Young

Publications and source records attributed to D B Young.

At least 163 records · Page 9Linked to original sources
PubMed1987

Cloned human T lymphocytes reactive with Dermatophagoides farinae (house dust mite): a comparison of T- and B-cell antigen recognition.

In this report, T-cell and B-cell recognition of the house dust mite Dermatophagoides farinae (D. far.) is compared. Nitrocellulose immunoblots of polyacrylamide gel electrophoresis (SDS-PAGE)-fractionated D. far. were added to proliferation assays to map the antigen specificity of cloned human helper T cells and a long-term line induced with D. far. T-cell recognition was of a polypeptide of molecular weight 9000-13,000, that migrates with the serologically defined allergen Der fII (12,500 MW). Since the cloned T cells, unlike the polyclonal response, failed to respond to Dermatophagoides pteronyssinus (D. pter.), this suggests that they recognize a species-specific epitope. In contrast, analysis of the B-cell response using Western blotting demonstrated that, in addition to Der fII, antibodies reactive with the major allergens Der fI (26,000 MW) and Der fIII (29,000 MW) were present in the serum. Similar specificities were seen in the antibody response to D. pter., and while it has been reported that the B-cell response to D. far. and D. pter. are predominantly cross-reactive, our observations suggest that species-specific CD4-positive T cells are present in the overall cellular response to D. far.

Adult↗
PubMed1986

The effect of lincomycin on exoprotein production by Vibrio cholerae.

Lincomycin has a differential effect on exoprotein production by Vibrio cholerae. The production of some proteins, such as cholera toxin and deoxyribonuclease, is stimulated by low concentrations of the drug while production of other proteins, such as protease and alkaline phosphatase, is unaffected. Possible mechanisms of the lincomycin effect are discussed.

Alkaline Phosphatase↗
PubMed1986

Effects of graded changes in reflex renal nerve activity on renal function.

The effects of reflexly produced graded increases in renal nerve activity on excretion of sodium and potassium, urinary flow, glomerular filtration rate (GFR), renal plasma flow (RPF), renin release, and renal venous norepinephrine (NE) overflow were examined in anesthetized dogs. Renal nerve activity was increased by carotid artery occlusion while renal perfusion pressure was held constant. Linear correlation was determined by plotting the percent change from control for each dependent variable vs. the percent change in mean renal nerve activity (MRNA). The percent changes from control for sodium excretion and urinary flow were negatively correlated with percent change from control in MRNA (P less than 0.01), and the percent change from control for renin release was positively correlated with percent change from control in MRNA (P less than 0.05). NE overflow was observed to increase as renal nerve activity increased. These results indicate that physiologically elicited increases in MRNA from 10 to greater than 100% are significantly correlated with changes in sodium excretion, urine flow, and renin release with little or no measurable change in GFR, RPF, or potassium excretion.

Animals↗
PubMed1986

T lymphocytes respond to solid-phase antigen: a novel approach to the molecular analysis of cellular immunity.

Using cloned human T lymphocytes reactive with a 24 amino acid peptide (p20) of the carboxyl terminus of the HA-1 molecule of influenza haemagglutinin (HA), we have investigated the ability of solid-phase antigen to induce antigen-specific T-cell proliferation. The activation by nitrocellulose-bound virus and p20 was accessory-cell dependent and was not caused by immobilized antigen directly cross-linking the specific receptors. Furthermore, we report that separation of complex antigen mixtures such as influenza virus and HA by polyacrylamide gel electrophoresis under denaturing conditions (SDS-PAGE) followed by transfer to a nitrocellulose membrane can be used to allow direct screening of individual polypeptides in T-cell proliferation assays. With this immunoblotting procedure the antigenic site recognized by HA-reactive T cells was confirmed to reside in the HA-1 molecule of influenza virus of only the appropriate subtype. The general application of this approach is discussed in the case of infections and autoimmune diseases in which the immune response is predominantly T-cell mediated and where antibody studies may fail to identify key antigenic determinants involved in the activation of T cells.

Antigen-Presenting Cells↗
PubMed1985

Use of a polysulfone membrane support for immunochemical analysis of a glycolipid from Mycobacterium leprae.

Polysulfone membranes have been used as a solid support for chromatography and immunoblotting of phenolic glycolipid I from Mycobacterium leprae. These membranes have an advantage over other supports such as nitrocellulose and silica gel in that very little non-specific background binding of antibodies occurs and assays can readily be carried out with IgM antibodies from human sera. An example of use of the polysulfone chromatography system for detection of phenolic glycolipid I in sera from leprosy patients is described.

Antigens, Bacterial↗
PubMed1985

Effect of extracellular protease production on bacteriophage sensitivity of Vibrio cholerae.

The effect of varying levels of extracellular protease production on the bacteriophage type of Vibrio cholerae 1621 serotype 01, biotype E1 Tor, has been investigated. It has been shown that the production of high levels of exoprotease can alter the apparent type of the strain by rendering it insensitive to infection by a number of bacteriophages. Prevention of a productive infection appears to be due to altered surface characteristics rather than to specific damage to the bacteriophages. Such altered surface characteristics may be due to auto-digestion. The importance of this observation to epidemiological studies of V. cholerae is noted and discussed.

Bacteriophage Typing↗
PubMed1985

Immunochemical characterization of a protein associated with Mycobacterium leprae cell wall.

A panel of nine monoclonal antibodies to Mycobacterium leprae were used to characterize a protein antigen of the bacillus. Two monoclonal antibodies (IVD8 and IIIE9) were specific for M. leprae and reacted with an epitope (CWPa) present on a protein molecule associated with the cell wall fraction of M. leprae. This protein, designated cell wall-associated protein (CWP), lost its immunoreactivity upon treatment with trypsin and had an apparent molecular weight of 65,000, though additional lower-molecular-weight forms of the protein were observed by immunoblotting. Four other cross-reactive epitopes (CWPb, CWPc, CWPd, and CWPe) were defined on the same molecule using seven independent monoclonal antibodies. Therefore, M. leprae possesses a trypsin-sensitive, heat-stable protein associated with the cell wall which contains at least one species-specific and four cross-reactive antigenic determinants.

Antibodies, Monoclonal↗
PubMed1985

Analysis of long-term potassium regulation.

Potassium regulation is maintained by a system which affects the rate of renal excretion of the ion and its distribution between the intra- and extracellular spaces. Long-term regulation is accomplished by the interactions of several components of the control system. The direct effect of changes in plasma potassium concentration on potassium secretion by the cells of the distal nephron is the most powerful regulator of K excretion. Changes in aldosterone concentration interact multiplicatively with the effect of plasma K on K excretion, and changes in aldosterone also affect the distribution of the ion so that elevations in aldosterone shift a greater proportion of K into the cells of the body. Sodium intake affects K excretion, increases in intake resulting in a higher rate of K excretion. Aldosterone secretion is regulated by a multiplicative interaction between angiotensin II and potassium concentration. An hypothesis that states in essence that long-term K regulation is determined by the interaction of several component systems is developed. A mathematical model constructed from the hypothesis employing data from experiments designed to quantitatively analyze the functions of the individual components is presented. The model is used to test the hypothesis by comparing the operation of the model with the results of experiments in which the potassium control system is subjected to a wide range of challenges and perturbations. General agreement between model predictions and experimental results was obtained, thereby providing support for the validity of the hypothesis. Building the model drew attention to several areas in which experimental investigation is required to obtain understanding of several important physiological processes. Finally, several predictions obtained from the model may have clinical relevance in the areas of renal medicine and hypertension.

Adrenal Cortex↗
PubMed1985

Monoclonal antibodies to a 28,000 mol. wt protein antigen of Mycobacterium leprae.

Monoclonal antibodies (MoAb) have been used to analyse a protein antigen from Mycobacterium leprae with a subunit mol. wt of 28,000 daltons. Three different patterns of species specificity were observed with two antibodies being specific for M. leprae, two partially specific, and one broadly cross-reactive amongst all mycobacteria. Competitive binding and sandwich assays demonstrated that the specific and partially specific antibodies recognized closely related regions of the molecule while the cross-reactive antibody recognized a spatially separate epitope on the same polypeptide chain. Identification of specific and cross-reactive epitopes on a single antigenic molecule may be of considerable importance for understanding the functioning of the cell-mediated immune system during leprosy infection and the use of MoAb for such analyses is discussed.

Antibodies, Monoclonal↗
PubMed1984

Humans respond predominantly with IgM immunoglobulin to the species-specific glycolipid of Mycobacterium leprae.

The immunoglobulin classes of the antibody response to the species-specific phenolic glycolipid antigen of Mycobacterium leprae have been characterized for serum specimens from 78 patients with leprosy. These patients included the entire clinical spectrum from paucibacillary to multibacillary disease, including polar tuberculoid (TT; 11 patients), borderline tuberculoid (BT; 15), borderline (BB; 17), borderline lepromatous (BL; 13), and lepromatous (LL; 22)--clinical classifications according to Ridley-Jopling criteria. In each patient group, the levels of IgM antibody to phenolic glycolipid were significantly higher than levels of IgG or IgA. Inhibition experiments with purified antigen showed that antibodies to the phenolic glycolipid dominated the human IgM antibody response to the surface of M. leprae.

Antibodies, Bacterial↗
PubMed1984

The pathogenic role of the kidney.

The discussions of this article suggest that the pressure natriuresis mechanism of the kidneys is the most important of all long-term regulators of arterial pressure. This is especially so because of the infinite-gain feature of this mechanism, a feature that is explained here. However, experiments have shown that it is not the accumulation of sodium per se in the body that causes hypertension. Instead, it is the increase in extracellular fluid volume that usually accompanies sodium accumulation that increases the arterial pressure. If the increase in fluid volume is prevented, hypertension will not occur despite marked sodium retention. Long-term autoregulation in hypertension plays a very important role for two major reasons: (a) it greatly increases the total peripheral resistance when the cardiac output increases only a small amount, and (b) when it promotes arteriolar constriction, capillary pressure is reduced, which in turns allows a very large proportion of the extracellular fluid to remain in the blood rather than to leak into the interstitium. Marked loss of renal mass usually does not cause hypertension because, as long as there is a proper balance between glomerular filtration capability and tubular reabsorption capability, as little as 10% of the normal kidney mass theoretically can excrete the normal daily load of salt without a significant rise in arterial pressure. However, whenever the ratio of glomerular filtration capability to tubular reabsorption capability falls below normal, salt and water are retained until enough hypertension develops to overcome the deficit in glomerular filtration.

Adaptation, Physiological↗
PubMed1984

Generation and characterization of monoclonal antibodies to the phenolic glycolipid of Mycobacterium leprae.

Nine cloned cell lines producing antibodies to the unique phenolic glycolipid of Mycobacterium leprae have been established as a result of fusions with spleens from mice immunized with the glycolipid complexed with methylated bovine serum albumin. One of the antibodies was relatively nonspecific, binding to a related glycolipid from Mycobacterium kansasii, but the remaining antibodies were specific for the M. leprae lipid. Some of the antibodies required the intact (trisaccharide) carbohydrate portion for recognition of the glycolipid antigen, whereas others recognized partially hydrolyzed forms lacking one or two sugar residues. Monoclonal antibodies directed at the terminal saccharide of the glycolipid showed the greatest specificity for M. leprae in enzyme-linked immunoassays. These antibodies brightly labeled whole mycobacteria in indirect immunofluorescence experiments, demonstrating the surface location of M. leprae-specific determinants of the glycolipid antigen. In addition to their use in providing information about the antigenic properties of the phenolic glycolipid, these antibodies have potential applications for elucidating the roles of glycolipid in the pathogenesis of leprosy.

Animals↗
PubMed1984

Multiplicative interaction between angiotensin II and K concentration in stimulation of aldosterone.

The interaction of angiotensin II and plasma K concentration in stimulating aldosterone secretion was studied in a group of six dogs by determining the aldosterone response to three levels of angiotensin II while the dogs were maintained on three levels of K intake. The levels of angiotensin were 1) the endogenous level, 2) the concentration resulting from infusion of 5 ng X kg-1 X min-1, and 3) the concentration resulting from infusion of 10 ng X kg-1 X min-1. Each level was maintained for 5 days. The three rates of K intake were 10, 100, and 200 meq/day, each maintained for 3 wk. Data were analyzed from days 1, 2, and 5 of the angiotensin infusion periods. The regressions obtained from plotting plasma K (PK) versus aldosterone concentration on day 5 of each level of infusion were 1) for no infusion (endogenous PRA = 0.4 to 0.5 ng ANG I X ml-1 X h-1), aldosterone = 5.04 X PK - 16.56; 2) for 5 ng X kg-1 X min-1 infusion, aldosterone = 12.20 X PK - 39.09; and 3) for 10 ng X kg-1 X min-1 infusion, aldosterone = 35.50 X Pk - 119.31. Each regression was significantly different (P less than 0.001) from the other two. The plasma K axis intercepts, which are the points at which aldosterone secretion is zero, were 3.29, 3.20, and 3.36 for the regression from the 0, 5, and 10 ng X kg-1 X min-1 infusion rates, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1984

Effects of sodium intake on steady-state potassium excretion.

The effects of changes in sodium intake on the steady-state relationship between plasma potassium concentration and potassium excretion were studied in 15 chronically adrenalectomized dogs. Throughout the experiments the dogs received aldosterone at a rate of 50 micrograms/day and methylprednisolone at 1 mg/day. The relationship between plasma potassium and steady-state potassium excretion was obtained by changing potassium intake from 10 to 30 to 100 meq/day, each level being maintained for 7-10 days. At the conclusion of each period at a given level of potassium intake, plasma potassium and excretion were measured and plotted, plasma potassium being the independent variable. Such a relationship was obtained while the dogs were on three different levels of sodium intake: 10, 100, and 200 meq/day. The curves from the data obtained at 100 and 200 meq/day sodium intake both were shifted to the left of the curve obtained at 10 meq/day (P less than 0.05), although the 100 and 200 meq/day curves were not different from each other. On the basis of these data one could predict that, at a plasma potassium concentration of 4.0 meq/liter, the animals would excrete potassium at a rate of 17 meq/day on a 10 meq/day sodium intake, 37 meq/day on a 100 meq/day sodium intake, and 47 meq/day on a 200 meq/day sodium intake. Urine flow and electrolyte concentration data are consistent with the hypothesis that the sodium intake effect on potassium excretion was mediated through increases in distal nephron flow rate and decreases in distal nephron potassium concentration.

Aldosterone↗