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Biomedical subjects

M Silverman

Publications and source records attributed to M Silverman.

At least 361 records · Page 20Linked to original sources
PubMed1981

Circulating catecholamines in exercise and hyperventilation induced asthma.

Plasma noradrenaline, adrenaline, and cyclic 3'5' AMP (cAMP) were measured in seven asthmatic patients with known exercise-induced bronchospasm and six matched non-atopic control subjects during a standard treadmill exercise test and then during matched isocapnic hyperventilation. Normal subjects showed a 5.5 fold rise in noradrenaline and a 3.2 fold rise in adrenaline during exercise compared with a 2.1 fold rise in noradrenaline and no significant rise in adrenaline in asthmatics who all developed bronchoconstriction after exercise (mean fall in peak flow rate 28.4 +/- 5.8%). Plasma cAMP rose 1.4 fold in controls but showed no significant rise in asthmatics. This reduced sympatho-adrenal response to exercise in asthmatics is difficult to explain. The failure of circulating catecholamines to rise and stimulate beta adrenoceptors on the mast cell may facilitate the release of bronchoconstrictor mediators. Matched hyperventilation produced bronchospasm in asthmatics (mean fall in peak flow rate 29.0 +/- 4.4%) but no change in catecholamines in either group suggesting that circulating catecholamines have no direct role in exercise-induced bronchospasm but may play a permissive role via the mast cell.

Adolescent↗
PubMed1981

The mechanism of maleic acid nephropathy: investigations using brush border membrane vesicles.

Brush border membrane vesicles from dog kidney proximal tubule have been used to investigate the pathogenesis of glucosuria resulting from maleic acid nephropathy. Direct exposure of brush border vesicles to 9 mM maleic acid for up to 36 minutes has no effect of the Na+-dependent D-glucose uptake mechanism. Brush border membrane vesicles were then prepared from dogs in which glucosuria had first been induced by prior administration of maleic acid (250 mg/Kg body weight). The timed uptake of D- and L-glucose was measured in the presence in the presence of both Na+ chemical and electropotential driving forces and compared to uptake in vesicles prepared from matched control kidneys from the same animal. Maleic acid treated and control vesicles were also assayed for the presence of the Na+-dependent high affinity phlorizin receptor. Our results indicate that there is no alteration in behavior of the Na+-dependent transport system for glucose at the brush border membrane in the model Fanconi state produced by maleic acid. Moreover, there is no change in the coupling of sugar transport either to the Na+ chemical or the electrical potential gradient across the brush border membrane. These studies imply that further efforts to define the pathogenesis of maleic acid nephropathy are probably best carried out using intact tissue or cells because the molecular defect is at the level of the Na+ pump and/or at some intracellular site affecting production of ATP.

Animals↗
PubMed1980

Phase variation: evolution of a controlling element.

Phase variation in bacteria is regulated by homologous recombination at a specific DNA site. This recombinational event causes the inversion of a 970-base-pair DNA sequence that includes the promoter necessary for transcription of a flagellar gene. The invertible segment is flanked by two sites that are necessary for the inversion and contains a gene (hin) whose product mediates the inversion event. The hin gene shows extensive homology with the TnpR gene carried on the Tn3 transposon. It is also homologous with the gin gene carried on bacteriophage mu. These relationships suggest that the phase variation system may have evolved by the association of a transposon with a resident gene and the subsequent specialization of these elements to regulate flagellar antigen expression.

Amino Acid Sequence↗
PubMed1980

Participation of the ring oxygen in sugar interaction with transporters at renal tubular surfaces.

The pulse-injection indicator-dilution technique in vivo has been used to study the interaction of 5-thio-D-glucose and methyl-beta-D-thiogalactopyranoside with renal tubular surfaces in dog kidney. (i) 5-Thio-D-glucose and methyl-beta-D-thiogalactopyranoside have nor antiluminal interaction. (ii) 37 +/- 5% of 5-thio-D-glucose is extracted at the luminal surface relative to simultaneously filtered creatinine. (iii) Luminal extraction of 5-thio-D-glucose is blocked by preloading with D-glucose and phlorizin. (iv) Methyl-beta-D-thiogalactopyranoside in contrast to D-galactose has not luminal interaction. It is concluded that 5-thio-D-glucose shares the glucose transporter at the luminal surface of the proximal tubule. The data also suggest that the ring oxygen participates in the interaction of pyranosides with luminal and antiluminal membrane carriers. At the luminal surface, its absence is quantitatively important while at the antiluminal surface it is apparently essential for the sugar-transporter interaction.

Animals↗
PubMed1980

Testing carrier models of cotransport using the binding kinetics of non-transported competitive inhibitors.

The kinetic equations representing the binding of a non-transported competitive inhibitor are derived from three variations of the carrier model of cotransport. These are (a) the model in which the binding sequence of activator and substrate is random (random bi-bi); (b) the model in which activator must bind before substrate (ordered bi-bi, activator essential), and (c) the model in which substrate must bind before activator (ordered bi-bi, activator non-essential). In general it is found that the kinetic equations for inhibitor binding are considerably simpler and easier to test than the corresponding transport equations. The effect of trans-inhibitor, transported substrate, activator concentration and membrane potential on inhibitor binding are examined in some detail. The use of these results to test and characterize the three transport models is emphasized. Applications to transport mechanisms which are not of the mobile carrier type are also discussed. A summary of relevant experimental data interpreted in terms of the theoretical models concludes the paper.

Biological Transport↗
PubMed1980

Building bacterial flagella.

Most bacterial movement is the result of the action of a subcellular structure, the flagellar organelle. Bacterial flagella propel the cell by rotating, and this rotation is regulated in response to information transmitted by chemoreceptors on the surface of the cell. Rotation is driven by a motor anchored in the cell membrane. To understand such processes as the assembling of flagellar organelles, energy transduction to produce flagellar rotation, and the integration of sensory information necessary for chemotaxis, one prerequisite is the determination of the architecture of flagella. Emphasis is given here to experimental approaches using Escherichia coli and Salmonella in order to identify the flagellar components and to determine how these components are used to construct the functional organelle. The purification of apparently intact organelles has revealed an intricate structure composed to at least 11 polypeptide components. Genetic techniques have been developed which enable the identification of the components of the flagellar system. More than 35 genes which are necessary for flagellar function have been defined in E. coli, and the gene products of 17 of the genes have been identified. From such genetic studies, it is apparent that the flagellar system is complex and includes many elements in addition to those found in the intact flagellar structures purified from the cell membrane. Proteins required for energy and sensory transduction have been identified and located in the cytoplasm and cell membrane. Since these components are not integral parts of the isolated organelle, it is clear that flagellar movement requires the interaction of several functionally distinct and spatially separate systems. The organelle appears to be constructed in discrete stages consisting of the sequential association of individual components. As with bacteriophage assembly, some flagellar proteins function not as structural components, but to regulate the assembly of the organelle. A structural variation is found in Salmonella, which have the ability to alternately express one of two components of the flagellar filament. The unique genetic control mechanism regulating this structural variation is discussed.

Bacterial Physiological Phenomena↗
PubMed1980

Inorganic anion transport in kidney and intestinal brush border and basolateral membranes.

The efflux of inorganic anions from purified brush border and basolateral membrane vesicles from dog kidney cortex was measured under equilibrium exchange conditions. Marked differences in temperature sensitivity and effects of inhibitors were found between the Cl and SO4 transport pathways and between the two types of membranes. SO4 transport in both brush border and basolateral membranes was markedly reduced by cooling, but significant inhibition by 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS) was only observed in basolateral vesicles. In contrast, Cl efflux from both types of vesicles was neither substantially inhibited by DIDS nor by lowering the temperature to 0 degrees C. Phosphate efflux from basolateral membrane vesicles was found to be only partially sensitive to DIDS. Attempts to label the stilbene-sensitive SO4 pathway in basolateral vesicles using [3H2]DIDS as a marker were unsuccessful due to the nonspecific labeling of many membrane components. The asymmetry in inorganic anion transport behavior exhibited by brush border and basolateral membrane vesicles from dog renal proximal tubule was also observed in equivalent vesicles prepared from rat small intestine.

Alkaline Phosphatase↗
PubMed1980

Improved esophageal balloon technique for use in infants.

Esophageal balloons of three different wall thicknesses, two different lengths, and two different diameters were made to assess which type of balloon gave the most consistent and reliable measurements of dynamic compliance (CL) and pulmonary resistance (Rp). The balloons were subjected to in vitro testing to determine their pressure-volume characteristics and working range and then used in infants to compare in vivo results from one balloon to another. The optimal balloon was found to have a length of 35--50 mm, a diameter of 7.6 mm, and a wall thickness of 0.045--0.075 mm. The use of unsuitable balloons or inappropriate volumes of air within the balloon resulted in applied pressures being under-recorded, both in vitro and in vivo, with consequent overestimation of CL and underestimation of Rp during infant lung function tests. Recommendations are made concerning the techniques of making and using esophageal balloons.

Esophagus↗
PubMed1980

Antiabsence drugs and inhibitory pathways.

Conditioning stimuli to the coronal gyrus or periventricular gray matter inhibit the activity of spinal trigeminal neurons. Valproate decreased the corticofugal inhibition of the spinal trigeminal nucleus, as did ethosuximide, trimethadione, and imipramine. Valproate and ethosuximide also decreased the periventricular inhibition of the spinal trigeminal nucleus, indicating that antiabsence drug depress subcortical inhibitory pathways as well as pathways of cortical origin. These results support the hypothesis that ability to depress inhibitory pathways is an important characteristic of antiabsence drugs. The effect of valproate and ethosuximide on periventricular inhibition also suggests that these anticonvulsants may act by preventing the spread of seizure activity through subcortical pathways.

Animals↗
PubMed1980

Quantitative approach to the study of regional lung function in children using krypton 81m.

Krypton 81m has many advantages for paediatric lung imaging, although the proper interpretation of ventilation and perfusion lung scans requires the quantitative analysis of the steady state images and clearance curves. Both the theory and practice are described and illustrated by means of 11 paediatric cases aged from 18 days to 14 years. It was possible to calculate the regional distributions of ventilation and perfusion and the normalized ventilation-perfusion (V/Q) ratios. Of greater functional significance was the detection of differences between the clearance rates of inhaled and infused 81Krm within single regions, since such differences reflected the dispersion of V/Q ratios amongst lung units within individual regions.

Adolescent↗
PubMed1980

Pathogenicity of a highly purified brush border membrane preparation in Heymann nephritis.

The pathogenicity of highly purified brush border membrane (BBM) antigens in Heymann Nephritis was compared to that of a crude renal tubular Fx1A preparation and was found to be equally pathogenic. Both antigen preparations induced formation of autologous antisera. Double immunodiffusion studies demonstrated a reaction of identity between anti-BBM and anti-Fx1A antisera. Both antisera detected the same number of antigenic components when reacted against BBM or Fx1A preparations. When antibody was eluted from the kidneys of rats with Heymann nephritis it reacted in vitro with the renal BBM as shown by indirect immunofluorescence. Eluted antibody also cross reacted with epididymal tubules, but not with other epithelia, showing that the pathogenic antigens have a restricted tissue distribution. Heymann nephritis was readily induced in rats, but could not be induced in dogs, suggesting a species difference in susceptibility to this form of nephritis. Injection of heterologous anti-BBM or anti-Fx1A antisera resulted in rapid localization to the GBM in a granular pattern, suggesting reaction with circulating antigen or in situ immune complex formation with native or planted glomerular components. Rats with aminonucleoside nephrosis showed BBM localization of injected heterologous antisera, demonstrating their specificity in vivo. Our data provide a rationale for using purified BBM antigens for the production of a homogeneous model of Heymann nephritis.

Animals↗