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Biomedical subjects

R L Hall

Publications and source records attributed to R L Hall.

At least 73 records · Page 4Linked to original sources

Renal resistance to mercuric chloride toxicity during prolonged exposure in rats.

An attempt was made to develop a model of chronic renal disease in the rat through repeated administration of a nephrotoxin specific for proximal tubular epithelium. Mercuric chloride was administered by subcutaneous injection in gradually increasing amounts over a period of 21 weeks. The dose ranged from 1.125 mg/kg once a week to 2.0 mg/kg twice a week. Measured parameters of renal function include plasma urea nitrogen, plasma creatinine, 24-hour urine output volume, and 24-hour urinary protein excretion. When compared to their own pretreatment values and those of the age/weight-matched control animals, the mercuric chloride-treated rats exhibited no significant abnormalities in these parameters of kidney function with the exception of a mild proteinuria at 21 weeks. Light microscopic examination of the kidneys of the mercury-treated rats revealed mild tubular, interstitial, and glomerular lesions which were significantly worse than those in the kidneys of the controls. This study demonstrates the ability of the kidney to sustain a considerable degree of resistance to inorganic mercury toxicity when exposure is continuous over a prolonged period of time. It also demonstrates the inability of commonly measured clinical laboratory parameters of kidney function to identify the effects of chronic mercuric chloride toxicity in the rat.

Animals↗

Captopril slows the progression of chronic renal disease in partially nephrectomized rats.

The effect of captopril, an angiotensin-converting enzyme inhibitor, on the progression of chronic renal disease was studied in rats subjected to partial nephrectomy. Following ablation of approximately 70% of their renal mass, rats were divided into three treatment groups: group I received a placebo treatment; group II received daily po administrations of captopril; group III received captopril at the same dosage schedule as group II, but the drug was not given for 4 weeks in the middle of the treatment period. Measurements of renal function were performed at 4-week intervals, and light microscopic evaluation of the remnant kidneys was performed following 19 weeks of treatment. Deterioration of renal function, as measured by endogenous creatinine clearance, plasma creatinine, and plasma urea nitrogen, progressed more rapidly in group I than the other two groups. Twenty-four-hour urinary protein excretion was higher in group I than the others, except in group III following the 4-week period when captopril was not administered. Morphologic damage in the remnant kidney was significantly greater in group I than group II (p = 0.007). The renal lesions in the rats of group III were intermediate in severity. Histopathologic ranking of the remnant kidneys was correlated with antemortem laboratory parameters (r greater than or equal to 0.50; p less than 0.05). In a second experiment, similarly nephrectomized rats receiving po captopril daily had significantly longer survival, at 260 days, postnephrectomy than rats receiving a placebo (p = 0.0045). We conclude that captopril retards the progression of renal damage and increases survival time in this model of chronic renal disease. The mechanism may involve the alteration of potentially harmful intraglomerular hemodynamic changes which occur in the remnant kidney model.

Animals↗

Laboratory evaluation of liver disease.

With respect to liver disease, the primary function of the laboratory is to identify its presence. Tests are not available that permit a specific diagnosis and an accurate prognosis. Several tests should be present in a minimum data base that can help identify hepatobiliary disease. They are ALT, SAP, total serum bilirubin, urine bilirubin, cholesterol, albumin, BUN, glucose, red cell morphology, and urine sediment. It is sometimes possible to tentatively identify whether a disease is primarily hepatocellular or biliary from the pattern of changes that occur in these tests. In addition, an estimate of the severity is sometimes possible when abnormal values are extreme. The keys are to avoid overinterpretation, use serial evaluations, and rely on a liver biopsy when definitive answers are needed. If liver disease is suspected but there are only marginal changes in the routine tests, the more sensitive tests of function, BSP retention and ammonia tolerance, are warranted. In the future, as more knowledge is gained about the responses of ARG, GGT, and ICG retention to naturally occurring diseases, these tests may join or replace some of those currently used. Also, as the ability to accurately and economically measure the various bile acids improves, a sensitive, yet noninvasive, method to detect and define modest changes in hepatobiliary function may result.

Ammonia↗

Cutaneous lymphosarcoma and leukemia in a dog resembling Sézary syndrome in man.

A dog with a lymphoproliferative disease resembling the Sézary syndrome variant of mycosis fungoides in man had large numbers of circulating morphologically abnormal lymphoid cells, multicentric cutaneous nodules and plaques, and extracutaneous involvement of lymph nodes and viscera. The presence of Pautrier's microabscesses, intracutaneous hyperchromatic cells, and leukemic cells with convoluted nuclei distinguished the disease from other types of cutaneous lymphoma.

Animals↗

Diseased dogs isoamylases in clinically normal and diseased dogs.

Isoamylases in normal canine sera were separated on cellulose acetate membranes using a discontinuous buffer system without EDTA. Four peaks of amylase activity were present in 17 of 24 sera. Normal values were established. The majority of activity was present in Peak 4 (cathodal isoamylase). Tissue extracts of pancreas, duodenum, kidney, lung, testis, spleen and uterus-ovaries contained Peak 4 isoamylase. Liver and salivary gland lacked all isoamylase activity. Pancreas contained Peak 3 in addition to Peak 4 isoamylase. A tissue origin for Peaks 1 and 2 was not identified. An overall lack of resolution resulted from the inclusion of EDTA in the electrophoresis buffer system. This may account for previous findings suggesting that pancreatic amylase is not present in normal canine serum. An increase in the Peak 3 isoamylase was present in dogs with pancreatitis while dogs with pancreatic atrophy had a decrease in all isoamylases. Total amylase activity was significantly (p < 0.05) decreased in dogs with pancreatic atrophy.

Journal Article↗

The effect of serum on the secretion of radiolabeled mucous macromolecules into the lumen of the cat trachea.

We studied the effect of placing serum within a segment of trachea on secretion into its lumen in the cat. A segment of cervical trachea was isolated from the rest of the airway in situ. Secretions were radiolabeled biosynthetically by the administration of two radiolabeled precursors: [35S]sodium sulphate and [3H]glucose. Autologous serum placed in the segment at a dilution of 1 in 8 increased the output of radiolabeled macromolecules: [35S] by 80% and [3H] by 159% (p less than 0.001). At a dilution of 1 in 24, serum still increased the output of both isotopes. At dilutions of 1 in 48 and 1 in 80 the increases were significant for [35S] but not for [3H]. Heating the serum to 90 degrees C diminished its effects. Fractionating the serum by dialysis and gel filtration showed that the components of molecular weight less than about 13,000 daltons had no effect on secretion, whereas three higher molecular weight fractions all increased secretion. Two alien proteins (horseradish peroxidase and bovine serum albumin) stimulated secretion but a large molecular weight carbohydrate (carboxymethyl cellulose) did not. Atropine and propranolol, at doses that greatly reduced the effect of parasympathetic and sympathetic nerve activity, did not diminish the effects of serum, which therefore appeared to be independent of nerve activity. Gel filtration of the secretions elicited by serum showed that the predominant component was excluded even by Sepharose CL-2B and thus had a high molecular weight. We conclude that there are several components of serum that promote the secretion of mucus glycoproteins into the cat trachea. The relevance of these findings to diseases of human airways is considered.

Animals↗

Analyses of human tracheobronchial mucus from healthy subjects.

Tracheobronchial mucus was obtained from four healthy subjects by fibreoptic bronchoscopy. The material was fractionated by gel exclusion chromatography on a Sepharose CL2B column. One peak of optical density 280 nm was found in the excluded volume and another in the included volume suggesting that these contained the majority of the aromatic amino acids. Alcian Blue was used to precipitate acidic glycoproteins in each fraction. When the dye had been redissolved two peaks of optical density at 620 nm were detected, in the excluded and included volumes respectively, and these peaks corresponded with the absorbance at 280 nm. The elution profiles were similar to those given by mucins from other systems. Treatment with urea and dithiothreitol caused no change in the elution profile so there is no evidence that disulphide bonds link glycoprotein subunits in airway mucus from healthy subjects.

Adult↗

Trajectories of human granulocytes.

The spatial trajectories of human granulocytes moving on glass in two dimensions under an isotropic medium may be characterized as realizations of a correlated walk. The present model is similar to an earlier one for slime-mold amebae. The correlation from step to step is essentially via the relative angle theta, represented for granulocytes as a random variable with a symmetric bimodal density. As the cells age, they appear to turn less and the degree of correlation increases. Even under chemotaxis the angle theta and the step length r appear to be statistically independent.

Cell Movement↗

Separation and partial characterization of guinea-pig caseins.

1. Guinea-pig caseins A, B and C were purified free of each other by a combination of ion-exchange chromatography and gel filtration. 2. Determination of the amino acid composition showed all three caseins to contain a high proportion of proline and glutamic acid, but no cysteine. This apart, the amino acid composition of the three caseins was markedly different, though calculated divergence values suggest that some homology may exist between caseins A and B. Molecular-weight estimates based on amino acid composition were in good agreement with those based on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 3. N-Terminal analysis showed lysine, methionine and lysine to be the N-terminal residues of caseins A, B and C respectively. 4. Two-dimensional separation of tryptic digests revealed a distinctive pattern for each casein. 5. All caseins were shown to be phosphoproteins. The casein C preparation also contained significant amounts of sialic acid, neutral and amino sugars. 6. The results suggest that each casein represents a separate gene product, and that the low-molecular-weight proteins are not the result of a post-translational cleavage of the largest. All were distinctly different from the whey protein alpha-lactalbumin.

Amino Acids↗

The roles of mediators, irritants and allergens in causing mucin secretion from the trachea.

Two species, the cat and the goose, have been investigated to determine whether a variety of pharmacological mediators, irritants and allergens change the rate at which mucins (mucus glycoproteins) are secreted into the trachea. Mucins were labelled by the administration of radioactive precursors which the mucous cells took up and incorporated into glycoproteins. These were periodically washed out of a segment of trachea with physiological saline solution. Changes in the amount of mucin secreted were estimated from measurements of the amount of bound radioactivity in tracheal washings. Histamine increased mucin secretion but the effects were stronger and more consistent in the goose than in the cat. A variety of prostaglandins increased the secretion in both species. 5-Hydroxytryptamine failed to stimulate mucin output in the cat. Ammonia and cigarette smoke both increased mucin secretion in the cat and preliminary results suggest that this was by a combination of local and reflex mechanisms. O-Chlorobenzilidine malononitrile increased secretion from the goose trachea entirely by a local mechanism. Preliminary experiments in which sensitized cats were challenged by various routes have equivocal results on whether anaphylaxis increases airway mucin secretion. It is concluded that irritants cause mucin secretion both by reflexes and local mechanisms. The mechanisms for the latter may well include release of pharmacological mediators.

Allergens↗