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Biomedical subjects

M F Heath

Publications and source records attributed to M F Heath.

At least 37 records · Page 2Linked to original sources
PubMed1990

Pretreatment with pentoxifylline improves the hemodynamic and histologic changes and decreases neutrophil adhesiveness in a pig fecal peritonitis model.

We investigated pentoxifylline (PTF) as a pretreatment of septic syndrome in pigs with fecal peritonitis. In the untreated group there was a progressive decrease in mean arterial pressure (MAP), cardiac output, mean pulmonary artery wedge pressure (WP), and a progressive rise in mean pulmonary artery pressure (MPAP), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), heart rate (HR), and core temperature (T). In those pigs given PTF there was a significantly smaller increase in SVR throughout and in PVR after 270 min. No significant differences were seen in MAP, MPAP, WP, HR, and T. Neutrophil adhesiveness did not change in the untreated group. However, it decreased markedly with PTF, both before and after peritonitis induction. Electron microscopy of the lungs, liver, and spleen in the test group showed severe damage, with endothelial disruption, capillary or sinusoidal occlusion, leukostasis, and neutrophil degranulation. Pretreatment with PTF attenuated these changes.

Animals↗
PubMed1989

Primary hyperoxaluria (L-glyceric aciduria) in the cat: a newly recognised inherited disease.

The clinical features of a newly recognised inherited disease, primary hyperoxaluria in the cat, are reported. Affected cats developed acute renal failure between five and nine months old owing to the deposition of oxalate crystals in the tubules of the kidney. In addition to the signs attributable to kidney failure the affected animals became profoundly weak; there was evidence of denervation atrophy in skeletal muscle, and accumulations of neurofilaments were found in the proximal axons of the ventral horn cells and dorsal root ganglion cells of the spinal cord. Examination of urine from affected cats revealed L-glyceric aciduria and intermittent hyperoxaluria suggesting that the disease is a feline analogue of the human disorder, primary hyperoxaluria type 2. This supposition was confirmed by liver enzyme studies.

Acute Kidney Injury↗
PubMed1989

Enzymological characterization of a feline analogue of primary hyperoxaluria type 2: a model for the human disease.

This paper concerns an enzymological investigation into a putative feline analogue of the human autosomal recessive disease primary hyperoxaluria type 2. The hepatic activities of D-glycerate dehydrogenase, using both D-glycerate and hydroxypyruvate as substrates, and glyoxylate reductase, which are the deficient enzyme activities in human primary hyperoxaluria type 2, were markedly depleted in four affected cats (0-6% of controls). The activities of a number of other enzymes, lactate dehydrogenase, glutamate dehydrogenase, D-amino acid oxidase, aspartate:2-oxoglutarate amino-transferase, glutamate:glyoxylate aminotransferase and alanine:glyoxylate aminotransferase (the deficient enzyme in primary hyperoxaluria type 1) were unaltered. The intracellular distribution of D-glycerate dehydrogenase and glyoxylate reductase in cat liver was shown to be cytosolic, as they are in human liver. The activities of D-glycerate dehydrogenase and glyoxylate reductase were determined in unaffected related cats and putative heterozygotes were identified. The correlation between D-glycerate dehydrogenase and glyoxylate reductase activities in the related cats and their combined deficiency in the affected cats confirmed previous suggestions that they are identical gene products.

Alcohol Oxidoreductases↗
PubMed1989

Multi-organ damage resulting from experimental faecal peritonitis.

1. Using specific-pathogen-free New Zealand White rabbits, we have compared the effects of faecal peritonitis over a period of 5 h in eight test animals with eight controls in which a sham operation was performed. 2. There was morphological damage to lungs, liver and spleen of test animals. Lung capillaries and sinusoids of the liver showed occlusion by cell debris and leucocytes, with endothelial damage. The lungs also showed alveolar epithelial disruption, basement membrane exposure and type II pneumocytes lacking lamellar bodies. In the liver there was fibrin deposition and swollen Kupffer cells. The spleen showed degranulating neutrophils, fibrin deposits, platelet aggregates and activated macrophages, with no damage to the endothelium. 3. There was no morphological damage to the kidney or heart of test animals or to any organs of sham-operated animals. 4. There were mixed anaerobes and aerobes in faecal material used to induce peritonitis. Cultures of liver, spleen and kidney isolated four different types of micro-organisms. Blood cultures showed two types of micro-organisms. Cultures of lung and heart showed one type of micro-organism. 5. The presence of micro-organisms in an organ could not be correlated with the degree of histological damage to that organ. 6. In test animals an early significant reduction in circulating leucocytes and platelets was sustained for the duration of the experiment with significant diffuse intravascular coagulation. 7. There was no change in test animal neutrophil adhesiveness until 120 min, when significant reduction was observed. 8. Serum phospholipase A2 (EC 3.1.1.4) activity in the test group showed a threefold increase at 300 min.

Animals↗
PubMed1989

Pentoxifylline reduces pulmonary leucostasis and improves capillary patency in a rabbit peritonitis model.

This study examines the changes in pulmonary leucostasis and capillary ultrastructure in 18 rabbits divided into three groups. Those in the first group were sham operated, and those in the second and third groups underwent peritonitis induction; those in the latter group were treated with pentoxifylline (PTF). White blood cells (WBC) were counted, and tissue area, total capillary area, and capillary patency were measured from electron micrographs of lung tissue. Pulmonary WBCs were 1.2 per unit field in the sham group, 9.7 in the test group (P less than 0.001 compared with sham), and 2.5 in the PTF group (P less than 0.001 compared with sham). Capillary patency was 53 +/- 5% in the sham group, 12 +/- 4% (P less than 0.001 compared with sham) in the test group, and 24 +/- 2% (P less than 0.001 compared with sham) in the PTF group. Pentoxifylline treatment attenuates pulmonary leucostasis, pulmonary capillary occlusion, and endothelial and epithelial damage associated with peritonitis in rabbits. This study shows that PTF warrants investigation into its potential protective effects on the lungs in clinical sepsis.

Animals↗
PubMed1985

The induction of pulmonary phospholipidosis and the inhibition of lysosomal phospholipases by amiodarone.

Administration of high doses of amiodarone to young adult rats leads to phospholipidosis of the lung, with extensive phospholipid storage by type II pneumonocytes and alveolar macrophages. Biochemical analysis reveals an increase in the total phospholipid content of the lung and in the proportion of phosphatidylcholine. The cause of the phospholipidosis is suggested to be the inhibition of lysosomal phospholipases, responsible for catabolizing phospholipids. It is shown that amiodarone is a potent inhibitor of phospholipases prepared from the soluble fraction of adult rabbit lung lysosomes.

Amiodarone↗
PubMed1984

The effect of components of rabbit pulmonary surfactant on the activity of phospholipases.

This study investigates the ability of two components of pulmonary surfactant, protein and phosphatidylglycerol, to inhibit the action of phospholipases against phosphatidylcholine. Broncho-alveolar protein, prepared by de-lipidation of rabbit lung lavage material had an inhibitory effect on phospholipases A1 and A2 from rabbit lung lysosomes, comparable to the effect of bovine serum albumin. The degree of inhibition was found to increase with increasing enzyme activity. De-lipidated broncho-alveolar protein was separated into two fractions by gel chromatography. Inhibitory activity was associated only with the second peak, corresponding to rabbit albumin. The effect of phosphatidylglycerol (PG) on the activity of phospholipases A against dipalmitoyl phosphatidylcholine and unsaturated phosphatidylcholine (USPC) was investigated, and compared with the effects of two substrate analogues on the hydrolysis of USPC. There was no indication of true inhibition by PG, but some stimulation of USPC hydrolysis by 10 mol % PG. The relevance of these findings to the fate of surfactant in vivo is discussed.

Animals↗
PubMed1984

Developmental changes in enzyme activities in fetal and neonatal rabbit lung. Cytidylyltransferase, cholinephosphotransferase, phospholipases A1 and A2, beta-galactosidase, and beta-glucuronidase.

Lungs were obtained from rabbit fetuses (on each day from d 24 to d 30 of gestation), neonates and adults, and were fractionated for enzyme assays. The developmental profile of cytidylyltransferase shows a decrease in specific activity from d 25 to d 29 (P less than 0.05) then a sharp rise from d 30 to adult values in d 0 neonates (P less than 0.05). Cholinephosphotransferase specific activity changes little from d 25 to birth, apart from a non-significant peak on d 29. There is a sharp rise from neonatal d 0 to adult values on d 1 (P less than 0.01). The specific activity of microsomal phospholipase A2 declines from d 25 to reach adult values in the neonate (P = 0.05). In contrast, the specific activity of lysosomal phospholipase A2 rises from d 24-28 then falls in the neonate (P less than 0.05). Adult values are higher than those in the fetus and neonate. Three other lysosomal enzyme specific activities rise to d 28 then decline: phospholipase A1, beta-galactosidase, and beta-glucuronidase. The results demonstrate that the level of microsomal phospholipase A2 does not control the extent of remodelling of phosphatidylcholine for surfactant production. Lysosomal phospholipase A2 only increases in parallel with the other lysosomal enzymes, indicating an increase in the number of lysosomes in the lung.

Age Factors↗
PubMed1980

The action of lung lysosomal phospholipases on dipalmitoyl phosphatidylcholine and its significance for the synthesis of pulmonary surfactant.

Subcellular fractions were prepared from rabbit lung and characterized by marker enzyme assays. Phospholipases A of lysosomal type (activity at pH 4.0 in the absence of Ca2+) show a peak of specific activity in fraction P3 (13000 x g; 20 min; pellet). About 70% of the phospholipase A activity of P3 can be obtained in a soluble extract. The rates of hydrolysis of dipalmitoyl (saturated) and unsaturated phosphatidylcholine molecules, presented to enzyme preparations in liposomes of varying composition, are shown in Tables 3 to 5. Although the rate of unsaturated molecules is unaffected by liposome composition, saturated molecules are hydrolyzed significantly faster in 5 mol % dipalmitoyl phosphatidylcholine liposomes than in 95 mol %. With enzyme preparation I (60% A1: 40% A2) the increase was 6-fold (P less than 0.01). Preparations I and II hydrolyzed both kinds of molecules at similar rates in 50 mol % dipalmitoyl phosphatidylcholine liposomes, but preparation III, with a higher proportion of A2 (80%), gave a notably lower rate of hydrolysis of saturated molecules. Phosphatidylglycerol (10 mol %) also decreased the rate of hydrolysis of saturated molecules. These results are discussed in relation to fluidity of the liposomes and to the functions of the lysosomal-type phospholipases A of the lamellar inclusion bodies of the lung.

Animals↗
PubMed1980

The nature of the phospholipases A of lung lamellar bodies.

Phospholipases A1 and A2 from rabbit lung lysosomes have maximal activity at pH 4.0 (Fig. 1). Lamellar bodies from rabbit lung contain phospholipases A which resemble the lysosomal enzymes in being active at pH 4 and showing sensitivity to inhibition by calcium ions (80% inhibition at 10 mM Ca2+). Lamellar body phospholipases hydrolyse dipalmitoyl phosphatidylcholine (containing 10% phosphatidylglycerol and thus approximating the phospholipid composition of mature lamellar bodies) at only 1% of their rate of hydrolysis of unsaturated molecules (Tables 1 and 2). This substrate preference corresponds to that shown by phospholipases from lysosomes.

Animals↗
PubMed1976

Phospholipases A1 and A2 in lamellar inclusion bodies of the alveolar epithelium of rabbit lung.

1. A lamellar body-enriched fraction was prepared from rabbit lung and characterized by electron microscopy, surface activity studies, phospholipid assay and marker enzymes. 2. Both phospholipases A1 and A2 were found to be present in lamellar bodies. After these had been ruptured both enzymes were found to be principally in the soluble phase. 3. The possible roles for phospholipases in lamellar body development and in the respiratory distress syndrome of the newborn are discussed.

Animals↗
PubMed1973

A hydroxyproline-containing glycopeptide released from the walls of sycamore tissue-culture cells by hydrazinolysis.

Degradation of the sycamore cell wall by hydrazinolysis yielded soluble glycopeptides. The peptide portion of the predominant glycopeptide was shown to be cyclic (4-trans-hydroxy-l-prolyl)-4-trans-hydroxy- l-proline. From this structure and the composition of the major glycopeptide it was deduced that only short oligosaccharides are attached to the hydroxyprolyl residues of the wall glycoprotein. Detailed evidence for the structure of the peptide is given in a supplementary paper that has been deposited as Supplementary Publication SUP 50020, at the National Lending Library for Science and Technology, Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973) 131, 5.

Arabinose↗
PubMed1971

Glycoprotein of the wall of sycamore tissue-culture cells.

1. A glycoprotein containing a large amount of hydroxyproline is present in the cell walls of sycamore callus cells. This protein is insoluble and remained in the alpha-cellulose when a mild separation procedure was used to obtain the polysaccharide fractions of the wall. The glycoprotein contained a high proportion of arabinose and galactose. 2. Soluble glycopeptides were prepared from the alpha-cellulose fraction when peptide bonds were broken by hydrazinolysis. The soluble material was fractionated by gel filtration and one glycopeptide was further purified by electrophoresis; it had a composition of 10% hydroxyproline, 35% arabinose and 55% galactose, and each hydroxyproline residue carried a glycosyl radical so that the oligosaccharides on the glycopeptide had an average degree of polymerization of 9. 3. The extraction of the glycopeptides was achieved without cleavage of glycosyl bonds, so that the glycoprotein cannot act as a covalent cross-link between the major polysaccharides of the wall. 4. The wall protein approximates in conformation to polyhydroxyproline and therefore it probably has similar physicochemical properties to polyhydroxyproline. This is discussed in relation to the function of the glycoprotein and its effect on the physical and chemical nature of the wall.

Arabinose↗