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Biomedical subjects

J M Howell

Publications and source records attributed to J M Howell.

At least 109 records · Page 6Linked to original sources
PubMed1981

An investigation of the effects of intravenous administration of thiomolybdate on copper metabolism in chronic Cu-poisoned sheep.

1. Fourteen sheep were dosed repeatedly with a solution of copper sulphate (2 g/l) in order to induce chronic copper poisoning and four similar undosed animals acted as controls 2. Thiomolybdate (TM) was intravenously administered to all control sheep and to all except two of the test sheep. A variety of biochemical factors were studied before and after injections of TM. 3. The direct-reacting Cu, whole-blood Cu and plasma Cu concentrations were elevated in animals given TM injections and at the "haemolytic crisis" of untreated chronic Cu-poisoned animals. But most of the increased Cu observed on injecting TM was insoluble in trichloroacetic acid (TCA) and did not enter erythrocytes. The results indicate that uptake of Cu by erythrocytes is essential for haemolysis to occur and that for this to happen the Cu must be in a direct reacting, TCA-soluble form. 4. Increased amounts of Cu were excreted in the urine at haemolysis and at commencement of TM injections. High levels of direct-reacting Cu were found in plasma at these times. 5. Marked changes were not found in caeruloplasmin activity, packed cell volume or the osmotic fragility of erythrocytes except at haemolysis. TM injection s did no alter these factors in any of the sheep studied.

Animals↗
PubMed1980

An ultrastructural and morphometric study of the liver of normal and copper-poisoned sheep.

In sheep given copper (Cu) at the level of 10 ml of a 0.2% solution of CuSO4.5H2O/kg body weight, the volume density of nuclei and cytoplasm of hepatocytes increased and the volume density of the sinusoids and the space of Disse decreased. These changes were interpreted as an indication of cellular swelling. There was a significant increase in volume density, number, and absolute volume of lysosomes when Cu was given. The greatest increase in number occurred during the pre-hemolytic period (mean = 48 days), and the highest increase in volume occurred thereafter. Thus, the most extensive proliferation of lysosomes occurred in livers of the pre-hemolytic sheep, and the hemolytic sheep had the largest and heaviest lysosomes. The liver necrosis in sheep undergoing hemolysis was possible caused by hydrolytic enzymes released by the rupture of the enclosing lysosomal membranes. The significant increase in volume density of mitochondria observed in livers of sheep given Cu was due to an increase in volume (swelling) rather than an increase in number.

Animals↗
PubMed1980

Creatine kinase release and muscle changes in chronic copper poisoning in sheep.

Chronic copper poisoning was induced in sheep by repeated dosing with an aqueous solution of copper sulphate. A sudden rise in the level of plasma creatine kinase (CK) occurred at haemolysis but the level returned to normal once the 'crisis' was over. The level of CK in the cerebrospinal fluid remained normal throughout the experiments. An isoenzyme study showed that the CK was liberated from muscle. Light microscopic studies failed to reveal consistent changes in muscle structure but ultrastructural changes in mitochondria, similar to those described as the earlies changes in muscle fibres in vitamin E deficiency, were seen in sheep killed during and after haemolysis. The elevations of CK levels and the mitochondrial changes were most marked in sheep that did not receive selenium and vitamin E supplements. It is suggested that the CK release at haemolysis may occur because of a transient increase in the permeability of muscle membranes which may be brought about by a number of factors such as: (a) hypoxia, (b) hypercupraemia, (c) decrease in vitamin E and/or selenium content in blood and tissues.

Animals↗
PubMed1979

Intracellular distribution of copper in the liver of normal and copper loaded sheep.

Thirteen sheep were dosed repeatedly with copper sulphate in order to induce chronic copper poisoning. Twelve similar sheep acted as controls. Three dosed sheep were killed before haemolysis, six at haemolysis and four after cessation of the haemolytic crisis. The subcellular distribution of Cu, Zn, Fe and lysosomal marker enzymes was investigated in the livers of normal sheep and copper loaded sheep. In control sheep the highest concentration of Cu was in the nuclear fraction. Copper loading increased the concentration of Cu in all fractions. The proportion of Cu in the nuclear fraction continued to increase while that in the heavy mitochondrial fraction decreased. Significant increase in lysosomal enzymes along with electron microscopic studies on pellets of fractions indicated: (a) proliferation of lysosomes, (b) possible localisation of Cu in lysosomes, and (c) sedimentation of the denser lysosomes on N and MH fractions in test sheep with the majority being in the N fraction. Thus the increase in Cu observed in the N fraction is at least partly due to the storage of Cu by lysosomes which sediment with the heavier nuclei. The excessive deposition of Cu in lysosomes and nuclei may lead to cell damage. With increase in hepatic Cu concentration the proportion of Zn and Fe in the cytosol decreased.

Acid Phosphatase↗
PubMed1979

Clinical and electrocardiographic findings in suspected viral myocarditis of pups.

Surviving puppies from three separate litters in which deaths had occurred from suspected viral myocarditis were examined clinically and electrocardiographically. Of 11 puppies examined, 5 subsequently died or were euthanised within 11 days of initial examination. ECG changes present in these puppies for 1 to 11 days prior to death were small R waves (less than 0.4 mV in lead II), S-T segment elevation, QRS notching and paroxysmal ventricular tachycardia (PVT). No clinical signs referable to the ECG changes were present before the terminal episodes of apparent sudden death or death following a brief period of dyspnoea. Multifocial subacute myocarditis was present on post-mortem examination. A sixth puppy with small R waves remained clinically normal for a further 4 weeks. It then developed severe dyspnoea which persisted for 24 hours before euthanasia. Extensive fibrosis of the left ventricle was present on post-mortem examination.

Animals↗
PubMed1979

Copper, zinc and iron levels in the cerebrospinal fluid of copper poisoned sheep.

Copper, zinc and iron levels were measured in cerebrospinal fluid (CSF) of normal and copper poisoned sheep. Copper values were within the range recorded for humans but zinc levels were six to 20 times and iron levels were 20 to 30 times higher than values reported for humans. The amount of copper, zinc and iron in the CSF did not increase in sheep dosed with copper and hence it is unlikely that the level of copper in the CSF is related to the changes in the nervous system that have been reported in copper poisoned sheep.

Animals↗
PubMed1977

Copper toxicity in sheep: the effects of repeated intravenous injections of copper sulphate.

Four Clun Forest, Suffolk cross sheep were given daily intravenous injections of copper sulphate. Three similar sheep acted as controls. The copper dosed sheep developed haemolysis and showed liver, kidney and brain damage similar to that seen in chronic copper poisoning. All animals survived for 30 days and two would have lived longer. Reticulocytes were produced after four days and continued to be produced, sometimes in high number throughout the course of the experiment.

Animals↗
PubMed1975

Experimental chronic copper toxicity in sheep. Changes that follow the cessation of dosing at the onset of haemolysis.

Eight sheep were given daily oral doses of copper sulphate until haemolysis occurred. Three of the sheep developed further periods of haemolysis after dosing ceased. Serum enzyme and urea levels were measured throughout the experiment and compared to those obtained from three undosed control sheep. Serum enzyme levels rose prior to haemolytic crises and urea levels rose subsequent to haemolysis in animals that died or were killed in extremis. Severe morphological changes were seen in liver, kidney and brain. Tissue levels of copper and iron were markedly elevated. It is concluded that tissue damage continues even after the cessation of ingestion of copper and that the damage can be severe enough to lead to repeated haemolytic crises.

Alcohol Oxidoreductases↗