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Biomedical subjects

D Doyle

Publications and source records attributed to D Doyle.

At least 199 records · Page 11Linked to original sources
PubMed1978

Ischaemic brain damage in fatal non-missile head injuries.

The incidence and distribution of ischaemic brain damage in a consecutive series of 151 patients who died as a result of a non-missile head injury in the Institute of Neurological Sciences was determined on the basis of a comprehensive neuropathological and neurohistological examination. Ischaemic damage was identified in 138 cases (91%) even after excluding cases who only had necrosis and infarction related to contusions or fat embolism, and infarction in the brain stem of the type conventionally associated with raised intracranial pressure. The ischaemic damage was assessed as severe in 37 (27%), moderately severe in 59 (43%) and mild in 42 (30%), and in the 138 cases with ischaemic brain damage it was found more frequently in the hippocampus (122 cases; 81%), and in the basal ganglia (119 cases; 79%) than in the cerebral cortex (70 cases; 46%) and in the cerebellum (67 cases; 44%). There were statistically significant correlations between ischaemic brain damage and either an episode of hypoxia or of raised intracranial pressure. From the nature of the brain damage it seems likely that much of it was due to a reduction in the cerebral perfusion pressure. This study has shown that ischaemic brain damage is common after head injury, that at least a proportion of it is probably avoidable, and that it is more important as a cause of mortality and morbidity after head injury than has been hitherto realised.

Adolescent↗
PubMed1978

Genetics of the large, external, transformation-sensitive (LETS) protein: assignment of a gene coding for expression of LETS to human chromosome 8.

Techniques have been developed to analyze the genetics of the large, external, transformation-sensitive (LETS) protein (fibronectin). External membrane proteins of human-mouse somatic cell hybrids with reduced numbers of human but not mouse chromosomes were labeled by lactoperoxidase-catalyzed iodination. Cell surface proteins were identified after sodium dodecyl sulfate/polyacrylamide gel electrophoresis by autoradiography of the dried gel. The LETS protein was identified in parental human cells, and LETS segregated in human-mouse cell hybrids formed from human WI-38 fibroblasts and a mouse L-cell line not expressing LETS. The LETS protein segregated concordantly with the chromosome 8 enzyme marker glutathione reductase (EC 1.6.4.2) and human chromosome 8. These findings demonstrate that a gene, LETS, encoded on chromosome 8, is responsible for the LETS protein expression in humans. Because LETS has been implicated in tumorigenicity and cellular transformation, it is of interest that rearrangement or modifications in the number of chromosome 8 have been associated with certain forms of cancer.

Animals↗
PubMed1978

Changes in the nuclei of astrocytes following portacaval shunting and portacaval transposition in the rat.

Structural abnormalities are found in the astrocytes of the dentate nuclei of animals after portacaval shunting (PCS). These changes are also found in man in association with portal-systemic encephalopathy. To investigate the relationship between portal-systemic shunting and hepatocellular dysfunction in the pathogenesis of these changes, PCS and protacaval transposition (PCT) were performed in rats. PCT diverts portal blood into the systemic circulation, but retains normal total hepatic blood flow by perfusion with systemic venous blood. Liver function and mass are better preserved than after PCS. Abnormal glial cells were found in 4.03% of animals following sham operation, 13.45% following PCT, and 19.09% following PCS. Both experimental groups differed significantly from control animals, and the number of abnormal cells was significantly higher after PCS than after PCT. These findings are in keeping with the hypothesis that hepatocellular dysfunction plays an important role in addition to portal-systemic shunting in the aetiology of the structural changes in the brain associated with hepatic encephalopathy.

Animals↗
PubMed1977

Diffuse brain damage of immediate impact type. Its relationship to 'primary brain-stem damage' in head injury.

In a neuropathological analysis of 151 fatal non-missile head injuries, there were 19 cases with focal lesions in the dorsolateral quadrant of the brain-stem in the corpus callosum, and histological evidence of diffuse damage to white matter. Eight of these cases had not experienced a high intracranial pressure during life. All 19 cases had been rendered unconscious at the moment of impact and had remained so or in the persistent vegetative state until death. It is therefore concluded that diffuse damage to white matter may occur as a primary event at the moment of impact, that is, it is one type of immediate impact damage to the brain. It is also concluded that this type of damage is the pathological basis of 'primary brain-stem injury' since in no patient thought clinically to have sustained 'primary brain-stem injury' were abnormalities confined to the brain-stem. Since no patient with this type of brain damage recovered consciousness after injury, it is probable that diffuse damage to white matter is the most important single factor governing the outcome in a patient who sustains a non-missile head injury.

Adolescent↗
PubMed1977

Neuroectodermal tumours in the cerebellum in two sisters.

Two sisters, one 5 years and the other 2 years old, with intrinsic tumours of the cerebellum are reported. One of the tumours was interpreted as being a ganglioneuroma with neuroblastomatous change. The other was a desmoplastic medulloblastoma.

Cerebellar Neoplasms↗
PubMed1976

Abnormal purine metabolism and purine overproduction in a patient deficient in purine nucleoside phosphorylase.

To delineate the normal function of purine nucleoside phosphorylase and to understand the pathogenesis of the immune dysfunction associated with deficiency of this enzyme, we studied purine metabolism in a patient deficient in purine nucleoside phosphorylase, her erythrocytes and cultured fibroblasts. She exhibited severe hypouricemia and hypouricosuria but excreted excessive amounts of purines in her urine, the major components of which were inosine and guanosine. Her urine also contained deoxyinosine, deoxyguanosine and uric acid 9-N riboside. The patient's erythrocytes but not her cultured fibroblasts contained increased concentrations of phosphoribosylpyrophosphate and inosine. The metabolic abnormalities resembled those in the erythrocytes of patients with the Lesch-Nyhan syndrome. Purine nucleoside phosphorylase is a necessary component of the major, if not the sole, pathway for the conversion of purine nucleosides and nucleotides to uric acid. The increased intracellular concentrations of inosine may, by inhibiting adenosine deaminase, be related to the immunologic dysfunction.

Child↗
PubMed1976

Synthesis of functional aldolase tetramers in a heterologous cell-free system.

The present report describes the complete synthesis of a functional oligomeric enzyme in a heterologous cell-free system. Polysomal RNA from chicken skeletal muscle was used to direct the production of functional aldolase tetramers in wheat germ extracts. The aldolase product was (a) specifically precipitated with monospecific antibodies raised against pure muscle aldolase, (b) had the same subunit molecular weight (40,000) as that of native aldolase (as determined by acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate), (c) presumably contained a functional active site since it co-purified with authentic muscle aldolase upon substrate elution from phosphocellulose, and (d) had associated into tetrameric units (Mr=160,000) as shown by centrifugation in sucrose gradients. The present work suggests that, within the cell, post-translational processing of aldolase polypeptide chains is not involved in the formation of functional aldolase tetramers.

Animals↗
PubMed1976

Turnover of the plasma membrane proteins of hepatoma tissue culture cells.

The turnover of the plasma membrane proteins of hepatoma tissue culture cells was examined by three different methods--loss of polypeptides labeled in situ by lactoperoxidase-catalyzed iodination, loss of membrane polypeptides labeled with amino acid precursors, and loss from the membrane of fucose-labeled polypeptides. In both logarithmically growing and density-inhibited cells the proteins of the membrane are degraded with a half-life of about 100 hours. This is longer than the half-life of total cell protein, 50 to 60 hours, and longer than the doubling time of the cells, about 30 hours. Similar values for the rate of degradation of the membrane proteins were obtained by each of the three techniques. The same fucose-labeled polypeptides are present in the microsomal and the plasma membrane fractions of hepatoma tissue culture cells as analyzed by electrophoresis in dodecyl sulfate-acrylamide gels. But the fucose-labeled polypeptides were lost from the microsomal fraction at a faster rate than from the plasma membrane. Autoradiographic and double labeling techniques using 125I and 131I, or [3H]leucine and [14C]leucine were used to measure the relative rates of degradation of the proteins in the plasma membrane. All of the leucine-labeled polypeptides and the iodinated polypeptides had similar rates of degradation. These results support a model for the biogenesis of the plasma membrane in which the proteins are incorporated and removed in large structural units.

Carcinoma, Hepatocellular↗
PubMed1976

Proteins of the hepatoma tissue culture cell plasma membrane.

The specificity of lactoperoxidase-catalyzed iodination for the proteins of the hepatoma tissue culture cell plasma membrane was examined by histochemical, biochemical, and cell fractionation techniques. Light microscope autoradiography of sectioned cells shows the incorporated label to be localized primarily at the periphery of the cell. Most of this label can be released from the cell by trypsin but not by collagenase or hyaluronidase. The label is recovered from the cells as either monoiodotyrosine or diiodotyrosine after hydrolysis of cell extracts with a mixture of proteolytic enzymes. The label co-purifies during cell fractionation with an authentic liver cell plasma membrane marker enzyme, 5'-nucleotidase. Thus, the incorporated iodide is itself a valid marker for those membrane polypeptides having tyrosine residues accessible to the lactoperoxidase. The polypeptide complexity of the purified plasma membrane was examined by high resolution dodecyl sulfate-polyacrylamide gel electrophoresis. At least 50 polypeptides in the membrane are accessible to iodination. These polypeptides probably represent the bulk of the protein mass of the membrane and iodinating them does not affect cell viability, growth rate, or cell function. Labeling experiments with fucose and glucosamine show that at least nine of the iodinated peptides may be glycoproteins.

Carcinoma, Hepatocellular↗
PubMed1975

Superficial antigens of Campylobacter (Vibrio) fetus: characterization of antiphagocytic component.

A glycoprotein responsible for the antiphagocytic properties of Campylobacter fetus has been identified by comparing cells of a wild-type strain with those of a mutant lacking this substance. The antiphagocytic component is demonstrable through electron microscopy as a discrete, negatively charged structure on the periphery of the cell. CLT is readily removed from the cell by mild extraction procedures and contributes to the inagglutinability in O antiserum normally displayed by C. fetus. Cells possessing this antigen are refractory to ingestion by macrophages except in the presence of specific antiserum. In its absence maximum phagocytosis occurs without a requirement for opsonins. It is concluded that the antiphagocytic component comprises a critical virulence factor of the bacterium.

Animals↗
PubMed1975

Flagellar ultrastructure and flagella-associated antigens of Campylobacter fetus.

Ultrastructural examinations of the flagellum of Compylobacter (Vibrio) fetus were performed throughout the growth cycle. Filament diameters, exceeding 17.6 nm during the exponential phase, were substantially greater than those reported for unsheathed flagella of other genera with the exception of Pseudomonas fluorescens. Filament diameters increased during growth, reaching a mean width of 21.2 nm in middle to late stationary phase. Internal flagellar structure, principally of the parallel lined variety, was observed during the later periods of growth but not during exponential or early stationary phase. Despite the unusually large filament sizes, no evidence of a flagellar sheath was observed after selected treatments (0.01 N HCl, 6 M urea, tris(hydroxymethyl) amino-methane-hydrochloride buffer, warm water) or examination of thin sections. To determine whether alterations in filament size and variable ability to demonstrate filament fine structure were correlated with progressive changes in serological activity, agglutination and immobilization tests were conducted with antisera directed against intact flagella, the principal flagellar antigen, the O antigen, and a superficial glycoprotein which has been found in association with the flagellum and the cell envelope. Significant differences in the serological activity of cells at different growth intervals were not noted with any of the sera employed.

Agglutination Tests↗
PubMed1975

Acute lead poisoning: Five cases resulting from self-injection of lead and opium.

Five cases of acute lead poisoning resulted from the self-injection of lead and opium pills which were crushed, heated and suspended in water. Two of the five patients died of illnesses in which hepatic failure and reversible acute tubular necrosis were prominent features. One of these two had a severe neuropathy, with flaccid quadriplegia and respiratory paralysis. The other three patients had relatively minor symptoms but unequivocal biochemical evidence of lead toxicity. Autopsy changes included hepatic degeneration with inclusion bodies, regenerating renal tubular epithelium and wasting of skeletal muscle. Hepatic lead content was extremely high in one case. Chelation therapy in the other fatal case resulted in a fall in blood lead to within normal limits and a clinical improvement, which was terminated by massive haemorrhage from a ruptured innominate artery.

Acute Disease↗
PubMed1974

Myopathy with mitochondrial inclusion bodies: histological and metabolic studies.

Apparently new information about a metabolic abnormality has been obtained by measuring biochemical and respiratory responses to controlled exercise in a patient with abnormal mitochondria in muscle fibres. A male patient (49 years old) presented with bilateral ptosis of 15 to 20 years' duration and weakness for one to two years. Biopsies from the deltoid and triceps muscles were subjected to histological, histochemical, and electron microscopical examination. Routine histology showed only minor changes; 2-5% of muscle fibres had pale borders in which there were aggregates of mitochondria and 1-5% of fibres showed atrophy. Histochemical examination showed increased activity of succinic dehydrogenase in mitochondria and lactate dehydrogenase in cytoplasm. Electron microscopy showed crystalline inclusions in many subsarcolemmal mitochondria. Metabolites were studied during and after exercise on an ergometer and revealed remarkable differences from normal. Blood lactate rose to 12·5 μmol/ml and pyruvate to 0·39 μmol/ml compared with up to 4·0 and 0·16 μmol/ml respectively in controls exercising to a comparable percentage of capacity. Concentrations of ketone-bodies and free fatty acids fell during and after exercise, while they rose in the controls. These observations imply a major mitochondrial defect which causes dramatic biochemical changes in fuel supply in blood during exercise. The changes suggest that fat metabolism was accelerated (in this patient) and was related to a block of carbohydrate utilization as fuel.

Biopsy↗