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Biomedical subjects

D Doyle

Publications and source records attributed to D Doyle.

At least 73 records · Page 4Linked to original sources
PubMed1989

Diffuse axonal injury in head injury: definition, diagnosis and grading.

Diffuse axonal injury is one of the most important types of brain damage that can occur as a result of non-missile head injury, and it may be very difficult to diagnose post mortem unless the pathologist knows precisely what he is looking for. Increasing experience with fatal non-missile head injury in man has allowed the identification of three grades of diffuse axonal injury. In grade 1 there is histological evidence of axonal injury in the white matter of the cerebral hemispheres, the corpus callosum, the brain stem and, less commonly, the cerebellum; in grade 2 there is also a focal lesion in the corpus callosum; and in grade 3 there is in addition a focal lesion in the dorsolateral quadrant or quadrants of the rostral brain stem. The focal lesions can often only be identified microscopically. Diffuse axonal injury was identified in 122 of a series of 434 fatal non-missile head injuries--10 grade 1, 29 grade 2 and 83 grade 3. In 24 of these cases the diagnosis could not have been made without microscopical examination, while in a further 31 microscopical examination was required to establish its severity.

Adolescent↗
PubMed1989

Fatal head injury in children.

A comprehensive neuropathological study was undertaken on 87 children aged between 2 and 15 years with fatal head injuries to identify those features which occurred at the time of head injury (fractured skull, contusions, intracranial haematoma and diffuse axonal injury) and those which were subsequently produced by complicating processes (hypoxic brain damage, raised intracranial pressure, infection and brain swelling). The types of brain brain damage identified were remarkably similar to those seen in adults. The only difference was the prevalence of diffuse brain swelling in children.

Adolescent↗
PubMed1989

Ischaemic brain damage is still common in fatal non-missile head injury.

A detailed neuropathological examination has been undertaken on a consecutive series of head injuries dying in the Institute of Neurological Sciences, Glasgow, between 1968-72 (151 cases) and 1981-82 (112 cases) in order to determine the frequency and distribution of any ischaemic brain damage. Ischaemic damage was found in the brains of 92% of the 1968-72 cases and in 88% of the 1981-82 cases: there was no statistical difference in the amount of moderately severe and severe ischaemic damage in the two groups, 55% and 54% respectively. There was evidence, however, that an increased number of patients with severe ischaemic brain damage was admitted in 1981-82 as a result of a changed admission policy of the Department of Neurosurgery that resulted in an increased detection of intracranial haematomas. It is concluded that ischaemic brain damage is still common after severe head injury, and it seems likely that it remains an important cause of mortality and morbidity.

Adolescent↗
PubMed1989

Brain damage in fatal non-missile head injury in relation to age and type of injury.

Brain damage in a series of 635 fatal non-missile head injuries has been analysed with particular reference to the age of the patient and the type of injury. The differences in the type of brain damage in relation to age were less than we had anticipated, lending further support to the contention that the aged brain has a reduced potential for recovery. The analysis confirms the relationship between road traffic accidents, diffuse axonal injury, gliding contusions and 'basal ganglia' haematomas, and the importance of diffuse brain swelling resulting from a head injury in children.

Adolescent↗
PubMed1989

Acute renal failure due to McArdle's disease.

A 37-year-old previously fit man developed acute renal failure associated with rhabdomyolysis following a brief period of strenuous exercise. Subsequent muscle biopsy and ischaemic arm exercise confirmed the diagnosis of McArdle's disease. This case illustrates that McArdle's disease can present with acute renal failure in the absence of a past history of exercise-induced muscle pain and stiffness.

Acute Kidney Injury↗
PubMed1989

Light and electron microscopic changes in sural nerves in Ethiopian diabetics.

The light and electron microscopic morphological changes in sural nerve biopsies from 32 Ethiopian diabetics and 4 malnourished non-diabetic subjects were studied in order to determine the role of malnutrition in the development of diabetic neuropathy. The most prominent finding in diabetics with clinical neuropathy was reduction in the density of myelinated axons of all diameters especially the large ones. Affected nerves showed abundant intraneural collagen, and evidence of nerve regeneration in some cases. Demyelination, though present, was less marked. Changes in the vasa nervorum were seen in only one case. The morphological changes correlated with the duration and severity of the diabetes and with nerve conduction velocity. No changes were seen in malnourished non-diabetics and diabetics without clinical neuropathy, thus suggesting that malnutrition by itself does not contribute significantly to the development of diabetic neuropathy. Axonal degeneration appears to be the predominant feature in diabetic neuropathy.

Adolescent↗
PubMed1988

Membrane orientation of rat gp110 as studied by in vitro translation.

We have recently isolated a full-length cDNA clone for a membrane glycoprotein with apparent Mr of 110,000, denoted gp110, that is expressed in rat liver, kidney, small intestine, and lung. Analysis of the amino acid sequence derived from cDNA sequencing demonstrated that there is a highly hydrophobic domain at the amino terminus (amino acid residues 1-29) that looks like the amino-terminal signal sequence. Using in vitro transcription and translation systems, we have expressed the full-length gp110 cDNA transcript, as well as transcripts derived from truncated gp110 cDNA that terminate translation at different sites. As expected, the amino-terminal signal sequence can promote the translocation across microsomal membranes of the downstream sequence. Like most translocations, the cotranslational translocation of the downstream sequence initiated by the gp110 amino-terminal signal sequence is mediated by signal recognition particle and docking protein. Unlike most amino-terminal signal sequences of lysosomal, secretory, and membrane proteins, the amino-terminal signal sequence of gp110 is not cleaved and may be involved in anchoring the polypeptide to the membrane. We, therefore, predict that the membrane orientation of gp110 is of type II with an extremely small amino-terminal cytoplasmic domain (6 residues).

Amino Acid Sequence↗
PubMed1988

Identification of a complex of the three forms of the rat liver asialoglycoprotein receptor.

We have generated antibodies against synthetic peptides which represent the carboxyl terminus of either the major, or the two minor, forms of the rat hepatic lectin which recognizes galactose-terminated glycoproteins (asialoglycoproteins). The antibodies were shown to be specific for the form of the lectin containing the immunizing peptide sequence by the following: reaction with purified lectin after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoprecipitation of sodium dodecyl sulfate-denatured lectin, immunoprecipitation of lectin synthesized in vitro. These antibodies, however, precipitated all three rat hepatic lectin forms from nonionic detergent extracts of hepatocytes labeled with 125I via the lactoperoxidase catalyzed technique. A similar result was obtained if antibody was bound to intact cells prior to solubilization with detergent and collection of the immune complexes. We conclude that at least the plasma membrane-associated fraction of the rat hepatic lectin forms exists as a heterotypic complex.

Animals↗
PubMed1988

Differential phosphorylation of murine class I major histocompatibility antigens.

Recent studies have shown that the H-2K and H-2D transplantation antigens are expressed differentially in different tissues of mouse. Our previous investigations also established that in thioglycolate-stimulated peritoneal macrophages the H-2Dk antigen exists in distinct cell surface and intracellular forms. These two forms are glycosylated differently. In this report, we have found that (1) H-2Dk antigen is phosphorylated whereas H-2Kk antigen is not, and (2) only the cell surface form of H-2Dk antigen is phosphorylated in thioglycolate-stimulated macrophages derived from C3H/Heha mice. This differential phosphorylation of H-2 antigens will provide a model system for further studies on the molecular mechanism and function of phosphorylation of H-2 antigens.

Animals↗
PubMed1988

Analysis of renal and hippocampal type I and type II receptors by fast protein liquid chromatography.

Type I and Type II adrenal steroid receptors from rat renal and hippocampal cytosols were studied by the technique of Fast Protein Liquid Chromatography. Type I receptors were labelled with [3H]aldosterone plus excess RU26988, and Type II receptors with [3H]dexamethasone. On a Mono Q anion exchange column the molybdate-stabilized renal and hippocampal Type I receptors both eluted as single symmetrical peaks at 0.27 M NaCl, with a recovery of approximately 90% and 60-fold purification (renal) and 10-15-fold (hippocampal). Molybdate-stabilized Type II binding sites from both hippocampal and renal cytosols co-eluted with the Type I sites. On Superose gel filtration renal Type I receptor-steroid complexes consistently eluted two fractions later than hippocampal Type I complexes, suggesting that the renal complexes are smaller; Type II receptor-steroid complexes from both cytosols co-eluted, consistently one fraction behind hippocampal Type I sites. Sequential gel filtration and anion exchange chromatography achieved a 1000-fold purification of renal Type I binding sites, with an overall recovery of 10%.

Androstanols↗
PubMed1988

Asialoglycoprotein receptor genes are linked on chromosome 11 in the mouse.

The asialoglycoprotein receptor on the hepatocyte plasma membrane recognizes galactose-terminated glycoproteins and internalizes them for subsequent degradation in lysosomes. The rat receptor, also known as rat hepatic lectin (RHL), is comprised of three protein subunits called RHL-1, RHL-2, and RHL-3; two genes code for RHL-1 and RHL-2/3, respectively. We have cloned and sequenced the gene for RHL-2/3, and demonstrated that homologous asialoglycoprotein receptor genes exist in the mouse genome. Biochemical studies have demonstrated that receptor subunits exhibit the same temporal expression during development and function in a coordinate manner. This study asks if mouse receptor genes are linked and thus could possibly respond to shared cis-acting regulatory elements. Using restriction fragment length polymorphisms (RFLPs) and recombinant inbred lines, we mapped two closely linked mouse hepatic lectin (MHL) genes to chromosome 11. Asgr is designated to name asialoglycoprotein gene loci. Coordinate regulation of this linked gene family is discussed.

Animals↗
PubMed1988

Brain damage in fatal non-missile head injury without high intracranial pressure.

As part of a comprehensive study of brain damage in 635 fatal non-missile head injuries, the type and prevalence of brain damage occurring in the absence of high intracranial pressure were analysed. Of 71 such cases, 53 sustained their injury as a result of a road traffic accident; only 25 experienced a lucid interval. Thirty eight had a fractured skull, a mean total contusion index of 12.9 and diffuse axonal injury in 29: severe to moderate ischaemic damage was present in the cerebral cortex in 25, brain swelling in 13, and acute bacterial meningitis in nine. The prevalence and range of brain damage that may occur in the absence of high intracranial pressure are important to forensic pathologists in the medicolegal interpretation of cases of fatal head injury.

Adolescent↗
PubMed1988

Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatine kinase.

Enterovirus-specific probes have been prepared by reverse transcription of conserved sequences in purified Coxsackie B2 virus genomic RNA and molecular cloning techniques. These probes were used in quantitative slot blot hybridizations to test for the presence of enterovirus-specific RNA in skeletal muscle biopsy specimens from 96 patients who had suffered from the postviral fatigue syndrome myalgic encephalomyelitis for up to 20 years. Biopsy specimens from 20 patients were positive for the presence of virus-specific RNA with hybridization signals more than three standard deviations greater than the mean of the normal muscle controls. Biopsies from the remaining 76 patients were indistinguishable from the controls. These data show that enterovirus RNA is present in skeletal muscle of some patients with postviral fatigue syndrome up to 20 years after onset of disease and suggest that a persistent virus infection has an aetiological role.

Adolescent↗
PubMed1988

Medtronic-Hall prosthesis: valve related deaths and complications.

The purpose of this retrospective study was to assess the clinical performance of the Medtronic-Hall prosthesis based on a review of all valve related complications over a period of nine years. From January 1978 until December 1986, 502 prostheses were implanted in 450 patients. There were 200 aortic valve replacements, 198 mitral valve replacements and 52 double valve replacements. There were 234 associated procedures performed, the most frequent being coronary grafting in 129 patients and tricuspid annuloplasty in 35 patients. The mean age of the patients (230 men and 220 women) was 54.08 +/- 11.7 years. Preoperatively, 92.2% were in NYHA class III or IV. Early mortality was 7.1% and late mortality 16.7%. The follow-up totalled 1733 patient-years (mean 49.8 +/- 31.7 months). Over a period of nine years, the valve related complication rate was 4.4% per patient-year. Thromboembolic events occurred in 37 patients (2.1% per patient-year), anticoagulant related hemorrhage in 23 patients (1.3% per patient-year), endocarditis in 11 patients (0.6% per patient-year), perivalvular leak in six patients (0.3% per patient-year) and death and reoperation in 28 patients (1.6% per patient-year). At eight and one-half years, the survival rate was 71.28 +/- 2.7% for the whole group. The actuarial rate of patients free from all valve related complications was 75.92 +/- 2.7%, rate of freedom from thromboembolism was 86.01 +/- 2.4%, freedom from anticoagulant related hemorrhage was 92.7 +/- 1.6%, freedom from endocarditis was 97.17 +/- 0.8%, freedom from perivalvular leak was 98.27 +/- 0.7% and freedom from death and reoperation was 90.70 +/- 1.9%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Isolation and characterization of a Mr = 110,000 glycoprotein localized to the hepatocyte bile canaliculus.

A Mr = 110,000 glycoprotein, GP 110, was partially purified using wheat germ agglutinin-Sepharose affinity chromatography from a bile canalicular-enriched membrane fraction denoted N2u of rat liver. This fraction was subjected to preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the Mr = 110,000 polypeptide was excised and used as an immunogen in rabbits. The antisera were found to specifically recognize a Mr = 110,000 polypeptide, named GP 110, in the N2u membrane fraction. In isolated hepatocytes, GP 110 was readily accessible to cell surface iodination catalyzed by lactoperoxidase at 4 degrees C and was judged by immunoprecipitation studies to contain about 2% of total radioactivity incorporated into externally oriented proteins of the cell. Immunoprecipitated GP 110 was shown by two-dimensional polyacrylamide gel electrophoresis to migrate with an approximate pI of 4.9. Indirect immunofluorescence on frozen liver sections demonstrated that GP 110 was primarily localized in the bile canaliculus. In corroborative studies employing subcellular fractionation, it was found that GP 110 was enriched nearly 19-fold in P2, a plasma membrane fraction primarily derived from the sinusoidal domain, and 44-fold in N2u. In contrast, only low levels of GP 110 were present in endoplasmic reticulum, mitochondrial, cytosolic, and nuclear-enriched fractions of liver. The physiological function of GP 110 is as yet unknown; antisera to it did not immunoprecipitate other known bile canalicular proteins of similar molecular weights. GP 110 was found to be extensively glycosylated relative to other known membrane proteins; approximately 33% of the apparent molecular weight appear to be carbohydrate. In agreement, limited removal of N-linked carbohydrate chains indicated that there are approximately eight chains/GP 110 polypeptide. Neuraminidase treatment of GP 110 resulted in a desialylated Mr = 85,000 polypeptide suggesting that the majority of carbohydrate chains on GP 110 are of the complex type.

Animals↗
PubMed1987

Biosynthesis and turnover of a Mr = 110,000 glycoprotein localized to the hepatocyte bile canaliculus.

Antiserum was raised in rabbits against a bile canalicular glycoprotein of Mr = 110,000 purified to homogeneity from of rat liver. The antisera specifically immunoprecipitated a Mr = 110,000 polypeptide from hepatocytes metabolically labeled with [35S]methionine. When hepatocytes in primary culture were incubated with tunicamycin before labeling with [35S]methionine in the presence of tunicamycin, the major polypeptide immunoprecipitated by the specific antiserum from Triton X-100 extracts of cells had a molecular weight of 59,000. Enzymatic removal of N-linked carbohydrates from the Mr = 110,000 glycoprotein by N-glycanase digestion also yielded a polypeptide with minimum Mr = 59,000. In pulse-chase experiments using [35S]methionine, the Mr = 110,000 protein detected by the specific antisera first appears as Mr = 85,000 and 75,000 intermediate species which are endoglycosidase H sensitive. The Mr = 85,000 intermediate form is lost first with time followed by the Mr = 75,000 form giving rise to the Mr = 110,000 form that is endoglycosidase H resistant. Neuraminidase digestion of the Mr = 110,000 form generated an Mr 85,000 form but with a different carbohydrate structure than the intermediate Mr 85,000 form detected in the pulse-chase experiments. The time required to accomplish the processing of the Mr = 85,000 and 75,000 forms is relatively slow. Finally, the terminal sugars are added and the mature Mr = 110,000 glycoprotein is rapidly transported to the cell surface. A minimum time of 90 min is required for the Mr = 110,000 bile canalicular glycoprotein to be synthesized, processed, and reach the cell surface which is long relative to the time required (10 min) for another domain-specific protein, the receptor for asialoglycoproteins, to reach the sinusoidal surface. The Mr = 110,000 bile canalicular glycoprotein turns over in the bile canalicular domain with a half-life of 43 h while the asialoglycoprotein receptor turns over in the sinusoidal domain with a half-life of 23 h.

Animals↗