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Biomedical subjects

D Doyle

Publications and source records attributed to D Doyle.

At least 127 records · Page 7Linked to original sources

Deep intracerebral (basal ganglia) haematomas in fatal non-missile head injury in man.

Deep intracerebral (basal ganglia) haematomas were found post mortem in 63 of 635 fatal non-missile head injuries. In patients with a basal ganglia haematoma, contusions were more severe, there was a reduced incidence of a lucid interval, and there was an increased incidence of road traffic accidents, gliding contusions and diffuse axonal injury than in patients without this type of haematoma. Intracranial haematoma is usually thought to be a secondary event, that is a complication of the original injury, but these results suggest that a deep intracerebral haematoma is a primary event. If a deep intracerebral haematoma is identified on an early CT scan it is likely that the patient has sustained severe diffuse brain damage at the time of injury. In the majority of head injuries damage to blood vessels or axons predominates. In patients with a traumatic deep intracerebral haematoma, it would appear that the deceleration/acceleration forces are such that both axons and blood vessels within the brain are damaged at the time of injury.

Adolescent↗

Life-threatening respiratory failure due to a previously undescribed myopathy.

The case of a young man with a previously undescribed myopathy associated with polydactyly is reported. Although both limb girdles were affected, the major effect of the disease was upon the respiratory muscles leading to his presentation with life-threatening respiratory failure. A further feature was pronounced stiffness of the vertebral column and limb girdles, similar in some respects to the 'rigid spine syndrome'. Muscle biopsy appearances were unique but showed some similarities to both nemaline myopathy and myotonic dystrophy. Ventilatory assistance at night using a rocking bed led to a marked improvement and has enabled the patient to return to full-time employment.

Adult↗

Osteoarthritis.

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Female↗

Gliding contusions in nonmissile head injury in humans.

"Gliding" contusions, ie, hemorrhagic lesions in the parasagittal white matter, were analyzed in 434 fatal nonmissile head injuries in humans. It is concluded that gliding contusions are a type of diffuse brain damage occurring at the moment of injury. Gliding contusions are significantly associated with road-traffic accidents, with the absence of a skull fracture or a "lucid interval," and with the presence of diffuse axonal injury and deep hemispheric traumatic hematomas.

Accidents, Traffic↗

N-Linked oligosaccharides of the H-2Dk histocompatibility protein heavy chain influence its transport and cellular distribution.

The H-2K and H-2D proteins encoded by the K and D region of the major histocompatibility complex of the mouse were isolated by immunoprecipitation with specific antisera and resolved by two-dimensional gel electrophoresis. Of these two polypeptides, the H-2Dk glycoproteins isolated from macrophages of C3H/HeHa mice exhibit distinct cell surface and cytoplasmic forms although they share a strong degree of homology in the polypeptide backbone. Structurally they differ in their oligosaccharide structures. The structure of the oligosaccharides on the intracellular forms is of the high mannose type while the same structures on the cell surface forms are of the complex type. In the absence of all three oligosaccharide side chains, the unglycosylated polypeptides are expressed on the cell surface. In contrast, polypeptides containing one, two, or all three oligosaccharide side chains of the high mannose type are not transported to the cell surface. Cell surface expression of these glycoproteins requires processing of the oligosaccharide side chains from the high mannose form to the complex type. However, not all oligosaccharide antennae have to be terminally modified since H-2Dk glycoproteins synthesized in the presence of oligosaccharide-processing enzyme inhibitors such as swainsonine or monensin are also transported to the cell surface. H-2Dk glycoproteins containing oligosaccharide structures of the complex type but lacking terminal sialic acids are found on the cell surface, suggesting that sialylation is not required for transport. These results indicate that the oligosaccharide structures of the H-2Dk glycoproteins act to influence their cellular distribution.

Animals↗

Turnover of plasma membrane proteins in rat hepatoma cells and primary cultures of rat hepatocytes.

The half-lives of turnover of plasma membrane proteins in rat hepatoma tissue, culture cells, and in primary cultures of rat hepatocytes have been analyzed after resolution by two-dimensional gel electrophoresis. Cell membranes were externally labeled via iodination catalyzed by lactoperoxidase and glucose oxidase. A bimodal pattern of turnover was found for the externally oriented plasma membrane proteins of rat hepatoma cells. Three glycoproteins analyzed in these cells had an average t 1/2 of 22 h while eight proteins which did not bind to concanavalin A had an average t 1/2 of 80 h. In contrast, more heterogeneous rates of turnover were found for the externally oriented plasma membrane proteins of primary cultures of hepatocytes. Most, if not all, of the membrane proteins accessible to iodination in these cells were glycoproteins. Among the glycoproteins resolved by two-dimensional polyacrylamide electrophoresis, the receptors for asialoglycoproteins had the shortest half-lives (18 h). Other glycoproteins, mostly with higher molecular weights and different isoelectric points, showed a spectrum of half-lives ranging from 16 to 99 h. The turnover rates of membrane proteins of primary cultures of rat hepatocytes were also determined with [3H]- and [35S]methionine labeling of cells. Heterogeneous rates of turnover again were found among the labeled glycoproteins and nonglycoproteins. Among the 10 glycoproteins individually analyzed, the half-lives range from 17 to 67 h. Among the 21 proteins which do not bind to concanavalin A, the half-lives range from 18 h to more than 100 h. Three proteins analyzed showed an apparent biphasic pattern of turnover, having a fast phase with a half-life of 4-6 h and a slow phase with a half-life of 15-29 h. Several nonglycoproteins, including clathrin and actin associated with membrane vesicles had extremely long half-lives. The more than 5-fold difference in the half-life between clathrin and the receptors for asialoglycoproteins, which coexist in coated pits indicates that intrinsic proteins of the coated pits turn over at a different rate than peripheral components.

Actins↗

Developmental regulation of the hepatocyte receptor for galactose-terminated glycoproteins.

The receptor which recognizes glycoproteins that have had their terminal sialic acids removed, thus exposing penultimate galactose residues (asialoglycoproteins), was examined for expression in rat liver during development. The level of asialoglycoprotein receptor binding activity in fetal rat livers was present in very low amounts but rose dramatically at the time of birth and reached adult levels by the second day after birth. Using immunoquantitation methods, it was found that the increased binding capacity of rat liver for asialoglycoproteins during development reflected accumulation of receptor molecules rather than activation of previously existing ones. The relative rates of synthesis of the predominant polypeptide of Mr 42,000 and the lesser abundant polypeptides of Mr 50,000 and 58,000 which comprise asialoglycoprotein receptor were found to increase in livers of fetuses near term and attain adult synthesis rates around birth. Thus, the accumulation of receptor protein molecules during development reflected increased synthesis of receptor polypeptides. These results suggest that the different gene products which code for the three forms of the receptor are coordinately expressed during development. Copurifying with asialoglycoprotein receptor during ligand affinity chromatography were polypeptides of Mr 25,000 and 27,000. These polypeptides display several characteristics similar to hepatic mannose binding lectin described by others. Onset of synthesis of the mannose binding lectin during development was analogous to asialoglycoprotein receptor but, in contrast, did not reach adult synthesis rates immediately after birth.

Animals↗

Hemimegalencephaly--a case for hemispherectomy?

Two infants are described with intractable, drug-resistant seizures from birth associated with an enlarged cerebral hemisphere. The first died at sixteen months and demonstrated arrested head growth. Histology of the abnormal hemisphere showed disturbed cortical architecture, and subcortical heterotopias with multinucleate cells resembling tuberous sclerosis cells. Continuous fitting persisted in the second infant following callosal section. Hemispherectomy was undertaken in an attempt to preserve function of the "normal" hemisphere. Seizures ceased and head growth velocity accelerated. The neuropathology of the excised hemisphere is compared with the first case. From the literature this is the first report of a favourable outcome after hemispherectomy for hemimegalencephaly. The finding of an echodense enlarged hemisphere may allow presumption of this diagnosis in a neonate with unilateral seizures. After CT scan the diagnosis may be confirmed histologically providing that a precisely orientated frontal biopsy is submitted to the neuropathologist. We suggest that very early hemispherectomy may be the treatment of choice for this condition.

Brain↗

Diaphragmatic paralysis due to spinal muscular atrophy. An unrecognised cause of respiratory failure in infancy?

An unusual form of spinal muscular atrophy presenting with respiratory failure was observed in four infants from two families. In one, whose death was attributed to pneumonia, the diagnosis was inferred retrospectively after two siblings died from an identical illness and were shown to have diaphragmatic paralysis and the typical electrophysiological and histological features of spinal muscular atrophy. Other signs of skeletal muscular weakness were absent or inconspicuous. The fourth, unrelated infant presented in an identical way but has survived for over a year on a ventilator. Two months after the onset of respiratory paralysis, more extensive skeletal muscular weakness was seen. Other infants, dying of unexplained respiratory illness, may have this disorder and some may be included in the miscellany of disorders that constitute the sudden infant death syndrome.

Female↗

Oligodendroglioma and cerebral cavernous angioma. Case report.

The authors report a case of frontal lobe oligodendroglioma associated with a cavernous angioma. The patient presented with signs and symptoms of raised intracranial pressure. Computerized tomography with contrast enhancement failed to detect the vascular component. The clinical and pathological significance of the presence of this vascular malformation in an oligodendroglioma is discussed.

Adult↗

Diffuse axonal injury in head injuries caused by a fall.

82 cases of diffuse axonal injury were found at necropsy in 635 patients with fatal nonmissile head injuries. 13 of these injuries were attributable to falls, and in all the patients fell from a considerable height. Diffuse axonal injury was not found in those with head injuries caused by a simple fall--ie, a fall from not more than the person's own height--but there was a statistically significant association between the presence of diffuse axonal injury and falls from a considerable height. These results indicate that diffuse axonal injury rarely, if ever, occurs as a result of a fall unless the patient has fallen some distance.

Accidents↗

An immunological study of delta-aminolevulinic acid dehydratase specificity consistent with the phylogeny of species.

Rabbit antibody directed to homogeneously purified mouse liver delta-aminolevulinic acid dehydratase cross-reacted with the enzyme in erythrocytes, spleen, kidney and brain in the mouse. The antibody also cross-reacted with the enzyme in the rat, hamster and gerbil, but not in the rabbit, guinea pig, cattle, chick embryo, and human. In contrast, rabbit antibody against the human enzyme partially recognized the monkey enzyme, but not the enzyme in the other species. The species specificity of delta-aminolevulinic acid dehydratase in this study was consistent with the phylogenetic evolution of the species examined.

Animals↗

Transfer of plasma membrane proteins between cells using reconstituted membrane vesicles as shuttle vehicles.

Purified membrane glycoproteins from liver or hepatoma tissue culture cells were incorporated in a right-side-out orientation into reconstituted phospholipid vesicles by a detergent dialysis method. The phospholipids were purified from membrane preparations of rat liver. The protein:phospholipid ratio of the reconstituted vesicles was optimized for efficient transfer of vesicle contents to the recipient cells, usually mouse L cells. Fluoresceinated albumin incorporated into the lumen of reconstituted vesicles was used as a marker for transfer after polyethylene glycol-mediated fusion. The redistribution and fate of both the lipids and the transferred membrane proteins were analysed by microscopic and biochemical methods. A hepatocyte-specific binding protein for galactose- or galactosamine-terminated serum glycoproteins and a set of hepatoma cell plasma membrane glycoproteins were successfully transferred to the plasma membrane of mouse fibroblasts by these methods. The biological function of the hepatic binding protein, namely delivery of the galactose-terminated glycoprotein ligand to the lysosome for degradation, was imparted to the mouse fibroblast after transfer. Further, both the polypeptide and the carbohydrate moieties of a set of membrane proteins were degraded at about the same relative rates as they had in the original donor cells, after transfer to the plasma membrane of recipient mouse fibroblasts. These studies show that the technique of inserting membrane constituents into the plasma membrane of another cell can help to elucidate the route and mechanism of membrane protein function and turnover.

Animals↗

Experience with operative transluminal balloon-catheter dilatation of the coronary arteries.

A technique is presented for hand dilatation of coronary artery segments not amenable to bypass with a balloon catheter. This technique is used in 8% of patients undergoing routine coronary artery bypass surgery. Problems with catheter design, although troublesome, have resulted in no adverse sequelae to the coronary arteries. Postoperative angiography has revealed a good result in 71% of the lesions dilated. The technique is simple, is performed under direct visualization, and has proved to be safe.

Angioplasty, Balloon↗

Elective cardiac operation in a patient with severe hemophilia and acquired factor VIII antibodies.

This paper describes a successful cardiac operation in a young boy with hemophilia, congenital heart disease, severe factor VIII deficiency, and an acquired high titer antibody to factor VIII. To our knowledge, there have been no published cases of elective cardiac operations in a person with severe hemophilia and an accompanying complex problem. Utilizing the team approach, we administered a megadose bolus of factor VIII concentrate preoperatively (eight times the calculated dose), followed by a continuous intravenous infusion at 500 units/hr throughout the procedure and at a reduced dose for the first 5 postoperative days. With the anamnestic rise in factor VIII antibody on day 5, activated prothrombin complex concentrates were substituted for factor VIII and provided continued adequate hemostasis during the remaining 9 postoperative days. The rapid infusion of large quantities of factor VIII was effective in neutralizing the low titer inhibitor and providing normal hemostasis during the procedure. In addition, activated prothrombin complex concentrates were substituted for factor VIII coagulant without recurrent bleeding or thromboembolic phenomena.

Antibodies↗