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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

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↗

Fifty-four months' experience with an improved tilting disk valve (Medtronic-Hall).

Between 1978 and 1982, 230 consecutive patients underwent valve replacement with the Medtronic-Hall valve prosthesis. There were 95 patients with aortic valve replacement (AVR), 107 with mitral valve replacement (MVR) and 28 with aortic and mitral valve replacement (DVR). Operative mortality was 7.8%. Follow-up studies included 212 patients with a mean follow-up time of 26.5 months. Incidence of thromboembolism was 1.2%/patient year after AVR, 2.4%/patient year after MVR and 0 after DVR. Freedom from any kind of complications was 80% at 3 years. Recatheterization showed mean pressure gradients of between 0.0 and 6.0 mmHg in aortic prostheses and between 0.0 and 3.5 mmHg in mitral prostheses. It is concluded that the Medtronic-Hall valve prosthesis is a durable substitute with a low complication rate and good hemodynamic performance.

Adult↗

Establishment of plasma membrane domains in hepatocytes. I. Characterization and localization to the bile canaliculus of three antigens externally oriented in the plasma membrane.

A membrane fraction denoted N2 upper was isolated from homogenates of rat liver by sucrose gradient centrifugation. This fraction, which was enriched 65-fold over the homogenate in 5'-nucleotidase activity, was used as an immunogen in goats. The antisera obtained contained antibodies to three predominant polypeptides in the N2 upper membrane fraction, as shown by crossed immunoelectrophoresis. These polypeptides had molecular weights of 105,000, 110,000, and 160,000 after recovery from the crossed immunoelectrophoretic gels and are denoted PM105, PM110, and PM160. Each was a distinct polypeptide, as shown by the distinct peptide patterns resulting from limited proteolysis in the presence of detergents. The three polypeptides were synthesized by primary cultures of hepatocytes and were externally oriented at the surface of these cells, as shown by their accessibility in situ to iodination catalyzed by lactoperoxidase. They were not detectable in the serum by crossed immunoelectrophoresis. The three antigens were present at very low (PM110) or nondetectable (PM105, PM160) concentrations in intracellular membrane fractions derived from the Golgi and smooth and rough endoplasmic reticulum of liver. The antigens also were reduced in concentration in a plasma membrane fraction most likely derived from the sinusoidal surface of the hepatocyte. The three membrane antigens bind to concanavalin A; hence, they are probably glycoprotein constituents of a discrete domain of the hepatocyte plasma membrane. Immune complexes were isolated after crossed immunoelectrophoresis and injected into rabbits. Each of the antisera obtained was reactive to one of the membrane polypeptides. Sections of fixed rat livers were reacted with each of the antibodies and then the primary antibody was localized by indirect immunocytochemical methods using horseradish peroxidase or colloidal gold as labels. Each of the three antigens was localized by this method to the bile canalicular domain of the hepatocyte plasma membrane.

Animals↗

Glioma of the optic chiasm and its management.

The clinical features, radiological investigation and pathology of 9 cases of glioma of the optic chiasm are described and the place of radiotherapy in their management considered.

Adolescent↗

The oxygen cost of an escape from an underground coal mine.

Six 27- to 63-year-old coal miners performed an "escape" maneuver from an underground mine along a passageway that required walking and running erect or stooped, duck walking and crawling. The miners traveled at different speeds, for each mode of locomotion. The minute pulmonary ventilation (VE), O2 uptake (VO2) and heart rate (HR), recorded continuously on a magnetic tape via lightweight meters carried on the miners' waists, indicated similar average and peak values for all modes of locomotion. The mean VE, VO2 (L X min1, STPD) and HR (b X min1) were, respectively, 49, 1.63 and 143 for the average values, and 52, 1.92 and 161 for the peak values. Compared to the aerobic capacity obtained during graded treadmill test to exhaustion, the average effort of the "escape" was performed at 64% and the peak effort at 70% of the miners aerobic capacity for an "escape" time of 58 minutes.

Adult↗