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Biomedical subjects

J H Adams

Publications and source records attributed to J H Adams.

At least 73 records · Page 4Linked to original sources

The Duffy receptor family of Plasmodium knowlesi is located within the micronemes of invasive malaria merozoites.

Plasmodium vivax and Plasmodium knowlesi merozoites invade human erythrocytes that express Duffy blood group surface determinants. A soluble parasite protein of 135 kd binds specifically to a human Duffy antigen. Using antisera affinity purified on the 135 kd protein, we cloned a gene that encodes a member of a P. knowlesi family of erythrocyte binding proteins. The gene is a member of a family that includes three homologous genes located on separate chromosomes. Two genes are expressed as major membrane-bound products that give rise to soluble erythrocyte binding proteins: the 135 kd Duffy binding protein and a 138 kd protein that binds only rhesus erythrocytes. These different erythrocyte binding specificities may result from sequence divergence of the homologous genes. The Duffy receptor family is localized in micronemes, an organelle found in all organisms of the phylum Apicomplexa.

Amino Acid Sequence↗

Glycogen accumulation in axons after stretch injury.

Thin-section cytochemistry has been used to demonstrate the formation of glycogen deposits within axons after stretch injury to the optic nerve of adult guinea pigs in a model of focal axonal injury. Glycogen deposits occurred within 17% of structurally normal but, we suggest, damaged fibres within the stretched optic nerve. Adjacent fibres did not stain for glycogen. Small numbers of beta glycogen particles were present 15 min after injury within damaged axons and increasing numbers of particles occurred until 72 h. Degeneration bulbs formed by 72 h, but beta glycogen particles were sparse within these. By 7-14 days after injury there was a marked reduction in the numbers of glycogen particles within axons. Alpha rosettes of glycogen were infrequent within damaged axons. Deposition of glycogen particles within astrocytes after nerve injury was confirmed. Alpha rosettes of glycogen occurred within astrocytes by 6 h and remained until 14 days after injury. Possible mechanisms for the development of glycogen deposits within damaged axons are discussed in relation to a hypothesized influx of Ca2+ at the time of injury into damaged axons. We suggest that glycogen deposition within reactive axons reflects Ca2+ mediated alteration of glycogen synthase activity and compromized axonal transport.

Animals↗

Cerebral lymphomas: review of 70 cases.

Seventy cerebral lymphomas from 37 men and 33 women were reviewed and reclassified using the modified Kiel classification. Fifty two of the patients were over the age of 50 years (age range 23-85 years). Only two patients were known to be immune deficient--one case of AIDS and one renal transplant recipient. Necropsies only were performed on 31 cases, biopsies only in 23 cases, and both biopsies and necropsies in 16 cases. Systemic tumour was found in 16 of 47 necropsy cases. All the tumours available for review were classic diffuse non-Hodgkin's lymphomas. Where immunocytological studies were positive, the tumour cells were of B cell origin. None was of T cell origin, although reactive T cells in the tumours were frequently identified. It is concluded from this and other studies that the incidence of intrinsic cerebral lymphomas is increasing.

Adult↗

Cerebral radiation necrosis complicating stereotactic radiosurgery for arteriovenous malformation.

A patient presented with symptoms and signs of raised intracranial pressure and increasing focal deficit 13 months after stereotactic radiosurgical treatment of an arteriovenous malformation (AVM). Computed Tomography (CT) showed a mass lesion at the site of the previous abnormality typical of radiation necrosis, but with features identical to those of a malignant neoplasm. Biopsy confirmed cerebral radiation necrosis. The radiation dose was 25 Gray to the periphery of two overlapping 14 mm collimator fields, delivered in a single dose. Treatment with steroids led to improvement in the symptoms and signs of raised intracranial pressure, but not the focal deficit. Radiation necrosis is a consequence of the large doses required to obliterate AVMs and is a limiting factor in their treatment. It is important for clinicians referring patients for stereotactic radiosurgery to be aware of this complication, and to be able to recognise and treat it.

Adult↗

Changes in the hippocampus and the cerebellum resulting from hypoxic insults: frequency and distribution.

Detailed neurohistological studies were undertaken on 35 cases of cardiac arrest, 17 of hypoglycaemia and 16 of status epilepticus. It was found that the frequency and pattern of selective vulnerability in the hippocampus were similar following cardiac arrest, hypoglycaemia and status epilepticus with the exception that the lateral limb of the dentate fascia was more frequently involved in hypoglycaemia than in the other two groups of cases. Within each group, however, CA1 was the most vulnerable. The cerebellum was less frequently affected in hypoglycaemia and status epilepticus than after cardiac arrest. These findings are compared with recent experimental studies in the rodent which have suggested that the pattern of neuronal damage in each of the three conditions is different.

Cerebellum↗

Post-exercise ketosis and the glycogen content of liver and muscle in rats on a high carbohydrate diet.

Post-exercise ketosis is known to be suppressed by physical training and by a high carbohydrate diet. As a result it has often been presumed, but not proven, that the development of post-exercise ketosis is closely related to the glycogen content of the liver. We therefore studied the effect of 1 h of treadmill running on the blood 3-hydroxybutyrate and liver and muscle glycogen concentrations of carbohydrate-loaded trained (n = 72) and untrained rats (n = 72). Resting liver and muscle glycogen levels were 25%-30% higher in the trained than in the untrained animals. The resting 3-hydroxybutyrate concentrations of both groups of rats were very low: less than 0.08 mmol.l-1. Exercise did not significantly influence the blood 3-hydroxybutyrate concentrations of trained rats, but caused a marked post-exercise ketosis (1.40 +/- 0.40 mmol.l-1 h after exercise) in the untrained animals, the time-course of which was the approximate inverse of the changes in liver glycogen concentration. Interpreting the results in the light of similar data obtained after a normal and low carbohydrate diet it has been concluded that trained animals probably owe their relative resistance to post-exercise ketosis to their higher liver glycogen concentrations as well as to greater peripheral stores of mobilizable carbohydrate.

3-Hydroxybutyric Acid↗

Nematospiroides dubius: influence of adjuvants on immunity in mice vaccinated with antigens isolated by affinity chromatography from adult worms.

Five adjuvants were examined for their ability to potentiate the immune response of mice to soluble antigens from adult Nematospiroides dubius prepared by affinity chromatography against antibodies from repeatedly infected mice as ligands (IMIgAg). Immunized mice were better protected against N. dubius by IMIgAg injected intraperitoneally with either pertussigen (75%) or aluminium hydroxide (Alum) (67%) as adjuvants than with Freud's complete (54%) or incomplete adjuvants (31%). Protection was correlated with elevated specific antibody values and with cellular responses. Quil A was toxic to recipient mice at the concentration used. Alum may be a more practical adjuvant than pertussigen, which may activate protective immunity only in specific recipient genotypes and oil-based adjuvants which appear to be less efficient, to vaccinate mice with soluble parasite antigens.

Adjuvants, Immunologic↗

Immunity in mice vaccinated with a molecular weight 60,000 glycoprotein secreted by adult Nematospiroides dubius.

A mol. wt 60,000 glycoprotein was purified from adult Nematospiroides dubius excretory-secretory products (ES) by polyacrylamide gel electrophoresis and electroelution and used to vaccinate BCF1 mice. This molecule is also released from the surface of the parasite and can be cleaved by pepsin. Mice immunized twice with ES 60,000 in Alum adjuvant harboured similar numbers of N. dubius as did control mice but voided 40% fewer parasite eggs in their faeces. The mol. wt 60,000 component in ES and from the surface of the parasite appears to influence how the parasite reproduces and may be important to its survival.

Animals↗

Low molecular weight immunosuppressors secreted by adult Nematospiroides dubius.

Adult Nematospiroides dubius excretory-secretory products (ES) were collected from worms cultured in vitro, separated by sodium dodecyl sulphate--polyacrylamide gel electrophoresis (SDS-PAGE) into four fractions (FI-IV), electroeluted and assessed for their ability to inhibit the proliferation of mouse lymphocytes stimulated by mitogens in vitro. The proliferation of mitogen- and ES-stimulated mouse spleen lymphocytes from normal and infected mice was inhibited by low mol. wt ES F-IV (less than 26,000).

Animals↗

Proteolytic enzymes in excretory-secretory products from adult Nematospiroides dubius.

Excretory-secretory products (ES), collected from in vitro cultures of adult Nematospiroides dubius, were examined for proteolytic enzyme activity. ES enzymes had a pH optimum of 8.0 and their activity was sensitive to serine-proteinase inhibitors. Three SDS-resistant proteases were identified in ES at molecular weight (mol. wt) 200,000, 105,000 and 48,000 by incorporating substrates into the matrices of sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE) gels.

Animals↗

Heterologous antibody responses of calves to Anaplasma centrale and A. marginale.

Antigens of Anaplasma centrale, Onderstepoort isolate, and A. marginale, Wacol isolate, were analysed by a Western blotting technique. Sera from A. centrale-infected calves reacted to 41- and 38-kDa antigens in A. centrale and a 41-kDa antigen in A. marginale. Serum collected during the primary reaction from an A. marginale-infected calf reacted only to the 41-kDa antigen of A. marginale; heterologous antibody response to the 41-kDa antigen of A. centrale did occur later during the infection, but remained markedly weaker than the homologous response. The serologic cross-reactivity to this 41-kDa Anaplasma antigen confirms that it is common to the genus and also that it is a heterogeneous complex.

Anaplasma↗

Excretory-secretory antigens from adult Nematospiroides dubius.

Adult Nematospiroides dubius excretory-secretory (ES) products were collected from worms cultured in vitro, radiolabelled and separated by sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE). The components were characterized and assessed for molecular weight (MW) after autoradiography and gel staining, for antigenicity in immunoblots, for sensitivity to protease enzymes, and for carbohydrate content. ES contained at least 18 denatured components from MW less than 20,000 to greater than 200,000. At least one of the surface proteins of adults was found with the ES antigens recovered when adults were cultured in vitro. Molecules with MW 200,000, 78,000 and 60,000 were glycoproteins and reacted with immune mouse serum in Western blots. The dominant ES, MW 60,000 component stained with periodic acid-Schiff (PAS), bound lectins with affinity for D-mannose, and was resistant to peptic and tryptic but not V8 protease digestion.

Animals↗

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↗

Glycogen metabolism and post-exercise ketosis in carbohydrate-restricted trained and untrained rats.

Liver and muscle glycogen, and blood 3-hydroxybutyrate concentrations were studied during and for 2 h after treadmill running for 1 h, in 144 carbohydrate-starved trained and untrained rats. The resting liver glycogen concentration of the trained animals was 227 +/- 8 (mean +/- S.E.M.) mumol glucosyl units/g wet mass, compared with 162 +/- 12 mumol/g in the untrained animals. The muscle glycogen levels were 42 +/- 1 and 28 +/- 1 mumol/g respectively. Exercise reduced muscle and liver glycogen concentrations by approximately the same absolute amounts in both animal groups, leaving the trained rats with nearly 3 times as much residual glycogen as the untrained animals. There was very little resynthesis of muscle glycogen recovery, but the trained animals replenished approximately 43% of the liver glycogen used during exercise. The blood 3-hydroxybutyrate concentrations were negatively correlated with the simultaneous liver glycogen concentration of our experimental animals (r = -0.55; P less than 0.001). It is concluded that trained animals primarily owe their resistance to post-exercise ketosis to their large stores of glycogen.

3-Hydroxybutyric Acid↗

Release of merozoite dense granules during erythrocyte invasion by Plasmodium knowlesi.

We used immunoelectron microscopy to study the fate of dense granules during the invasion of erythrocytes by Plasmodium knowlesi merozoites. When merozoites entered host cells, dense granules moved to the pellicle, released their contents into the parasitophorous vacuole space, and then moved into fingerlike channels of the vacuole membrane. This is the first report showing that the content of dense granules of P. knowlesi is different from the contents of rhoptries and micronemes and is associated with the formation of channels from the parasitophorous vacuole.

Animals↗

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↗

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↗