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Biomedical subjects

R J Wilson

Publications and source records attributed to R J Wilson.

At least 109 records · Page 6Linked to original sources
PubMed1988

Glucose-6-phosphate dehydrogenase activity of the malaria parasite Plasmodium falciparum.

Schizonts of Plasmodium falciparum, grown either in normal or glucose-6-phosphate dehydrogenase (G6PDH) deficient human red cells, contain an electrophoretically slow-moving form of G6PDH. The slow mobility of the G6PDH in non-dissociating polyacrylamide gels is due to its large size (Mr ca. 450,000) rather than to its charge. The activity of this enzyme was less than 10% of normal red cell G6PDH. These characteristics of the parasite-associated G6PDH were unaltered when parasites were grown in red cells from a G6PDH A+B+ heterozygote or following the introduction of a heterologous G6PDH into resealed ghosts. Differential absorption of the parasite-associated and red cell G6PDHs was demonstrated with antisera containing antibodies to red cell G6PDH. These studies show that a novel form of G6PDH is associated with P. falciparum in normal red cells without the requirements for induction by one or several cycles of multiplication in G6PDH deficient red cells.

Animals↗
PubMed1988

Lack of biochemical progression or continuation of accelerated bone loss in mild asymptomatic primary hyperparathyroidism: evidence for biphasic disease course.

We studied the natural history of primary hyperparathyroidism in patients in whom the disease was discovered fortuitously by multichannel biochemical screening and who were selected for conservative management because they were asymptomatic, had no renal stone disease or radiographic osteitis fibrosa, and had serum calcium values below 3.00 mmol/L, serum creatinine levels below 133 mumol/L, and forearm bone density not more than 2.5 SD below the mean expected for age, sex, and race. One hundred and seventy-four patients meeting these criteria were encountered during a 10-yr period, of whom 80 (mean age, 61 yr) had adequate follow-up; they did not differ significantly in any initial characteristic from the remaining 94 patients. These 80 patients were followed for 1-11 yr (mean, 46 months; median, 38 months), during which there was no change, mean or individual, in any index of PTH secretion or any of its biochemical effects and no decline in forearm bone density apart from that expected from increased age. There were 4 deaths from causes unrelated to hyperparathyroidism, and the overall death rate was not increased. The data suggest that no change occurred in either the number of parathyroid cells or secretory set-point, the 2 principal determinants of basal PTH secretion. This implies a biphasic course, with a short period of disease progression followed by a long period of disease stability. Our data support the decision to withhold surgical intervention in such patients, but to establish this as the correct policy for all asymptomatic patients will require a controlled clinical trial.

Aged↗
PubMed1988

Conditioning of physical symptoms after neurotoxic exposure.

Psychologic reactions to a neurotoxic exposure can produce prolonged physical symptoms which are as debilitating as the direct effects of the neurotoxic substance. A group of patients exist who experience reoccurrence of exposure-related symptoms when exposed to a variety of common environmental substances, such as perfume, gasoline, and cigarette smoke. We propose a classical conditioning model to explain the development of this phenomenon. Identification and treatment of these individuals are also discussed.

Adult↗
PubMed1987

Possible pitfalls in the identification of glycophorin-binding proteins of Plasmodium falciparum.

Plasmodium falciparum proteins that bind to the putative erythrocyte receptor (glycophorin) have been identified in several laboratories by their ability to bind to glycophorin immobilized on aminoethyl-BioGel (AE-BioGel). We here report that several parasite proteins bind to AE-BioGel in the absence of coupled glycophorin. Binding is apparently due to the strong ion-exchange properties of the matrix, and is sensitive to ionic conditions such as the degree of equilibration of the matrix and the pH. The parasite proteins that bind to the blank column under appropriate conditions include proteins with the serological activities of S-antigen and Ag 23, which also bind to glycophorin-coupled AE-BioGel. In the light of these results, the glycophorin-binding specificity of these and other proteins reported to bind to glycophorin-coupled AE-BioGel will have to be reevaluated, preferably using a different support matrix.

Carrier Proteins↗
PubMed1987

Potentiation of the antimalarial activity of qinghaosu by methoxylated flavones.

Interaction between the flavones casticin and artemetin and the antimalarial activity of chloroquine and qinghaosu (QHS) was examined using an in vitro growth assay based on [3H]hypoxanthine incorporation in synchronized cultures of a cloned line of Plasmodium falciparum. Casticin, and to a lesser extent artemetin, selectively enhanced the inhibition of growth by QHS, but had little effect on the activity of chloroquine. The findings suggest that flavones indigenous to Artemisia annua, from which QHS is isolated, might significantly alter the clinical potential of this novel antimalarial drug in the treatment of chloroquine-resistant malaria.

Animals↗
PubMed1987

[Coat's type retinitis pigmentosa].

A twenty-two-year-old woman with a history of long-Standing retinitis pigmentosa and recently discovered bilateral exudative retinal detachments of the Coats' type is described. This widely unrecognized association has been reported to occur in up to 2% of patients with retinitis pigmentosa. Unlike the usual Coats' syndrome, it is more often bilateral, shows no sex preference and occurs in older individuals. Heightened awareness of this potentially treatable complication of retinitis pigmentosa may facilitate earlier recognition of the problem, which may lead to more timely treatment and a better prognosis.

Adult↗
PubMed1987

Cytoplasmic factor required for entry of malaria parasites into RBCs.

Resealed ghosts of human RBCs, containing diluted cytosol, are susceptible to invasion by Plasmodium falciparum. If ATP is present, a dilution of up to about 30-fold, corresponding to an intracellular hemoglobin concentration of approximately 10 mg/mL, can be tolerated without total loss of susceptibility to invasion. Up to a dilution of about one-half this, the parasites also develop normally. When the cytosol is diluted by more than the critical amount, invasion of the resulting resealed ghosts falls off abruptly. If the diluent buffer is replaced by extraneous concentrated hemolysate, an indefinite dilution is possible without loss of invasion. There is thus an intracellular constituent, which must be present at a concentration above some critical level if the parasite is to enter the cell. The factor in question is not dialyzable. It is largely inactivated when the hemolysate is kept for approximately 1 day in the cold or for approximately 20 minutes at 45 degrees C. The inability of a heat-treated hemolysate to support invasion is not due to the generation of inhibitory products, because such a solution can be used as a diluent of a fresh hemolysate without inhibition of invasion. When the inactivated hemolysate is present as a major component, however, the parasites fail to develop to the trophozoite stage. The invasion-linked factor remains in the strongly adsorbed nonheme fraction when a batchwise separation from hemoglobin on an anion exchanger is made and is thus probably acidic in character; the adsorbed fraction, recovered from the ion-exchanger, substantially restores capacity for invasion when sealed into ghosts. Its activity is destroyed by treatment with trypsin. The adsorbed fraction contains many proteins. When fractionated on a gel filtration column by fast liquid chromatography, active material eluted at a volume corresponding to a mol wt for a globular protein in the region of 10,000. A component of apparent subunit mol wt of 13,000 was observed in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of this eluate fraction.

Adenosine Triphosphate↗
PubMed1986

Plasmodium falciparum: protease inhibitors and inhibition of erythrocyte invasion.

Invasion of human red blood cells by Plasmodium falciparum is inhibited by the protease inhibitors, leupeptin and chymostatin. The efficacy of chymostatin was reduced if the cells were first treated with chymotrypsin. On the other hand, exposure of fresh cells to the supernatant from a synchronous culture at the reinvasion stage showed no such effect. This suggests that a proteolytic step occurs in the course of invasion and may be confined to the region of contact between the invading parasite and the erythrocyte. To test this, leupeptin or chymostatin was introduced into lysed cells, which were then resealed. The intracellular inhibitor strongly reduced invasion. Leupeptin also caused a striking effect on the development of the trophozoite stage of the parasites: a massive vacuole, apparently containing undigested haemoglobin, developed within the parasite. This did not totally stop development and the vacuolated parasites could be recovered in relatively pure form by lysis of the parasitised host cells with saponin.

Animals↗
PubMed1986

Immunoprecipitation of malarial acid endopeptidase.

Electrophoresis of extracts of schizonts of Plasmodium knowlesi in non-dissociating polyacrylamide gels, separates several bands of acid endopeptidase activity. A polyclonal antiserum, produced by immunization with purified merozoites, failed to distinguish between different bands of the parasite enzyme, indicating that they are serologically related. Apart from the loss of one minor peak, extraction in Triton X-100 did not reduce the enzyme's electrophoretic heterogeneity. The antiserum did not react with red cell acid proteases.

Animals↗
PubMed1986

Antibodies to the glutamate dehydrogenase of Plasmodium falciparum.

Polyclonal antisera raised against Plasmodium knowlesi reacted with NADP-specific glutamate dehydrogenase (GLDH) of P. knowlesi, GLDH of P. falciparum and GLDH of Proteus spp. The antisera did not react with NAD(P) GLDH from bovine liver. Polyclonal antisera raised against the GLDH of Proteus spp. cross-reacted with GLDH from P. falciparum. Monoclonal antibodies (McAbs) obtained from mice immunized with Proteus GLDH were either specific for the bacterial enzyme or cross-reacted with P. falciparum GLDH. The selected McAbs did not react with GLDH from P. knowlesi, P. chabaudi or P. berghei. The GLDH of P. falciparum was shown to be a cytosolic protein (by FAT) with a subunit molecular weight of approximately 49 000 Da (by immunoprecipitation) having a predominantly hexameric form (by sucrose density gradient). Implications of the conserved sequences of GLDHs and other enzymes are discussed.

Animals↗
PubMed1986

Inhibition of malarial invasion by intracellular antibodies against intrinsic membrane proteins in the red cell.

It has previously been shown that antibodies against the transmembrane proteins, band 3 and glycophorin A, inhibit entry of the merozoite into the red cell and, in the case of band 3, it was established that attachment of the parasite to the cell is not prevented. We have found that antibodies against the cytoplasmic domains of band 3 and of glycophorin A, when present in the interior of resealed ghosts of human red cells, also inhibit invasion by P. falciparum. It is inferred that attachment of the merozoite to the red cell causes structural effects that are transduced to the membrane cytoskeleton and the antibodies against transmembrane proteins interfere with the invasion sequence at this level.

Animals↗
PubMed1986

Antigenic diversity and size diversity of Plasmodium falciparum antigens in isolates from Gambian patients. I. S-antigens.

Ring-stage asexual parasites of P. falciparum were collected from six Gambian children and the S-antigens radiolabelled by 3H-glycine uptake during in vitro culture up to rupture of infected cells and merozoite release. Ouchterlony double diffusion of boiled culture supernatants against a panel of adult Gambian sera identified one S-antigen precipitin arc for five isolates and two precipitin arcs for one isolate. Five of the six isolates were serologically distinct. Analysis of S-antigens by comparison of SDS-polyacrylamide gel electrophoresis patterns of heat-treated soluble proteins revealed a more complex pattern of 3H-labelled S-antigens that was different for each isolate. There were between two and six different 3H-labelled bands for each isolate in the size range of molecular weight 137 000 to 285 000. This result confirms the large size range of S-antigens identified with culture adapted P. falciparum. Several bands were relatively weakly labelled with 3H-glycine, suggesting that natural isolates contain one or two predominant S-antigen phenotypes and several other S-antigen phenotypes expressed by minor parasite subpopulations. Immunoprecipitation was performed using a panel of sera from Gambian adults, or, acute and 3 week convalescent sera from the same patients used for S-antigen radiolabelling. Adult sera generally immunoprecipitated some of the S-antigens in each isolate, including antigens that must represent extremely minor parasite subpopulations since they could not be seen in the patterns of non-immunoprecipitated heat-stable proteins. Sera from convalescent children were generally negative on immunoprecipitation, even with the homologous isolate. In one case we observed the acquisition of specific immunoprecipitating antibody to one of the homologous S-antigens during the convalescent period. The antigenic and structural complexity of S-antigens in natural isolates that have not been submitted to the selection pressure of adaptation for in vitro culture is clearly greater than for culture adapted P. falciparum.

Adult↗
PubMed1986

Subconjunctival hemorrhage: overview and management.

Subconjunctival hemorrhage is a commonly presenting clinical problem for the optometrist. Although it is usually benign, it can be caused by a variety of entities, each with their own important sequelae. It is necessary to perform a comprehensive work-up of a patient with this problem including a thorough case history to rule out trauma, infection, medications, or systemic disease as the causative agent. The anatomy of the conjunctiva is reviewed, examination procedures are described, management issues are discussed, and case reports are presented.

Adult↗
PubMed1985

Stage-specific production of S-antigens of Plasmodium falciparum in vitro.

Stage-specific synthesis and release of the S-antigen of Plasmodium falciparum was demonstrated using 3H-glycine-labelled, synchronous, cloned parasite populations. The release of S-antigens into culture supernatants was first evident 25 to 30 hours after initiation of the parasite cycle and correlated with the rupture of the most mature schizonts. S-antigen release reached a peak at 37 to 43 hours at the height of the reinvasion cycle. Intracellular production of S-antigens was evident slightly earlier (19 to 24 hours) and correlated with the initial appearance of schizonts.

Animals↗
PubMed1985

Nuclear and mitochondrial DNA of the primate malarial parasite Plasmodium knowlesi.

Restriction analyses and DNA/DNA hybridisation of parasite DNA isolated from monkeys infected with the malarial parasite Plasmodium knowlesi has permitted unambiguous identification of the nuclear DNA of this species. Its (G+C) content, as determined by estimations of buoyant density as well as by direct analysis, is about 38%, essentially indistinguishable from that of its primate laboratory host, and grossly different from that of the major human malaria parasite, P. falciparum, which has a (G+C) content of approx. 19%. In addition, gradient fractionation of total P. knowlesi DNA revealed a minor DNA component (approx. 1% of the total) with a (G+C) content of about 19%. This DNA comprises covalently closed circular molecules which have a contour length about 11.6 microns, carry a small cruciform structure, and are thought to originate in the parasite's mitochondria.

Animals↗