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Biomedical subjects

R J Wilson

Publications and source records attributed to R J Wilson.

At least 91 records · Page 5Linked to original sources

Differential expression of the psbB and psbH genes encoding the 47 kDa chlorophyll a-protein and the 10 kDa phosphoprotein of photosystem II during chloroplast development in wheat.

The nucleotide sequence of a region of wheat chloroplast DNA containing the psbB gene for the 47 kDa chlorophyll a-binding protein of photosystem II has been determined. The gene encodes a polypeptide of 508 amino acid residues which is predicted to contain six hydrophobic membrane-spanning regions. The psbB gene is located 562 bp upstream of the psbH gene for the 10 kDa phosphoprotein of photosystem II. A small open reading frame of 38 codons is located between psbB and psbH, and on the opposite strand the psbN gene, encoding a photosystem II polypeptide of 43 amino acid residues, is located between orf38 and psbH. S1 nuclease mapping indicated that the 5' ends of transcripts were located 371 and 183 bp upstream of the psbB translation initiation codon. Predominant transcripts of 2.1 kb and 1.8 kb for psbB and 0.4 kb for psbH were present in RNA isolated from etiolated and greening wheat seedlings. Immunodecoration of Western blots indicated that the 47 kDa polypeptide was absent, or present in very low amounts, in dark-grown tissue and accumulated on greening, whereas the 10 kDa polypeptide was present in similar amounts in both dark-grown and greening seedlings. The 10 kDa polypeptide was phosphorylated in vitro by incubating wheat etioplast membranes with [gamma 32P] ATP.

Amino Acid Sequence↗

Organisation and expression of small subunit ribosomal RNA genes encoded by a 35-kilobase circular DNA in Plasmodium falciparum.

A restriction map of the 35-kb circular DNA molecule of Plasmodium falciparum showed that a region of about 6 kb, encoding both a large and a small subunit ribosomal RNA gene, has been duplicated in inverted orientation. The complete sequence of one small subunit rRNA gene is presented as well as an analysis of transcripts from erythrocytic stage parasites. Comparative sequence analysis of the rRNA gene and the proposed secondary structure of the rRNA suggest that it is of organellar origin. Intriguingly, while some characteristics of the small subunit rRNA gene are similar to mitochondrial sequences, others are more like those of plastids. The origin of the circular DNA molecule and evolutionary implications of its genetic content are discussed.

Animals↗

A circular DNA in malaria parasites encodes an RNA polymerase like that of prokaryotes and chloroplasts.

A 3.5-kb Sau3AI fragment was cloned from a circular DNA molecule isolated from the human malaria parasite Plasmodium falciparum and found to contain two contiguous open reading frames. These encode portions of beta and beta' subunits of an RNA polymerase similar to prokaryotic and chloroplast RNA polymerases, and contain highly conserved structural elements. The Plasmodium genes are arranged in a polycistronic transcription unit, as in both Escherichia coli and chloroplast genomes, and are transcribed in erythrocytic stages. These results suggest that the circular DNA may be an unusual mitochondrial DNA, or derived from an unidentified organelle. Because the beta subunit of prokaryotic RNA polymerases is the specific target of the antibiotic rifampicin, our observations may explain the high sensitivity of P. falciparum to this drug in vitro and indicate a new target for chemotherapy.

Amino Acid Sequence↗

Have malaria parasites three genomes?

Recent efforts to define the mitochondrial genome of malaria parasites have uncovered an unexpected complexity: there are two almost totally dissimilar organellar DNA molecules. lain Wilson, Malcolm Gardner, Jean Feagin and Donald Williamson discuss the surprising possibility that Plasmodium may have, in addition to the nuclear genome, two unrelated organellar genomes, one evidently mitochondrial and the other of unknown function.

Journal Article↗

Four-year follow-up results of a WHO-recommended multiple-drug regimen in paucibacillary leprosy patients in Malawi.

An evaluation of a World Health Organization-recommended multidrug therapy (WHO/MDT) in 499 paucibacillary leprosy patients is described. Patients were followed for 48 months after completion of treatment. Overall relapse rates after treatment were found to be 6.5 per 1000 person years (95% confidence interval 3.4-11.4). There were 12 relapses. A relative lack of cell-mediated immunity, as suggested by number of lesions, clinical classification and lepromin test results, and poor compliance with the dapsone component of WHO/MDT, appeared to be associated with a marginally increased risk of relapse. Severe type 1 reactions after completion of treatment occurred in 17 (3.5%) patients, 15/17 during the first 12 months of follow-up. Overall, 12 (2.5%) patients developed new disabilities during or after WHO/MDT.

Adolescent↗

Rate nephelometric determination of rheumatoid factor: comparison between Kallestad QM-300 and Beckman ICS-II (RF) methods.

The Kallestad Corporation recently suggested that their new buffer system for the nephelometric detection of rheumatoid factor conferred advantages over existing systems. Two rate nephelometric procedures, the Kallestad QM-300 and the Beckman ICS-II (RF), were therefore compared. Sera (n = 157) were selected on the basis of a previous ICS-II value. The results on the QM-300 of sera with an initial rheumatoid factor value of less than 400 IU identified two groups. Group 1 (n = 109) showed a good correlation with the ICS-II method while group 2 (n = 13) was highly discordant with the QM-300, producing significantly higher values. The values of 35 sera with an initial rheumatoid factor of greater than 400 IU were likewise highly discordant, with the QM-300 producing significantly lower values. Dilution recovery experiments implied that the Beckman buffer was likely to be contributory. As the formulae of the buffers remain proprietary, the reasons for the differences are speculative. The findings could be taken to indicate that the Kallestad value is a more accurate indicator of the quantity of rheumatoid factor than the Beckman value.

Buffers↗

Biochemistry of red cell invasion.

We are still far from an explicit understanding of the events that characterize the invasion of red cells by malarial parasites at the structural and biochemical levels. The nature of the interaction between the attached parasite and the host cell; the origin of the parasitophorous vacuole; the identity, disposition, and arrangement of the propulsive proteins of the parasite; the functions of the rhoptry organelles; and the rearrangement of the host cell membrane to permit entry of the parasite remain to be elucidated. A hypothetical scheme is presented that pursues the processes involved in invasion from the biochemical events generated by attachment of the parasite, to the steric rearrangement of red cell membrane proteins, which culminates in invasion.

Animals↗

Detection of antibodies to extractable nuclear antigens using calf thymus and rabbit thymus. A comparative study of 1000 consecutive anti-nuclear antibody positive patients.

A comparison between calf thymus extract and rabbit thymus extract to determine their suitability for clinical laboratories in detecting antibodies to extractable nuclear antigens (ENA) was undertaken. Calf thymus extract (CTE) detected 90% more ENA positive patients and 155% more lines than rabbit thymus extract (RTE). In contrast to RTE, CTE resolved Sm and RNP into two distinct lines, had superior stability at -80 degrees C and produced greater clarity of definition of precipitin lines.

Animals↗

A study of red cell membrane properties in relation to malarial invasion.

The shape and mechanical properties of human red cells were modified in several ways and the consequences for the efficiency of invasion by Plasmodium falciparum in culture were investigated. Inhibition of invasion by depletion of ATP was shown to be unrelated to cell shape or deformability changes. Treatment of cells with N-ethylmaleimide (NEM), which dissociates some 70% of the native spectrin tetramers into the dimer, grossly reduced deformation of the cells under shear and increased by a factor of two or more the shear elastic modulus, as measured by the micropipette aspiration technique. Cells thus treated were efficiently invaded by P. falciparum (ca. 75% of control). In a population of cells pretreated with chlorpromazine, parasites were found in stomatocytic cells which were highly undeformable under shear. There was also considerable invasion into cells from subjects with hereditary pyropoikilocytosis, and two types of elliptocytosis. Cells treated with wheat germ agglutinin showed a dose-dependent increase in rigidity; a fivefold increase in elastic modulus (with total loss of deformation under shear in our conditions) still permitted invasion at a level of 50% of the control. The results suggest that gross mechanical properties of the membrane per se, at least within any physiologically relevant range, are unlikely to be the primary determinant of malarial invasion; this may instead be linked to the freedom of membrane proteins to migrate in the course of entry of the parasite.

2,3-Diphosphoglycerate↗

Red cell deformability and invasion by malaria parasites.

Malaria parasites enter red cells in a multi-step process involving attachment, membrane deformation, invagination and encapsulation. The molecular basis of red cell rigidity is examined by Geoff Pasvol and lain Wilson, and they discuss its effect on the efficiency of invasion by various Plasmodium spp.

Journal Article↗

Optometry in the multidisciplinary health care setting.

A variety of health care delivery settings and models have been established in the 1980s. The multidisciplinary setting encourages comanagement and continuity of care, provides convenient consultation and communication, and is cost effective. It stimulates learning, helps to consolidate management strategies, and results in improved quality of care. Therefore, the patient and the provider both benefit from this environment. In 1978, the problem-oriented record keeping system (PORS) was implemented in the eye care service of a Boston neighborhood multidisciplinary health center. It facilitated learning, established guidelines for peer review, and improved patient care by assisting the eye care service to communicate patient problems to the other health center services effectively. We review the background of urban multidisciplinary health care settings and the PORS, as well as present several cases in which optometrists participated in patient comanagement with other health care specialists to develop a comprehensive management plan. The benefits of the multidisciplinary approach to both patients and providers are discussed.

Adult↗

Red cell membrane protein distribution during malarial invasion.

Immuno-gold labelling electron microscopy of thin sections was used to determine the distribution of red cell membrane and membrane skeleton proteins in the vicinity of internalized malaria parasites. When examined immediately after invasion (young ring-stage parasites), the parasitophorous vacuole membranes of both Plasmodium falciparum and P. knowlesi were found to be characterized by the essentially complete absence of spectrin, ankyrin and the most abundant transmembrane protein, band 3. P. knowlesi merozoites were trapped in the attached but not internalized state by pretreatment with cytochalasin B. In this merozoite-red cell complex antibody labelling showed that band 3 had been eliminated from the region of the host cell membrane in contact with the parasite. Internal vesicles, originating apparently from the site of attachment, were often observed in the red cell. Opposite the attached parasite a cavity was also sometimes seen in the host cell, presumably representing an incipient internal vesicle. The membrane was intact, as judged by the absence of protein (haemoglobin) in the cavity, and, like the membranes surrounding the internal vesicles, was devoid of membrane proteins. A large multilamellar body was sometimes seen in the merozoite close to its point of attachment. The lamellar spacing was about 50 nm. The electron microscope images suggest a diffusion of electron-dense material from the lamellar body into the cavity in the host cell.

Animals↗

Why mandatory HIV antibody screening cannot work.

In 1985 this country introduced the first serologic screening test [enzyme immunoassays (EIAs)] designed to detect antibodies to the human immunodeficiency virus (HIV), the pathogen of acquired immunodeficiency syndrome (AIDS). Some people now suggest use of this test to identify people within the general population who are infected with the virus. This article will review technical and administrative problems pertaining to the use of EIAs to screen the general population for antibodies to HIV, and will explain why optometrists can provide safe and comprehensive care to all patients without knowledge of a patient's HIV antibody status. Prior knowledge by the optometrist of the patient's serological status is unnecessary if the practitioner 1) adheres to established guidelines pertaining to infection control, and 2) is aware of the various ocular manifestations of HIV disease. It concludes that mandatory HIV screening programs should not be adopted until the benefits to society have been more clearly elucidated and associated technical, administrative, and ethical problems have been resolved.

AIDS Serodiagnosis↗

Mild asymptomatic primary hyperparathyroidism is not a risk factor for vertebral fractures.

STUDY OBJECTIVE: To determine the prevalence of vertebral fractures in patients with mild asymptomatic primary hyperparathyroidism and to ascertain whether this prevalence is increased in comparison with the rate in a retrospective control group previously studied at the same institution or with current estimates of the risk for vertebral fractures in subjects of similar age. DESIGN: Prospectively collected data were retrospectively analyzed and compared with data from a historical control group at the same institution and with published data. SETTING: The outpatient department of a bone and mineral metabolism clinic. PATIENTS: A consecutive series of patients with mild asymptomatic primary hyperparathyroidism diagnosed between 1 January 1976 and 31 December 1985. Criteria for inclusion in the study were the absence of symptoms due to hyperparathyroidism, no current kidney stone disease, no radiographic evidence of osteitis fibrosa, a serum calcium level of less than 3.00 mmol/L, a serum creatinine level of less than 133 mumol/L, and a forearm bone density value not more than 2.5 standard deviations below the age-, sex-, and race-adjusted normal value. INTERVENTIONS: A conservative nonintervention study. MEASUREMENTS AND MAIN RESULTS: The prevalence of vertebral fractures in 174 patients (mean age, 62 years) with mild asymptomatic primary hyperparathyroidism was 1.7%; in a subset of white women, the prevalence was 2.8%. These rates were not higher than those expected, by comparison with the rate in a retrospective control group or with the risk for vertebral fractures in subjects of similar age, and may even be lower. CONCLUSIONS: The risk for vertebral fractures is not increased in patients with mild asymptomatic primary hyperparathyroidism and is not a reason to recommend surgical intervention in asymptomatic patients. The increased rates of vertebral fractures that occurred in other series are probably due to the use of inappropriate controls and the influence of referral or selection bias, the inclusion of patients with severer disease, and the effect of geographic differences in vitamin D nutrition on the expression of disease. Possible differences between lateral spine and lateral chest radiographs for determining vertebral body shape need further study.

Aged↗

Mitochondrial DNA of the human malarial parasite Plasmodium falciparum.

Covalently closed circular DNA molecules were isolated from Plasmodium falciparum total DNA by isopycnic centrifugation in CsCl gradients containing either ethidium bromide or 2',6-diamidino-2-phenylindole. The circular molecules had an average contour length of 11.1 +/- 0.5 micron, similar to the analogous molecules previously isolated from the simian malaria parasite P. knowlesi. Both circular molecules shared considerable sequence homology and conserved restriction sites. The nucleotide sequence of one 936 bp fragment of the P. falciparum molecule was determined and identified, by a data base homology search, as part of a mitochondrial small rRNA subunit, thus confirming the mitochondrial origin of the circular DNAs of both malarial species.

Animals↗