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Biomedical subjects

J Newman

Publications and source records attributed to J Newman.

At least 91 records · Page 5Linked to original sources
PubMed1996

Epidemiology of systemic sclerosis.

There have been few recent studies of the descriptive epidemiology of systemic sclerosis, but in recent work the limited form of the disease seems more prominent than reported in previous studies. Molecular genetic investigation of systemic sclerosis remains disappointing in identifying susceptibility alleles. There are some associations in relation to HLA class II alleles, specifically DP, DQ, and DR. These associations, however, seem to be more important in predicting the nature of the autoimmune response rather than describing disease susceptibility itself. The study of occupational and environmental influences has been dominated by studies on the role of silicone gel breast implants. These studies, driven by medicolegal constraints, have overwhelmingly failed to prove any association. Other studies confirm the continuing likelihood that organic solvents are implicated, at least in a proportion of cases.

Autoantibodies↗
PubMed1996

Chimeric hepatitis B virus core particles as probes for studying peptide-integrin interactions.

An RGD-containing epitope from the foot-and-mouth disease virus (FMDV) VP1 protein was inserted into the e1 loop of the hepatitis B virus core (HBc) protein. This chimeric protein was expressed at high levels in Escherichia coli and spontaneously assembled into virus-like particles which could be readily purified. These fusion particles elicited high levels of both enzyme-linked immunosorbent assay- and FMDV-neutralizing antibodies in guinea pigs. The chimeric particles bound specifically to cultured eukaryotic cells. Mutant particles carrying the tripeptide sequence RGE in place of RGD and the use of a competitive peptide, GRGDS, confirmed the critical involvement of the RGD sequence in this binding. The chimeric particles also bound to purified integrins, and inhibition by chain-specific anti-integrin monoclonal antibodies implicated alpha 5 beta 1 as a candidate cell receptor for both the chimeric particle and FMDV. Some serotypes of FMDV bound to beta 1 integrins in solid- phase assays, and the chimeric particles competed with FMDV for binding to susceptible eukaryotic cells. Thus, HBc particles may provide a simple, general system for exploring the interactions of specific peptide sequences with cellular receptors.

Animals↗
PubMed1996

Obstetric and gynaecological factors in susceptibility to peripheral joint osteoarthritis.

There is clear evidence that the age period coinciding with the peak age of the menopause is associated with an increased prevalence of osteoarthritis and this fits in with clinical observation of high likelihood of presentation at this age. A number of pieces of biological evidence also support the notion that changes in sex hormone status might influence risk of degenerative disease at peripheral joint sites. There do not appear, however, to be any important epidemiological predictors based on menstrual or obstetric history that might be useful in predicting who these women might be.

Aged↗
PubMed1996

Decision tree and postpartum management for preventing dehydration in the "breastfed" baby.

Dehydration and poor weight gain in breastfed infants are common but potentially preventable problems. Serious consequences are severe hypernatremic dehydration, severe weight loss, and severe hyperbilirubinemia with possible irreversible damage to the baby's brain or other vital organs. The dangers of dehydration have been emphasized by recent media reports of severe cases. These reports have resulted in increased, but often inappropriate, intervention in breastfeeding. On the basis of our experience at the Hospital for Sick Children, and the Doctors Hospital (Toronto), we have developed a decision tree and management protocol to assess breastfeeding, intervene effectively, and prevent such problems. If all breastfeeding mothers and babies are evaluated by qualified staff before discharge using this tool, it is expected that the serious consequences associated with babies leaving hospital appearing to be breastfeeding, but in fact not breastfeeding at all, will be prevented. Application of this approach, however, will require considerable upgrading of nurses' and physicians' skills and knowledge with regard to breastfeeding. A case report is presented.

Breast Feeding↗
PubMed1995

Mg- and Ca-actin filaments appear virtually identical in steady-state as determined by dynamic light scattering.

Dynamic light scattering measurements show that although Mg-actin polymerizes more rapidly than Ca-actin (actin at 0.04-0.4 mg/ml polymerized with 0.1 M KCl +/- 2 mM MgCl2 or CaCl2, at room temperature or at 10 degrees C), steady-state filaments exhibit nearly identical intensity autocorrelation functions and similar mean scattered intensities. The dynamic data are used to measure the persistence length of the filaments which is found to be 4.2 microns independent of the bound cation and of the actin concentration.

Actins↗
PubMed1995

A comparison of gene organization in the zwf region of the genomes of the cyanobacteria Synechococcus sp. PCC 7942 and Anabaena sp. PCC 7120.

The region of the genome encoding the glucose-6-phosphate dehydrogenase gene zwf was analysed in a unicellular cyanobacterium, Synechococcus sp. PCC 7942, and a filamentous, heterocystous cyanobacterium, Anabaena sp. PCC 7120. Comparison of cyanobacterial zwf sequences revealed the presence of two absolutely conserved cysteine residues which may be implicated in the light/dark control of enzyme activity. The presence in both strains of a gene fbp, encoding fructose-1,6-bisphosphatase, upstream from zwf strongly suggests that the oxidative pentose phosphate pathway in these organisms may function to completely oxidize glucose 6-phosphate to CO2. The amino acid sequence of fructose-1,6-bisphosphatase does not support the idea of its light activation by a thiol/disulfide exchange mechanism. In the case of Anabaena sp. PCC 7120, the tal gene, encoding transaldolase, lies between zwf and fbp.

Amino Acid Sequence↗
PubMed1995

Structural comparison of two strains of foot-and-mouth disease virus subtype O1 and a laboratory antigenic variant, G67.

BACKGROUND: Foot-and-mouth disease viruses (FMDVs) are members of the picornavirus family and cause an economically important disease of cloven-hoofed animals. To understand the structural basis of antigenic variation in FMDV, we have determined the structures of two viruses closely related to strain O1BFS whose structure is known. RESULTS: The two new structure are, like O1BFS, both serotype O viruses. The first, O1 Kaüfbeuren (O1K), is a field isolate dating from an outbreak of FMD in Europe in the 1960s. The second, called G67, is a quadruple mutant of O1K, generated in the laboratory, that bears point mutations conferring resistance to neutralizing by monoclonal antibodies, specific for each of the four major antigenic sites defined previously. The availability of the three related virus structures permits a detailed analysis of the way amino acid substitutions influence antigenicity. Structural changes are seen to be limited, in general, to the substituted side chain. For example, the GH loop of VP1, a highly antigenic and mobile protuberance which becomes ordered only under reducing conditions, was essentially indistinguishable in the three viruses despite the accumulation of up to four changes within its 15-residue sequence. At one of the other antigenic sites, however, changes between the two field strains did perturb both side-chain and main-chain structures in the vicinity. CONCLUSIONS: The conservation of conformation of the GH loop of VP1 adds to the evidence implicating an integrin as the cellular receptor for FMDV, since this loop contains a conserved RGD (Arg-Gly-Asp) sequence structurally similar to the same tripeptide in some other integrin-binding proteins. Structural changes required for the virus to escape neutralization by monoclonal antibodies are generally small. The more extensive type of structural change exhibited by the field isolates probably reflects differing selective pressures operating in vivo and in vitro.

Amino Acid Sequence↗
PubMed1995

Thalamic contributions to attention and consciousness.

A tacit assumption since the 19th Century has been that the neocortex serves as the "seat of consciousness." An unexpected challenge to that assumption arose in 1949 with the discovery that high-frequency EEG activation associated with an alert state requires the intactness of the brainstem reticular formation. This discovery became the impetus for nearly three decades of research on what came to be known as the reticular activating system. By the 1970s, however, methodological and philosophical controversies led to the general abandonment of subcortical theories of attention and consciousness, with a return to an almost exclusive focus upon the cortex. With recent advances in the neurosciences the focus is shifting once more, this time to the unique contributions of cortical, thalamic, and brainstem structures in mediating selective attention and perceptual awareness. This paper offers a nontechnical review of the history of these developments up to contemporary interest in the putative role of oscillatory EEG patterns in the integration of perceptual features of experience. It puts forward the thesis that a key to understanding attention and consciousness is an appreciation of the contributions of the thalamus to these cognitive processes.

Animals↗
PubMed1995

Structure and immunogenicity of experimental foot-and-mouth disease and poliomyelitis vaccines.

The physico-chemical properties and immunogenicity of experimental vaccines against foot-and-mouth disease (FMD) and poliomyelitis, prepared by treatment of the viruses with N-acetylethyleneimine (AEI), formaldehyde or neutral red, have been studied. None of these reagents affects the rate of sedimentation of the particles or their reaction with antibody against the major immunogenic sites. FMD vaccines prepared by inactivation with AEI or neutral red, behaved like the untreated virus, in that they were disrupted on lowering the pH below 7. The RNA of the AEI-inactivated virus was degraded into slowly sedimenting molecules. Unlike AEI-inactivated virus, from which all the RNA could be extracted with phenol-SDS, the recovery from the neutral red inactivated virus was variable and was sometimes as low as 40%; this RNA gave a heterogenous profile in sucrose gradients. The capsid proteins in the AEI preparation migrated in SDS-PAGE to the same positions as those of untreated virus, but in the neutral red preparation there was evidence of cross-linking. In contrast, the formaldehyde-inactivated vaccine was stable below pH 7 and the RNA could not be released by extraction with phenol-SDS at pH 5, because the capsid proteins had become cross-linked and/or linked to the RNA. As with foot-and-mouth disease virus (FMDV), poliovirus which had been inactivated with formaldehyde did not release its RNA on extraction with phenol-SDS and the capsid proteins were also cross-linked. Surprisingly, although AEI cleaved the viral RNA slowly in situ, the virus was no longer infectious after 6 h. Neutral red did not reduce the infectivity of the virus. All of the preparations gave similar levels of neutralizing antibody after a single inoculation. The high levels obtained with the formaldehyde-inactivated vaccines have implications for the processing of fixed particles by the antigen-presenting cells.

Animals↗
PubMed1995

Hydroxyl radical generation by coal mine dust: possible implication to coal workers' pneumoconiosis (CWP).

Occupational exposure to coal mine dust causes coal workers' pneumoconiosis (CWP) and other pulmonary diseases by mechanisms that remain unclear. Because the hydroxyl radicals (.OH) may play an important role in the pathogenesis of CWP, we studied the potential role of bituminous coal mine dust samples for catalyzing the generation of .OH from hydrogen peroxide (H2O2). These coal mine dusts evaluated represented two geographic areas with diversity in CWP prevalence. Electron spin resonance (ESR), with the aid of spin trapping techniques, was used to measure the .OH radical generation. Bituminous coal mine dusts representing the Pittsburgh seam in the eastern United States and Blind Canyon seam in the mid-western United States were used together with a standard coal dust obtained from the National Institute of Standards and Technology, Gaithersburg, MD. All the coal mine dust samples generated varying levels of .OH radicals from H2O2 in the presence of a .OH spin trap 5,5-dimethyl-l-pyrroline-N-oxide (DMPO). .OH radical generation by the coal from H2O2 was effectively inhibited by deferoxamine and catalase, but only partially inhibited by superoxide dismutase. Metal chelators DETAPAC and EDTA enhanced the radical generation. These results indicated that the Fenton reaction is predominantly involved in the generation of .OH radicals from H2O2. The .OH-generating potential of all the coal dusts showed a positive correlation with the surface iron content of coal mine dusts. In addition, the potential to induce lipid peroxidation by the coal samples exhibited a good correlation with the available surface iron. Based on the results presented here, we propose that higher concentrations of surface iron in coal mine dust may be involved in the generation of increased levels of .OH radicals and may play an important role in the development of CWP in different coal mining areas.

Chelating Agents↗
PubMed1995

Characterization of a zwf mutant of Synechococcus sp. strain PCC 7942.

A mutant of the cyanobacterium Synechococcus sp. strain PCC 7942 carrying a disrupted gene encoding glucose-6-phosphate dehydrogenase (zwf) produced no detectable glucose-6-phosphate dehydrogenase as assessed by enzyme assay and Western blot (immunoblot) analysis. This mutant exhibited significantly impaired dark viability.

Cyanobacteria↗