Search PubMed⌕ Search

Biomedical subjects

J Newman

Publications and source records attributed to J Newman.

At least 73 records · Page 4Linked to original sources
PubMed1997

Mesoscopic gels at low agarose concentration: perturbation effects of ethanol.

Aqueous agarose solutions at low concentrations (0.5 g/liter) were temperature quenched below the spinodal line to form mutually disconnected mesoscopic gels. In the presence of 6% ethanol, these solutions, obtained by quenching at the same temperature depth as in pure water, appear much more fluid, as determined by probe diffusion experiments. We show by static and dynamic light scattering that this can be explained by the solvent-mediated effects of ethanol, leading to a globular shape of mesoscopic agarose gels, rather than to an extended rodlike structure observed in pure water. Our findings show the significant effects of solvent perturbations on particle condensation and, therefore, may be useful in understanding the role of the solvent in the folding of biomolecules.

Biopolymers↗
PubMed1997

Lesions produced by the extravasation of urine from the upper urinary tract.

We present six cases which illustrate the spectrum of clinical features, macroscopic findings and light microscopic findings of urine extravasation from the upper urinary tract. The early lesions are characterized macroscopically by an oedematous, glistening or gelatinous appearance to the renal perihilar and peripelvic fat. Light microscopically there is lipolysis with associated foamy macrophages, multinucleate giant cells and lymphocytes. Immunohistochemical staining for Tamm-Horsfall protein is strongly positive in the extracellular space and in the foamy macrophages confirming urine extravazation. Later lesions are characterized by cicatrization of fibrous tissue around the renal pelvis and hydronephrosis. Microscopically there is relatively bland fibrosis with occasional lymphocytes and histiocytic cells. The late lesions are also characterized by extracellular deposits of weakly eosinophilic, granular or hyaline material, the so called 'urinary precipitates'. These deposits stain strongly with diastase PAS and weakly positive for Tamm-Horsfall protein. The staining of these urinary precipitates is analogous to renal tubular hyaline casts, thus supporting the theory that they are derived from uroproteins. We consider that these deposits are pathognomic of past urine extravasation.

Adolescent↗
PubMed1997

Prostaglandin E2 for cervical ripening: a multicenter study of patients with prior cesarean delivery.

To evaluate the maternal and fetal outcomes of a large cohort of women treated with prostaglandin E2 (PGE2) gel for cervical ripening prior to trial of labor after previous cesarean delivery. Beginning in 1990 all pregnant patients with previous cesarean delivery presenting for prenatal care at 10 California hospitals were prospectively studied. We analyzed multiple parameters to compare outcomes of cases in which PGE2 gel was used to outcomes in a control group in which PGE2 was not used. Data were examined by X2 testing. During the study period 5022 patients underwent trial of labor after prior cesarean delivery. Of these 5022 patients, 453 (9%) were treated with PGE2 gel. There was no significant difference in the incidence of uterine rupture between the PGE2 group and the control group. Indicators of maternal and perinatal morbidity were not significantly higher in the prostaglandin treated group. The use of PGE2 gel for cervical ripening appears to be relatively safe in patients with prior cesarean delivery.

Administration, Intravaginal↗
PubMed1997

Regulation of sesquiterpene cyclase gene expression. Characterization of an elicitor- and pathogen-inducible promoter.

The promoter for a tobacco (Nicotiana tabacum) sesquiterpene cyclase gene, a key regulatory step in sesquiterpene phytoalexin biosynthesis, has been analyzed. The EAS4 promoter was fused to the beta-glucuronidase (GUS) reporter gene, and the temporal and spatial expression patterns of GUS activity were examined in stably transformed plants and in transient expression assays using electroporated protoplasts of tobacco. No GUS activity was observed in any tissues under normal growth conditions. A low level of GUS activity was detected in wounded leaf, root, and stem tissues, whereas a much higher level was observed when these tissues were challenged with elicitors or microbial pathogens. The GUS expression pattern directed by the EAS4 promoter was identical to the induction patterns observed for the endogenous sesquiterpene cyclase genes. Neither exogenous salicylic acid nor methyl jasmonate induced GUS expression; and H2O2 induced GUS expression to only a limited extent. Although the EAS4 promoter contains cis-sequences resembling previously identified transcriptional control motifs, other cis-sequences important for quantitative and qualitative gene expression were identified by deletion and gain-of-function analyses. The EAS4 promoter differs from previously described pathogen-/elicitor-inducible promoters because it only supports inducible gene expression and directs unique spatial expression patterns.

Acetates↗
PubMed1997

Dissecting the roles of VP0 cleavage and RNA packaging in picornavirus capsid stabilization: the structure of empty capsids of foot-and-mouth disease virus.

Empty capsids of foot-and-mouth disease virus (FMDV) type A22 Iraq 24/64, whose structure has been solved by X-ray crystallography, are unusual for picornaviruses since they contain VP2 and VP4, the cleavage products of the protein precursor VP0. Both the N terminus of VP1 and the C terminus of VP4, which pack together close to the icosahedral threefold symmetry axis where three pentamers associate, are more disordered in the empty capsid than they are in the RNA-containing virus. The ordering of these termini in the presence of RNA strengthens interactions within a single protomer and between protomers belonging to different pentamers. The disorder in the FMDV empty capsid forms a subset of that seen in the poliovirus empty capsid, which has VP0 intact. Thus, VP0 cleavage confers stability on the picornavirus capsid over and above that attributable to RNA encapsidation. In both FMDV and poliovirus empty capsids, the internal disordering uncovers a conserved histidine which has been proposed to be involved in the cleavage of VP0. A comparison of the putative active sites in FMDV and poliovirus suggests a structural explanation for the sequence specificity of the cleavage reaction.

Aphthovirus↗
PubMed1997

Clinical and pathological characterization of northern elephant seal skin disease.

From 1984 through 1992, staff at The Marine Mammal Center (TMMC, Sausalito, California, USA) examined 207 northern elephant seals (Mirounga angustirostris) with a condition of unknown etiology called northern elephant seal skin disease (NESSD). The skin lesions were characterized by patchy to extensive alopecia and hyperpigmentation, punctate or coalescing epidermal ulceration, and occasionally, massive skin necrosis. Microscopic lesions included ulcerative dermatitis with hyperkeratosis, squamous metaplasia and atrophy of sebaceous glands. All diseased seals were less than 2 years of age and suffered from emaciation, depression, and dehydration. Mortality from septicemia increased significantly with severity of skin ulceration. Compared to 14 apparently unaffected seals, diseased seals had depressed levels of circulating thyroxine, triiodothyronine, retinol, serum iron, albumin, calcium, and cholesterol. Levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma glutamyl transpeptidase, blood urea nitrogen, and uric acid were elevated. Morphometrically, diseased animals were approximately 15% smaller than normal seals of the same sage. Serum and blubber concentrations of 36 polychlorinated biphenyl congeners (sigma PCB) and dichloro-diphenyl-dichloroethylene (p,p'-DDE) were negatively correlated with body mass. Mean concentrations of sigma PCB and p,p'-DDE in serum in diseased seals were elevated as compared to apparently normal seals. Etiology of this syndrome remains unknown, but the possibility of PCB toxicosis cannot be ruled out.

Alopecia↗
PubMed1996

Crystallization and preliminary X-ray diffraction studies of the influenza C virus glycoprotein.

Influenza C virus contains a single surface glycoprotein in its lipid envelope which is the hemagglutinin-esterase-fusion glycoprotein (HEF). HEF binds cell-surface receptors, is a receptor-destroying enzyme (a 9-O-acetylesterase), and mediates the fusion of virus and host cell membranes. A bromelain-released soluble form of HEF has been crystallized. Two different tetragonal forms have been identified from crystals with the same morphology [P(1(3))22, a = b = 154.5, c = 414.4 A, and P4(1(3))2(1)2, a = b = 217.4, c = 421.4 A]. Both crystal forms share a common packing scheme. Synchrotron data collection and flash cooling of crystals have been used for high-resolution data collection.

Journal Article↗
PubMed1996

Survey of the fragile X syndrome and the fragile X E syndrome in a special education needs population.

To begin to understand the population dynamics of the fragile X (FRAXA) mutation and to learn more about the fragile X E (FRAXE) syndrome, we have initiated a surve of children in special needs education programs in the public school system. With respect to the FRAXA syndrome, we found approximately 1/1,000 full mutations among males. No large alleles at the FRAXE locus were observed among 462 individuals. The allele distributions at the two loci among Caucasians and among African Americans were examined as well as the level of heterozygosity. We found a significant difference in the FRAXA allele distribution among the two ethnic groups; the major difference was due to the lack of smaller alleles among the African Americans. No difference was found for the FRAXE allele distribution among the two groups. The level of heterozygosity was less than predicted by the allele distribution at both loci. This is probably due to unidentified large alleles among females with a test result of a single band. Alternatively, this excess may indicate that the population is not at equilibrium.

Black or African American↗
PubMed1996

Identification of iron superoxide dismutase and a copper/zinc superoxide dismutase enzyme activity within the marine cyanobacterium Synechococcus sp. WH 7803.

Three constitutive forms of superoxide dismutase activity have been demonstrated in the cyanobacterial marine picoplankter Synechococcus sp. WH 7803 using polyacrylamide gel activity staining techniques. A protein which gave a positive non-haem iron stain on native polyacrylamide gels exhibited N-terminal similarity to both the iron superoxide dismutase and the manganese superoxide dismutase of Escherichia coli. The metal prosthetic group of each of the three activity bands was characterised by analysing their differential sensitivities to 5 mM H2O2, 2 mM cyanide and 2 mM of the copper chelator diethyldithiocarbamate. Three distinct superoxide dismutase activities were observed, an iron superoxide dismutase, a copper/zinc superoxide dismutase and a third form which has not been identified. Growth of Synechococcus cells in ASW medium containing no added iron resulted in no alteration in the activity of the iron superoxide dismutase. Growth of cultures in the absence of copper or zinc resulted in differential changes in the activities of the copper/zinc superoxide dismutase and the unidentified superoxide dismutase.

Amino Acid Sequence↗
PubMed1996

Perturbations in the surface structure of A22 Iraq foot-and-mouth disease virus accompanying coupled changes in host cell specificity and antigenicity.

BACKGROUND: Foot-and-mouth disease virus (FMDV) is an extremely infectious and antigenically diverse picornavirus of cloven-hoofed animals. Strains of the A22 subtype have been reported to change antigenically when adapted to different growth conditions. To investigate the structural basis of this phenomenon we have determined the structures of two variants of an A22 virus. RESULTS: The structures of monolayer- and suspension-cell-adapted A22 FMDV have been determined by X-ray crystallography. Picornaviruses comprise four capsid proteins, VP1-4. The major antigenic loop of the capsid protein VP1 is flexible in both variants of the A22 subtype but its overall disposition is distinct from that observed in other FMDV serotypes (O and C). A detailed structural comparison between A22 FMDV and a type O virus suggests that different conformations in a portion of the major antigenic loop of VP1 (the GH loop, which is also central to receptor attachment) result in distinct folds of the adjacent VP3 GH loop. Also, a single mutation (Glu82-->Gly) on the surface of VP2 in the suspension-cell-adapted virus appears to perturb the structure of the VP1 GH loop. CONCLUSION: The GH loop of VP1 is flexible in three serotypes of FMDV, suggesting that flexibility is important in both antigenic variability and structural communication with other regions of the virus capsid. Our results illustrate two instances of the propagation of structural perturbations across the virion surface: the change in the VP3 GH loop caused by the VP1 GH loop and the Glu82-->Gly change in VP2 which we believe perturbs the GH loop of VP1. In the latter case, the amplification of the sequence changes leads to differences, between the monolayer- and suspension-cell-adapted viruses, in host-cell interactions and antigenicity.

Antigens, Viral↗
PubMed1996

Electrostatic Protein-Protein Interactions: Comparison of Point-Dipole and Finite-Length Dipole Potentials of Mean Force.

Based on summation of Coulombic interactions, a model is developed for finite-length dipole potentials of mean force in a salt-free dielectric continuum. Point-dipole and finite-length dipole potentials of mean force are compared for protein-protein interactions using parameters for bovine alpha-chymotrypsin. The two approximations made in the commonly used analytical point-dipole potentials of mean force are not valid at distances near contact. Relative to the finite-length dipole model, the high-temperature approximation overpredicts, and the point-dipole approximation underpredicts charge-dipole and dipole-dipole attractions.

Journal Article↗
PubMed1996

Cigarette smoking increases the risk of rheumatoid arthritis. Results from a nationwide study of disease-discordant twins.

OBJECTIVE: To test the hypothesis that cigarette smoking is associated with susceptibility to rheumatoid arthritis (RA) by comparing smoking history between twins with RA and their unaffected co-twins. METHODS: Interview questionnaires on smoking history were administered to 79 identical (monozygotic [MZ]) and 71 same-sex nonidentical (dizygotic, [DZ]) twin pairs who were discordant for RA, recruited from the Arthritis and Rheumatism Council Twin Study. Results were expressed as odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Although most twin pairs were concordant for smoking history, there was a strong association between ever smoking and RA in the MZ pairs (OR 12.0, 95% CI 1.78-513), with a similar trend observed in the DZ pairs (OR 2.5, 95% CI 0.92-7.87). CONCLUSION: The discordance in cigarette smoking history for individuals who are at presumed identical genetic risk for RA supports other data suggesting the role of smoking in disease susceptibility.

Arthritis, Rheumatoid↗
PubMed1996

Paget's disease of bone and unvaccinated dogs.

The etiology of Paget's disease is unknown, but several observations suggest a viral cause. Since canine distemper virus is among those proposed to be a causal agent, we investigated the hypothesis that dog ownership may increase the risk of Paget's disease of bone by means of a case control study. One hundred and fifty patients with Paget's disease and 185 controls were interviewed using a structured questionnaire administered by the same interviewer. Participants were asked about their socioeconomic background and their exposure to pets. The risk of Paget's disease was not significantly increased in individuals. However, ownership of a mongrel dog was associated with a significant increase in risk (OR = 1.6; 95% CI = 1.0-2.4) and the risk increased still further with the ownership of an unvaccinated dog (OR = 2.8; 95% CI = 1.8-4.5). Additionally, ownership of cats and birds excluding dog owners, increased the risk of Paget's disease (OR = 2.5; 95% CI = 1.0-5.0; OR = 2.3; 95% CI = 1.0-5.3, respectively). These data suggest that previous exposure to cats, birds, and dogs unvaccinated for canine distemper may increase the risk of an individual developing Paget's disease of bone.

Adult↗
PubMed1996

The bundling of actin with polyethylene glycol 8000 in the presence and absence of gelsolin.

Actin filament and bundle formation occur in the cytosol under conditions of very high total macromolecular concentration. In this study we have utilized the inert molecule polyethylene glycol 8000 (PEG) as a means of simulating crowded conditions in vitro. Column-purified Ca-actin was polymerized in the absence and presence of gelsolin (to regulate mean filament lengths between 50 and 5000 mers) and PEG (2-8%) using various concentrations of KCl and/or 2 mM divalent cations. Bundling was characterized by the scattered light intensity and mean diffusion coefficients obtained from dynamic light scattering, as well as by fluorescence and phase-contrast microscopy. The minimum concentration of KCl required for bundling decreases both with increasing concentration of PEG at a fixed mean filament length, and with decreasing filament length at a fixed concentration of PEG. In the absence of divalent cation, bundling is reversible on dilution, as determined by intensity levels, diffusion coefficients, and microscopy. However, with either 2 mM Mg2+ or Ca2+ added, bundling is irreversible under conditions of higher PEG concentrations or longer filaments, indicating that osmotic pressure effects cannot fully explain actin bundling with PEG. Weaker divalent cation-binding sites on actin as well as disulfide bonds appear to be involved in the irreversible bundling.

Actins↗
PubMed1996

Hospital input price indexes in Australia: are they worth the effort?

This paper summarises aspects of the design and use of hospital input price indexes, and describes four indexes produced in Australia in the last decade. It argues that there would be some benefit in establishing a routine national index, if it were designed to be low-cost. However, care should be taken to avoid excessive reliance on the results in the resource allocation and funding context. Input prices contribute relatively little in hospitals' expenditure changes. It is also necessary to monitor and manage changes in the volumes of inputs, and this is likely to be a more rewarding task.

Australia↗
PubMed1996

A comparison of disease status in rheumatoid arthritis patients attending and not attending a specialist clinic.

The objective was to test the hypothesis that rheumatoid arthritis (RA) patients currently not receiving specialist care have milder and less active disease than clinic attenders. The subjects were recruited from a media campaign aimed at identifying RA patients for a nationwide twin study. All subjects were interviewed at home and examined. Data from serological and radiological investigations were obtained. Data were also obtained about any specialist care, including the date, where relevant, of the most recent hospital appointment. For subjects reporting ever attending a specialist clinic, the current status (discharged/under current care) and the date of their most recent appointment were verified from hospital records. Data from 149 patients were analysed, of whom 114 (76%) were current hospital clinic attenders at the time of interview, 10 (7%) had never attended and 25 (17%) were ex-attenders. There was a similar proportion with current morning stiffness (> 1 h) in all three groups (60%). The median number of (i) swollen (S) joints, (ii) tender (T) joints and (iii) swollen and tender (ST) joints was almost identical-current attenders: (S) 7, (T) 9, (ST) 11; ex-attenders: (S) 5, (T) 8, (ST) 10; never attenders: (S) 7, (T) 14, (ST) 17. There were similar proportions with radiological erosions in the current and ex-attenders (79 and 72%, respectively). Current attenders were, however, substantially more likely to be taking disease-modifying drugs. In these volunteer patients, those currently managed entirely in primary care did not have less severe or active disease.

Antirheumatic Agents↗