Search PubMed⌕ Search

Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 91 records · Page 5Linked to original sources

Small nucleolar RNP scleroderma autoantigens associate with phosphorylated serine/arginine splicing factors during apoptosis.

OBJECTIVE: Proteins that are phosphorylated during apoptosis are commonly precipitated by autoantibodies found in the sera of patients with systemic lupus erythematosus. We sought to determine whether scleroderma autoantigens such as small nucleolar RNPs (snoRNP) also associate with phosphoproteins in response to various cellular stressors. METHODS: We screened a panel of monoclonal antibodies derived from mice exposed to mercury, a well-characterized murine model of the anti-snoRNP autoimmune response, for the ability to selectively precipitate phosphoproteins from radiolabeled lysates prepared from Jurkat T cells subjected to stressful stimuli. RESULTS: Monoclonal antibodies reactive with snoRNPs precipitated a phosphoprotein complex (pp42, pp34, and pp23) from lysates prepared from apoptotic cells. Several novel phosphoproteins (pp62 and pp18) were also observed. The phosphorylation and/or recruitment of these proteins to the snoRNP complex is induced by multiple apoptotic stimuli (e.g., Fas ligation, anisomycin, or ultraviolet irradiation), an effect that is blocked by overexpression of Bcl-2. We were unable to demonstrate an association of the phosphoprotein complex with snoRNPs in cells treated with the xenobiotic agent mercury. The snoRNP-associated phosphoprotein complex is composed of serine/arginine (SR) splicing factors, including SRp40. CONCLUSION: The association of phosphorylated SR proteins with snoRNPs in cells undergoing apoptosis suggests that the immune response to fibrillarin that characterizes a subset of patients with scleroderma may be related to cell death induced by apoptotic stimuli (e.g., Fas ligation, irradiation, or chemical toxins), or by exposure to mercury.

Animals↗

Sublethal lead affects pituitary function of rainbow trout during exogenous vitellogenesis.

Sexually maturing female rainbow trout, Oncorhynchus mykiss, were exposed to 10 microg/L of waterborne lead Pb(NO(3))(2) for 12 days during endogenous vitellogenesis and 12 days during exogenous vitellogenesis. Lead had no significant effect on either gonadosomatic indices or mean maximum diameters of developing oocytes during early vitellogenesis. When females were exposed during exogenous vitellogenesis, however, both GSI and oocyte growth were significantly different from controls on day 12. Similarly GSI and oocyte growth was significantly reduced in lead-exposed fish. Atomic absorption spectroscopy measurements of lead levels in liver, ovaries, and blood tissues showed significant levels of lead in the blood. Lead did not accumulate in either the ovaries or the liver. Analysis of pituitary basophils during both endogenous and exogenous vitellogenesis and subsequent comparison with reproductive parameters in the ovaries indicated that GtH-basophils did not significantly increase in controls during endogenous vitellogenesis, and there was no significant change in GSI or ovarian growth in either controls or lead-exposed females. However during exogenous vitellogenesis, control basophils significantly increased over the 12-day experiment, but were not significantly different over 12 days in lead-exposed females. Both GSI and oocyte growth were significantly different from controls in lead-exposed females. The results suggest that naturally occurring changes in GTH-producing basophils during vitellogenesis alters GSI and oocyte growth in female rainbow trout exposed to lead during exogenous vitellogenesis, but not during endogenous vitellogenesis.

Animals↗

Multidomain and multifunctional glycosyl hydrolases from the extreme thermophile Caldicellulosiruptor isolate Tok7B.1.

DNA sequencing techniques have revealed widespread molecular diversity of the genomic organization of apparently closely related bacteria (as judged from SSU rDNA sequence similarity). We have previously described the extreme thermophile Caldicellulosiruptor saccharolyticus, which is unusual in possessing multi-catalytic, multidomain arrangements for the majority of its glycosyl hydrolases. We report here the sequencing of three gene clusters of glycosyl hydrolases from Caldicellulosiruptor sp. strain Tok7B.1. These clusters are not closely linked, and each is different in its organization from any described for Cs. saccharolyticus. The catalytic domains of the enzymes belong to glycosyl hydrolase families 5, 9, 10, 43, 44, and 48. The cellulose binding domains (CBDs) of these enzymes from Caldicellulosiruptor sp. Tok7B.1 are types IIIb, IIIc, or VI. A number of individual catalytic and binding domains have been expressed in Escherichia coli, and biochemical data are reported on the purified enzymes for cellulose degradation encoded by engineered derivatives of celB and celE.

Amino Acid Sequence↗

Antennal response of codling moth males, Cydia pomonella L. (Lepidoptera: Tortricidae), to the geometric isomers of codlemone and codlemone acetate.

Single sensillum recordings from Cydia pomonella male antennae showed three different types of receptor neurons. The most abundant type was most sensitive to the main pheromone compound (E,E)-8,10-dodecadienol, while its response to the geometric isomers E,Z, Z,E and Z,Z was comparable to a tenfold lower dose of (E,E)-8,10-dodecadienol. This neuron type also responded to the four behaviorally antagonistic isomers of (delta,delta)-8,10-dodecadienyl acetate, among which it was most sensitive to the E,E isomer. Cross-adaptation studies showed that these compounds were all detected by the same receptor neuron type. Receptor neurons specifically tuned to (E,Z) or (Z,Z)-8,10-dodecadienol were not found, although these two compounds are behaviorally active. A second type of receptor neuron responded to all isomers of (delta,delta)-8,10-dodecadienyl acetate and was most sensitive to the E,E isomer. This neuron type did not respond to any of the isomers of (delta,delta)-8,10-dodecadienol. A third receptor neuron type was highly sensitive to the plant compound alpha-farnesene. The finding that the receptor neuron type tuned to the main pheromone compound responded even to strong behavioral antagonists aids the interpretation of ongoing behavioral studies for the development of the mating disruption technique in codling moth.

Animal Structures↗

Preparation and characterisation of monoclinic hydroxyapatite and its precipitated carbonate apatite intermediate.

Five 100 g batches of a carbonate apatite (the intermediate) were produced by heating an aqueous slurry of CaCO3 and CaHPO4 with an overall Ca/P mole ratio of 5/3 with vigorous stirring. Each intermediate produced by boiling off water was heated in vacuum at 1100 degrees C to remove carbonate, then steamed at 900 degrees C to ensure complete hydroxylation. Comparison of calculated and observed X-ray diffraction patterns showed final products containing 50-100 wt% monoclinic hydroxyapatite (remainder hexagonal). Rietveld refinements in P6(3)/m gave structures similar to several hydroxyapatite standards, including NIST SRM 2910, although there was no evidence from X-ray diffraction that the latter was in the monoclinic form. Refinements from standards and final products were slightly different from published single crystal data for Holly Springs hydroxyapatite. This is attributed to known impurities in mineral hydroxyapatite and indicates that parameters from the Rietveld refinements are closer to the true values for pure hydroxyapatite. Rietveld refinements for intermediates showed small, but significant differences from the final product, the largest being in O1x, O2x and O(H)z. All P-O bond lengths were shorter than in the final product, resulting in a 3.2% lower PO4 tetrahedron volume. The occupancies of P and Ca(2) were reduced. These differences are attributed to partial replacement of PO4(3) by CO3(2-) ions.

Apatites↗

Disability, space and sexuality: access to family planning services.

In this paper we examine, from a social perspective, access to family planning clinics for disabled people. We argue that disabled people are commonly understood to be either asexual, uninterested in sex or unable to take part in sexual activity, or sexual 'monsters' unable to control their sexual drives and feelings. These understandings are reproduced through the use of cultural representations and myths, and are evidenced in the planning and design of family planning clinics and the information and services they provide. To illustrate our arguments we present the findings of a short questionnaire survey of all family planning clinics in Northern Ireland. Physical access to these clinics was partial, and access to information and services were extremely limited. These results indicate that disabled people are not expected to be using the services (consultation, treatment, information) that family planning clinics provide. As such, family planning clinics in Northern Ireland represent a landscape of exclusion, denying disabled people access to services and reproducing cultural ideologies concerning disability and sexuality.

Ambulatory Care Facilities↗

The apoptosis-promoting factor TIA-1 is a regulator of alternative pre-mRNA splicing.

We report here that the apoptosis-promoting protein TIA-1 regulates alternative pre-mRNA splicing of the Drosophila melanogaster gene male-specific-lethal 2 and of the human apoptotic gene Fas. TIA-1 associates selectively with pre-mRNAs that contain 5' splice sites followed by U-rich sequences. TIA-1 binding to the U-rich stretches facilitates 5' splice site recognition by U1 snRNP. This activity is critical for activation of the weak 5' splice site of msl-2 and for modulating the choice of splice site partner in Fas. Structural and functional similarities with the Saccharomyces cerevisiae splicing factor Nam8 suggest striking evolutionary conservation of a mechanism of pre-mRNA splicing regulation that controls biological processes as diverse as meiosis in yeast, dosage compensation in fruit flies, or programmed cell death in humans.

Alternative Splicing↗

Bone fracture analysis on the short rod chevron-notch specimens using the X-ray computer micro-tomography.

Mechanical fatigue of bone leads to micro-cracking which is associated with remodeling, establishing a balance in the microcrack population of the living tissue, thus, in the steady-state, the microstructure of bone provides sites of discontinuity acting as stress raisers. Hence fracture toughness plays a decisive role in bone functionality by determining the level to which the material can be stressed in the presence of cracks, or, equivalently, the magnitude of cracking which can be tolerated at a given stress level. Cortical bone, which behaves as a quasi-brittle solid when fractured, was tested as short-rod chevron-notched tension specimens (CNT). The main features of the CNT specimen are its geometry and the V shaped notch. The notch leads to steady-state crack propagation whilst the requested geometry allows a diameter 40% smaller than the thickness of a standard compact tension specimens (CT). These features are essential to distinguish the inhomogeneties in the fracture properties of materials like bone. Bone structure and crack propagation of the CNT specimens were analyzed using X-ray computed micro-tomography (XMT), which is a non-invasive imaging technique. The unique feature of the micro-CT is the high resolution three-dimensional image which consists of multi-sliced tomographs taken in a fine pitch along the rotational axis. Fracture toughness (K(IC)) computed according to the peak load was 4.8 MNm(-3/2) while that derived from experimental calibration tests using XMT was 4.9 MNm(-3/2).

Journal Article↗

Life and death decisions: regulation of apoptosis by proteolysis of signaling molecules.

Caspases are the major executioners of cell death, serving as molecular guillotines to behead many proteins required for maintenance of cellular homeostasis. Identification of caspase substrates has taken on increasing importance as we attempt to better understand the molecular mechanisms involved in regulating the struggle between life and death. Many caspase substrates have been described and include RNA binding proteins such as La and U1-70 kD, structural proteins such as keratin and nuclear lamins, and transcription factors or their regulatory proteins that include IkappaB, SP1, and SREBP. Kinases and other signaling proteins are perfectly suited to regulate life and death decisions in response to cellular stressors and have only recently been identified as important caspase substrates. Here we review the current status of signaling pathways that are activated, inactivated or dysregulated by proteases such as caspases and calpain to control entry into apoptosis. The emerging concept that some caspase pathways may be inhibited by cellular and viral apoptosis inhibitory proteins while other caspase pathways are preserved suggests that a subset of these kinases may exist as cleaved 'isoforms' in cells that are not destined to perish. By acting as executioners and as important 'molecular sensors' of the degree of cellular injury, the signaling proteins described in this review are strong candidates to mediate downstream events, both in condemned and in viable cells.

Animals↗

Column leaching and sorption experiments to assess the mobility of potentially toxic elements in industrially contaminated land.

Made-up ground collected from layers of a trial pit excavated on a former industrial site was treated with artificial rainwater in a series of column leaching and sorption experiments. Metal mobility and the ability of various layers of material obtained from the pit to act as sources or sinks of potentially toxic elements were assessed. Samples from different layers varied in their abilities to raise the pH of rainwater applied at pH 3.5 and 4.3, and this was reflected in the amounts of metals mobilised by the rainwater as it percolated through the soil column. Material from the top two layers of the pit released cadmium, copper, manganese, lead, nickel and zinc to the aqueous phase, but the lower layers, with higher buffering capacity, were able to resist acidification even when the equivalent of 12 months' rainfall (western UK) was applied. Column sorption experiments confirmed the ability of material from layer 4 (48-50 cm) to take up copper, manganese and zinc. Metals were determined in the leachates by flame and electrothermal atomic absorption spectrometry and principle anions by ion chromatography.

Adsorption↗

X-ray microtomographic study of mineral distribution in enamel of mandibular rat incisors.

X-ray microtomography was used to study the mineral concentrations in sequential slices of enamel of 5 mandibular incisors which showed an increase from approximately 1.0 to approximately 2.7 g cm(-3) from the apex towards the incisal end. For points at the same distance from the apex, there were differences up to 0.6 g cm(-3) between the teeth. The change of mean concentrations in the slices with distance could be modelled as (different) saturating exponentials. Under the assumption of a uniform growth rate of a mandibular incisor of 0.6 mm per day and a common time origin for the start of maturation (taken as a mineral concentration of 1 g cm(-3)), the distances were transformed to a common time frame to give a pooled data set. A single saturating exponential could be fitted to this pooled transformed data; this was: Cm = 2.84-1.94exp (-0.18d) where Cm is the mean mineral concentration (g cm(-3)) and d the time (days) from the start of maturation. This gives an asymptotic concentration of 2.84 g cm(-3) towards the incisal end, with a time constant of 7.7 days. The mineral concentration distribution functions were found to be more positively skewed closer to the apex, but more negatively skewed towards the incisal end. The difference between the higher mineral concentration in the outer enamel and the enamel near the amelodentinal junction (ADJ) was approximately 3%. The direction of maximum increase in concentration from the outer enamel surface to the ADJ meets the boundary of the ADJ at approximately 80 degrees. Three dimensional surface rendering of isodensity contours showed that the previously described C-shaped pattern of mineralisation is not solely a surface phenomenon, but extends through the depth of the enamel.

Animals↗

Policy interventions to reduce the harm from smoking.

The other papers in this series on reduced smoking discuss interventions focused on individuals. This paper illustrates possible smoking reduction interventions focused on policies rather than individuals. Target 12 of the new WHO Health For All Policy aims to significantly reduce the harm from addictive substances, including tobacco, in all member states by 2015, and the WHO Third Action Plan for Tobacco-Free Europe focuses on reducing the harm from tobacco. These documents recommend five key policy strategies: market regulation, product liability, smoke-free environments, support for smoking cessation and education, public information and public opinion. Interventions such as price increases, restricting availability, advertising bans and product control could all be used to achieve harm reduction. Research on reducing the harm of smoking needs to include policy as well as treatment research.

Advertising↗

The patient's burden: physical and psychological effects of acute exacerbations of chronic bronchitis.

In this prospective qualitative study we evaluated the subjective perspectives of the quality of life of patients with chronic bronchitis. Individuals with diagnoses which fulfilled the clinical criteria of chronic bronchitis, i.e. daily production of sputum for at least three consecutive months in two consecutive years, were recruited into four focus groups from general practices in two industrial cities. Younger patients (those of pre-retirement age) of both sexes-a significant, but frequently 'invisible' minority in this patient population-were targeted. The groups were constituted with the aim of stimulating variation in the discussions. Twenty sufferers (10 males and 10 females, ranging in age from 30 to 86 years) were eventually included in the study; there were five in each group. Group discussions were recorded and transcribed verbatim and the data were analysed thematically. It was evident from the discussions that chronic bronchitis had led to a high degree of psychological distress in the participants, particularly in relation to dependency on medication, and disruption of social and family relationships. Acute exacerbations of chronic bronchitis (AECB) were met with dread. They brought about further reductions in quality of life, increased anxieties about breathlessness, fear of atmospheric pollution and of changes in and extremes of temperature, embarrassment about coughing up phlegm in public and suspicion of medical practitioners' motives if they were unwilling to prescribe antibiotics on request. Patients' health-related behaviour and beliefs were often contradictory. For example, AECB in some patients led to increased smoking. There were also gender and age differences; for example, it was the perception of males that they received more support from their partners than did females. Younger participants appeared more distressed by AECB than older ones. The results of this study suggest that raising the standard of care for patients with chronic bronchitis requires that greater attention be paid to patients' subjective experiences of the disease.

Acute Disease↗

Pluripotential mesenchymal cells repopulate bone marrow and retain osteogenic properties.

Precursor cells, isolated from bone marrow, can develop into various cell types and may contribute to skeletal growth, remodeling, and repair. The D1 cell line was cloned from a multipotent mouse bone marrow stromal precursor and has osteogenic, chondrogenic, and adipogenic properties. The osteogenic phenotype of these precursor cells is relevant to the process of fracture healing and osteointegration of prosthetic implants. The D1 cells were labeled genetically using a replication incompetent retroviral vector encoding beta-galactosidase, an enzyme which is used as a marker. Labeled cells are readily identifiable by staining with 5-bromo-4-chloro-3-indoyl-beta-D-galactoside and by flow cytometry, and retain the desired osteogenic characteristics in vivo as shown by von Kossa staining, alkaline phosphatase assay, an increase in cyclic adenosine monophosphate in response to parathyroid hormone, osteocalcin messenger ribonucleic acid production, and bone formation in diffusion chambers. In addition, the cells cloned from marrow stroma repopulate the marrow of host mice, persist for several weeks, and retain their osteogenic potential ex vivo. The data suggest that such cells may be used to replenish the number of osteoprogenitors in marrow, which appear to decrease with age, thereby leading to recovery from bone loss and improved bone growth and repair. Labeling these cells creates a model in which to study the potential of such cells to participate in fracture repair, ingrowth around prosthetic implants, treatment of osteoporosis, and to explore the possibility of gene delivery to correct mutations or defects in metabolism that are responsible for certain skeletal abnormalities.

Animals↗

Thermally induced shrinkage of joint capsule.

Thermal shrinkage of collagen currently is being used in orthopaedic surgery to treat ligamentous laxity. Understanding the kinetics of collagen shrinkage is key to revealing the events that take place during application of thermal energy. To elucidate the thermokinetic properties of collagen, punch biopsies of bovine joint capsule were immersed in a heated saline bath at temperatures between 20 degrees and 90 degrees C for periods up to 60 minutes. The resulting tissue thermal shrinkage was measured by the change in the cross-sectional area of the specimens. Only a small amount of shrinkage occurred at temperatures below 63 degrees C, and increasing amounts and rates of shrinkage were seen at temperatures between 63 degrees and 72 degrees C. The denaturation kinetics of bovine knee collagen, which could be described by a first order reaction rate, had an activation energy of 2.3 x 10(5) kJ/mol.

Animals↗

A high degree of natural immunologic priming to the capsular polysaccharide may not prevent Haemophilus influenzae type b meningitis.

BACKGROUND: A current debate is whether the immunologic priming of infants with Haemophilus influenzae type b (Hib) conjugate vaccines would be protective in the absence of circulating antibody to the capsular polysaccharide (PS). Data from the prevaccine era on the PS antibody responses of older children to Hib meningitis may be informative on this issue. METHODS: PS antibody was assayed by radioantigen binding in sera taken in the first month postadmission in 47 children ages 2 to 136 months with culture-proved Hib meningitis. RESULTS: Sera obtained on admission had very low antibody concentrations, and the subsequent response during convalescence was age-dependent. The major finding is that some patients, including 10 of 11 children older than 2 years, had substantial antibody elevations within a few days of admission, increases resembling the response to PS vaccine in infants primed with PS-protein conjugate vaccines. CONCLUSIONS: In this group of patients with Hib meningitis, natural priming did not prevent infection. Hib may have the ability to invade despite the capacity for a vigorous antibody response.

Age Factors↗

Recruiting good employees in tough times.

In tough hiring times, health care employers must develop a fresh approach to their recruitment techniques and practices in order to capture a desired segment of the labor market. While some of these techniques and practices are new, many are a variation of conventional ones. Successful organizations will simultaneously use a variety of methods, thus enabling them to recruit good employees continually. A tight labor market requires that organizations become creative recruiters.

Competitive Behavior↗