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Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 127 records · Page 7Linked to original sources
PubMed1999

CD1high B cells: a population of mixed origin.

A specialized subpopulation of T lymphocytes is reactive to the MHC class I-like molecule CD1d. It is not clear which cells are the major antigen-presenting cells in vivo in the activation of CD1-restricted immune responses. We have characterized a subset of B lymphocytes expressing six- to eightfold higher levels of CD1 than the bulk of B cells. The cells have a surface phenotype (CD21(high), CD23(low), IgM(high), IgD(low)) found previously to characterize B cells residing in the splenic marginal zones. CD1(high) B cells localize preferentially to the spleen, and appear late in ontogeny, at 3 - 4 weeks of age. The CD1(high) B cells were present in mice lacking conventional helper T cells, ruling out an exclusive origin from T cell-dependent immune responses. Still, some CD1(high) B cells had been involved in T cell-dependent immune responses as suggested by mutations in their rearranged immunoglobulin gene regions. The population could still be found in mice with severely reduced B cell reactivity to bacterial lipopplysaccharides (C3H / HeJ mice) and in mice unable to respond to thymus-independent type 2 antigens (NFR.Xid mice), as well as in germ-free mice, indicating that bacterial antigens are not major stimuli for the induction of CD1(high) B cells. In contrast, the CD1(high) B cell population was severely reduced in CD19-deficient mice. Taken together, the results imply that the CD1(high) population is heterogenous and of mixed origin, dependent for its development or maintenance on signaling through the CD19 molecule.

Animals↗
PubMed1999

Appetitive learning of odours with different behavioural meaning in moths.

Moth behaviour is to a great extent guided by olfactory stimuli with different relevance. We investigated whether olfactory learning of odours is influenced by the behavioural significance of the odorant. In proboscis extension conditioning experiments species-specific sex pheromones, which normally elicit an innate behaviour in males, and a flower odour were used as olfactory stimuli. After 10 conditioning trials, both sexes showed similar response levels to individual pheromone components and to the flower odour geraniol. However, when the female gland extract was used as conditioning stimulus, the response level was significantly lower than that for geraniol in both sexes. Significant learning nevertheless occurred in females, but not in males. Experiments with different numbers of training trials revealed that, in females, fewer learning trials with individual pheromone components were necessary for significant memory formation than in males.

Animals↗
PubMed1999

Real-time measurement of in vitro enamel demineralization in the vicinity of the restoration-tooth interface.

An X-ray attenuation method using photon counting (scanning microradiography) is presented for the real-time study of in vitro demineralization of dental tissues in the vicinity of the restoration-tooth interface. By repeated measurement of mineral content profiles during the course of demineralization, the pattern of lesion development and the rate of mineral loss can be studied. The method is illustrated by comparison of enamel demineralization near a polyacid-modified composite resin restoration, near a bis-GMA/TEGMA composite resin restoration, and in an unrestored control. The method has potential for study of the influence of restorative materials on susceptibility of tooth tissue to demineralization.

Journal Article↗
PubMed1999

Assessment of mucociliary transport in patients with chronic mucoid rhinitis.

Chronic rhinitis is the manifestation of a heterogeneous group of disease entities and often proves difficult to manage successfully. We present the investigations of the mucociliary system in 40 patients with mucoid rhinorrhoea as their principal symptom of whom 20 had pan respiratory disease. The saccharin clearance time (SCT) was measured and classified as normal if it was below 20 min. Objective measurement of clearance was made using 99mTechnetium-labelled human serum albumin (99mTc-HSA). We have standardized our method using a micrometer syringe driver to produce a droplet of consistent size (droplet size, 0.01 ml, SD 0.0002 ml) that reduces the dose of radiation. The movement of the droplet was measured over 20 min (RLT). The mean, maximum rate and percentage moved were calculated. Patients were divided into those who had chest disease (20) and those without and a chi 2-test was performed for the mean RLT time between the two groups. There was a strong correlation between mean and maximum rates (r = 0.91). One patient has a normal SCT and normal RLT. Patients with chest disease had a significantly lower mean RLT (P > 0.01). Assuming that RLT is the standard investigation, six patients were normal but had an abnormal SCT, this is a false positive error of 15%. The false negative error was 4/40 (10%). The association between sinus and chest disease with abnormal mucociliary clearance is stressed.

Chronic Disease↗
PubMed1999

The monitoring of contaminated impervious planar surfaces.

The responses of several types of surface contamination monitor have been investigated for three typical working surfaces contaminated by three radionuclides commonly used in diagnostic or analytical biomedical applications. Of the three radionuclides, 99mTc is an intermediate-energy gamma emitter, 125I decays by electron capture, emitting low-energy x-rays, and 32P is a moderate-energy beta emitter. For each radionuclide monitored values have generally been found to be within 30% of projected response, this being based on calibrations which make use of standard radionuclide sources and conditions. The several types of contaminated non-absorbent surface that have been investigated produce monitored values which for a given type of monitor and radionuclide cannot be differentiated from each other.

Equipment Contamination↗
PubMed1999

smg-7 is required for mRNA surveillance in Caenorhabditis elegans.

Eukaryotic mRNAs that contain premature stop codons are degraded more rapidly than their wild-type counterparts, a phenomenon termed "nonsense-mediated mRNA decay" (NMD) or "mRNA surveillance." Functions of six previously described Caenorhabditis elegans genes, smg-1 through smg-6, are required for NMD. Whereas nonsense mutant mRNAs are unstable in smg(+) genetic backgrounds, such mRNAs have normal stability in smg(-) backgrounds. Previous screens for smg mutations have likely not identified all genes involved in NMD, but efforts to identify additional smg genes are limited by the fact that almost 90% of smg mutations identified in genome-wide screens are alleles of smg-1, smg-2, or smg-5. We describe a modified screen for smg mutations that precludes isolating alleles of smg-1, smg-2, and smg-5. Using this screen, we have identified and cloned smg-7, a previously uncharacterized gene that we show is required for NMD. smg-7 is predicted to encode a novel protein that contains an acidic carboxyl terminus and two probable tetratricopeptide repeats. We provide evidence that smg-7 is cotranscribed with the previously characterized gene lin-45 and show that null alleles of smg-7 confer a temperature-sensitive defect in NMD.

Amino Acid Sequence↗
PubMed1999

FlbT couples flagellum assembly to gene expression in Caulobacter crescentus.

The biogenesis of the polar flagellum of Caulobacter crescentus is regulated by the cell cycle as well as by a trans-acting regulatory hierarchy that functions to couple flagellum assembly to gene expression. The assembly of early flagellar structures (MS ring, switch, and flagellum-specific secretory system) is required for the transcription of class III genes, which encode the remainder of the basal body and the external hook structure. Similarly, the assembly of class III gene-encoded structures is required for the expression of the class IV flagellins, which are incorporated into the flagellar filament. Here, we demonstrate that mutations in flbT, a flagellar gene of unknown function, can restore flagellin protein synthesis and the expression of fljK::lacZ (25-kDa flagellin) protein fusions in class III flagellar mutants. These results suggest that FlbT functions to negatively regulate flagellin expression in the absence of flagellum assembly. Deletion analysis shows that sequences within the 5' untranslated region of the fljK transcript are sufficient for FlbT regulation. To determine the mechanism of FlbT-mediated regulation, we assayed the stability of fljK mRNA. The half-life (t(1/2)) of fljK mRNA in wild-type cells was approximately 11 min and was reduced to less than 1.5 min in a flgE (hook) mutant. A flgE flbT double mutant exhibited an mRNA t(1/2) of greater than 30 min. This suggests that the primary effect of FlbT regulation is an increased turnover of flagellin mRNA. The increased t(1/2) of fljK mRNA in a flbT mutant has consequences for the temporal expression of fljK. In contrast to the case for wild-type cells, fljK::lacZ protein fusions in the mutant are expressed almost continuously throughout the C. crescentus cell cycle, suggesting that coupling of flagellin gene expression to assembly has a critical influence on regulating cell cycle expression.

Bacterial Proteins↗
PubMed1999

SMG-2 is a phosphorylated protein required for mRNA surveillance in Caenorhabditis elegans and related to Upf1p of yeast.

mRNAs that contain premature stop codons are selectively degraded in all eukaryotes tested, a phenomenon termed "nonsense-mediated mRNA decay" (NMD) or "mRNA surveillance." NMD may function to eliminate aberrant mRNAs so that they are not translated, because such mRNAs might encode deleterious polypeptide fragments. In both yeasts and nematodes, NMD is a nonessential system. Mutations affecting three yeast UPF genes or seven nematode smg genes eliminate NMD. We report here the molecular analysis of smg-2 of Caenorhabditis elegans. smg-2 is homologous to UPF1 of yeast and to RENT1 (also called HUPF1), a human gene likely involved in NMD. The striking conservation of SMG-2, Upf1p, and RENT1/HUPF1 in both sequence and function suggests that NMD is an ancient system, predating the divergence of most eukaryotes. Despite similarities in the sequences of SMG-2 and Upf1p, expression of Upf1p in C. elegans does not rescue smg-2 mutants. We have prepared anti-SMG-2 polyclonal antibodies and identified SMG-2 on Western blots. SMG-2 is phosphorylated, and mutations of the six other smg genes influence the state of SMG-2 phosphorylation. In smg-1, smg-3, and smg-4 mutants, phosphorylation of SMG-2 was not detected. In smg-5, smg-6, and smg-7 mutants, a phosphorylated isoform of SMG-2 accumulated to abnormally high levels. In smg-2(r866) and smg-2(r895) mutants, which harbor single amino acid substitutions of the SMG-2 nucleotide binding site, phosphorylated SMG-2 accumulated to abnormally high levels, similar to those observed in smg-5, smg-6, and smg-7 mutants. We discuss these results with regard to the in vivo functions of SMG-2 and NMD.

Alleles↗
PubMed1999

Managing the temperamental employee.

In today's fast-paced, competitive, and quality-centered health care environment, dealing effectively with a temperamental employee and the resultant impact on the organization presents particular challenges. Considerations include the requirement of timely action in order to alleviate the real problems of unprofessional behavior in the workplace. This article discusses the major issues associated with such situations, including why there often is a reluctance for management to take action, the consequences that are accentuated by inaction, prescriptions for preventing the problem, and steps to be taken in dealing effectively with the temperamental employee.

Affective Symptoms↗
PubMed1999

The human renin infused rat: use as an in vivo model for the biological evaluation of human renin inhibitors.

The human renin infused rat model (HRIRM) was used as an in vivo small-animal model for evaluating the efficacy of a collection of inhibitors of human renin. The intravenous infusion of recombinant human renin (2.4 microg x kg(-1) x min(-1)) in the ganglion-blocked, nephrectomized rat produced a mean blood pressor response of 47+/-3 mm Hg (1 mm Hg = 133.3 Pa), which was reduced by captopril, enalkiren, and losartan in a dose-dependent manner following oral administration, with ED50 values of 0.3+/-0.1, 2.5+/-0.9, and 5.2+/-1.6 mg/kg, respectively. A series of peptidomimetic P2-P3 butanediamide renin inhibitors inhibited purified recombinant human renin in vitro in a concentration-dependent manner, with IC50 values ranging from 0.4 to 20 nM at pH 6.0, with a higher range of IC50 values (0.8-80 nM) observed at pH 7.4. Following i.v. administration of renin inhibitors, the pressor response to infused human renin in the HRIRM was inhibited in a dose-dependent manner, with ED50 values ranging from 4 to 600 microg/kg. The in vivo inhibition of human renin following i.v. administration in the rat correlated significantly better with the in vitro inhibition of human renin at pH 7.4 (r = 0.8) compared with pH 6.0 (r = 0.5). Oral administration of renin inhibitors also resulted in a dose-dependent inhibition of the pressor response to infused human renin, with ED50 values ranging from 0.4 to 6.0 mg/kg and the identification of six renin inhibitors with an oral potency of <1 mg/kg. The ED50 of renin inhibitors for inhibition of angiotensin I formation in vivo was highly correlated (r = 0.9) with the ED50 for inhibition of the pressor response. These results demonstrate the high potency, dose dependence, and availability following oral administration of the butanediamide series of renin inhibitors.

Administration, Oral↗