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Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 181 records · Page 10Linked to original sources

Advances in the molecular genetic analysis of the flax-flax rust interaction.

The L6 and M rust-resistance genes, representing two of the five rust-resistance gene loci in flax (Linum usitatissimum), have been cloned. The molecular data are fully consistent with earlier genetic data: the L locus is a single gene with multiple alleles expressing different rust resistance specificities, and the M locus is complex, containing an array of about 15 similar genes. Thus, while L6 and M resistance genes have 86% nucleotide identity, their locus structure is very different. These genes encode products belonging to the nucleotide binding site-leucine-rich repeat class of disease-resistance proteins. Analysis of alleles from the L locus and chimeric genes is providing evidence suggesting that important specificity determinants occur in the C-terminal half of the proteins, the region containing the leucine-rich repeats. The isolation and characterization of the rust (Melampsora lini) avirulence genes that correspond to the cloned rust-resistance genes is one of the major challenges remaining to the understanding of this system.

Journal Article↗

Left ventricular function and remodeling after myocardial infarction in aging rats.

Adaptations of the aging left ventricle (LV) to hemodynamic overload are functionally and structurally distinct from those of the young organism. This study describes the influence of aging on LV hemodynamics and remodeling late after myocardial infarction (MI) in Fischer 344 Brown Norway rats. In sham rats at 23 mo, LV weight, myocyte cross-sectional area (CSA), and myocardial fibrosis were increased, whereas LV dP/dt, LV relaxation, and maximal LV systolic function declined with respect to younger rats (7, 12, and 18 mo of age). Isometric myocardial function was evaluated in papillary muscles of 12- and 23-mo-old sham rats. Myocardial systolic function was decreased in older rats. To determine how aging affects LV function and remodeling after MI, rats were infarcted at 7 and 18 mo of age and were studied 5 mo later. Infarct size was similar in each group. Right ventricular weight, LV end-diastolic pressure, and volume index were increased, whereas LV dP/dt, peak cardiac index, and peak developed LV pressure declined after MI. However, there were no significant differences between young and older rats in any variable of LV systolic function or remodeling after MI. Myocyte CSA increased in younger rats after MI but was unchanged in 23-mo-old rats. After MI, myocardial fibrosis was significantly increased from baseline only in younger rats. The negative interaction of aging and MI on myocyte hypertrophy and fibrosis was highly significant. The findings indicate that baseline LV and myocradial function decline with age. In the aging rat after MI, despite limited compensatory hypertrophy and more advanced baseline myocardial fibrosis, the long-term functional and structural adaptations to MI are similar to those of the mature adult heart.

Aging↗

Behavioural analysis of olfactory conditioning in the moth spodoptera littoralis (Boisd.) (Lepidoptera: noctuidae)

We studied the associative learning capabilities for behaviourally relevant cues in the moth Spodoptera littoralis. The moths were trained to associate a conditioned stimulus (CS), geraniol odour, with an unconditioned stimulus (US), a sucrose solution. The occurrence of a proboscis extension reflex (PER) was tested. The PER performance during acquisition increased steadily with the number of training trials. Non-associative control procedures did not result in learning. PER conditioning was achieved when the CS was presented 1-3 s before the US. A wide range of inter-trial intervals was able to support conditioning. Males and females learned equally well. Moths could to some degree learn the CS-US association after a single trial. These results demonstrate that S. littoralis females and males have a good capability to associate an odour with a reward. The neural basis of olfactory coding in moths has been well studied; thus, the moth provides a powerful system in which to examine the neurobiology of olfactory learning.

Journal Article↗

Efficacy of metered-dose inhaler administration of albuterol in intubated infants.

STUDY OBJECTIVE: To compare the safety and efficacy of metered-dose inhaler (MDI) albuterol to nebulized (NEB) albuterol administration. DESIGN: A randomized, triple-blinded, crossover study. SETTING: A pediatric ICU in a tertiary care children's hospital. PATIENTS: Eleven intubated infants with bronchiolitis. INTERVENTIONS: Subjects received four puffs of MDI albuterol (360 microg) and 3 mL of NEB saline solution placebo or 0.3 mL of NEB albuterol (1.5 mg) and MDI saline solution placebo. Each set of albuterol and saline solution placebo was administered after direct attachment of delivery device to the endotracheal tube and bag-valve system. Subjects received the opposite sequence 4 h after the initial sequence. The second sequence was given first the next day, and the first sequence was administered 4 h later. MEASUREMENTS AND RESULTS: Respiratory system compliance and resistance were measured at baseline and 30 min, 1 h, 2 h, and 4 h after each set of placebo and albuterol. There was an appreciable improvement in compliance and resistance for up to 2 h following both methods of administration. However, the degree of improvement was not significantly different (p>0.05) between the two methods. Neither method caused a significant change in resistance when measured at 4 h after albuterol/placebo administration. No evidence of toxicity was detected. CONCLUSIONS: MDI-administered albuterol is as safe and efficacious as nebulized-administered albuterol in intubated infants with bronchiolitis. Generalizability of these results is limited by differences in drug delivery with different brands of nebulizers and spacers and sites of attachment.

Administration, Inhalation↗

Team-based participation in the hiring process.

In most health care settings today, effective patient service results from medical staff members working together as a high performance team. These teams evolve through the process of hiring employees who combine the necessary technical skills, knowledge, and abilities (SKAs) to perform the job and whose interpersonal attributes will add value to services provided by the team. This article promotes the concept that those who are in the best position to determine whether a job candidate will become a productive team member are, in most cases, the team members themselves. Discussion includes types of teams and degree of member involvement. For those health care professionals interested in using greater team-based participation in employment matters, specific advantages and realistic challenges are provided.

Decision Making, Organizational↗

Cytotoxicity and apoptosis in human renal allografts: identification, distribution, and quantitation of cells with a cytotoxic granule protein GMP-17 (TIA-1) and cells with fragmented nuclear DNA.

In the present study, we analyzed human renal allografts using immunohistochemical techniques to determine the site, identity, and frequency of (a) cytotoxic and apoptotic cells, as identified by staining for GMP-17 (TIA-1), a component of cytotoxic granules; and (b) DNA fragmentation in situ, as detected by the TUNEL method. In acute cellular rejection (n = 15), GMP-17+ mononuclear cells accounted for 29% +/- 12% of the infiltrating cells in the interstitium (341 +/- 164/mm2) and were significantly more concentrated in tubulitis lesions, where they amounted to 65% +/- 14% of the mononuclear cells (96 +/- 61/mm2) (p < 0.01 versus interstitium). GMP-17+ mononuclear cells were also found in sites of endothelialitis. An estimated 80% of the GMP-17+ lymphocytes expressed CD8, and 10% to 20% expressed either CD4 or the macrophage marker CD14. The latter finding led us to analyze normal peripheral blood monocytes by flow cytometry, all of which were found to contain GMP-17. NK cells and neutrophils, which are known to express GMP-17, were detected only rarely in allografts. Specimens with cyclosporine A toxicity (n = 7) or acute tubular necrosis (n = 13) showed fewer GMP-17+ cells in the interstitium (22 +/- 46/mm2 and 62 +/- 50/mm2, respectively) and tubules (2 +/- 6/mm2 and 10 +/- 10/mm2, respectively) (all p < 0.01 versus rejection). These differences were due largely to less intense mononuclear cell infiltration. In cyclosporine A toxicity, however, the percentages of GMP-17+ mononuclear cells within tubules and the interstitium were significantly lower than in rejection (p = 0.02), whereas in acute tubular necrosis significantly lower percentages were found in the tubules (p = 0.04) but not in the interstitium. Native kidneys with end-stage diabetic nephropathy (n = 5) had very low proportions of GMP-17+ cells in interstitial infiltrates (7% +/- 6%) and in tubules (11% +/- 15%), although the infiltrates were focally intense (517 +/- 355/mm2). TUNEL+ cells were found in acute cellular rejection, predominantly in areas with intense mononuclear infiltrates and also within lesions of tubulitis and endothelialitis. Although some TUNEL+ cells were intrinsic renal cells, most appeared to be infiltrating mononuclear cells, and we were able to detect CD3 in some. In areas of intense cellular infiltration, the percentages of TUNEL+ cells (range, 0.5% to 4.2%) were comparable to those seen in the rat thymus, indicating a high level of apoptosis. Overall, in the allograft samples, the numbers of GMP-17+ cells and TUNEL+ cells were significantly correlated (r = 0.79; p < 0.01). These data provide new evidence that T cell (and possibly macrophage)-mediated cytotoxicity plays an important role in acute renal allograft rejection, particularly in the case of tubular injury, and furthermore suggest that apoptosis may be a mechanism not only for graft cell destruction, but also for elimination of activated T cells in the infiltrate.

Apoptosis↗

The 1996 Albert Lasker Medical Research Awards. Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines.

The development of Haemophilus influenzae type b (Hib) conjugate vaccines has led to the virtual elimination of systemic infections caused by that pathogen, has provided insights into the pathogenesis of and immunity to other capsulated bacteria, and has contributed to the development of new vaccines. Meningitis, a common and serious infection of children, and other infections caused by Hib have been virtually eliminated in countries that have achieved widespread vaccination with Hib conjugates, including the United States, Canada, the United Kingdom, Iceland, Scandinavia, France, and Germany. Hib conjugates have also been shown to be highly effective in developing countries. The principles derived from the use of these vaccines, along with studies of other capsulated pathogens, should allow the rapid inclusion of new polysaccharide-based conjugates into routine vaccination schedules of infants, and should help to realize further reductions in serious systemic infectious diseases.

Animals↗

Structure, tissue distribution and genomic organization of the murine RRM-type RNA binding proteins TIA-1 and TIAR.

TIA-1 and TIAR are RNA binding proteins of the RNA recognition motif (RRM)/ribonucleoprotein (RNP) family that have been implicated as effectors of apoptotic cell death. We report the structures of murine TIA-1 and TIAR (mTIA-1 and mTIAR) deduced from cDNA cloning, the mRNA and protein tissue distribution of mTIA-1 and mTIAR, and the exon-intron structures of the mTIA-1 and mTIAR genes. Both mTIA-1 and mTIAR are comprised of three approximately 100 amino acid N-terminal RRM domains and a approximately 90 amino acid C-terminal auxiliary domain. This subfamily of RRM proteins is evolutionarily well conserved; mTIA-1 and mTIAR are 80% similar to each other, and 96 and 99% similar to hTIA-1 and hTIAR, respectively. The overall exon-intron structures of the mTIA-1 and mTIAR genes are also similar to each other, as well as to the human TIA-1 gene structure. While Northern blot analysis reveals that mTIA-1 and mTIAR mRNAs have a broad tissue distribution, mTIA-1 and mTIAR proteins are predominantly expressed in brain, testis and spleen. At least two isoforms of both mTIA-1 and mTIAR are generated by alternative splicing. Murine TIA-1 isoforms including or lacking the exon 5 encoded sequences are expressed at a ratio of approximately 1:1, whereas mTIAR isoforms including or lacking the 5'-end of exon 3 sequences are expressed in a approximately 1:6 ratio. Molecular characterization of murine TIA-1 and TIAR RNA binding proteins provides the basis for a genetic analysis of the functional roles of these proteins during mammalian development.

Amino Acid Sequence↗

G proteins are required for spatial orientation of early cell cleavages in C. elegans embryos.

Heterotrimeric G proteins are signal-transducing molecules activated by seven transmembrane domain receptors. In C. elegans, gpb-1 encodes the sole Gbeta subunit; therefore, its inactivation should affect all heterotrimeric G protein signaling. When maternal but no zygotic gpb-1 protein (GPB-1) is present, development proceeds until the first larval stage, but these larvae show little muscle activity and die soon after hatching. When, however, the maternal contribution of GPB-1 is also reduced, spindle orientations in early cell divisions are randomized. Cell positions in these embryos are consequently abnormal, and the embryos die with the normal number of cells and well-differentiated but abnormally distributed tissues. These results indicate that maternal G proteins are important for orientation of early cell division axes, possibly by coupling a membrane signal to centrosome position.

Animals↗

X-ray microtomography: a novel technique for the quantification of effects in enamel following CO2 laser application.

X-ray microtomography (XMT) is a miniaturised version of the technique of computer axial tomography as used in medical diagnosis. As an example of the dental research applications of the technique, a pilot study is described in which the effects of a continuous wave carbon-dioxide laser on dental enamel are investigated and the use of XMT for the non-invasive measurement of mineral density changes within dental hard tissues is demonstrated. The results show clearly the ability of XMT to display graphically, and to quantify, changes in mineral density occurring within lased specimens, compared with a conventional SEM view of similar material. There have been many reports of the problems found when using lasers to cut dental hard tissues, and this paper demonstrates that XMT is of particular value in the study of the cracking induced by many lasers. We also suggest that XMT might be used in many studies investigating mineral density changes within dental hard tissues.

Adult↗

Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells.

Human natural killer (NK) cells are bone marrow (BM)-derived CD2+CD16+CD56+ large granular lymphocytes (LGL) that lack CD3 yet contain the T-cell receptor zeta-chain (zeta-TCR). NK cells provide requisite interferon-gamma (IFN-gamma) during the early stages of infection in several experimental animal models. A number of studies have shown that human CD3-CD56+ NK cells can be obtained from BM-derived CD34+ hematopoietic progenitor cells (HPCs) cultured in the presence of interleukin-2 (IL-2) and an allogeneic feeder cell layer, or IL-2 and other hematopoietic growth factors such as the c-kit ligand (KL). The failure to detect the IL-2 gene product within the BM stroma and the presence of NK cells in IL-2-deficient mice suggested that cytokines other than IL-2 may participate in NK cell differentiation from HPCs in vivo. IL-15 is a cytokine which, while lacking any sequence homology in IL-2, can activate cells via the IL-2 receptor. Here we show that human BM stromal cells express the IL-15 transcript, and supernatants from long-term BM stromal cell cultures contain IL-15 protein. In vitro, CD3-CD56+ NK cells can be obtained from 21-day cultures of CD34+ HPCs supplemented with IL-15 in the absence of IL-2, stromal cells, or other cytokines. The addition of the KL to these cultures had no effect on the differentiation of the CD3-CD56+ cytotoxic effector cells, but greatly enhanced their expansion. The majority of these cells lack CD2 and CD16, but do express zeta-TCR. Similar to NK cells found in peripheral blood, the CD2-CD16-CD56+ NK cells grown in the presence of IL-15 were found to be potent producers of IFN-gamma in response to monocyte-derived cytokines. Thus IL-15, like KL, appears to be produced by BM stromal cells. IL-15 can induce CD34+ HPCs to differentiate into CD3-CD56+ NK cells, and KL can amplify this. Therefore, IL-15 may be a physiologically relevant ligand for NK cell differentiation in vivo.

Antigens, CD34↗