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M R MacDonald

Publications and source records attributed to M R MacDonald.

33 records · Page 2Linked to original sources
PubMed1993

New onset wheezing in an older male population: evidence of allergen sensitization in a longitudinal study. Results of the normative aging study.

BACKGROUND: Thirty-nine male subjects, with new-onset wheezing, were selected from participants in the Department of Veterans Affairs Normative Aging Study and compared with 74 age-matched controls. Wheezing was defined by responses to a standardized and regularly administered questionnaire. The subjects with wheezing had a reduced FEV1 compared with controls (p = 0.005), but most had values above 80% predicted. Current smoking was more common in subjects with wheezing (36.8% vs 8.11% in controls, p < 0.001). The mean age of both subjects and controls was 64 years. METHODS: Allergen-specific IgE antibodies were measured, starting with sera at the time of the most recent questionnaire, and on the average 3.1, 7.6, and 12.3 years before that, with use of stored serum samples. RESULTS: Total IgE did not differ significantly between the groups. IgE binding to dust mite antigen was detected in 13% to 15% of the subjects with wheezing compared with fewer than 7% of the controls over four time intervals (p = 0.014). IgE binding to cat and ragweed antigens did not differ significantly between groups. If current nonsmokers were analyzed separately, IgE binding to cat allergen was also slightly greater in subjects with wheezing compared with controls (p = 0.054). Sequential analysis of IgE antibody levels to mite antigen, over time, indicated that IgE antibody antedated the onset of wheezing. CONCLUSIONS: New-onset wheezing in an older adult male population is significantly associated with allergic sensitization to dust mite. There was a borderline association with sensitization to cat in noncurrent smokers only. This supports the hypothesis that a subgroup may have allergic triggers to their symptoms.

Adult↗
PubMed1989

Multiple tachykinins are produced and secreted upon post-translational processing of the three substance P precursor proteins, alpha-, beta-, and gamma-preprotachykinin. Expression of the preprotachykinins in AtT-20 cells infected with vaccinia virus recombinants.

The rat preprotachykinin I gene mRNA is alternatively spliced to yield three different mRNA species differing in their protein coding regions. We have produced recombinant vaccinia viruses expressing alpha-, beta-, and gamma-preprotachykinin to examine the tachykinin-related peptides produced upon post-translational processing of each individual precursor. Infection of BSC-40 or AtT-20 cell lines with a beta-preprotachykinin-encoding vaccinia virus recombinant results in the expression of the precursor protein. The pro-form (signal peptide removed) can be immunoprecipitated from extracts of infected cells. Infected cells of both types secrete into the culture medium a product(s) which reacts in radioimmunoassay with an antiserum shown to recognize precursor as well as mature substance P. Infected AtT-20, but not BSC-40, cells secrete into the culture medium a processed form(s) of beta-preprotachykinin which reacts in radioimmunoassay with an anti-serum which recognizes the amidated carboxyl terminus of substance P. The molecular nature of the tachykinin products produced in and secreted from AtT-20 cells infected with alpha-, beta-, and gamma-preprotachykinin-encoding recombinants was analyzed by combined high performance liquid chromatography and radioimmunoassay. Peptides were identified based on comigration with synthetic standards and antisera cross-reactivity. We determined that alpha-preprotachykinin is processed to the mature undecapeptide, substance P. beta-Preprotachykinin was processed into multiple products, including substance P, neurokinin A, neurokinin A(3-10), and neuropeptide K. gamma-Preprotachykinin was processed into substance P, neurokinin A, neurokinin A(3-10), and neuropeptide gamma. These five tachykinin peptide products were all routed through the regulated secretory pathway and were secreted into the medium in a cAMP-stimulatable fashion. Since all of these peptides have been shown to be biologically active, it is important to consider the biological consequences of their co-secretion in vivo.

Animals↗
PubMed1989

Solution hybridization-nuclease protection assays for sensitive detection of differentially spliced substance P- and neurokinin A-encoding messenger ribonucleic acids.

In this chapter we discussed methods that can be used for the sensitive detection and quantitation of differentially or alternatively spliced mRNAs as well as mRNAs of low abundance. Although mechanisms responsible for splicing (and differential splicing in particular) have not been fully determined, many RNAs derived from a variety of genes have been observed to undergo the process. The impact of splicing with regard to the expanded potential of gene expression emphasizes the usefulness of the solution hybridization-nuclease digestion technique described here, compared to Northern blot analysis. The use of radiolabeled cRNA(s) provides for an assay of both high specificity and high sensitivity. While end-labeled cDNA probes can be used, they do not have the sensitivity inherent in the assay performed with uniformly radiolabeled cRNAs. If multiple mRNAs are derived from a single gene as a result of differential or alternative precursor RNA splicing, however, the results with a cRNA probe may initially appear to be quite complicated, and end-labeled cDNAs may yield more easily interpretable results. Nonetheless, both types of probes are useful in the context of gene expression analysis, and it is clear that for routine purposes of quantitation cRNA probes in solution hybridization-nuclease protection assays are clearly more desirable than RNA blot analyses due to their truly quantitative nature as well as ease of assay.

Autoradiography↗
PubMed1988

Posttranslational processing of alpha-, beta-, and gamma-preprotachykinins. Cell-free translation and early posttranslational processing events.

We have used an in vitro transcription-translation system to study initial protein processing events of the rat substance P/neurokinin A gene products. cDNA clones for three different mRNA species, which are derived by differential RNA splicing, were subcloned into a plasmid, pGEM1, which contains the promoter for the bacteriophage SP6 RNA polymerase. In vitro synthesized mRNAs for alpha-, beta-, and gamma-preprotachykinin were translated in a wheat germ or rabbit reticulocyte cell-free system. When analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the translated protein products migrate consistent with the deduced molecular masses of alpha (13,035 Da)-, beta (15,003 Da)-, and gamma (13,343 Da)-preprotachykinin. The addition of dog pancreatic microsomal membranes to either cell-free translation system causes the production of a protease-resistant form of each of the three preprotachykinins which migrates with an apparent increase in molecular mass of approximately 2,000 Da. Each of these modified preprotachykinins lacks the putative signal peptide of the prepro- form, with signal peptidase cleavage occurring after the alanine residue at position 19. Both the prepro- and proforms of each tachykinin precursor molecule are recognized by antiserum R-140, an antiserum specific for the mid-portion of the undecapeptide substance P. The most likely explanation for the apparent increase in molecular mass is anomalous electrophoretic migration, since beta-preprotachykinin mRNA lacking the signal peptide encoding sequence is translated, in the absence of microsomal membranes, into a protein with the same apparent molecular mass as the modified form of beta-preprotachykinin. Therefore, each of the three preprotachykinin mRNAs are translatable, and their products are targeted to the secretory pathway by the presence of a cleavable signal peptide.

Animals↗
PubMed1987

Depression and activity patterns of spinal cord injured persons living in the community.

The present study examined the effects of depression and injury level (paraplegics/quadriplegics) on respondents' daily activity (ADL) patterns for 53 spinal cord injured (SCI) persons living in the community. This investigation involved the administration of the Beck Depression Inventory, the Clinical Depression Measure, the Multiple Affect Adjective Check List, and the Activity Pattern Indicators. The first issue of interest was the incidence of clinical depression in this community-based sample. Evidence of clinical depression was found in only 15% of the sample, with 45% of respondents showing evidence of mild depression. A second issue concerned the independent and/or interactive effects of depression and injury levels across several different types of ADL. Independent depression effects were found for personal activities, such that mildly depressed respondents reported fewer personal activities than nondepressed individuals. Independent injury level effects were found for overall frequency of activities, with quadriplegics achieving lower scores than paraplegics. Interactive effects were obtained between depression and injury level for work and travel. For each of these activities, similar levels were found for nondepressed quadriplegic, mildly depressed quadriplegic, and mildly depressed paraplegic respondents, all of whom were less active than nondepressed paraplegics. These results suggest that for some activities depression may play as important a role in long-term rehabilitation as degree of disability.

Activities of Daily Living↗
PubMed1981

Effect of 5''-methylthioadenosine and its analogs on murine lymphoid cell proliferation.

The effect of 5'-deoxy-5'-methylthioadenosine (MTA) on the growth of culture murine lymphoid cells was examined. MTA inhibited the growth of murine lymphoid cell lines of both B- and T-cell origin in a reversible, nontoxic, and dose-dependent fashion. When measured 2 days after the addition of MTA to the cells, the concentration that inhibited proliferation by 50% for MTA was about 250 muM. Cells incubated in the presence of 0.5 mM MTA for 1, 2, or 3 days were able to recover from the inhibitory effect of the nucleoside and resumed growth. Six structural analogs of MTA were also found to inhibit cell growth. Five of these analogs served as alternative substrates for MTA phosphorylase, while one, the 7-deaza analog (5'-deoxy-5'-methylthiotubercidin), was not a substrate for the phosphorylase but was a potent inhibitor of enzyme activity. Inhibition of growth by 5'-deoxy-5'-methylthiotubercidin was dose dependent (the concentration that inhibited proliferation by 50% approximately or equal to 10 muM) and at 50 muM was reversible and nontoxic.

Adenosine↗
PubMed1975

Treatment of Candida peritonitis by peritoneal lavage with amphotericin B.

A 14-year-old girl, who was a renal transplant recipient, developed Candida tropicalis peritonitis during peritoneal dialysis and immunosuppressive and broad-spectrum antibiotic therapy. Therapeutic cure of the peritonitis followed a ten-day course of amphotericin B administered solely by peritoneal lavage.

Amphotericin B↗
PubMedDate not supplied

The polyprotein nature of substance P precursors.

Substance P and related tachykinin peptides probably act as neurotransmitters or modulators of neurotransmission, and regulate biological processes as diverse as salivary secretion and transmission of pain signals. Substance P peptide sequences are expressed in three distinct mRNAs that are generated from one gene by differential RNA splicing. In addition to substance P, as many as three other tachykinin peptides can be generated from the polyprotein precursors by differential posttranslational processing. Three tachykinin receptor subtypes have been extensively characterized which differentially interact with the naturally occurring tachykinin peptides. Therefore, the generation of diversity of tachykinin peptides results from differential precursor RNA splicing and differential posttranslational processing. The specificity of peptide responses is the result of selective receptor subtype expression.

Amino Acid Sequence↗
PubMedDate not supplied

Southern blot analysis of DNA extracted from paraffin wax-embedded tissue.

Genetic analysis of multi-generation families using RFLP is often incomplete because fresh tissue is not available for the isolation of DNA. However, in many instances archival material exists, usually formalin-fixed in paraffin blocks. Procedures have been described for extracting DNA from such specimens. Many parameters affect the quality of the DNA eventually extracted and this in turn determines whether the DNA can be successfully digested with restriction enzymes and probed (Dubeau et al., 1986; Warford et al., 1988). In essence, the procedures followed at the time of fixation largely determine whether archival material will yield useful results. We have re-examined the effect of varying the fixation time but, more importantly, we have assessed the validity of RFLP results obtained from fixed tissue.

Blotting, Southern↗
PubMedDate not supplied

Developing a collective future: creating a culture specific nurse caring practice model for hospitals.

Nurses continue to struggle with the knowledge that practice within a conceptual context is imperative, yet operationalizing theory-based practice has been fraught with challenges and frustrations. It is timely, given the current environment, for nurses to reflect personally and collectively on the processes and meanings of nursing. Caring theories have been examined with increasing frequency recently, as nurse leaders and theorists explore the profession using alternative frames of reference. The authors discuss the concepts central to development of a practice-based nurse caring model in a community hospital and review the process of nurse-caring model development. Concepts central to the development of the model include: individual;-collective experience as theory; cargiver-client congruence in perceptions of nurse caring; institutions as culture-specific environments. The ongoing process of theory development was initiated by data collection through focus group discussions on nurse-caring experiences and definitions. Twenty-four staff RNs and RNAs were interviewed by a trained facilitator. Audiotaped data were later transcribed and subjected to content analysis for initial theme and definition development. A parallel exercise was carried out with hospital patients using the same methodology. Subsequent analysis included validation of findings by both groups. Examinations of constructs as the theory development evolves will be expedited by both staff and in consultation with Dr. Madeleine Leininger and other external nurse-caring theorists. The Health Centre intends to operationalize and implement its nurse-caring model as an outcome of this long term project. Assumptions integral to the purpose of the project have been validated by staff response. Concepts and their relationships appear to achieve acceptance and be congruent with this nursing group's values and the way in which they practice. Observations to date indicate that collective development of a practice model is providing the means for growth and change in the institution's nursing practice.

Empathy↗