Biomedical subjects
Publications and source records attributed to M C Ryan.
A Cluster Care Aide Model of home care was implemented within a senior apartment complex in New York City. Many unforeseen difficulties arose when traditional home health aides were teamed with newly dependent elderly. Cooperation between the administrators of the two agencies created a specialized orientation and in-service program with positive outcomes.
This study examined the relationships between and among the variables of loneliness, social support, depression, and cognitive functioning in adults over 60, living in senior housing in a metropolitan area. Other variables, namely, life-satisfaction and ability to perform activities of daily living, were also measured. Although the research hypotheses were not supported, relationships between subjects' health status, life satisfaction, and self-assessment of health were significant. Assessment of these variables by community and advanced practice nurses who work with community elderly, to effect positive client outcomes, is presented within the context of Roy's adaptation model.
Atrial natriuretic peptide (ANP) is one of three structurally homologous natriuretic peptides present in heart and brain, which is thought to be involved in the regulation of water and salt intake, blood pressure, and hormone secretion. In the present study, the distribution of preproatrial natriuretic peptide (ppANP) mRNA in the central nervous system of the rat was examined by in situ hybridisation histochemistry by using [35S]-labelled oligonucleotides. Cells expressing ppANP mRNA were apparent in several major neuronal systems, being present in hypothalamic, limbic, pontine and forebrain olfactory regions. Relatively high densities of ppANP mRNA-positive neurones were found in the anterior medial preoptic hypothalamic nucleus, medial habenular nucleus, and in Barrington's nucleus in the pons. Moderate numbers of ppANP mRNA-positive cells were present in a number of amygdaloid nuclei, including the posterolateral and anterior cortical nuclei, in the zona incerta, and the pedunculopontine tegmental nucleus. Other areas, including the ventromedial hypothalamic nucleus and the laterodorsal tegmental nucleus, displayed only low densities of ppANP mRNA-positive neurones. A number of structures in which ppANP mRNA (or ANP-like immunoreactivity) has not previously been reported were found to contain moderate to high numbers of ppANP mRNA-positive neurones including several nuclei associated with the olfactory system, such as the anterior olfactory nucleus and neurones of the tenia tecta and ventrolateral orbital cortex. Although ppANP mRNA in CA1 pyramidal cells of the hippocampus has been described, we also detected labelling in CA2 and ventral CA3 regions of the hippocampus. Conversely, nuclei such as the bed nucleus of the stria terminalis and the nucleus of the solitary tract, which are reported to possess ANP-like immunoreactivity, were found not to contain ppANP mRNA. Overall, these results demonstrate the presence of ANP gene expression in discrete neuronal populations of the rat central nervous system and provide additional evidence to support a putative role for this peptide in regulating and integrating hypothalamic, olfactory, limbic, and neuroendocrine systems.
The interaction of a novel series of heterocyclic amino alcohols with the sigma receptor site was assessed using radioligand binding and computerized molecular modelling. All heterocyclic amino alcohols, like the structurally related ifenprodil, fully inhibited the specific binding of [3H]R(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ([3H]3-PPP) to rat cerebral cortical membranes. All compounds recognised two populations of binding sites labelled by [3H]3-PPP and the proportion of sites in the high affinity state was 60-80% of the total sites. Some of the heterocyclic amino alcohols also displayed similar affinity for alpha 1-adrenoceptors labelled by [3H]prazosin, where the pattern of inhibition appears to be stereospecific, unlike that seen with the binding of [3H]3-PPP. The amino alcohols had negligible affinity for sites labelled by the N-methyl-D-aspartate channel ligand, [3H]-(N-1-[thienyl]cyclohexyl)piperidine. Quantitative conformational analyses indicated that the heterocyclic amino alcohols and ifenprodil fitted well to a sigma receptor site model; low energy conformers could be superimposed like other potent sigma receptor ligands with confidence to the sigma receptor model. Our results define a new class of sigma receptor ligands and extend the understanding of the molecular requirements for drugs active at the sigma receptor.
We have isolated cDNA clones encoding the entire 170-kDa chain of epiligrin (alpha 3Ep) and a genomic clone encoding the alpha 3Ep gene (LamA3). Analysis of multiple cDNA clones revealed two distinct transcripts (alpha 3EpA and alpha 3EpB). Sequencing of the alpha 3EpA transcript indicated sequence and structural homology to laminin alpha 1 and alpha 2 chains that extend from domain IIIa through the carboxyl-terminal G domain. The alpha 3EpB transcript encodes a larger amino-terminal domain and contains additional epidermal growth factor repeats and sequences corresponding to domain IV of alpha 1 laminin. Fluorescence in situ hybridization indicated that the LamA3 gene is located on chromosome 18q11.2, a locus distinct from the LamA1 gene (18p11.3). The G domain of the epiligrin alpha 3 chain contains five subdomains that are individually related to the G subdomains reported for Drosophila and vertebrate laminin alpha chains. Sequence divergence within the G domain of alpha 3 epiligrin suggests that it is functionally distinct from laminin, consistent with our previous report showing that epiligrin interacts with different integrin adhesion receptors. Analysis of RNA from human foreskin keratinocytes (HFKs) identified multiple epiligrin transcripts that were down-regulated by viral transformation and differentiation. In contrast, epiligrin expression was up-regulated in wound sites of human skin.
Junctional epidermolysis bullosis (JEB) is a heterogeneous inherited blistering disorder of human epithelial basement membranes (BMs). Characteristically, the epidermis detaches from the BM between the basal cells and the lamina lucida due to reduced numbers of hemidesmosomes (HDs). Attempts to identify a candidate gene for JEB led to the characterization of nicein, a protein complex in normal BMs that is absent from BMs of patients with JEB gravis. In independent research, two related BM glycoproteins, epiligrin and kalinin, were identified as functional adhesion components of HDs. Epiligrin was characterized as a BM ligand for basal cell adhesion via integrins alpha 3 beta 1 in focal adhesions and alpha 6 beta 4 in HDs. Kalinin was characterized as an adhesive ligand and a component of anchoring filaments. Recent antibody and sequence studies on epiligrin/nicein/kalinin have identified limited homologies with laminin. Ongoing studies in multiple laboratories seek to identify mutations in one or more of the three subunits of epiligrin that are causal in JEB gravis. Consistent with the genetic heterogeneity of JEB, we have identified a patient with a variant form of JEB that is associated with pyloric atresia. This patient has negligible HDs, normal epiligrin, but reduced expression of integrin beta 4. A defect in the beta 4 expression may define a subset of JEB cases that also present with pyloric atresia. These results testify to the dual requirements for epiligrin in the BM and integrin beta 4 in the plasma membrane in regulating function of HDs in epithelium.
Conditioned media from 14 short term fibroblast cell lines were mitogenic for human breast cancer cells with different steroid receptor profiles in serum-free culture. Fibroblast-conditioned medium stimulated tritiated thymidine incorporation in short term culture and growth in a longer proliferation study as measured by the MTT colorimetric assay. Conditioned media from benign and malignant epithelial cells were non-stimulatory for breast cancer cells but that derived from endothelial cells showed similar stimulation to fibroblasts. Partial purification of fibroblast-conditioned medium identified a peptide with a molecular weight of approximately 8 kDa that showed no affinity for heparin and was mitogenic for MCF-7 breast cancer cells.
Recent papers from established trauma centers reported average elapsed times from emergency department (ED) admission to the operating room (OR) of greater than 100 minutes for patients judged to be in immediate need of surgery. This study was undertaken to determine whether patients treated at an institution desiring level II trauma center designation in a geographic area with a low incidence of penetrating trauma suffered any adverse effects because of lack of a 24-hour in-house OR staff. Trauma registry data at The Stamford Hospital, a suburban community teaching hospital without OR nursing staff in-house at night, were reviewed and compared with data from three affiliated level I trauma centers and with established national standards using TRISS methodology. Of 659 major trauma patients, 86 (44 blunt, 42 penetrating) underwent surgery within 12 hours of admission. Patients' injuries were similar in severity to those seen at the affiliated trauma centers and to the Major Trauma Outcome Study population. Mortality rates were also similar. No statistically significant differences were seen in elapsed times from ED arrival to OR arrival even in the subgroup of patients with systolic blood pressure values of < or = 90 mm Hg. No unexpected adverse outcomes could be ascribed to the lack of 24-hour OR staffing in this setting. The estimated cost of providing additional OR staffing is $145,000 per year. Since times to the OR and outcomes were similar to those at level I centers, this expense may not be warranted.
Epiligrin is a new glycoprotein in most epithelial basement membranes (BMs) and is a ligand for cell adhesion via integrin alpha 3 beta 1. In the extracellular matrix of human foreskin keratinocytes (HFKs), epiligrin contains three disulfide-bonded, glycoprotein subunits, E170, E145, and E135, based on molecular size in kilodaltons. Epiligrin, immunopurified with MAb P1E1, induced cell adhesion and localization of integrin alpha 3 beta 1 in focal adhesions (FAs). Cell adhesion to epiligrin was inhibited with an anti-alpha 3 beta 1 MAb. Epiligrin also colocalized with integrin alpha 6 beta 4 in hemidesmosome-like stable anchoring contacts (SACs). alpha 3 beta 1-FAs encircled alpha 6 beta 4-SACs in a complex adhesion structure. alpha 3 beta 1 and epiligrin localized in BM junctions of epithelial cells primarily in organs of endodermal/ectodermal origin. In epidermis, epiligrin was detected in the lamina lucida of BMs. alpha 3 beta 1 localized in plasma membranes of basal cells in contact with epiligrin and also in lateral/apical membranes. Epiligrin is the ligand of an adhesion super complex composed of alpha 3 beta 1-FAs and alpha 6 beta 4-SACs (hemidesmosomes).
Type II collagen, like other fibrillar collagens, is synthesized as a procollagen containing amino (NH2)-and carboxyl (COOH)-terminal extension peptides. Based on cDNA cloning of human (Baldwin, C. T., Reginato, A. M., Smith, C., Jimenez, S. A., and Prockop, D. J. (1989) Biochem. J. 262, 521-528) and rat (Kohno, K., Martin, G. R., and Yamada, Y. (1984) J. Biol. Chem. 259, 13668-13673) type II procollagen, it was concluded that much of the NH2-terminal propeptide seen in pro-alpha 1(I) was missing. Analysis of human genomic clones for type II collagen revealed an additional exon encoding a 69-amino acid cysteine-rich domain in the NH2-terminal propeptide. This exon (exon 2) is expressed in the mRNA population of chondrocytes isolated from human fetal skeleton and notochord, juvenile costal cartilage, and bovine articular cartilage. Oligonucleotide probes spanning specific exon boundaries were used to detect two populations of procollagen mRNA by Northern blot analysis. Amplification of cDNA templates using polymerase chain reaction provided direct evidence for two distinct pro-alpha 1(II) collagen mRNAs. DNA sequence analysis showed that the two mRNAs resulted from the alternative splicing of exon 2. The protein domain encoded by exon 2 is conserved between the fibrillar collagens and two other extracellular matrix proteins, thrombospondin and von Willebrand factor. In fibrillar collagens, this protein domain may play a regulatory role in fibrillogenesis and feedback inhibition of collagen biosynthesis. Consequently, the differential expression of this protein domain could alter the biosynthesis or fibril formation of type II collagen. In addition, the expression of exon 2 may be a marker for a distinct population of chondrocytes.
The complete DNA sequence (6 kb) of the 5' portion of the human type II procollagen gene (COL2A1) was determined from the promoter through the third exon including intron sequences and 690 bp of 5' flanking sequence. Three regions between -501 and -649 in the human promoter share high sequence homology to the rat type II procollagen gene and suggest that the functional sequences within the promoter may extend to at least 649 bp upstream from the start site of transcription. The first intron of the human gene contains elements known to play a role in transcription of other genes: three GC boxes, an inverted repeat with homology to a serum responsive element, a viral core enhancer motif, a high-affinity recognition sequence for nuclear factor-1, and an alternating purine/pyrimidine stretch composed of GT repeats. Both the promoter and a portion of the first intron have a high percentage of G + C residues and a high frequency of CpG dinucleotides. In addition, a protein domain that has been identified in the human COL2A1 gene is present in pro-alpha 1(I) and pro-alpha 1(III) collagen but was not previously described for pro-alpha 1(II) collagen. On the basis of this new information we present a modified gene structure for the exons encoding the pro-alpha 1(II) collagen NH2-propeptide.
The process by which people attempt to make sense of an event, such as hospitalization, is referred to as "meaning making" by Kegan. Because the ways in which the elderly define their feelings generated by illness and hospitalization influence their behavioral responses, understanding this interpretation increases the predictions that can be made about their behaviors. Interventions aim at helping clients integrate their experience of illness to form a new self. The nurse acts as the matrix from which patients explore the meaning of illness and hospitalization.
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We have developed an effective and well-accepted method of providing mist for children with acute respiratory distress. This method can be especially useful in areas of the world where resources are limited.
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Pregnant C3H/Anfcum mice were injected ip with 150 micrograms benzo(a)pyrene (BP)/g body weight at the second trimester (12 days). Quantitative and differential changes were assayed in the peripheral blood leukocytes and erythrocytes at various times before and after mating and treatment. Within 5 days after injection, a 2- to 4-fold reduction in leukocytes was observed when compared to controls [corn oil (vehicle for BP)-injected pregnant females] which persisted into the 10th postpartum day. The erythrocytes were also significantly reduced but not to the same degree (1.2- to 1.5-fold). Depression in white blood cells is attributed to lymphocyte depletion since the granulocytes were virtually unchanged and the lymphocyte to granulocyte ratio, ordinarily greater than 2 was 1 or less than one. No change in monocytes was observed and none of the cell populations, including the erythrocytes, appeared to be abnormal (e.g., no increase in reticulocytes). A moderate reduction (1.5-fold) in erythrocytes and leukocytes also occurred in the controls (vs virgin females). Pregnancy also led to transient decreases in medium sized lymphocytes and 3- to 4-fold increase in small lymphocytes shortly after mating to about 3 days before parturition. These results show that, although pregnancy depresses the leukocyte profile, exposure to BP exacerbates this change, and preferentially affects the lymphocytes. These blood profile changes may have important health consequences in the mother and her progeny.