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Biomedical subjects

J F Murphy

Publications and source records attributed to J F Murphy.

At least 19 recordsLinked to original sources
PubMed1996

Replacement of the tyrosine residue that links a potyviral VPg to the viral RNA is lethal.

Mutants of tobacco vein mottling virus (TVMV) were constructed in which the tyrosine residue (Tyr1860) that links the VPg to the viral RNA was changed to phenylalanine or serine or was inverted in position with the adjacent glycine residue. In another mutant, the tyrosine residue nearest to Tyr1860 (Tyr1867) was changed to a phenylalanine residue. The resulting mutants were tested for their ability to infect Nicotiana tabacum plants or protoplasts. The Tyr1860 mutants did not accumulate to detectable levels in infected plants when tested by ELISA and Northern blot analysis. Moreover, the Tyr1860-associated mutants were not infectious in protoplasts, indicating that mutations involving the linking amino acid of the TVMV VPg abolished viral replićation. In contrast to the Tyr1860 mutants, transcripts from the mutation of Tyr1867 to a phenylalanine residue infected both protoplasts and plants. Analysis of progeny RNA from plants inoculated with the Tyr1867 mutant indicated that a reversion to wild type had occurred in systemically infected leaves.

Amino Acid Sequence↗
PubMed1996

Age and gender differences in health services utilization.

The purpose of this study was to examine the health service utilization patterns of elderly male and female enrollees of a large urban staff model Health Maintenance Organization (HMO). This HMO offered a wide spectrum of managed care services for its beneficiaries. A cross-sectional design was employed. The 759 randomly sampled elderly enrollees ranged in age from 66 to 99, with an average of 77.15 years. Approximately 60% were male and 40% were female; thus, the sample was not representative of the national older adult population. Three utilization patterns indicated that there were (a) nonsignificant relationships between age or gender and urgent care visits, prescribed pharmaceuticals, and out-of-pocket costs for pharmaceuticals; (b) linear relationships between age and gender and visits to HMO primary care providers (-), home-health care visits (+), emergency care visits (+), hospitalizations (+), and MD visits during hospitalizations (+); and (c) age was curvilinearly related to use of both HMO specialists and non-HMO specialists. These findings suggest that use of acute care services, including hospitalizations, inpatient physician visits, and emergency services increase with age but the use of primary care providers decreases with age. Gender was not a significant modifier of the relationship between age and utilization.

Age Factors↗
PubMed1996

Caring for the caregivers.

The relationship between disabled elderly veteran care receivers' functional status and their in-home family caregivers' strain was examined in this study. The convenience sample was composed of 93 dyads. Data were obtained from care receivers' health care records and included the Folstein Mini-Mental State Examination (MMS), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (ADL), and Robinson's Caregiver Strain Index (CSI). Major findings were: 52% of caregivers experienced significant strain; 59% of care receivers were cognitively impaired to some extent and were severely impaired in IADL and ADL; and the relationships between care receivers' functional status (cognitive, ADL and IADL) and caregiver strain were statistically significant.

Activities of Daily Living↗
PubMed1995

A potyvirus polymerase interacts with the viral coat protein and VPg in yeast cells.

The two-hybrid system was used to test for pairwise interactions between the tobacco vein mottling virus (TVMV)-encoded RNA-dependent RNA polymerase (or NIb protein) and two other TVMV-encoded proteins: the NIa protein, which consists of genome-linked protein (VPg) and proteinase domains, and the viral coat protein (CP). Using this approach, we find that the NIb protein interacts with both the NIa protein and the CP in yeast cells. Moreover, we find that a mutation in the conserved GDD domain of the NIb protein diminishes the NIb-CP interaction but not the NIb-NIa interaction. Likewise, mutations in the vicinity of the NIa protein to which the genomic RNA is covalently attached eliminate the NIb-NIa interaction. We conclude that the NIb protein interacts with the VPg domain of the NIa protein and that this interaction requires a functional RNA attachment site. This interaction may be important for the initiation of viral RNA synthesis in infected cells. We also conclude that the CP interacts with the NIb in a manner that is sensitive in changes in the highly conserved GDD motif. The role of this interaction in the functioning of the NIb protein or the CP is unclear, but may involve regulation of viral RNA synthesis in infected cells.

Amino Acid Sequence↗
PubMed1995

Functional expression of an epitope-tagged G protein-coupled K+ channel (GIRK1).

An epitope-tagged form of an inwardly rectifying and G protein-coupled K+ channel (GIRK1-cp) was expressed at high levels in transfected mammalian cells. Immunoblot analysis of transfected human embryonic kidney cells (HEK293) and mouse insulinoma cells (beta TC3) revealed several GIRK1-cp polypeptides, including the major 59-kDa band, corresponding to the predicted mass of the GIRK1 polypeptide plus the epitope tag. Immunohistochemical staining using two anti-tag antibodies showed abundant immunoreactive material, which was predominantly concentrated in the perinuclear area in both transfected cell types. While functional GIRK1-cp message was present in poly(A)+ RNA prepared from HEK293 cells expressing GIRK1-cp protein, appropriate K+ currents could not be detected. In contrast, whole cell recordings made directly from transfected beta TC3 cells expressing GIRK1-cp revealed inwardly rectifying, pertussis toxin-sensitive currents activated by norepinephrine and galanin. Single channel recordings in excised patches of beta TC3 cells expressing GIRK1-cp showed rectifying K+ currents when activated by 50 microM guanosine 5'-O-(thiotriphosphate), with a slope conductance of 39.1 +/- 1.0 picosiemens. This is the first report of stable heterologous expression of a functional G protein-coupled K+ channel in mammalian cells. The activity of an epitope-tagged channel in insulinoma cells demonstrates the utility of this system for further biochemical and biophysical analyses of G protein-K+ channel interactions.

Animals↗
PubMed1995

Oxidized low-density lipoprotein induces the expression of P-selectin (GMP140/PADGEM/CD62) on human endothelial cells.

It is now well established that monocytes adhere to endothelial cells activated by oxidized low-density lipoproteins (LDL). However, the adhesive receptors on endothelial cells involved in binding monocytes, following an insult by oxidized LDL, remains to be elucidated. In this study we have looked at the effect of native or oxidized LDL on the expression of P-selectin. Native LDL (N-LDL) was oxidized by incubation with either endothelial cells (EC-LDL) or copper (Cu-LDL), or in culture medium as a control (C-LDL). Expression of P-selectin was assayed with an anti-P-selectin (CD62) monoclonal antibody (LYP20). Results show that EC-LDL and Cu-LDL, but not N-LDL or C-LDL, induce the expression of P-selectin by human umbilical-vein endothelial cells (HUVECs). Induction of P-selectin by low concentrations (20 micrograms/ml) of LDL is directly related to the state of oxidation of the LDL particles. In addition, high concentrations (100 micrograms/ml) of N-LDL also activate HUVECs by inducing P-selectin expression. This expression was sustained for a period of over 1 h on LDL-activated endothelial cells, in contrast with thrombin- or histamine-activated endothelial cells, whose P-selectin levels fall within 15-20 min after induction. E-selectin, in contrast with P-selectin, could not be induced by endothelial cells treated with low or high concentrations of oxidized LDL. Results in this study show that P-selectin expressed by oxidized-LDL-treated endothelial cells are involved in mediating the adhesion of a monocytic cell line (U937) or monocytes in peripheral-blood mononuclear cells. An anti-P-selectin monoclonal antibody (LYP20) inhibited the binding of U937 cells and monocytes. These results strongly suggest that P-selectin is involved in the early stages of atherogenesis.

Cell Adhesion↗
PubMed1995

Well-being of caregivers of spouses with Parkinson's disease.

This study examined the relationship among stages of Parkinson's disease (PD), elderly care receivers' physical and social functioning, and spousal caregivers' physical, social, psychological, and economic well-being. The nonrandom, convenience study sample comprised 30 spousal caregivers of elderly individuals diagnosed with PD; all attended group support sessions. Findings indicated a statistically significant linear relationship between stages of PD and care receivers' functional ability and between care receivers' functional and social ability and caregivers' hours of caregiving. Caregivers' health was associated with diminished physical functioning of care receivers. Caregivers' age, years of marriage, and educational level were associated with their social, psychological, and financial well-being. The main implication for nursing practice is that elderly family caregivers must be included in mutually developed care plans; they are at high risk for diminished well-being because of the time and energy involved in providing needed care.

Aged↗
PubMed1995

Elderly spousal caregivers: knowledge of cancer care, perceptions of preparedness, and coping strategies.

1. Care of a chronically ill or frail elderly individual is increasingly a normative family function, with negative and positive outcomes for those family members providing care. 2. Practitioners in nursing must be aware of the impact stress can have on family members when one member has been diagnosed with cancer. Nurses must assess potential caregivers' knowledge, skills, and preparedness in order to assist them in assuming their caregiving roles. 3. Nurses are in an ideal situation to provide the needed assessments and to develop individualized interventions that can support the efforts and care provided by the family caregiver.

Adaptation, Psychological↗
PubMed1995

A probability database for decision-analytic models of coronary revascularization procedures.

The time required to extract probabilities from medical literature is a primary reason decision analysis is not used more frequently for individual patient management decisions. Objective clinical trial information from the medical literature for one management decision was placed in a database which provided probabilities when queried. The database was tested with decision-analytic models of specific patient cases from the medical literature. Performance was assessed in terms of the ability to select trials which resembled the patients' individual characteristics, the number of trials providing probabilities for a given outcome, and the number of follow-up points available for that outcome. The timely assistance the database provides in expediting literature review and synthesis could enable the more common use of decision analysis in management decisions for individual patients.

Adult↗
PubMed1994

The vitronectin receptor (alpha v beta 3) is implicated, in cooperation with P-selectin and platelet-activating factor, in the adhesion of monocytes to activated endothelial cells.

In this study we have investigated the presence on endothelial cells of potential glycoprotein receptors, other than P-selectin, which are involved in the adhesion of monocytes at the early stages of activation. We report that the majority of cells binding to thrombin-activated endothelial cells from a peripheral blood mononuclear cell (PBMC) preparation are monocytes. The adhesion of PBMC to thrombin-activated, but not resting, endothelial cells was inhibited (66%) by a monoclonal antibody (mAb) directed against alpha v beta 3. Elutriated monocytes or a monocytic cell line (U937) were also inhibited by this antibody, its F(ab)'2 fragments and three other anti-(alpha v beta 3) mAbs. alpha v beta 3 isolated from endothelial-cell lysates significantly inhibited the adhesion of monocytes and U937 cells to endothelial cells. A peptide motif (RGDF) known to interact with alpha v beta 3 inhibited U937 cell adhesion to activated endothelial cells by 53%. Finally, an anti-(P-selectin) mAb (LYP20) or a platelet-activating factor (PAF)-receptor antagonist (WEB 2086) inhibited monocyte adhesion to activated endothelial cells. This study shows for the first time that alpha v beta 3 is implicated, in addition to P-selectin and PAF, in the adhesion of monocytes to activated endothelial cells.

Amino Acid Sequence↗
PubMed1994

Two sites on P-selectin (the lectin and epidermal growth factor-like domains) are involved in the adhesion of monocytes to thrombin-activated endothelial cells.

P-selectin, also known as GMP-140, PADGEM or CD62, is expressed on the surface of thrombin-activated platelets and endothelial cells (EC). It is a member of the selectin family of adhesion molecules that regulate leucocyte interactions with the blood vessel wall. In this study we have found that peptides derived from both the lectin (residues 19-34 and 51-61) and epidermal growth factor (EGF)-like (residues 127-139) domains inhibit the adhesion of peripheral blood mononuclear cells (PBMC), elutriated monocytes and a monocytic cell line (U937) to thrombin-activated EC. This inhibition occurred in a concentration-dependent manner and the peptide most active at the lowest concentrations was the one derived from the EGF-like motif (127-139). The scrambled forms of these peptides, identical in amino acid composition to the authentic peptides but with altered sequences, were not inhibitory. Thrombin-activated platelets supported adhesion of U937 cells and this adhesion was dramatically inhibited by the two peptides derived from the lectin-like domain (residues 19-34 and 51-61). All three peptides, when conjugated to BSA and coated on plastic plates, mediated U937 cell adhesion. This study shows, for the first time, that two sites on P-selectin, the lectin and EGF-like domains, are involved in the adhesion of monocytes to thrombin-activated EC.

Amino Acid Sequence↗
PubMed1994

The echogenic thalamus in hypoxic ischaemic encephalopathy.

This paper reports 16 term infants in whom an echogenic thalamus was identified on cranial ultrasonography. Fourteen of the patients suffered severe birth asphyxia. The prognostic significance of this finding and the underlying pathogenesis is assessed.

Asphyxia Neonatorum↗
PubMed1994

Maternal erythropoietin in singleton pregnancies: a randomized trial on the effect of oral hematinic supplementation.

OBJECTIVE: Our purpose was to study the effect of hematinic supplementation on the maternal erythropoietin response during singleton pregnancy. STUDY DESIGN: In a randomized, double-blind trial 97 patients with a first-trimester hemoglobin level > or = 14.0 gm/dl received either iron and folic acid (hematinic group, n = 53) or a placebo (n = 44). Serial hemoglobin, hematocrit, and serum erythropoietin were recorded from maternal blood and from cord blood on delivery. Serum ferritin was measured in the first trimester, at 36 weeks' gestation, and in cord blood. RESULTS: In both groups (1) the mean hemoglobin was lower (p < 0.01) at 40 weeks' gestation than when first examined and (2) the mean serum erythropoietin was higher (p < 0.01). The mean serum ferritin was lower (p < 0.001) in both groups at 36 weeks' gestation than at presentation but higher (p = 0.04) in the hematinic group than in the placebo group. The mean hemoglobin and hematocrit were similar in the two groups until the third trimester but thereafter were higher (p < 0.05) in the hematinic group. The mean maternal serum erythropoietin was higher (p < 0.05) in the placebo group than in the hematinic group after 24 weeks' gestation. The mean cord blood hematologic values were similar in the two groups. CONCLUSION: Maternal serum erythropoietin increased during pregnancy, but this response was reduced in the third trimester in the hematinic-supplemented group.

Double-Blind Method↗
PubMed1994

Interactive electronic whiteboards in the medical classroom.

Most research on computer-assisted instruction has concentrated on developing systems to be used outside the teaching environment to supplement or complement in-class teaching. We believe that interactive large-screen computers can be used effectively in the classroom as electronic whiteboards to more effectively teach select medical school courses. We describe our experience with one such device, the Xerox LiveBoard, to teach a course on computer-assisted clinical decision analysis to a group of first-year medical students.

Computer-Assisted Instruction↗
PubMed1994

Construction of a literature database and its use to provide probabilities for decision-analytic models of thrombolytic therapy.

Probabilities for decision-analytic models are routinely obtained from the medical literature. This study describes development and use of a literature database to facilitate obtaining probabilities for decision-analytic models of thrombolytic therapy for acute myocardial infarction. Implementation demonstrates the concept of a literature database to be both feasible and effective. Specific difficulties encountered in the evaluation of continuous variables, the potential storage of actual probabilities, and the advantage for easy growth with the literature are discussed.

Databases, Bibliographic↗
PubMed1993

Plants that express a potyvirus proteinase gene are resistant to virus infection.

Transgenic tobacco plants that express the genome-linked protein/proteinase-coding region of the potyvirus tobacco vein mottling virus (TVMV) were produced and tested for their reaction to inoculation with TVMV and two other potyviruses. These plants did not develop disease symptoms after being inoculated with large doses of TVMV but were as susceptible to infection by the other potyviruses as were control plants. Lines of tobacco that express the coat protein- or the nonstructural cylindrical inclusion protein-coding regions were also produced. The coat protein transgenic plants were protected against all three potyviruses, and the cylindrical inclusion transgenic plants were susceptible to all three potyviruses. These results indicate that some, but not all, TVMV genes can be used to confer protection against potyviruses in plants. The results also suggest that combinations of viral genes in transgenic plants might improve protection against potyviruses.

Base Sequence↗