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Biomedical subjects

J F Murphy

Publications and source records attributed to J F Murphy.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The development of enzyme-linked immunosorbent assays (ELISA) for the catecholamines adrenalin and noradrenalin.

Monoclonal antibodies have been raised against adrenalin and noradrenalin and used as the basis of enzyme-linked immunosorbent assays (ELISA) to detect and estimate the concentrations of these catecholamines. Inhibition assays are described, with sensitive quantification in the range from 1 mg/ml to 100 pg/ml. Cross-reactivity assays reveal that neither assay is subject to interference by catecholamine metabolites at concentrations less than 100 ng/ml and 1 micrograms/ml respectively. Isolation and quantification of both catecholamines from clinical samples is discussed and the potential application of these ELISAs in a clinical setting is proposed.

Animals↗

Radiographic screening at four months of infants at risk for congenital hip dislocation.

We report on a radiographic screening programme at four months of age for infants who were clinically normal at neonatal examination but were considered to be 'at risk' for congenital dislocation of the hip because of their family history, breech presentation, or a persistent click. From a total population of 13,662 live births over a two-year period, 357 (2.6%) infants at risk were identified. Of these 46 had abnormal radiographs (six subluxations, 40 acetabular dysplasia). In 12 infants treatment resulted in a normal hip; 34 required no treatment but were followed up until their radiographs were normal and walking had begun. Of the 311 infants with normal radiographs, 256 (82%) were examined after 15 months of age; none had any detectable abnormality. We suggest that radiography of the hip at four months is a valuable adjunct to neonatal screening for infants at increased risk of congenital dislocation of the hip.

Acetabulum↗

En bloc radical vulvectomy and lymphadenectomy with modifications of separate groin incisions.

A new modification of radical vulvectomy and lymphadenectomy through separate groin incisions involves dissection of the intervening skin bridge and allows an en bloc dissection. The results in 26 women treated with this technique are compared with those of seven treated with separate incisions without an en bloc dissection. All 33 women had squamous carcinoma of the vulva and were treated between 1985-1989. The incidence of advanced disease was high, with nodal metastases present in 52% of cases. Dissection of the tissue beneath the skin bridge did not alter the morbidity of the procedure in terms of the incidence of wound infection, number of units of blood transfused, or duration of hospitalization. The only case of an isolated recurrence in the skin bridge occurred in a woman who did not have an en bloc dissection, although there was no significant difference in the overall local recurrence rate between the groups. Further evaluation with larger numbers is required, but we suggest that an en bloc dissection using separate incisions may reduce the risk of isolated recurrence in the skin bridge, particularly in patients with advanced disease.

Adult↗

Outpatient loop diathermy conization as an alternative to inpatient knife conization of the cervix.

A knife cone biopsy of the cervix is usually performed as an inpatient procedure under general anesthesia and is associated with significant morbidity. Loop diathermy conization was performed under local anesthesia on colposcopy outpatients as an alternative to knife conization. In 33 consecutive patients studied the procedure was well tolerated, there were no operative complications, and a satisfactory specimen for histologic examination was obtained in every case. One case of unsuspected invasive cancer and two of suspected microinvasive cancer were diagnosed. The diagnosis of cervical precancer was made in 24 (73%) of the cases. The introduction of outpatient loop diathermy conization of the cervix instead of knife conization would decrease hospitalization costs, avoid the need for general anesthesia and potentially reduce short-term patient morbidity.

Adult↗

VPg-mediated aggregation of potyviral RNA.

RNA prepared from the potyvirus tobacco vein mottling virus contained aggregates of the 9.5 kb genomic RNA with electrophoretic mobilities corresponding to 20 and 41 kb species. Similar aggregates were present in preparations of the RNAs of two other potyviruses. Aggregation occurred during or after purification of the RNA by sucrose gradient centrifugation and alcohol precipitation and was dependent upon the presence of a protein apparently bound covalently to a region at or near the 5' terminus of the viral RNA. This protein is probably the VPg. The RNAs of tobacco mosaic virus and cowpea mosaic virus did not form aggregates when isolated from purified virus by similar procedures.

Electrophoresis, Agar Gel↗