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Biomedical subjects

R Stewart

Publications and source records attributed to R Stewart.

At least 145 records · Page 8Linked to original sources

Synthetic murine epidermal growth factor sequence 20-31 is mitogenic and angiogenic.

Epidermal growth factor (EGF) and its homologue, transforming growth factor alpha (TGF alpha), are mitogenic, angiogenic and tumour-promoting polypeptides. Much effort has therefore been directed towards the development of EGF/TGF alpha antagonists as a potential cancer therapy. Initial reports that some EGF/TGF alpha synthetic fragments possess EGF-receptor binding activity have not been confirmed in subsequent studies. We have found, however, that the murine EGF B-loop sequence: Ac-[(S-acetamidomethyl)-Cys20,31]-EGF-(20-31)-NH2 [(mEGF-(20-31)] produces biological effects consistent with the parent molecule in bovine, murine, chick and human, but not rat, model systems. In parallel experiments, both mEGF and mEGF-(20-31) elicit migratory, cytoprotective, growth-stimulatory, growth-inhibitory and angiogenic responses. The reverse B-loop sequence, mEGF-(31-20), is also mitogenic and angiogenic. The C-loop sequence, mEGF-(33-42), has no mitogenic or angiogenic activity when applied alone, does not block the mitogenic effect of mEGF, but does block the angiogenic effect of mEGF. It has not been established that the EGF receptor is the target for these fragments, but the results suggest that the residual biological activities of EGF fragments merit further investigation.

3T3 Cells↗

The BIMDA shuttle flight mission: a low cost microgravity payload.

This paper presents the design, operation and experiment protocol of the Bioserve sponsored flights of the ITA Materials Dispersion Apparatus Payload (BIMDA) flown on the Space Shuttle on STS-37. The BIMDA payload represents a joint effort between ITA (Instrumentation Technology Associates, Inc.) and Bioserve Space Technologies, a NASA Center for the Commercial Development of Space, to investigate the methods and commercial potential of biomedical and fluid science applications in the microgravity environment of space. The BIMDA payload, flown in a Refrigerator/Incubator Module (R/IM) in the Orbiter middeck, consists of three different devices designed to mix fluids in space; four Materials Dispersion Apparatus (MDA) Minilabs developed by ITA, six Cell Syringes, and six Bioprocessing Modules both developed by NASA JSC and Bioserve. The BIMDA design and operation reflect user needs for late access prior to launch (<24 h) and early access after landing (<2 h). The environment for the payload is temperature controlled by the R/IM. The astronaut crew operates the payload and documents its operation. The temperature of the payload is recorded automatically during flight. The flight of the BIMDA payload is the first of two development flights of the MDA on the Space Shuttle. Future commercial flights of ITA's Materials Dispersion Apparatus on the Shuttle will be sponsored by NASA's Office of Commercial Programs and will take place over the next three years. Experiments for the BIMDA payload include research into the following areas: protein crystal growth, thin film membrane casting, collagen formation, fibrin clot formation, seed germination, enzymatic catalysis, zeolite crystallization, studies of mixing effects of lymphocyte functions, and solute diffusion and transport.

Biotechnology↗

Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression.

Since tumor progression is dependent on the ability of malignant cells to interact with the extracellular matrix, molecules on the cell surface which mediate cell-substratum interactions are likely to be important regulators of tumor invasion and metastasis. The purpose of this study was to examine the distribution of one such group of cell adhesion receptors, the integrins, in benign and malignant lesions of human melanocytes. The distribution of integrin adhesion receptors was defined on cells in culture derived from normal and malignant melanocytes and in tissue sections from benign to increasingly malignant melanocytic lesions using a panel of monoclonal antibodies against specific integrin subunits. Cells in culture expressed a large variety of integrins, including all of the previously characterized members of the beta 1 subfamily plus the alpha v/beta 3 vitronectin receptor. The expression of integrins was similar in cells cultured from either benign or malignant lesions. In contrast, consistent differences were noted in integrin expression by cells within tissues containing metastatic and vertical growth phase melanomas when compared to radial growth phase melanoma cells and cells within nevi. Most notably, the expression of the beta 3 subunit was restricted exclusively to cells within vertical growth phase and metastatic melanomas. The presence of this integrin may be important in the development of tumor invasiveness and could be useful as a marker of melanoma cells entering the more aggressive phase of the malignant process.

Humans↗

Use of the thoracic aorta for renal revascularization.

We describe the performance of renal revascularization by placement of an interposition saphenous vein graft from the thoracic aorta to the renal artery. This technique is applicable to selected patients with renal artery stenosis and severe atherosclerosis of the abdominal aorta.

Aged↗

Effect of scavenging on ambient levels of nitrous oxide in ambulances.

Nitrous oxide scavenging devices have not been tested in the prehospital setting. We studied two nitrous oxide scavenging devices and their effect on ambient levels of nitrous oxide in the patient compartment of a stationary ambulance. We compared the ambient levels of gas when nitrous oxide scavenging was in use versus when it was not. In addition, we evaluated the effect of two different mask designs on ambient levels of nitrous oxide. With eight healthy male volunteers acting as their own controls using a series of mask/scavenger combinations, we found that there was a significant difference in the ambient levels of nitrous oxide when a scavenger was in use. The mean time-weighted average was 776 parts per million/min when no scavenger was used. When gas scavenging was in use, the mean time-weighted average never exceeded 150 parts per million/min. (P less than .0001). There was no significant difference between nitrous oxide scavengers or between the masks tested in their effect on nitrous oxide ambient levels in the atmosphere. We conclude that nitrous oxide scavengers are effective in lowering nitrous oxide ambient levels in the prehospital setting and merit consideration as adjuncts to nitrous oxide delivery systems in this setting.

Air Pollutants, Occupational↗

Experience with cardiopulmonary bypass and deep hypothermic circulatory arrest in the management of retroperitoneal tumors with large vena caval thrombi.

From June 1984 to September 1989, 43 patients with large vena caval tumor thrombi from retroperitoneal malignancies underwent surgical treatment with cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). The primary malignancies were renal cell carcinoma (RCC) (n = 39), renal pelvic transitional cell carcinoma (n = 1), adrenal pheochromocytoma (n = 1), and renal (n = 1) or retroperitoneal (n = 1) sarcoma. The level of the caval thrombus was either suprahepatic (n = 27), intrahepatic (n = 14), or subhepatic (n = 2). In all cases the primary tumor and caval thrombus were completely removed. Concomitant procedures included coronary artery bypass grafting (n = 5), pulmonary resection (n = 2), and hepatic lobectomy (n = 1). The time of circulatory arrest ranged from 10 to 44 minutes (mean, 23.5 minutes). There were two operative deaths (4.7%), neither of them due to to the use of DHCA. Major postoperative complications occurred in 13 patients (30.2%). There were no ischemic or neurologic complications and no cases of perioperative tumor embolization. The median postoperative hospital stay was 9 days. Twenty-two patients (51%) are alive and enjoying a good quality of life. The 3-year patient survival rates in patients with localized (n = 24) versus metastatic (n = 15) RCC are 63.9% and 10.9%, respectively (p = 0.02). We conclude that CPB with DHCA facilities excision of retroperitoneal malignancies with large caval thrombi and provides the potential for cure with low morbidity and mortality rates.

Adult↗

Survival associated with renovascular disease in Glasgow and Newcastle: a collaborative study.

Data from 121 consecutive patients with hypertension and renovascular disease, first diagnosed between 1975 and 1982 in Glasgow and Newcastle, were analysed retrospectively to determine the factors which influenced their outcome. Thirty-six patients died between the data of arteriography and 1st January 1987, giving five and ten year survival rates of 83% and 67%. Survival was greatly reduced in comparison with that of age-sex-matched controls in the general population of the West of Scotland, and was also less than that of essential hypertensives matched for age, sex, initial diastolic blood pressure and smoking habit who had attended the Glasgow Blood Pressure Clinic during the same period. Multivariate analysis showed that age, cigarette smoking and presence of atheromatous disease were significantly and independently related to outcome among the patients with renovascular disease, whereas male sex, centre of origin, severity of hypertension when first seen, initial renal function and presence of bilateral disease were not. Despite a trend towards benefit from surgical intervention (ten year survival in medical group 62%, in surgical group 71%; p = 0.19) our data do not prove that intervention is better than medical treatment, largely because the decision on intervention was not randomised. A prospective trial would be required to answer this important question.

Adult↗

Nursing students' preferences in the use of computer assisted learning.

One hundred and ten student nurses in the second year of a 3-year diploma program were surveyed following their use of computer assisted learning (CAL) programs. The questionnaire was designed to elicit responses concerning the preferred number of users per terminal, the level of supervision (supervised/unsupervised) and their general affective response to this type of learning. The results showed that the majority (56.4%) of students preferred to work in a group (a group constituted no more than three students per terminal). Whereas 31.8% preferred to work through the program alone, just over 50% would rather be supervised while running the program, and 26.4% expressed a preference for no supervision. There was no relationship found between program content and running the program alone or with others. However, in 10% of the sample there was a positive relationship found between the need for supervision and program content. The reasons given for these preferences and the advantages and disadvantages of CAL, as perceived by the students, are also discussed.

Adolescent↗

Growth of the chick area vasculosa in ovo and in shell-less culture.

The rates of growth and cell proliferation of the chick area vasculosa (Days 2-5 of incubation) were examined in windowed eggs and in shell-less culture preparations. For embryos of developmental Stages 15 to 23, the area vasculosa in shell-less cultures was significantly smaller than in corresponding eggs; however there was no significant difference in the radial growth between these groups. The cultivation of embryos in shell-less culture did not affect the normal macroscopic or histological appearance of the membrane, or the rate of proliferation of its constituent cells, as assessed by tritiated thymidine incorporation. These results indicate that the area vasculosa in shell-less culture provides a suitable assay of factors which regulate angiogenesis.

Animals↗

Characterization of the subgingival microbial flora around endosteal sapphire dental implants in partially edentulous patients.

The microbiota associated with oral endosteal sapphire ceramic implants was studied using cultural methods. Samples were taken from both implant and control (tooth) sites, and comparisons were made between healthy and diseased and between implant and control sites. Diseased sites harbored a microbiota with a large number and proportion of Gram-negative anaerobic rods, black-pigmented Bacteroides, and surface translocating bacteria. Healthy sites in the same patients had smaller amounts of bacteria dominated by facultative Gram-positive cocci and rods. The microbiota in diseased and healthy implant and control sites was very similar. It is suggested that peri-implant tissues behave very similarly to periodontal tissues and that peri-implantitis lesions should be considered as site-specific infections harboring a high number of periodontal pathogens, mainly Gram-negative anaerobic rods.

Aluminum Oxide↗

Antigenic profile of tumor progression stages in human melanocytic nevi and melanomas.

Sixteen monoclonal antibodies that were obtained after immunization of BALB/c mice with intact melanoma cells or extracts of melanoma cells were tested for reactivity with normal and malignant melanocytic cells in situ, using an immunoperoxidase technique on frozen tissue sections. Sections representing six histopathologically defined stages of tumor progression, ranging from normal melanocytes to highly malignant metastatic lesions, were used. Thirteen monoclonal antibodies (MAbs) did not stain normal melanocytes in situ, whereas three MAbs weakly stained between 1 and 12.5% of melanocytes in 6-22% of the skin sections examined. MAb B 73.1, which was produced by immunization of mice with human natural killer cells and which binds to the Fc receptor of natural killer cells and granulocytes, reacted exclusively with malignant cells that represent the last two stages of tumor progression, vertical growth phase (VGP) primary melanoma and metastatic melanoma. All other antibodies showed variable reactivity with benign proliferative lesions or radial growth phase (RGP), an early stage of primary melanoma. Staining by MAbs that were reactive with gangliosides, unknown antigens, receptors, and two proteins (120/94 kDa protein and 250 kDa glycoprotein) showed a gradual increase in subsequent stages of tumor progression. Two steps in tumor progression were characterized by significant quantitative changes in the expression of antigens detected by the MAbs used in this study. First, mature nevus cells showed significantly higher reactivity with a panel of six MAbs, when compared to normal melanocytes. Second, a separate panel of six MAbs discriminated between RGP and VGP primary melanoma cells. No significant differences in antigen expression were found between dysplastic nevus cells and RGP melanoma, except that some antigens (nerve growth factor receptor and GD2/GD3 gangliosides) appear to be expressed at lower levels in RGP lesions, nor did VGP primary and metastatic melanomas show significant differences in antigen expression. These results suggest that (a) tumor progression of melanocytic cells in vivo is accompanied by significant quantitative differences in the expression of antigens, (b) some of the antigens examined here are associated with biologically aggressive malignant lesions but not normal or premalignant melanocytic cells, and (c) RGP primary melanoma cells are antigenically more similar to nevus cells than to VGP primary melanoma cells.

Antibodies, Monoclonal↗

Psychobiological effects of gastric restriction surgery for morbid obesity.

A sample of 36 patients who had undergone gastric reduction surgery for severe obesity was seen postoperatively and psychobiological changes assessed. Subjects reported substantial weight losses with reduced food intake and normalisation of eating habits. In the majority of patients positive changes had occurred in attitudes and improvements were found in mood, social and sexual functioning. Low rates of psychological disturbance were reported.

Adaptation, Psychological↗

Personality as modifier of the life change-distress relationship. A longitudinal modelling approach.

We present a structural equation model of the way in which personality factors may modify the response to changes in life situation, based on two-wave panel data from a random sample of 296 Dutch adults. Three definitions of vulnerability were studied: high neuroticism (N), low self-esteem (SE), and an external locus of control (LC). The multigroup LISREL analysis led to the following conclusions: First, previous symptom level was strongly related to current symptom level. The strength of this relationship was independent of SE and LC but modified by N. Secondly, the impact of life situation changes on distress level was moderately strong and similar to what others have reported. Thirdly, a marked modifier effect was found for neuroticism; responsiveness significantly increased with N level. For SE and LC we observed reduced responsiveness among low vulnerability subjects, but the differences did not reach statistical significance. The implications of the findings are discussed.

Adult↗

Epidermal growth factor promotes chick embryonic angiogenesis.

The response of the early extraembryonic vasculature to epidermal growth factor (EGF) was studied. Millipore filter discs containing 10ng-1 microgram of EGF were placed onto the advancing edge of the area vasculosa of 3-day chick embryos, and the effect examined macroscopically and histologically 24 hours after disc application. The capillary density at the site of application increased significantly, and the effect was seen to be dose-dependent; a similar but more marked response was observed in the vessel cross-sectional area per unit length. This change in vascularity was accompanied by tortuous folding of the mesoderm and endoderm (which normally lie parallel to the ectoderm in a trilaminar arrangement) into the yolk substance: this may indicate precocious development of all three layers (ectoderm, mesoderm and ectoderm) of the membrane, and the proliferative effects of EGF may not be confined to the vascular endothelium.

Angiogenesis Inducing Agents↗

Pressures and constraints on general management.

A discussion of pressures and constraints on general management is not straightforward. Pressures and constraints can be seen both as external influences and as individually determined. This dual origin is important so that general managers can help themselves, and be helped, to be more in control of their jobs and their environment. Drawing on the findings from the Templeton tracer study of DGMs and from the Templeton DGMs' group, the paper considers a range of possible pressures and constraints on DGMs. It argues that an effective general manager will know which pressures and constraints are external and which are self-imposed and will know which can and should be changed.

Administrative Personnel↗