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Biomedical subjects

S Hunter

Publications and source records attributed to S Hunter.

At least 91 records · Page 5Linked to original sources

Transfection of an Fc gamma receptor cDNA induces T cells to become phagocytic.

The human receptor Fc gamma RIIA for the Fc portion of IgG (Fc gamma) was expressed in a human T-cell line and conferred on these cells the ability to perform IgG antibody-stimulated phagocytosis. Crosslinking Fc gamma RIIA with anti-Fc gamma RII monoclonal antibody also induced tyrosine phosphorylation of multiple proteins including Fc gamma RIIA, ZAP-70, p72SYK, and phospholipase C gamma 1 subunit and an increase in intracellular Ca2+ concentration. The T cell receptor-associated zeta-chain was not tyrosine-phosphorylated after crosslinking of Fc gamma RIIA, suggesting that the Fc gamma RIIA-mediated signals were independent of CD3. Fc gamma RIIA-mediated signal transduction was defective in a transfected mutant T-cell line exhibiting reduced expression of the tyrosine kinases LCK and FYN. These studies indicate that certain T cells can assume phagocytic properties after transfection of cDNA encoding an Fc gamma receptor with the capability of inducing a phagocytic signal.

Antibodies, Monoclonal↗

Tumor angiogenesis as a prognostic factor in oral cavity tumors.

BACKGROUND: Lymph-node metastasis is the single greatest predictor of survival in patients with oral cavity cancers. Tumor angiogenesis has been correlated with metastasis in breast cancer and may have prognostic value in other tumors. PATIENTS AND METHODS: Sixty-six patients with clinically node-negative oral cavity squamous cell cancers were reviewed. Samples were cut and stained for factor VIII. The percentage of area of tissue stained for factor VIII was quantitated by a computerized image analyzer. Tumor depth was measured with an ocular micrometer to the nearest 0.1 mm. Variables were statistically examined against regional recurrence. RESULTS: The probability of metastasis (%) was 2 for tumor staining of < or = 10% and 93 for tumor staining > 10% (P < 0.0001). The tumor depth was < or = 4 mm in 10 and > 4 mm in 83 (P < 0.0001). Patients with < or = 4 mm and < or = 10% staining had a 2% rate of recurrence, and patients with > 4 mm and > 10% staining had a 100% rate of recurrence (P < 0.0001). CONCLUSION: Although tumor thickness was suggestive of predictability, only angiogenesis was a statistically significant predictor of recurrence in a multivariate analysis (P < 0.0001). Angiogenesis showed a strong correlation with regional recurrence and may be used as an independent prognostic indicator.

Adult↗

Cardiovascular abnormalities in end stage renal failure: the effect of anaemia or uraemia?

Children with end stage renal failure and anaemia have an increased cardiac index and often gross ventricular hypertrophy. Correction of anaemia with recombinant human erythropoietin (r-HuEpo) for less than six months results in a reduction in the cardiac index without a significant reduction in left ventricular hypertrophy. Seven children receiving dialysis (group 1) were studied to determine whether a reduction in left ventricular hypertrophy would occur after a 12 month period of r-HuEpo. A decrease in the cardiac index was seen by six months, and a significant reduction in left ventricular mass index and cardiothoracic ratio was seen by 12 months. Successful renal transplantation also results in a reduction in the cardiac index and left ventricular hypertrophy, but the relative contributions of correction of anaemia and correction of biochemical disturbance is unknown because they usually improve simultaneously. To investigate this, six children (group 2) who already had a mean haemoglobin concentration of 107 g/l while receiving dialysis were followed up for 12 months after successful transplantation. They showed no significant change in haemoglobin concentration, but a dramatic improvement in biochemistry. There was no significant change in cardiovascular function. Anaemia is the more dominant influence on cardiovascular function in end stage renal failure.

Adolescent↗

Natural history of trisomy 13.

The poor prognosis of patients with trisomy 13 has long been accepted and has been ascribed to brain and heart malformations. It has been suggested, however, that the long term survival is better than was previously thought and that cardiac surgery may be justified. This population based study reviews the incidence, antenatal diagnosis, spectrum of survival from congenital heart disease, and mode of death for patients with trisomy 13 in the Northern Health Region from 1985 to 1992. There was an observed prevalence at birth of 0.049/1000 live births and an expected prevalence, allowing for antenatal diagnosis, of 0.077. None of the cardiac lesions found would cause early death. The median survival in this series was four days; the longest survival was 3.5 months. The principal mode of death was apnoea in 14 of 16 children, irrespective of the presence of a cranial abnormality. In the light of these findings, cardiac surgery cannot be justified in patients with trisomy 13.

Adult↗

End-on aortogram: improved identification of important coronary artery anomalies in tetralogy of Fallot.

OBJECTIVE: To identify coronary artery anomalies in patients with tetralogy of Fallot with an aortogram taken with steep caudal and left oblique angulation ("end-on" aortogram). DESIGN: Prospective evaluation of end-on aortogram in the preoperative angiographic assessment of consecutive patients with tetralogy of Fallot. SETTING: Regional paediatric cardiology centre. PATIENTS: 34 patients, aged 3 months to 12 years (median age 9 months). METHODS: An aortogram was performed with steep caudal (38 degrees-45 degrees) and left oblique (0 degrees-30 degrees) angulation under general anaesthetic as part of routine preoperative angiographic assessment. RESULTS: The origins and courses of the coronary arteries were visualised in all patients and important coronary artery anomalies were identified in four patients: single left coronary artery; single right coronary artery (two patients); separate high origin of left anterior descending. These anomalous coronary vessels crossed the right ventricular outflow tract. CONCLUSIONS: It is important to identify preoperatively coronary arteries that may interfere with right ventricular outflow tract reconstruction. An aortogram with steep caudal and left oblique angulation is useful in identifying anomalous coronary arteries and more importantly it defines the relation of these vessels to the right ventricular outflow tract.

Aortography↗

Eighth survey of staffing in cardiology in the United Kingdom 1992.

The Eighth Survey of Staffing in Cardiology was conducted with an index date of 30 September 1992. The total number of cardiologists in England and Wales, defined as individuals trained in the specialty and spending at least 40% of their professional time working in it, was 358. Of these 11 were part time, defined as six sessions or less, giving a number in whole time (or near whole time) equivalents of 352.5. The number of individuals increased from 1991 by 18 (5.3%). There were 71 cardiologists in Scotland and Northern Ireland, making a total for the United Kingdom of 429 individuals (423.5 whole time equivalents), which is 7.3 per million population. A total of 44 Districts serving 8.8 million people have no resident cardiologist. There has been little improvement since the 1991 survey. An additional 34 Districts with populations greater than 250,000 have only one cardiologist: we have clear evidence of inadequate provision of care in most of these, a situation that is inevitable within the resources provided. A wider threat to the provision of a satisfactory level of cardiological care throughout the United Kingdom will follow from changes in the organisation of the National Health Service and in the new requirements for training of future cardiologists because these changes will make major new demands on consultant time which cannot be met within existing resources. A crisis will be averted only if a rapid and major expansion of the consultant grade can be achieved.

Cardiology↗

Immunodetection and comparison of melaleuca, bottlebrush, and bahia pollens.

Pollen extracts of two trees, Callistemon citrinis (bottlebrush) and Melaleuca leucadendron (melaleuca), as well as the grass Paspalum notatum (bahia) were analyzed for antigenic and allergenic cross-reactivity using SDS-PAGE and Western blotting. SDS-PAGE analysis of all three pollen extracts revealed multiple antigenic components which were reactive with rabbit antisera made to each pollen extract. Comparison of reduced and nonreduced mobility patterns suggested the possible presence of multichain proteins linked by disulfide bonds. Clinical studies demonstrated that 81% of the patients skin test positive to at least one of the pollens were also positive to the other two. Sixty-three percent of allergic individuals studied showed a high correlation between skin test results and the number of IgE-binding components analyzed by immunoblotting. These IgE-reactive components were detected in the molecular weight range of 29-66 kD. Western blot analysis detected more IgE-binding components in bahia pollen extracts as compared with the tree pollens, consistent with other reports of grass pollens being more allergenic than those from trees and weeds. Each patient's serum had a unique IgE-binding pattern, indicating heterogeneity of immune response; however, common major determinants were detected by a large percentage of the allergic patient's sera.

Allergens↗

Aortobronchial fistula following aortic valve surgery.

We report the case of a 54-year-old man with an aortobronchial fistula following aortic valve replacement for prosthetic endocarditis. He presented with massive haemoptysis and the diagnosis was made following computerized tomography of the chest. Effective treatment was achieved by adhering to the basic principles of fistula management. The patient remains well at 1 year follow-up.

Aortic Diseases↗

Reduction of patient doses from barium meal and barium enema examinations through changes in equipment factors.

A study of patient doses for barium meal and barium enema examinations has been made for X-ray departments throughout Grampian Region. Dose-area products are substantially less than UK reference levels. Contributions from fluoroscopy and radiography varied significantly between different units, with fluoroscopy making up 35-92% of the mean doses for barium meals and 24-57% for barium enemas. Equipment related factors had a greater influence on patient doses than radiologists' techniques. The gain of the image intensifier and the exposure factors selected by the automatic exposure control (AEC) were the most important factors determining doses for fluoroscopy. Changes in kV/mA factors selected by the AEC have allowed reductions of 20-50% to be made in effective dose from fluoroscopy with some units. The method used for recording images was the major influence on radiographic doses. Digital spot images or fluorographic films taken from the intensifier gave only 10-20% of the dose with a film/screen system and are recommended where the image quality is satisfactory for the application. Changes in film/screen systems have given worthwhile reductions in radiographic doses. If all factors are optimized, mean doses for barium examinations could be reduced to 20% of current reference levels.

Barium Sulfate↗

Skin care strategies in a skilled nursing home.

1. Pressure ulcers continue to be a serious problem in nursing home settings. They are significant as a source of discomfort and disability among nursing home residents, as well as a source of financial concern for the institutional agencies responsible for resident care. 2. Prevention and intervention at the earliest stages of pressure ulcer development offer the most effective approaches to mediating the human and economic costs imposed by pressure ulcers. 3. Strategies that are effective in reducing both the development and severity of pressure ulcers can be successfully implemented in long-term care settings. Further studies are needed that will provide additional support for the strategies and protocols used in this study.

Adolescent↗

The high affinity Fc gamma receptor (CD64) induces phagocytosis in the absence of its cytoplasmic domain: the gamma subunit of Fc gamma RIIIA imparts phagocytic function to Fc gamma RI.

The high affinity Fc gamma receptor, Fc gamma RI, is unique among the three classes of macrophage Fc gamma receptors not only in its affinity for IgG, but also in the structure of its cytoplasmic domain. Fc gamma RIIA and the gamma subunit of Fc gamma RIIIA have tyrosine-containing motifs within their cytoplasmic domains that are phosphorylated when crosslinked and that are required for phagocytosis by COS-1 cell transfectants. In contrast to these other Fc gamma receptors, Fc gamma RI does not contain cytoplasmic tyrosines and does not induce phagocytosis in COS-1 transfectants. We transfected wild-type (WT) and mutant (MT) Fc gamma RI lacking the cytoplasmic domain into COS-1 cells and murine macrophages and assessed phagocytosis using IgG-coated red blood cells (RBCs) and RBCs conjugated with Fab anti-human Fc gamma RI monoclonal antibody (mAb). Fc gamma RI, in contrast to Fc gamma RIIA, did not induce phagocytosis in COS cells. However, both WT and MT Fc gamma RI induced phagocytosis in murine macrophages, and phagocytosis was inhibited by the tyrosine kinase inhibitor tyrphostin 23. Human monocytes also phagocytosed Fc gamma RI-targeted RBCs, and activation of Fc gamma RI on monocytes with Fab anti-Fc gamma RI induced phosphorylation of Fc gamma RII on tyrosine residues. However, Fc gamma RI activation of Fc gamma RI-Fc gamma RIIA COS-1 cotransfectants did not induce tyrosine phosphorylation of Fc gamma RIIA, and coexpression of Fc gamma RI and Fc gamma RIIA in COS cells did not confer Fc gamma RI phagocytic capability. In contrast, coexpression in COS-1 cells of Fc gamma RI with the gamma subunit of Fc gamma RIIIA conferred phagocytic function to both Fc gamma RI and the MT Fc gamma RI lacking the cytoplasmic domain. Thus, Fc gamma RI does not require its cytoplasmic domain to mediate a phagocytic signal and interacts with the gamma subunit of Fc gamma RIIIA to induce phagocytosis.

Animals↗

Release of platelet-derived growth factor activity from pig venous arterial grafts.

Intimal smooth muscle cell proliferation and superimposed atheroma are the main causes of late failure of saphenous vein bypass grafts. It has been suggested that these reactions are caused by the production of growth factors from the cells of the vessel wall. To test this hypothesis, we cultured segments of pig venous arterial grafts, removed 1 and 4 weeks after implantation, in serum-free medium for 24 hours. Tissue viability as assessed by adenosine triphosphate concentration was maintained throughout the 24-hour culture period (239 +/- 21 nmol/gm wet weight [standard error of the mean], n = 26, 0 hours; 240 +/- 24 nmol/gm wet weight, n = 17, 24 hours). Cell proliferation occurred and autoradiography showed proliferating cells to be located in the neointimal and medial layers. These cells were identified as smooth muscle cells by means of a monoclonal antibody to alpha-actin. Graft-conditioned media were tested for mitogenic activity by means of a fibroblast proliferation assay. Media conditioned for 24 hours produced significant stimulation of cell growth (284% +/- 30%, n = 17) above that obtained in culture medium alone (100%). This mitogenic activity was inhibited by 61% +/- 9%, n = 8, with a polyclonal-neutralizing antibody to platelet-derived growth factor. Reverse-transcription polymerase chain reaction analysis and Northern blots demonstrated platelet-derived growth factor B messenger ribonucleic acid (mRNA) in vein grafts but not in ungrafted vein. Analysis of graft tissue sections by in situ hybridization demonstrated an abundance of platelet-derived growth factor B mRNA positive cells in the endothelial and neointimal layers, as well as in the endothelial cells of the adventitial vessels. These data constitute direct evidence for active growth factor production within the cells of the vein graft. They also suggest that endogenously produced platelet-derived growth factor may play a role in regulating smooth muscle cell proliferation in this model.

Animals↗

Selecting DNA fragments for mutation detection by temperature gradient gel electrophoresis: application to the p53 gene cDNA.

Temperature gradient gel electrophoresis (TGGE) and related methods are widely employed to detect mutations in DNA fragments. DNA melting map calculations and GC clamps have been used to enhance the detection of mutations. While generally successful, these methods have not always revealed base changes within a DNA fragment. Previous work suggested that mutations are detected if they are in a DNA's first melting domain, and the melting domain is well separated from final strand dissociation. Two criteria from the DNA melting theory were established to determine when both of these conditions are met. The criteria involve calculating the derivative melting curve as well as the melting map of a DNA sequence. The approach was applied to the cDNA sequence of the human p53 gene. Mutations in the p53 gene are common in human cancers and are generally located in four 'hot spot' regions. Calculations indicated that three DNA fragments are needed to detect base substitutions in the four hot-spot regions. Predicted melting behavior was experimentally tested with eight single base substitutions distributed among the four hot-spot regions. All mutations tested behaved as predicted and were detected by vertical TGGE. Heteroduplex DNAs formed by melting and reannealing various ratios of wild type and mutant DNA fragments were also examined. Results indicated that point mutations can be detected by ethidium bromide staining from samples containing 10% mutant and 90% wild-type sequences.

Base Sequence↗

Y chromosome loss in esophageal carcinoma: an in situ hybridization study.

Carcinoma of the esophagus shows a strong male predominance and other epidemiologic differences from cancers arising at other sites. In this study, the prevalence of Y chromosome loss in 29 carcinomas of the esophagus and 53 carcinomas arising elsewhere in the aerodigestive tract was assessed by in situ hybridization of formalin-fixed paraffin-embedded tissue sections. Absence of the Y chromosome was defined as (1) negative staining for Y in neoplastic cells with positive staining for Y in immediately adjacent nonneoplastic epithelial and stromal cells, (2) positive staining of neoplastic cells with control probes for chromosomes X and 17, and (3) similar results at different stringencies and levels of protein digestion. According to these criteria, absence of the Y chromosome was observed in 13 of 14 (93%) adenocarcinomas of the esophagus, 8 of 13 (62%) squamous cell carcinomas of the esophagus, and 5 of 53 (9%) carcinomas arising in other sites. For the neoplasms examined, Y chromosome deletion was strongly and selectively associated with carcinomas, particularly adenocarcinomas, of the esophagus (P < .0001). These findings suggest that Y chromosome loss may be pathogenetically significant in these neoplasms.

Adenocarcinoma↗

Phosphatidylcholine-coated chest tubes improve drainage after open heart operation.

Occlusion of chest drainage tubes by thrombus is not uncommon after open heart operations. It has been suggested that by coating the tube with phosphatidylcholine (PC), the most prominent phospholipid in the erythrocytes outer membrane, it may be possible to overcome the blood-material interaction responsible for thrombus formation. To test this hypothesis 102 patients (75 males; mean age, 57 +/- 10 years) were randomly allocated to receive either PC-coated or noncoated 32F chest drainage tubes. Preoperative status, type and length of operation, and duration of drainage were similar in the two groups as was postoperative blood loss. Patients receiving PC-coated tubes, however, had less residual blood clot in the tube after removal (0.7 +/- 0.1 versus 3.1 +/- 0.3 g; p < 0.001), a reduced incidence of pericardial effusions (17.6% versus 41.2%; p < 0.01), fewer postoperative supraventricular arrhythmias (2 of 51 versus 10 of 51; p < 0.002), and a shorter hospital stay (8.4 +/- 0.3 versus 9.7 +/- 0.5 days; p < 0.05). Late cardiac tamponade developed in 2 patients in the noncoated group 6 and 10 days postoperatively, which required reexploration. The data show that PC-coated chest drainage tubes are less susceptible to occlusion by thrombus and their use is associated with a significant reduction in postoperative morbidity.

Aged↗