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Biomedical subjects

G Hamilton

Publications and source records attributed to G Hamilton.

At least 235 records · Page 13Linked to original sources

Variceal hemorrhage.

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Esophageal and Gastric Varices↗

Ewing's-sarcoma-associated HBA-71 tumor antigen represents a new differentiation marker of human thymocytes.

The monoclonal HBA-71 antibody recognizes a new human tumor-associated antigen of Ewing's sarcoma and peripheral neuroectodermal tumors, which is also expressed in some normal tissues, including thymus, islets of Langerhans, ependyme, adenohypophysis, Sertoli/Leydig and granulosa cells. Besides a tumor-specific reciprocal chromosomal translocation t (11:22), the expression of the HBA-71 antigen is the only marker which can be used for reliable differential diagnosis of these rare malignancies of childhood and adolescence among other small round cell tumors. The HBA-71 antigen is further characterized here by ultrastructural, functional and cell-matrix interaction studies. In immunohistochemical staining the HBA-71 reacted with the cell surface of human cortical thymocytes. The HBA-71 antigen was also found to be localized at the cell-surface glycocalyx of tumor cells using immunogold staining and electron microscopy. A panel of additional monoclonal antibodies with reactivity patterns similar to those of the HBA-71 antibody was obtained by immunization of mice with ES cell lines and boostering with thymocytes. The HBA-71 antibody triggers proliferation of thymocytes and to a lesser extent also stimulates peripheral mononuclear blood cells. Antibody-induced thymocyte cultures exhibit the phenotype of immature, CD3low thymocytes with uniform and stable expression of the HBA-71 antigen. In contrast to the thymocytes the HBA-71 antibody has an inhibitory effect on the continuous growth of the HBA-71+ tumor cell lines. The HBA-71 antigen may be involved in the regulation of growth of the positive normal and malignant tissues. Positive modulation of the antigen expression was induced in Ewing's sarcoma cell lines in response to insulin, insulin-like growth factor I (IGF-I) and by interaction of the cells with the extracellular matrix.

Animals↗

Expression of a new human THY-1 related antigen in Ewing's sarcoma and peripheral neuroectodermal tumors.

Ewing's sarcoma (ES), peripheral neuroectodermal tumor (PNET) and Askin's tumor of the chest wall share a reciprocal chromosomal translocation between the long arms of chromosomes 11 and 22 (q23-24; q12). In the absence of other distinguishing features this specific translocation is regarded as marker of a common and neuroectodermal origin for these rare tumors. A monoclonal antibody (HBA-71) developed in our laboratory has been found to recognize an unique ES and PNET associated antigen, which is also expressed in some normal tissues, including thymus, bone marrow, islets of Langerhans, ependyma and adenohypophysis. It is shown in this study that this HBA-71 antigen is closely related to the murine THY-1 antigens, major cell surface glycoproteins of thymocytes and brain in mice and rat. Both antigens have similar molecular ratios (18,000), amino acid compositions and sensitivity to tryptic digestion, show high cell surface expression, and binding of the appropriate antibodies to HBA-71 antigen triggers proliferation in thymocytes. The HBA-71 epitope may represent a primitive neuroectodermal marker of ES/PNET, or its expression may be directly linked to the reciprocal translocation invariably associated with HBA-71-positive ES and PNET tumors, which maps to the same region of chromosome 11 (q23-24) as the human Thy-1 gene.

Amino Acids↗

Response of skin photoplethysmography, laser Doppler flowmetry and transcutaneous oxygen tensiometry to stenosis-induced reductions in limb blood flow.

Photoplethysmography (PPG), transcutaneous oxygen tensiometry (TCpO2) and laser Doppler flowmetry (LDF) were used to measure changes in perfusion of the distal lower limb of the pig, in response to a stenosis created in the external iliac artery. The severity of stenosis was quantitated by the ratio of peak systolic distal pressure to peak systolic proximal pressure (distal systolic pressure index, DSPI). PPG and LDF were immediately responsive to changes in perfusion pressure while TCpO2 responded much more slowly. PPG dropped precipitously in response to even a small reduction in perfusion pressure, reaching zero at a DSPI of approximately 0.3. TCpO2 was insensitive to the presence of a mild stenosis (DSPI greater than 0.6), but was highly sensitive in the range 0.6 greater than DSPI greater than 0.3. At lower DSPI values, TCpO2 also became zero, due in part to electrode consumption of oxygen. LDF readings were sensitive to changes in blood flow throughout the entire range of stenosis, down to the point of total occlusion, although changes were not significant at DSPI values greater than 0.6. Because LDF measures not only nutritional blood flow, but flow in AV shunts and subdermal plexuses as well, high LDF readings could erroneously suggest tissue viability and good healing potential. Resting levels of TCpO2 and LDF can be used to follow the progress of peripheral vascular disease, and used complementarily, in many cases, to evaluate the severity of flow impairment.

Animals↗

Two-dimensional Doppler echocardiographic flow imaging--exploration of clinical impact and problems.

Recent advances in electronic engineering have allowed Doppler echocardiography to be presented in the form of a real-time two-dimensional image. The resulting image of blood flow has been described as a 'non-invasive angiogram', but the analogy with angiography should not be pushed too far since the technical determinants of these images are entirely different. Nevertheless, the colour flow map does allow rapid and direct exclusion, detection and quantitation of regurgitant and stenotic lesions, and semi-quantitative assessment of valvular regurgitation and shunts. To achieve optimum results, it is necessary to standardise recording procedure, to take account of patient variables which influence the image appearance and quality and to be aware of the possibility of artefact. As for all investigations, results which are not coherent with other echocardiographic data, with other investigations and with the clinical assessment should be subjected to particular scrutiny with the possibility of false diagnosis in mind.

Echocardiography, Doppler↗

[Selective effect of personality markers and psychosocial stress on T lymphocyte subpopulations].

Measurements were made of cellular immune system parameters in a group of healthy medical students. On the basis of psychosocial stress encountered during a five-day topic-centered self-awareness course, we investigated modulation in immunity in relation to personality characteristics. 6 days before the beginning of the seminar personality profiles were drawn and blood samples taken. Further immunological measurements were made on day four of the seminar and three weeks after its conclusion. On the fourth day of the seminar we observed throughout the group higher lymphocyte and suppressor/cytotoxic T lymphocyte counts in comparison with counts one week earlier, and likewise a heightened responsiveness to PHA- and IL-2 stimulation. The T lymphocyte counts had dropped. In subjects with a higher need for succorance/nurturance, the depression of the immune system was manifested in a drop in the helper/inducer T lymphocyte counts, and in the more achievement- and order-oriented subjects in a downregulation as observed by higher suppressor/cytotoxic T lymphocyte counts. Our results show that under psychosocial stress, healthy people experience on the one hand an activation of the immune system, and on the other hand an immunodepression bearing a specific relation to personality characteristics.

Adult↗

Atherosclerotic renovascular disease causing renal impairment--a case for treatment.

Renovascular disease is a potentially curable cause of renal failure. In a prospective survey over an eighteen month period atherosclerotic renal artery disease was the cause of renal failure in 14% of patients over the age of fifty years accepted for renal replacement therapy at this hospital. Ten patients were found to be suffering from atherosclerotic renovascular disease causing renal failure but in only one was treatment able to reverse renal failure. The major problem with this group of patients is the widespread nature of their disease affecting many other organs. Significant morbidity is associated with their investigation. Although potentially curable, atherosclerotic renovascular disease is a frequent cause of renal failure in patients over the age of fifty years but is also difficult to treat.

Aged↗

Zero-added-dose gastrointestinal film studies.

A technique is described to produce diagnostic quality 70 mm x 60 mm films of upper GI fluoroscopic examinations by photography of the video-displayed image on a "slave" monitor, obtained at a dose of 0.01 milligray (1 millirad) for a 20 cm water equivalent phantom. Because the photograph is the same image already being observed, the films require no added dose over that needed for an adequate fluoroscopic examination. Diagnostic films can be made from the replay of a videocassette recorder. With exposure times of 1/30th of a second, movement blur is easily prevented.

Barium Sulfate↗

Characterization of a human endocrine tissue and tumor-associated Ewing's sarcoma antigen.

The histogenesis of Ewing's sarcoma (ES), the second most frequent primary bone tumor in humans, remains controversial. A new cell line (SIM-1) was derived from a peripheral neuroectodermal tumor (PNET) and used for the production of a monoclonal antibody (HBA-71), which recognizes a novel cell surface antigen of ES- and PNET-derived cells and paraffin-embedded tumor sections. The HBA-71 antigen expression is restricted to PNET/ES and the antigen was not detected on cell lines or tissue sections of any other tumor tested, with the exception of ependymoma. Three proteins with molecular weights of 300,000, 185,000, and 90,000 were isolated from SIM-1 membrane extracts by HBA-71 affinity chromatography. Trypsin treatment of intact SIM-1 cells destroys the HBA-71 epitope and cleaves off two proteins with molecular weights of 210,000 and 95,000. HBA-71 antigen expression is not influenced by treatment of ES cell lines with differentiation inducers. Within normal tissues reactivity was observed with the adenohypophysis, ependymal cells, endocrine pancreas, Sertoli, and ovary granulosa cells. The reagent links ES with PNET and provides a highly valuable probe for (a) the immunohistological differential diagnosis of ES/PNET using fresh tissue or paraffin sections from other small round cell tumors, (b) the histogenetic studies of ES/PNET, and (c) the in vivo diagnostic and therapeutic procedures in patients with ES and PNET.

Adolescent↗

Natural killer cell activities of patients with breast cancer against different target cells.

Natural killer (NK) cell activity against K 562 erythroleukemic- and MCF-7 breast carcinoma-derived cells was monitored in short-term (3 h/K 562) and long-term (18 h/MCF-7) chromium release tests for 60 patients with untreated primary breast disease. Target cell lysis was the same for patient groups with benign (n = 13) and malignant (n = 47) breast disease (27% versus 36% mean chromium release; target:effector ratio 40:1 for K 562 and 28% versus 40% for MCF-7 cells). NK activity as defined by short-term lysis of K 562 cells did not correlate with MCF-7 cell lysis in long-term assays for the carcinoma patients. This functional heterogeneity of natural cytotoxic activities of breast cancer patients was confirmed by a different age distribution for K 562 and MCF-7 cell lysis and high levels of MCF-7-directed NK activity in the grade I tumor group (56.2%). Our results indicate that measurement of peripheral blood NK activity against a breast carcinoma-derived cell line (MCF-7) defines a disease-related natural cytotoxic activity which correlates better with prognostic tumor parameters (tumor grading) than NK activity as defined by the lysis of K 562 erythroleukemic cells. NK activity testing against breast carcinoma cell lines should be used to monitor natural cytotoxic activities in breast cancer patients and its modulation by different routes of treatment.

Adult↗

Influence of two glutamine-containing dipeptides on growth of mammalian cells.

The instability of the amino acid glutamine prompted us to investigate substitute compounds appropriate for culture conditions. The effect of two glutamine-containing dipeptides, alanylglutamine (Ala-Gln) and glycylglutamine (Gly-Gln), on the growth behavior of a hematopoietic cell line in culture (K562) was investigated. Growth rates and [3H]thymidine incorporation rates of cells cultivated in sterile-filtrated media, containing glutamine (Gln) or Ala-Gln or Gly-Gln, were not statistically different. Although heart-sterilization of media containing Gln caused approximately 95% decomposition of the Gln, both dipeptides remained unaltered. Consequently, cell growth was drastically decreased when autoclaved free Gln-containing media were used, but growth was unaffected in the presence of autoclaved dipeptides. Both Ala-Gln and Gly-Gln have an advantage over free Gln as growth factors for cell culture due to the stability of the dipeptides during both autoclaving and storage; the biological activity, however, is comparable.

Cell Division↗

Impaired cell-mediated immunity in the first week after burn injury: investigation of spontaneous blastogenic transformation, PHA, IL-2 response and plasma suppressive activity.

This study investigated alterations of cell-mediated immunity induced by trauma, operative treatment and infections in a group of 19 burned patients with a mean burn size of 42 +/- 22 per cent of the body surface area. We tested peripheral mononuclear blood cells (PMBC) for spontaneous blastogenic transformation (SBT), phytohaemagglutinin (PHA) and interleukin-2 (IL-2) responsiveness. Plasma samples were also assayed for inhibition of mitogen stimulation of control PMBCs. Mean values were calculated for the acute postburn period (days 0-3) and the following 4 days, before the development of septic complications. SBT was significantly increased in all patients during the second period of investigation (days 4-7) in comparison to normal controls and during the acute phase. The response to mitogen stimulation (PHA) was significantly suppressed during days 0-7 and the plasma samples showed high suppressive activities following PHA stimulation of control lymphocytes during the course of the study. No significant differences in rates of SBT, PHA responsiveness and plasma suppressive activity were found between those patients who developed bacteraemia and those with negative blood cultures. The latter group showed higher reactivity to added IL-2 in comparison to normal controls. Surgical treatment immediately after trauma (fasciotomy; day 0 or 1) resulted in further increased immunosuppression (PHA and IL-2 response), whereas after necrectomy (days 4-7) the immunological parameters showed no significant differences. It can be concluded that neither rates of SBT nor response to PHA can be used to identify patients at high risk for infection during the first week postburn.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prediction of aneurysm formation in vascular grafts of biologic origin.

Other than review of clinical experience, no assay exists that can reliably predict the long-term potential for aneurysm formation in an arterial prosthesis of biologic origin. Since mural degeneration probably results from proteolytic digestion, an in vitro assay was devised that used graft perfusion with 1% collagenase to induce rapid changes in mechanical properties. The effect of enzyme on graft diameter, compliance, permeability, and burst pressure was measured in ficin-digested, adipoyl chloride and glutaraldehyde-tanned bovine carotid artery and glutaraldehyde-tanned human umbilical vein. Both grafts have recently been reported to have a significant incidence of aneurysm within several years of implantation. Compliance and diameter were also measured noninvasively in patients with bovine carotid artery and human umbilical vein for more than 40 weeks after implantation. In vitro, the response to enzyme could be categorized into three groups. In group III, a diameter increase of more than 14% was associated with a significantly decreased compliance, and this paralleled the results found in aneurysmal grafts in vivo. In both grafts there was a strong correlation between postenzyme compliance change and initial compliance, loss of compliance being significantly greater in grafts with group III responses (p less than 0.01). This response may be a good predictor of a graft's overall susceptibility to aneurysmal degeneration, and initial compliance measurement may effectively identify inadequate fixation. Thus measurement of compliance may prove useful in quality control of a fixation process used in mass production. In conclusion, measurement of mechanical properties of biologic vascular grafts before and after collagenase exposure forms the basis for an effective in vitro assay of aneurysm susceptibility.

Aneurysm↗