Prosocial behavior as affected by eye contact, touch, and voice expression.
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Biomedical subjects
Publications and source records attributed to M Goldman.
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A vitamin A (retinyl acetate)-deficient diet enhanced liver cancer in rats exposed to aflatoxin B1 (AFB1) and also caused a 29% incidence of colon cancer. The following factors were considered in attempts to define conditions under which vitamin-A-deprived rats were more susceptible to colon cancer induced by AFB1: liver morphology, enterohepatic recirculation, level of reduced glutathione (GSH) in liver, and differing capacities for conjugation of aflatoxin to GSH. Enzyme concentrations in liver, in intestinal and colon mucosa, and in intestinal and colon contents suggested that AFB1 may have different metabolites and that there may be differing susceptibilities of colon mucosa to carcinogenesis. Binding studies supported this hypothesis. Previous studies have shown that colon epithelium from vitamin-A-deficient rats binds more AFB1 than colon epithelium from normal, vitamin-A-supplemented animals. In the present study, vitamin A supplementation to the vitamin-A-deficient rats before oral administration of 3H-AFB1 significantly decreased the binding capacity at 12 and 15 hours after dosing with the carcinogen. These results suggest that the effect of vitamin A on the metabolism of the carcinogen, particularly on binding of AFB1 to cellular macromolecules, may be the mechanism by which vitamin A modifies aflatoxin's carcinogenic potential, influenced in part through enzymatic mechanisms.
Twelve patients with Crohn disease were studied by computed tomography. Characteristic findings of small intestinal involvement include symmetrical bowel wall thickening, a "double halo" appearance on cross section of the diseased bowel segment, and an associated mesenteric fat mass. Computed tomography provided crucial diagnostic information in the management of some of the intestinal and extraintestinal complications of the disease.
1 Platelet inhibitory therapy may protect patency in prosthetic arterial grafts. 2 The effect of the thromboxane synthetase inhibitor dazoxiben (UK 37248) on 113Indium-labelled platelet deposition on Dacron arterial grafts was examined in an artificial circulation containing human blood which mimics the haemodynamics of femoropopliteal bypass. The influence of this drug on thromboxane production and platelet reactivity was measured during the experiment. The study was controlled and performed in two parts to assess in vitro and ex vivo drug effect. 3 Both in vitro and ex vivo dazoxiben reduced plasma thromboxane by about 80% and in citrated ex vivo blood increased mean (+/- s.e. mean) platelet aggregation threshold to collagen from control values of 4.8 +/- 1.7 mg/ml to 10.6 +/- 3.3 mg/ml (P less than 0.01). Dazoxiben, however, had no effect on platelet deposition on the arterial grafts. 4 Selective thromboxane inhibition failed to exert an antithrombotic effect in this model.
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To avoid the problems associated with whole-body radiation, pieces of X-irradiated normal or hyperplastic mammary tissue were transplanted to the host gland-free fat pad of nonexposed mice. The percentage of the fat pad filled by growth of the transplants at 4, 8, and 12 weeks after transplantation was measured. Growth of lobule transplants was moderately inhibited by 4 Gy. While some of the lobules survived 12 Gy, their growth was severely inhibited. The hyperplastic outgrowth lines were variable but more resistant than lobules to growth retardation. Line Z5D was more susceptible than D1, and Z5C1 was least susceptible, with 88% growing well after 12 Gy. In order to distinguish between transient and permanent growth retardation, tissue was taken from the irradiated and control transplants and retransplanted to new hosts without further radiation. The second generation of X-ray-exposed tissue filled more of the fat pad than the first-generation transplants, but significantly less than the nonexposed controls. The experiments described provide a means of demonstrating X-ray-induced changes in the mammary gland from growth inhibition to carcinogenesis.
Mice made neonatally tolerant to alloantigens were found to develop an immunologic disease resembling systemic lupus erythematosus. In BALB/c mice neonatally injected with C57BL/6 X BALB/c F1 hybrid spleen cells, features of autoimmunity were observed first. After 5-24 wk, antinuclear, anti-SS DNA, thymocytotoxic, and rheumatoid factor-like antibodies were detected in association with hypergammaglobulinemia and with the occurrence of circulating immune complexes and cryoglobulins. Some of the antinuclear antibodies were found to be produced by F1 donor B cells persisting in the host. Second, immunopathologic changes were detected in tolerant mice. In the kidneys, an immune complex glomerulonephritis of the membranous type was observed. Immunoglobulin deposits were also found in the choroid plexus and at the dermoepidermal junction. In addition, thrombocytopenia was a common finding, and a positive direct Coomb's test occasionally was detected. Features of autoimmune disease were closely associated with the effective induction of transplantation tolerance, as revealed by the inability of spleen cells to generate in vitro cytolytic responses against C57BL/6 alloantigens. It is suggested that, although transplantation tolerance is associated with a lack of cytolytic reaction of the host against F1 hybrid donor alloantigens, other types of allogeneic interactions could lead in this model to the development of autoimmunity and immunopathology.
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This is a review of our 5 1/2-year experience with the treatment of infrarenal abdominal aortic aneurysms by thrombosis induced by outflow obstruction while adequate lower limb perfusion is simultaneously ensured by axillofemoral bypass. Sixty high-risk patients who were considered to be unsuitable for direct aortic replacement have been so treated. Preoperative angiographic investigation of the pelvic and visceral vessels is mandatory. Thrombosis of the aneurysm occurred in 42 patients within 72 hours after surgical interruption of the iliac outflow, while in the remainder, persistent patency was dealt with by radiologic deposition of thrombotic material in the remaining outflow arteries. Contrary to our previous report, an augmented computerized tomographic scan has proved to be more accurate than radionuclide flow studies for the determination of complete aneurysmal thrombosis. There were four deaths within 40 days (7%), and the remaining patients were followed for 6 to 48 months. There were three fatal ruptures, all as the result of inaccurate indication of thrombosis by radionuclide flow scan. The rate of survival by life table analysis was 55% at 24 months. There has been no evidence of proximal extension of the infrarenal thrombosis to visceral vessels. This experience suggests that this technique offers a reasonable alternative to the treatment of abdominal aortic aneurysms when the indication is compelling and the risk of direct graft replacement is excessive.
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The measurement of platelet deposition in human thrombi is essential for the evaluation of platelet-inhibitory drugs and prosthetic materials for use in patients. The rate of 111Indium-labelled platelet accumulation on Dacron arterial grafts was measured in 27 patients randomised to take either aspirin and dipyridamole (ASA + DPM) or placebo. Autologous platelets were labelled and re-injected seven days following surgery and the graft thrombogenicity index calculated as the daily rise in the ratio of emissions from the graft over a reference site. The mean (+/- SD) thrombogenicity index in 12 patients undergoing femoro-popliteal bypass was 0.25 +/- 0.09 on placebo and 0.16 +/- 0.07 on ASA + DPM started pre-operatively (p less than 0.05). Post-operative ASA + DPM therapy started two days following platelet labelling in 15 patients with aorto-femoral grafts also significantly reduce thrombogenicity to 0.12 +/- 0.05 compared with 0.25 +/- 0.08 on placebo (p less than 0.01). In the latter patients the ratio of emissions from the graft over reference fell significantly on starting ASA + DPM, suggesting a net loss of platelets from the graft. These results indicate that the rate of in vivo platelet accumulation on Dacron grafts can be quantitated and that ASA + DPM reduced this rate in man.
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We investigated the possible role of idiotypic interactions in the pathogenesis of the glomerular lesions observed in mice undergoing polyclonal B cell activation. BALB/c mice were studied for the presence of renal deposits of T15 idiotype-anti-T15 idiotype-immune complexes (IC) after injection of bacterial lipopolysaccharides (LPS). The T15 idiotype is the major idiotype of BALB/c mice anti-phosphorylcholine (PC) antibodies, which are cross-reactive with the idiotype of the TEPC-15 myeloma protein. This model was used because T15 idiotype-anti-T15 idiotype IC have been detected in the circulation of BALB/c mice after polyclonal B cell activation. First, an idiotype-specific immunofluorescence technique allowed us to detect T15 idiotype-bearing immunoglobulins in glomeruli from day 6 to day 28 after LPS injection. Second, fluorescein isothiocyanate-conjugated TEPC-15 myeloma protein was found to localize in the glomeruli after in vivo injection 18 d after LPS administration. This renal localization was shown to be idiotype-specific and could be quantified in a trace-labeling experiment. Third, kidney-deposited immunoglobulins of mice injected with LPS were eluted, radiolabeled, and analyzed by radioimmunoassay. Both T15 idiotype-bearing immunoglobulins and anti-T15 idiotype antibodies were detected in the eluates, providing further evidence for a renal deposition of T15 idiotype-anti-T15 idiotype IC. Polyclonal B cell activation is likely to result in a simultaneous triggering of many idiotypic clones and of corresponding anti-idiotypic clones represented in the B cell repertoire. This could lead to the formation of a variety of idiotype-anti-idiotype IC that could participate in the development of glomerular lesions.
Prosthetic femoropopliteal grafts attract platelet thrombus and often occlude in the months following implantation. Hence a technique to measure the in vivo thrombogenicity of different vascular substitutes in patients has been developed. In 28 patients the rate of accumulation of 111-indium-labelled platelets in saphenous vein, polytetrafluoroethylene (PTFE) and double velour Dacron femoropopliteal grafts was studied. One week postoperatively autologous 111In-labelled platelets were injected and the isotope emissions over the graft and contralateral leg counted. Graft thrombogenicity was calculated as the daily rise over 7 days in the ratio of counts over the graft to those over the contralateral leg. Mean thrombogenicity index (+/- s.e.mean) was greatest in the Dacron grafts at 0.24 +/- 0.03 which compared with 0.13 +/- 0.02 in PTFE (P less than 0.05). Saphenous vein was markedly less thrombogenic than either prosthetic graft with a mean index of only 0.025 +/- 0.01 (P less than 0.01). Platelet survival failed to differentiate the three graft materials, demonstrating that the direct measurement of 111In platelet deposition was a more sensitive technique.
Prosthetic graft occlusion is most frequent in the early postoperative period when the luminal surface is highly thrombogenic. It is generally believed that graft maturation ultimately results in a non-thrombogenic surface. The accumulation of 111-indium-labelled autologous platelets in Dacron aortofemoral grafts has been measured 1 week following surgery and at intervals of 6 months to 1 year. Platelets from 9 patients were labelled with 111-indium oxine and re-injected. Isotope emissions over the graft and a reference site (aortic arch) were measured daily for 8 days and gamma camera images taken on alternate days. Graft thrombogenicity was calculated as the daily rise in the graft: reference ratio of emissions. All grafts, regardless of age, accumulated platelets and were imaged by gamma camera. Mean thrombogenicity (+/- s.e.mean) 1 week after surgery was 0.21 +/- 0.04 compared with 0.08 +/- 0.03 at follow-up (P less than 0.01). The platelet survival during the early study was reduced at 6.8 +/- 0.6 days but recovered to a value of 8.6 +/- 0.8 days (P less than 0.01) at follow-up. Further grafts, 2, 5 and 9 years old, were studied and all accumulated platelets, especially near the anastomoses. Platelet accumulation on Dacron grafts does diminish with time but persists beyond the period of altered platelet survival and perhaps indefinitely.
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