Effect of selective immunosuppression with FK 506, anti-IL-2R, and anti-ICAM-1 MAb in rat small bowel transplantation.
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Biomedical subjects
Publications and source records attributed to M Gasser.
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Prevention of allograft rejection remains a major problem after small bowel transplantation (SBT) and requires potent immunosuppressive regimens. In a variety of transplant models, e.g. liver or heart transplantation, the supplementary application of monoclonal antibodies (mabs) against adhesion molecules is effective in both prolonging graft survival and inducing long-term graft acceptance or tolerance in some cases. In this study anti ICAM-1 (1A29) and anti LFA-1 (WT1) mabs were used in combination with a subtherapeutic dose of FK 506 for 13 days after allogeneic SBT in the rat. The results of this study indicate that in contrast to the induction of allospecific tolerance after liver transplantation, the addition of anti ICAM-1 and/or of anti LFA-1 mabs after SBT reverses the FK 506 effect and results in early graft rejection. It has been shown that higher dosages of these mabs, given alone or in combination with CsA or FK 506, result in long-term survival of cardiac allografts in both, rats and mice [4-8]. Graft survival after pancreas transplantation is prolonged [6]. However, these negative therapeutic effects of the mabs 1A29 and WT1 after SBT have to be critically reevaluated and further analysed.
The fruitfly, Drosophila melanogaster, can be transfected with P-elements and induced to overexpress a transfected gene whose impact on lifespan can be measured. Here, it is reported that in previous experiments a transfected gene was not expressed. This suggested a new statistical analysis indicating that (1) the size of the insert, the position and the interactions of the insert with the genetic backgrounds into which the P-element are inserted have effects on lifespan similar to those attributed to overexpression; (2) these effects occur without expression of the transfected gene; and (3) effects of interactions with backgrounds and effects of positions are as large as responses to six generations of strong directional artificial selection. Reports of effects of overexpression of transfected genes on lifespan in Drosophila melanogaster may be experimental artefacts. Credible experiments on the phenotypic effects of transgenesis need proper controls for the effects of insert size and position and should estimate the magnitudes of interactions of treatment with genetic backgrounds.
In order to select those patients with colorectal liver metastases who may have benefit from an operation, preoperative detection and localization of tumors in the liver is necessary. In this study, the specificity and sensitivity of a CT arterial portography and magnetic resonance imaging with contrast media was compared with the results of operative findings and intraoperative ultrasonography. The combination of both preoperative methods led to an accuracy rate of more than 90%, and all patients who underwent laparotomy were resected or treated with an arterial infusion port system. Negative laparotomies were excluded completely.
We studied the psycho-social circumstances of HIV-positive women and their children, who were born between January 1, 1984 and June 30, 1991 and are being treated at the Department of Pediatrics. We interviewed 19 women out of 21 families using the problem-centered interview technique according to Witzel. 29 out of 30 children were older than 18 months. Four children were HIV-positive and the serology of one patient aged 12 months who had been perinatally exposed was yet unclarified. The study showed massive problems within these families, such as considerable partner problems, drug abuse and social isolation. Furthermore, there was a lack of child care to relieve the mothers. The predominance of drug problems and insufficient experience of social institutions with the problematic nature of HIV-infection in mothers and children require more efficient preventive measures.
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In this paper we describe a new assay for diphtheria toxin in bacterial cultures, based on a sandwich-dot immunobinding method. This method uses horse polyclonal diphtheria antitoxin as the coating antibody and mouse monoclonal diphtheria antitoxin as the detecting antibody. The sensitivity of this new method is within a range of 5-10 ng toxin per ml in Corynebacterium diphtheriae cultures. We did not observe any false-positive reactions. As a solid phase we used nitrocellulose disks which bind protein more strongly than the commonly used plastic solid phase. Results with strong toxin producers of C. diphtheriae can be obtained as soon as 11 h after starting a bacterial test culture. To detect weak toxin producers, the cultivation period must be extended to about 18 h and the results can be obtained after about 24 h. The method presented in this paper is simpler, faster and more reliable than currently used methods.
Two cases of imported cutaneous diphtheria from tropical areas are described. Vacationing in the Seychelles, a 29-year-old man injured his left malleolus a few weeks before his return to Switzerland. The wound did not heal and an ulcer developed. Microbiologic investigation yielded toxinogenic Corynebacterium diphtheriae. There were no signs of systemic intoxication. The man had not been vaccinated against diphtheria since childhood. In the second case a 51-year-old woman returned from Thailand and Nepal with two very painful ulcers between the toes of her right foot, which was reddish-coloured. Microbiologic investigation again yielded toxinogenic Corynebacterium diphtheriae and there was no sign of systemic intoxication. Treatment with erythromycin brought about complete healing of the ulcers.
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During an 18-mo period between 1981 and 1982, a prospective study was conducted in 119 adult patients with acute diarrhea. A diarrhea-inducing microorganism or toxin could be identified in 38.7% of the patients. Salmonella sp and Campylobacter jejuni were the leading agents that caused diarrheal illness in 25% of the investigated population. Clostridium difficile was found in 6%, mainly after previous antibiotic therapy. Rotavirus was rarely isolated and enterotoxigenic Escherichia coli were not found. Clinical features in patients in whom an invasive agent was isolated did not differ from those in patients in whom no enteropathogens were found, although the occurrence of fecal leukocytes and positive hemoccult tests in the former group was significantly more frequent. More than 30% of the patients with negative stool cultures, however, showed fecal leukocytes and positive occult blood, which is suggestive of the existence of one or more invasive agent(s) so far unknown or not recognized.
An ELISA technique is described which employs both solid phase and labelled free SpA. The technique allows the detection of anti-SpA antibodies in the rabbit. It is not suited for the same purpose with human sera, because human immunoglobulins are not saturated by non-specific interaction with solid phase SpA.
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In a study on the prevalence of hepatitis A virus (HAV) exposure among the Basel population in 1978/79, 763 sera matched for age were tested for HAV antibodies by radioimmunassay (HAVAB). Sera of patients with a recent history of liver disease were not included. The results show that the prevalence of HAV antibodies increases with age, a situation similar to that in poliomyelitis before vaccination. The prevalence of HAV antibodies rises from 15% in the 11-20 year age group to 90% in the over-71 age group. The fall in HAV exposure with decreasing age is attributed to a decline in infections due to improvements in hygienic standards during this century, and especially since World War II. The average prevalence of HAV antibodies found in this study is 52%. The results are partly influenced by the high proportion of subjects originating from foreign countries among the population investigated.
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