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Biomedical subjects

J Chabot

Publications and source records attributed to J Chabot.

At least 37 records · Page 2Linked to original sources

Pancreatic islet transplantation in cynomolgus monkeys. Initial studies and evidence that cyclosporine impairs glucose tolerance in normal monkeys.

Using a model of streptozotocin-induced, ketosis-prone, insulin-dependent diabetes mellitus (IDDM) in the cynomolgus monkey, we performed 11 intraportal transplants of collagenase-digested, Ficoll-purified pancreatic islets (9 ABO-compatible allografts and 2 concordant baboon xenografts). Islets were pretreated with ultraviolet-B irradiation and recipients received cyclosporine A immunosuppression. Two grafts never functioned, five grafts showed evidence of partial function, and four grafts (three allografts and one xenograft) showed evidence of good function, with the animals independent of exogenous insulin with morning fasting blood glucose levels less than 200 mg/dl. Because two grafts functioned only after CsA was either tapered or discontinued, we performed a related study that showed that therapeutic doses of CsA (morning trough serum level 150-250 ng/ml) impaired intravenous glucose tolerance tests (IVGTT) of normal monkeys and may contributed to graft dysfunction in our islet transplantation model. The results show that there is a decrease in release of serum insulin during an IVGTT leading to impairment of glucose utilization, while serum glucagon remains unaffected. After cessation of CsA, the IVGTT did not return to normal for 28 days. Oral glucose tolerance tests were unaffected in CsA-treated monkeys. These initial studies show that the streptozotocin-diabetic monkey is a valuable model to study IDDM and islet transplantation in nonhuman primates. We also confirm studies in rodents, dogs, and sheep by showing that CsA partially inhibits beta cell function in normal monkeys.

Animals↗

Mechanisms of immunologic unresponsiveness induced by ultraviolet-irradiated donor-specific blood transfusions and peritransplant cyclosporine.

Recipient pretreatment with UV-B irradiated donor-specific blood transfusions (UV-DST) combined with peritransplant cyclosporine on days 0, +1, and +2 leads to permanent cardiac allograft survival in the ACI-to-Lewis rat strain combination. This study investigates the mechanisms of immunologic unresponsiveness induced by UV-DST and CsA by examining several in vitro and in vivo parameters in long-term cardiac allograft recipients. The results of the in vitro studies demonstrate that thoracic duct lymphocytes (TDL) of treated and allografted Lewis rats respond less in a mixed lymphocyte reaction to donor splenic lymphocytes (SpL) by 69%, 75%, and 73% (P less than 0.001) at 30, 50, and 100 days after transplantation, respectively, compared with controls, while the response to a third-party (W/F) SpL is unimpaired. In coculture experiments, the TDL from treated recipients specifically suppressed the response of unmodified Lewis TDL to ACI SpL by 59% and 40% (P less than 0.01) at 30 and 50 days after transplantation, respectively, while responses to W/F SpL were suppressed by only 3-6%. The sera obtained from ungrafted rats transfused with UV-DST suppressed the MLR between unmodified Lewis TDL and ACI SpL by 31% (P less than 0.05) while the sera from UV-DST and CsA-treated and allografted rats specifically suppressed the MLR by 75%, 80% (P less than 0.001) and 37% (P less than 0.01) at 10, 30, and 50 days after transplantation, respectively. In vivo adoptive transfer of 10(4) donor-type dendritic cells (DC) into recipients of beating cardiac allografts at 40 or 60 days after transplantation led to rapid and acute allograft rejection, while the adoptive transfer of 10(8) unseparated SpL obtained at 50 days after transplantation from treated Lewis recipients to syngeneic naive hosts led to a modest but significant prolongation of ACI test cardiac allografts. The transfer of serum from treated and allografted recipients at 10, 30, and 50 days after transplantation led to specific and significant prolongation of test grafts in syngeneic naive hosts. These findings suggest that the mechanisms underlying the in vivo immunologic unresponsiveness induced by pretreatment with UV-DST and peritransplant CsA include inactivation without elimination of class II-antigen presenting cells (APC), generation of specific serum suppressor factor(s) and/or antiidiotypic antibody, and induction of donor-specific suppressor cells.

Animals↗

Primary health care is not cheap: a case study from Guinea Bissau.

In 1977 the Ministry of Health in Guinea Bissau started two regional community health projects. In this article we describe the progress of the Tombali project. Three aspects are discussed: the "Learning Process Approach" used in the project; measurement of the effectiveness of the project and the problems of collecting and interpreting these data; and the ratio of investment to recurrent costs and the proportions borne by government and by villagers. Primary health care projects evolve slowly, and the importance of the willingness of project workers, donor agencies, and the national government to work without a blueprint plan is emphasized. We discuss ways of evaluating the success of primary health care schemes; the measurement of any change in health status is difficult and discounts other benefits that may result, such as encouraging community participation and involving villagers in government activities. Both government and villagers contribute significantly to the scheme, the government and donors bearing most of the investment costs, while most of the recurrent costs fall on the villagers. The data show that for neither government nor villagers is the scheme a cheap option to secure health care for rural populations. Finally, we discuss the lessons to be learned by national governments, donor agencies, and health workers from this attempt to implement a primary health care program.

Budgets↗

Interaction of duramycin with artificial and natural membranes.

Duramycin is a polypeptide antibiotic (molecular weight 2012) obtained from culture filtrates of Streptomyces cinnamomeus forma azacoluta. In this work, we show that low concentrations of duramycin induced aggregation of lipid vesicles containing unsaturated phosphatidylethanolamine and unsaturated monogalactosyl diglyceride, and of sarcoplasmic reticulum vesicles from rabbit skeletal muscle. Furthermore, duramycin inhibited the ATP-dependent Ca2+ uptake in sarcoplasmic reticulum vesicles without affecting the hydrolysis of ATP or the permeability of Ca2+. Also, duramycin only inhibited the bacteriorhodopsin proton pump reconstituted into phospholipid vesicles containing phosphatidylethanolamine. We have isolated a duramycin-resistant strain of Bacillus subtilis and have mapped the location of duramycin resistance. In this strain, the secretion of protons and influx of calcium were resistant to duramycin, and its lipid composition was profoundly different from that of the parent strain. No phosphatidylethanolamine was detected in the resistant strain. Our findings are consistent with the idea that duramycin recognizes a particular membrane conformation determined by the presence of phosphatidylethanolamine or monogalactosyl diglyceride.

Adenosine Triphosphate↗

Progressive hearing loss following Haemophilus influenzae meningitis.

Loss of hearing is a sequelae of meningitis. This hearing loss has been known to fluctuate for as long as one year following the acute infection. This paper presents a case of an 11-year documented downward fluctuating hearing loss following Haemophilus influenzae meningitis. The case indicates that patients should be followed audiologically for years following meningitis. A review of the literature of hearing loss in meningitis is presented with special emphasis on cases in which the hearing loss fluctuated. The cases in the literature were usually not followed for more than one year. In this case of acquired hearing loss secondary to Haemophilus influenzae meningitis, the patient's hearing fluctuated over 11 years, in a downward progression. It is not clear what type of mechanism is involved in the ongoing damage to the cochlea that could account for this gradual fluctuation. It is suggested that as the possibility of long-term fluctuation exists, patients with meningitis should be monitored audiologically for many years.

Auditory Threshold↗

[Computer-assisted teaching in pneumology. Application to the diagnosis of pulmonary opacities].

Computer assisted teaching in thoracic medicine (E.A.O.) is described for the recognition and diagnosis of pulmonary opacities. Two programmes were used, both designed specially for medical study:--the first programme was for the recognition of shapes for the beginner to read abnormal radiographs (chest opacities), and--a programme to teach the beginner the diagnosis and to formulate a diagnostic strategy (diagnosis of pulmonary opacities). Working areas consisting of an alpha-numeric keyboard with a display screen and a slide projector are at present installed in two CHU hospitals in Paris and are connected by a special telephone line to the central computer C1T12 (in the Faculty of Medicine). Four practicals, lasting about 6 hours and 22 simulated cases lasting 8 hours are provided each with illustrated commentaries for the different stages, covering the overall educational objectives of the medical practitioner. After two years of experimentation the method was given a good reception by the medical students. Full confirmation of the technique as well as an evaluation to compare the method to other forms of teaching are at present under study.

Computer-Assisted Instruction↗

[Use of the computer in teaching rheumatology. Trial application in the diagnosis of an adult polyarthritis].

The immense possibilities offered by the computer can be utilized in medical education, through a free dialogue between the student and the machine thanks to a terminal. A diagnostic simulation program has been carried out in diagnosing adult polyarthritis. This program neccesitates an analysis of diagnostic behavior and, on this basis, the preparing of a diagnostic tree or graph. The reasons leading to the plan adopted in constructing the graph, are discussed. Cases of increasing difficulty are proposed to the student, who must follow the course plan in order to arrive at a diagnosis. This teaching method, applied for thing pedagogical advantages both for the teacher and the student. The operating cost seems reasonable.

Adult↗

[Sclerosis of the intestinal lymphatic vessels].

Fibrosis of the intestinal lymphatic vessels, produced in one case by tuberculosis and, in the other, by appendicitis and peritonitis, caused blockage of the main lymphatic vessels causing, clinically, a protein-losing enteropathy similar to that noted in congenital lymphatic diseases of childhood. In the laboratory, there was noted a fall in serum protein, lipid and cholesterol. A fat absorption test was very abnormal showing a flat curve. During laparotomy, there was discovered on the small intestine, the same layout of lymph vessels, resembling a lace network, as that observed in congenital malformations. Intestinal lymphography showed considerable stasis of the opaque substance and absence of injection of the lymph vessels in the mesentery.

Chylous Ascites↗