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Biomedical subjects

M Busson

Publications and source records attributed to M Busson.

At least 19 recordsLinked to original sources

Mitochondrial DNA sequence variation in human leukemic cells.

The Long PCR followed by the RFLP technique has been used to search for abnormally structured mitochondrial DNA (mtDNA) and specific sequence differences implicated in the pathogenesis of acute lymphoblastic leukaemia (ALL). We have studied 54 specific sites whose combinations define groups of mtDNA types, in 30 leukemic patients of French Caucasian origin. Results were compared with those in 100 French healthy individuals. Nucleotide substitutions have been defined in 11 patients. This polymorphism is expressed by single base substitution at 6 sites which corresponds to 5 morphs, 2 of which were not found in the reference group. Combining the 11 observed morphs, we have identified 7 different mtDNA types, defined in 30 patients with ALL. Two of the morphs (MspI-2 and AvaII-3) and 3 of the types (17-2, 55-2, NewFr150) were not found in the group of healthy individuals. We have observed significant statistical changes in type 28-2 in ALL patients compared with the controls.

Adult

T-cell recognition of mycobacterial GroES peptides in Thai leprosy patients and contacts.

We report here the mapping of T-cell-stimulatory determinants of the GroES 10-kDa heat shock protein homologues from Mycobacterium leprae and Mycobacterium tuberculosis, which are known as major immunogens in mycobacterial infections. Peripheral blood mononuclear cells (PBMC) from treated tuberculoid leprosy or lepromatous leprosy patients and from healthy household or hospital staff contacts of the patients were cultured with 20 16-mer peptides covering the entire sequences of both M. leprae and M. tuberculosis GroES. The total number of recognized peptides was found to be the largest in family contacts, while responder frequencies to the individual tested peptides varied (5 to 80%) with specificity between the patient and contact groups. Proliferative responses to some peptides showed positive or negative associations of low statistical significance with DR and DQ alleles, though responses to most GroES peptides were genetically permissive. Notably, the sequence of the 25-40 peptide of M. leprae, but not that of M. tuberculosis, was more frequently stimulatory in tuberculoid leprosy patients than in either group of sensitized healthy contacts. This peptide bound to a number of HLA-DR molecules, of which HLA-DRB5*0101 had the strongest affinity. The epitope core binding to this allele was localized to the 29-to-37 sequence, and its key residue was localized to the M. leprae-specific glutamic acid at position 32. This epitope may be of interest for the development of a blood test- or skin test-based diagnostic reagent for tuberculoid leprosy, subject to further clinical evaluation in untreated patients.

Amino Acid Sequence

Maintenance cyclosporin monotherapy after renal transplantation--clinical predictors of long-term outcome.

BACKGROUND: There is considerable debate about whether maintenance cyclosporin (CsA) monotherapy is advisable or not in renal transplantation. METHODS: Between August 1984 and December 1989, 463 adult patients received a first cadaver graft. Initial immunosuppression was sequential: antilymphocyte or antithymocyte globulins (10-14 days), prednisone and azathioprine were combined and CsA was introduced (6-8 mg/kg/day) when the antilymphocyte or antithymocyte globulins were discontinued. When the graft function was stable and the peak of preformed lymphocytotoxic antibodies was < or = 25% and/or the number of rejection episodes was < or = 1, the steroid therapy was stopped within 1.5-3 months after transplantation, and azathioprine within 3-12 months. Patients with both anti HLA antibodies > 25% and more than one rejection episode were excluded. Cyclosporin doses were adapted for whole-blood trough levels between 100 and 200 ng/ml (monoclonal antibody radioimmunoassay or high-performance liquid chromatography). Cyclosporin monotherapy was attempted in 234 of the 463 patients. RESULTS: At the end of the investigation in January 1993 (follow-up time > 36 months, mean 60.5 +/- 4.5 months), 135 patients were receiving CsA without steroids or azathioprine. The 99 CsA monotherapy failures were due to rejection episodes in 48 cases, CsA A nephrotoxicity in 26 cases, and other causes in 25 cases, including five deaths and four with poor compliance. Renal function was stable in patients with successful CsA monotherapy: mean creatininaemia was 124 +/- 10 mumol/l at the time of CsA monotherapy inclusion and 129 +/- 10 mumol/l at the end of follow-up (mean time of CsA monotherapy 52 +/- 6 months). The parameters for predicting monotherapy success were age (43.2 versus 37.8. P = 0.0014), timing of trial inclusion > or = 6 months post-transplant (7.9 +/- 3 versus 5.3 +/- 3.1 months, P = 0.04), and excellent and stable renal function at the time of inclusion (124 +/- 10 versus 145 +/- 32 mumol/l, P < 0.001). CONCLUSIONS: Maintenance CsA monotherapy was effective in 58% of low-immunological-risk first-graft patients and probably did not jeopardize overall results of our first grafts: patient and graft survival were respectively 90 and 73% at 6 years. We propose this policy to avoid long-term complications of glucocorticoid and azathioprine in selected compliant recipients with low immunological risk, follow-up time post-transplantation > 6 months, and stable creatininaemia levels.

Adult

Is matching for sex and age beneficial to kidney graft survival? Société Française de Transplantation and Association France Transplant.

A total of 6889 cadaver kidney grafts carried out in the French transplant network from 1 January 1989 to 31 December 1992 were analyzed using single and multifactorial methods in order to evaluate the impact on graft survival of matching for sex and age between donors and recipients. The mean graft survival rate was 75% at 3 yr with donors between 10 and 50 yr of age compared to 65% for donors under 10 yr of age and 67% at 3 yr for donors over 50 yr of age (p < 0.000001). For child recipients there were no significant differences in graft survival whatever the difference in age with the donor (+/- 10 yr). For young adults (17-49 yr of age) the prognosis at 3 yr was the same (75%) whether the donor was in the same age category or older than the recipient. For older adults (> 50 yr of age) a poorer prognosis was obtained when the donor was 10 yr or more older than the recipient (61% at 1 yr, p = 10(-4)). The grafts performed with male donors had a better prognosis (76% at 3 yr) than those using female donors (71% at 3 yr, p < 0.0002). The poorest results were obtained with female donors when the recipient was male (70% at 3 yr). The results of the multivariate analysis of seven parameters involved in graft survival show that the main parameters significantly controlling graft survival are preimmunization before the graft (p = 10(-6)), HLA-DR incompatibility (p = 0.004), retransplantation (p = 0.008), donor sex (p = 0.003), and matching for age between donor and recipient (p = 0.1). These results suggest that age and sex should be considered as criteria in the choice of donors and recipients in organ allocation.

Adolescent

Diabetes mellitus after renal transplantation: characteristics, outcome, and risk factors.

The incidence and risk factors of posttransplant diabetes mellitus were evaluated in 1325 consecutive renal transplant recipients. Thirty-three (2.5%) patients developed diabetes mellitus requiring insulin therapy. Onset occurred a mean of 5.7 +/- 1.5 months following transplantation. The patients were compared with 33 paired-control kidney recipients. The patients were significantly older than the controls (46.8 +/- 1.9 vs. 40.6 +/- 2.1 years) (P<0.05), and chronic renal failure was more often related to interstitial nephritis (P<0.05). A family history of diabetes mellitus, the body mass index, ethnic origin, HLA phenotype, and the total doses of steroids and cyclosporine were similar in the two groups. The number of patients with at least one rejection episode was significantly higher among the diabetic patients (21 versus 9) but the number of episodes was similar. Diabetes occurred a mean of 1.1 +/- 0.3 months following rejection treatment. Intravenous pulsed prednisolone was always used for anti-rejection therapy. Insulin was withdrawn in 16 cases after a mean of 4 +/- 1 months, independently of steroid dosage reductions. Actuarial patient and graft survival rates were not significantly different, although 6-year outcome tended to be better in the controls (86% versus 93% for patient survival and 67% versus 93% for graft survival). This study suggests that pulsed steroid therapy might be the critical factor in the onset of posttransplant diabetes and that the risk is increased in older patients with chronic interstitial nephrititis.

Adult

Analysis of cadaver donor criteria on the kidney transplant survival rate in 5,129 transplantations.

PURPOSE: To clarify the role of donor criteria we retrospectively analyzed a series of 5,129 cadaver kidney grafts harvested from January 1, 1989 to December 31, 1991. MATERIALS AND METHODS: Graft survival was calculated and analyzed using a multifactorial approach. RESULTS: Better graft survival was obtained with donors between 6 and 50 years old (80% versus 64% at 3 years), grafts performed from male donors (74% versus 69% at 3 years), donor deaths caused by cranial injury as opposed to cerebral hemorrhage (74% versus 70% at 3 years) and negative cytomegalovirus antibodies (75% versus 71% at 3 years). CONCLUSIONS: These factors may be used for kidney allocation.

Adolescent

[Epidemiology and results of organ grafts].

Using the complete, multicentric Registry of organ transplantation in France, from 1970 to 1992, including 26,485 transplantations (kidney, heart, heart-lungs, lungs, liver), we studied four statistical parametres: 1. movement on the waiting list; 2. mean waiting time; 3. actuarial survival of the graft for the kidney, heart and liver; 4. number of recipients surviving with a functioning graft as of 31 December 1992. Patients awaiting a kidney transplant comprise a group that differs epidemiologically from the others on the basis of the length of the waiting list, entering and existing flux, and for the mortality rate of patients waiting for a graft. Similarly, the actuarial survival profile is different for the first year in kidney transplant recipients compared to the others.

France

Absence of association between HLA antigens and chronicity of viral hepatitis in haemodialyzed patients.

The role of HLA antigens in the chronicity of viral hepatitis is still being debated. We analyzed the relation between HLA status and viral hepatitis in 558 consecutive haemodialyzed patients who underwent kidney transplantation. HLA A, B, DR status, ABO-Rh blood group, duration of haemodialysis, and number of blood units transfused during the dialysis period were known for all patients. Serological status for hepatitis B virus and hepatitis C virus and results of liver biopsies were available in 495, 300 and 316 patients, respectively. After correction for the number of tests performed, frequencies of HLA antigens did not differ significantly for: 1. hepatitis B virus infection (compared to HBsAg-positive and anti-HBc and/or anti-HBs-positive nonvaccinated patients); 2. hepatitis C virus infection (compared to anti-HCV-negative and -positive patients); 3. histopathological status (compared to patients who had chronic viral hepatitis and those who did not). These results suggest that there is no evidence for a significant role of a particular HLA antigen in the development of chronic viral hepatitis in haemodialysis patients with similar underlying immunosuppression and exposure to infection by hepatotropic viruses.

Adult