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Biomedical subjects

C Dufour

Publications and source records attributed to C Dufour.

At least 37 records · Page 2Linked to original sources
PubMed1999

Late graft failure 8 years after first bone marrow transplantation for severe acquired aplastic anemia.

A 14-year-old patient with acquired very severe aplastic anemia (VSAA) underwent bone marrow transplantation (BMT) from his HLA-identical brother. Preparative therapy was cyclophosphamide (CY) 200 mg/kg over 4 days. GVHD prophylaxis was with cyclosporin A (CsA) for a year. After an 8 year follow-up during which the patient was well with normal blood counts, graft failure occurred. At this time marrow chimerism studies demonstrated that 85% of hemopoiesis was of recipient origin. The patient was re-engrafted from the same donor after conditioning with CY 200 mg/kg over 4 days plus rabbit antithymocyte globulin (ATG) 3.5 mg/kg/day for 3 days. After 140 days follow-up he has a normal blood count. The possible causes of the graft failure are discussed. This case demonstrates that, although rarely, very late graft failure may occur after BMT for AA and highlights the need for long-term monitoring even in apparently successfully transplanted patients.

Adolescent↗
PubMed1999

Rabbit antithymocyte globulin (r-ATG) plus cyclosporine and granulocyte colony stimulating factor is an effective treatment for aplastic anaemia patients unresponsive to a first course of intensive immunosuppressive therapy. Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

About 30% of patients with severe aplastic anaemia (SAA) unresponsive to one course of immunosuppressive (IS) therapy with antithymocyte or antilymphocyte globulin can achieve complete or partial remission after a second IS treatment. Among various second-line treatments, rabbit ATG (r-ATG) could represent a safe and effective alternative to horse ALG (h-ALG). In a multicentre study, 30 patients with SAA (17 males and 13 females, median age 21 years, range 2-67) not responding to a first course with h-ALG plus cyclosporin (CyA) and granulocyte colony stimulating factor (G-CSF), were given a second course using r-ATG (3.5 mg/kg/d for 5 d), CyA (5 mg/kg orally from day 1 to 180) and G-CSF (5 microg/kg subcutaneously from day 1 to 90). The median interval between first and second treatment was 151 d (range 58-361 d). No relevant side-effects were observed, but one patient died early during treatment because of sepsis. Overall response, defined as transfusion independence, was achieved in 23/30 (77%) patients after a median time of 95 d (range 14-377). Nine patients (30%) achieved complete remission (neutrophils >/=2.0 x 109/l, haemoglobin >/=11 g/dl and platelets >/=100 x 109/l). The overall survival rate was 93% with a median follow-up of 914 d (range 121-2278). So far, no patient has relapsed. Female gender was significantly associated with a poorer likelihood to respond (P = 0.0006). These data suggest that r-ATG is a safe and effective alternative to h-ALG for SAA patients unresponsive to first-line IS treatment.

Adolescent↗
PubMed1998

Splicing of two internal and four carboxyl-terminal alternative exons in nonmuscle tropomyosin 5 pre-mRNA is independently regulated during development.

Four nonmuscle tropomyosin isoforms have been reported to be produced from the rat Tm5 gene by alternative splicing (Beisel, K. W., and Kennedy, J. E. (1994) Gene (Amst.) 145, 251-256). In order to detect additional isoforms that might be expressed from that gene, we used reverse transcriptase-polymerase chain reaction assays and evaluated the presence of all product combinations of two alternative internal exons (6a and 6b) and four carboxyl-terminal exons (9a, 9b, 9c, and 9d) in developing and adult rat brain. We identified five different combinations for exon 9 (9a + 9b, 9a + 9c, 9a + 9d, 9c, and 9d), and the exon combinations 9a + 9c and 9a + 9d were previously unreported. Each of these combinations existed with both exon 6a and exon 6b. Thus, the rat brain generates at least 10 different isoforms from the Tm5 gene. Northern blot hybridization with alternative exon-specific probes revealed that these isoforms were also expressed in a number of different adult rat tissues, although some exons are preferentially expressed in particular tissues. Studies of regulation of the 10 different Tm5 isoform mRNAs during rat brain development indicated that no two isoforms are coordinately accumulated. Furthermore, there is a developmental switch in the use of exon 6a to exon 6b from embryonic to adult isoforms. TM5 protein isoforms show a differential localization in the adult cerebellum.

Alternative Splicing↗
PubMed1998

Tropomyosin isoform diversity and neuronal morphogenesis.

Tropomyosins (Tm) are a large family of isoforms obtained from multiple genes and by extensive alternative splicing. They bind in the alpha-helical groove of the actin filament and are therefore core components of this extensive cytoskeletal system. In non-muscle cells the Tm isoforms have been implicated in a diversity of processes including cytokinesis, vesicle transport, motility, morphogenesis and cell transformation. Using immunohistochemical localization in cultured primary cortical neurons with an antibody that potentially identifies all non-muscle TM5 gene isoforms compared with one that specifically identifies a subset of isoforms, the possibility was raised that there were considerably more isoforms derived from this gene than the four previously described. Using polymerase chain reaction (PCR) analysis we have now shown that the rat brain generates at least 10 mRNA isoforms using multiple combinations of terminal exons and two internal exons. There is extensive developmental regulation of these isoforms in the brain and there appears to be a switch in the preferential use of the two internal exons 6a to 6b from the embryonic to the adult isoforms. Specific isoforms using alternate carboxyl-terminal exons are differentially localized within the adult rat cerebellum. It is suggested that the tightly regulated spatial and temporal expression of Tm isoforms plays an important role in the development and maintenance of specific neuronal compartments. This may be achieved by isoforms providing unique structural properties to actin-based filaments within functionally distinct neuronal domains.

Animals↗
PubMed1997

The influence of the angiotensin I converting enzyme genotype in familial hypertrophic cardiomyopathy varies with the disease gene mutation.

Familial hypertrophic cardiomyopathy is an autosomal dominant genetically heterogeneous disease characterized by a partial penetrance and variable expressivity. Previous studies showed that the extent of hypertrophy is influenced by the angiotensin I converting enzyme insertion/deletion (I/D) polymorphism. Recently, molecular genetic analysis revealed the existence of healthy carriers and that as many as a quarter of genetically affected individuals do not express the disease. This data prompted us to re-investigate the role of the angiotensin I converting enzyme polymorphism on hypertrophy by assessing both clinically affected individuals and healthy carriers. For this, several families with mutations in the cardiac myosin binding protein C or the beta-myosin heavy chain genes were analysed. The mean maximal intraventricular septum thickness was compared as a function of angiotensin I converting enzyme genotypes in all genetically affected individuals (n = 114), and in subsets of subjects carrying either a splice acceptor site mutation in the cardiac myosin binding protein C gene (n = 33), or various missense mutations in the cardiac beta-myosin heavy chain gene (n = 81) or finally, mutation in the Arg403 codon of the beta-myosin heavy chain gene (n = 54). Significant association between the D allele and hypertrophy was observed only in the case of Arg403 codon mutations (mean septum thickness for subjects with the DD genotype: 19.3 +/- 2.7 mm: with the ID genotype: 13.4 +/- 1.3 mm and with the II genotype: 11.0 +/- 0.9 mm; P < 0.02). These results were confirmed by the chi 2 test showing an over-representation of DD genotype in patients carrying an Arg403 codon mutation associated with septal hypertrophy (P < 0.05). Our data confirms that the angiotensin I converting enzyme genotypes can influence the phenotypic expression of hypertrophy and shows that this influence depends on the mutation, raising the concept of multiple genetic modifiers in familial hypertrophic cardiomyopathy.

Adult↗
PubMed1997

Retinol (vitamin A) and retinal-binding protein serum levels in children with cancer at onset.

The aim of the study was to evaluate vitamin A (Vit A) plasma levels in children with newly diagnosed neoplasia (NDN) admitted to the Department of Hematology-Oncology of G. Gaslini Institute. Vit A levels, retinol-binding protein (RBP), and nutritional status were evaluated in 54 children with NDN (22 solid tumors other than neuroblastoma, 16 neuroblastomas, 9 lymphomas, 7 acute lymphoblastic leukemia). Biochemical test results were also compared with those of 47 healthy controls (HC) comparable for sex and age. In children with NDN, mean Vit A plasma level results were 350 micrograms/L (95% CI 288-412); in HC they were 517 micrograms/L (95% CI 471-563), P < 0.001. Mean RBP value results were 3.2 mg/dL (95% CI 2.6-3.9) in NDN and 4.9 mg/dL in HC (95% CI 4.5-5.3), P < 0.001. Fifteen (28%) out of 54 children with NDN were classified as well-nourished, 27/54 (50%) were considered at risk of malnutrition, and 12 (22%) were malnourished. Children with NDN presented reduced Vit A and RBP mean values compared with those of HC. Further studies are needed to better evaluate Vit A metabolism in children with cancer at onset.

Adolescent↗
PubMed1995

[Adult HTLV-I positive leukemia-lymphoma in Argentina].

Human T-cell lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukaemia/lymphoma (ATLL) and tropical spastic paraparesis (TSP/HAM) in endemic and non-endemic areas. Serological studies have shown that HTLV-I is prevalent in some Latin American countries such as Brasil, Chile, Colombia, Perú and Uruguay. We describe here the clinical and laboratory features of five cases of ATLL diagnosed in Argentina. All patients (4 males, 1 female; median age 48.2 years) were of caucasian origin; 4 born in Argentina and 1 in Chile. High risk factors for HTLV-I infection were not apparent in Argentina patients, whereas the Chilean resident, who was a promiscuous heterosexual, travelled through Chile frequently. Positive results for antibodies to HTLV-I were detected in all five cases and in some of their relatives. This report suggests that HTLV-I infection may be endemic in, Argentina where TSP has also been described.

Adult↗