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J Laporte

Publications and source records attributed to J Laporte.

At least 55 records · Page 3Linked to original sources
PubMed1996

Interstitial pneumonitis following autologous bone-marrow transplantation conditioned with cyclophosphamide and total-body irradiation.

PURPOSE: To assess the influence of different total-body irradiation (TBI) regimens on interstitial pneumonitis (IP), we retrospectively analyzed our clinical data concerning an homogeneous group of patients conditioned with cyclophosphamide (CY) alone and single-dose or fractionated TBI before autologous bone-marrow transplantation (ABMT). METHODS AND MATERIALS: One hundred eighty-six patients with acute nonlymphoblastic leukemia (n = 101), acute lymphoblastic leukemia (n = 62), chronic myeloid leukemia (n = 11), non-Hodgkin's lymphoma (n = 10), and multiple myeloma (n = 2) referred to our department between May 13, 1981 and September 16, 1992, underwent TBI before ABMT. The male-to-female ratio was 123:63 (1.95), and mean and median age was 33 +/- 12 (6-63 years) and 35 years, respectively. Cyclophosphamide alone (60 mg/kg/day on each of 2 successive days) was used as conditioning chemotherapy in all patients. Patients were irradiated according to two techniques: either with single-dose (STBI) (n = 124; 10 Gy administered to the midplane at the level of L4, and 8 Gy to the lungs) or with fractionated (FTBI) (n = 62; 12 Gy in 6 fractions over 3 consecutive days to the midplane at the level of L4, and 9 Gy to the lungs) TBI. The mean instantaneous dose rate was 0.057 +/- 0.0246 Gy/min (0.0264-0.1692 Gy/min). It was < or = 0.048 Gy/min in 48 patients (LOW group), > 0.048 and < or = 0.09 Gy/min in 129 patients (MEDIUM group), and > 0.09 Gy/min in 9 patients (HIGH group). The median follow-up period was 5 years (24-120 months). RESULTS: In January 1994, the 5-year overall (including all causes of death) and disease-free survival (DFS) rates were 50 and 48%, respectively. The 5-year DFS was 47.9% in the STBI group, and 47.8% in the FTBI group (p = 0.77). It was 44% in the HIGH group, 53% in the MEDIUM group, and 34% in the LOW group (LOW vs. MEDIUM, p = 0.009). The 5-year IP incidence was 17% in all patients, 16% in the STBI group and 18% in the FTBI group (p = 0.37), but it was significantly higher in patients receiving high instantaneous dose rate TBI (56% in the HIGH, 13% in the MEDIUM, 20% in the LOW groups; HIGH vs. MEDIUM, p = 0.002). However, sex (p = 0.37), age (18% for > 20 vs. 10% for < or = 20 years, p = 0.37), and body weight (> 60 kg vs. < or = 60 kg, p = 0.09) did not influence the IP incidence in univariate analyses. Multivariate analysis (Cox model) revealed that the instantaneous dose rate (p = 0.05), and the age (p = 0.04) were the two independent factors influencing the incidence of IP. CONCLUSION: This retrospective study including only the patients transplanted with ABMT conditioned with CY alone and STBI or FTBI concluded that instantaneous dose rate and age significantly influenced the incidence of IP, whereas sex, body weight, and fractionation did not.

Adolescent↗
PubMed1996

Prenatal diagnosis of X-linked myotubular myopathy: strategies using new and tightly linked DNA markers.

X-linked myotubular myopathy (MTM1) is a severe congenital myopathy characterized by hypotonia, muscle weakness, and associated respiratory insufficiency. Perinatal death is common. The disease locus was shown to be linked to polymorphic markers in Xq28 and we have recently refined the MTM1 locus to a physical region of less than one megabase (Mb) at proximal Xq28. Two new microsatellite markers were developed and assigned in the MTM1 candidate region. We applied them and other DNA markers for prenatal diagnosis in two families. In one case, an affected fetus was predicted and a recombination event was observed with two more distal markers in the region. The second fetus was born unaffected as predicted. The new DNA markers and the precise location of the MTM1 gene provide an improvement for early prenatal diagnosis of the disease. We present suggestions for different combinations of linked and flanking DNA markers for maximal informativeness and accuracy.

Base Sequence↗
PubMed1996

X-linked myotubular myopathy: refinement of the gene to a 280-kb region with new and highly informative microsatellite markers.

We have recently refined the localization of the myotubular myopathy (MTM1) gene to a 430-kb region between DXS304 and DXS1345 in proximal Xq28. We report two new polymorphic microsatellite markers, DXS8377 and DXS7423, that were physically mapped within the critical interval. A recombination event in a family segregating for MTM1 placed the disease gene telomeric to the trinucleotide polymorphism DXS8377. Together with the recent mapping of two microdeletions associated with MTM1, the recombination refines the critical region to 280 kb. A second recombination event was observed distal to the tetranucleotide repeat DXS7423. This recombination has occurred in the off-spring of a female with a more than 67% probability of being a carrier and very likely restricts the MTM1 gene to a 130-kb region. This physical refinement is significant for positional cloning of the disease gene. The highly polymorphic markers and the precise localization of the MTM1 gene will facilitate genetic diagnosis of the disorder.

Alleles↗
PubMed1996

X-linked myotubular myopathy: refinement of the critical gene region.

X-linked recessive myotubular myopathy (XLMTM) is a severe neonatal neuro-muscular disease characterized by muscle weakness, hypotonia, and respiratory problems. The locus for the XLMTM gene (MTM1) has previously been mapped to Xq28 between the markers DXS304 and DXS497 by linkage analyses and by determining the breakpoints of deletion patients. We report linkage analysis data or 20 XLMTM families who were tested using the DNA markers DXS1113, DXS304, DXS455, DXS1684, DXS305 and DXS52 and present two families showing recombination between MTM1 and either DXS304, DXS334 or DXS305. We found each of the families to be informative for at least three markers. Based on these findings we excluded 30 women from being carriers, the carrier status of 17 obligate carrier mothers could be confirmed and eight mothers and sisters were identified as to be at high risk of carrying a MTM1 mutation. By combining recently published data with the results of our recombinant families, we suggest that the MTM1 locus maps between DXS334 and DXS497 narrowing the region of interest from 600 kb to an estimated < 500 kb interval. This additional refinement in the localization of MTM1 means a further step towards the isolation of the gene in the near future, and allows more reliable and efficient carrier detection and prenatal diagnosis.

Chromosome Mapping↗
PubMed1996

Leukotriene receptors in HL-60 cells differentiated into eosinophils, monocytes and neutrophils.

The expression of leukotriene B4 (LTB4) and leukotriene D4 (LTD4) receptors was determined, by binding assay, in HL-60 cells differentiated into the monocyte/macrophage, neutrophil, and eosinophil lineages. Monocyte/ macrophage- and neutrophil-differentiated cells developed specific LTB4 receptors with high affinities (Kd = 1.27 nM and 2.65 nM, respectively) and low affinities (Kd = 26.41 nM and 55.63 nM, respectively). These receptors were functional and specific as indicated by the ability of LTB4 to elicit an increase in intracellular calcium concentration antagonised by specific antagonists. Eosinophil-differentiated cells developed mainly LTD4 receptors (Kd = 41.91 nM), and stimulation with LTD4 induced an increase in intracellular calcium that was antagonised by a specific LTD4 antagonist. These results show, for the first time, that eosinophil-differentiated HL-60 cells express specific functional LTD4 receptors. These cells could be used for the study of the actions of peptidoleukotrienes on eosinophils, and for studies on the molecular mechanisms regulating LTD4 receptor expression.

Binding Sites↗
PubMed1996

A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.

X-linked recessive myotubular myopathy (MTM1) is characterized by severe hypotonia and generalized muscle weakness, with impaired maturation of muscle fibres. We have restricted the candidate region to 280 kb and characterized two candidate genes using positional cloning strategies. The presence of frameshift or missense mutations (of which two are new mutations) in seven patients proved that one of these genes is indeed implicated in MTM1. The protein encoded by the MTM1 gene is highly conserved in yeast, which is surprising for a muscle specific disease. The protein contains the consensus sequence for the active site of tyrosine phosphatases, a wide class of proteins involved in signal transduction. At least three other genes, one located within 100 kb distal from the MTM1 gene, encode proteins with very high sequence similarities and define, together with the MTM1 gene, a new family of putative tyrosine phosphatases in man.

Amino Acid Sequence↗
PubMed1996

Deletions in Xq28 in two boys with myotubular myopathy and abnormal genital development define a new contiguous gene syndrome in a 430 kb region.

We have recently described a female patient with myotubular myopathy (MTM1) and an interstitial deletion at Xq28. Characterisation of the deletion allowed us to position the MTM1 gene to a 600 kb region between DXS304 and DXS497. In order to further restrict the region we screened for deletions in a set of 38 patients. We found two overlapping deletions in boys that in addition to MTM1 showed an unexpected abnormal genital development. As the latter phenotype is not found in the other non-deleted MTM1 patients, our observations are best explained by a contiguous gene syndrome. The deletions define a 430 kb region that contains the MTM1 gene and most likely a gene implicated in male sexual development. A high resolution physical map of this region is presented.

Base Sequence↗
PubMed1996

Identification of a hot spot for microdeletions in patients with X-linked deafness type 3 (DFN3) 900 kb proximal to the DFN3 gene POU3F4.

Small mutations in the POU domain gene POU3F4 were recently shown to cause X-linked deafness type 3 (DFN3) in nine unrelated males. The POU3F4 gene was found to be located outside four of five deletions associated with DFN3. Two of these deletions were situated more than 400 kb proximal to POU3F4. Employing PCR analysis of sequence tagged sites from this region we initially identified novel deletions in two DFN3 patients. To investigate this chromosomal segment in more detail, we extended a previously established 850 kb cosmid contig in the centromeric direction to a total size of 1500 kb. Cosmids from this contig were hybridized to DNA of 11 unrelated males with DFN3. In two patients, we identified deletions encompassing the POU3F4 gene and variably sized segments of Xq21.1. In six of the nine remaining patients which lacked mutations in the POU3F4 gene, smaller deletions were identified which, with one exception, overlap in a 8 kb segment 900 kb proximal to the POU3F4 gene. In one patient, we identified several small deletions in the vicinity of the 8 kb DNA segment. Together, deletions account for 56% (13/23) of all known DFN3 mutations, most (10/13) of which do not encompass the POU3F4 gene. The combined molecular data suggest that the deletion hot spot region in Xq21.1 contains another DFN3 gene or, alternatively, a sequence element involved in transcriptional regulation of POU3F4.

Base Sequence↗
PubMed1996

Guinea pig Clara cells secrete endothelin 1 through a phosphoramidon-sensitive pathway.

We have developed a method to harvest and culture Clara cells isolated from guinea pig lungs. Their identity was confirmed by the presence of CC16kD protein specific for these cells; we studied their capacity to generate endothelin 1 (ET-1). Using monoclonal antibody and immunofluorescence techniques, ET-1 was localized in these cultured Clara cells. The basal release of immunoreactive endothelin (ir-ET), measured by radioimmunoassay, from cultured Clara cells incubated for 2, 6, and 10 h was 74.8 +/- 11.1, 230.0 +/- 32.0 and 331.0 +/- 22.9 pg/ml, respectively. Treatment of Clara cells with phosphoramidon (100 microM), an inhibitor of the endothelin-converting enzyme, caused a significant reduction of the ir-ET release by 40% after a 6-h incubation period (P<0.01). Following treatment with 1 mM phosphoramidon, ir-ET was decreased by 73% and 76% after 6- and 10-h incubation periods, respectively (P<0.01). In contrast, treatment with thiorphan (1 mM), an inhibitor of neutral endopeptidase, increased the levels of ir-ET in the cell supernatant. High-performance liquid chromatography of supernatants from cultured Clara cells revealed one peak corresponding to the retention time of synthetic ET-1. This peak was greatly reduced following treatment of the cells with phosphoramidon (1 mM) but not with thiorphan (1 mM). Our results suggest that Clara cells release ET-1, a potent bronchoconstrictive agent. Furthermore, the synthesis of ET-1 is dependent on a phosphoramidon-sensitive endothelin-converting enzyme. Secretion of this peptide by Clara cells may play a role, directly or indirectly, in lung pathophysiology.

Animals↗
PubMed1996

Bacterial endocarditis revealed by infectious discitis.

A study of 30 patients admitted for infectious discitis identified four cases with concomitant bacterial endocarditis. All four patients were male and had concomitant streptococcal septicemia. Two patients had known aortic valve disease. The vertebral infection was located to the thoracic or lumbar spine. Ultrasonography disclosed aortic lesions in all four patients and mitral lesions in two. Management consisted of intravenous antimicrobial therapy for four weeks followed by a three-month course of oral antimicrobial therapy. The outcome of the discitis was favorable within the usual period of time. However, the endocardial lesions continued to progress, and three patients rapidly required valve replacement. Analysis of available data in the 30 patients with discitis showed that half the patients with streptococcal discitis also had bacterial endocarditis and that the latter condition developed in all the patients with streptococcal discitis and a history of valve disease. A number of risk factors were identified. An echocardiogram should be done routinely in patients with infectious discitis and risk factors for bacterial endocarditis.

Adult↗
PubMed1996

Doppler-echocardiographic assessment of the carbomedics supra-annular 'Top-Hat' prosthetic heart valve in the aortic position.

Twenty-one CarboMedics 'Top-Hat' bileaflet prostheses were implanted in the aortic position between May 1993 and May 1994 at our institution. Valve performance was assessed by repeat echocardiography. We found it very easy to implant this prosthesis even in the small aortic annulus and it allowed us to implant a valve that is at least one size larger than implantation in the intra-annular position allows. The only contraindication to the implantation of this prosthesis is when the coronary ostia are displaced downwards, which would apply to any supra-annular prosthesis. The Doppler echocardiographic assessment showed acceptable transvalvular gradients and velocity indexes. The Top-Hat prosthesis is now our valve of choice in the small aortic annulus.

Adult↗
PubMed1995

Increased permeability of bovine aortic endothelial cell monolayers in response to a thromboxane A2-mimetic.

The present study was designed to investigate the ability of thromboxane to modulate the clearance rate of 125I-albumin through bovine aortic endothelial cell (BAEC) monolayer grown on polycarbonate micropore membrane. Stimulation of BAEC with the TXA2 mimetic U44069 (10(-8), 10(-7) and 10(-6) M) elicited a dose-dependent increase of labeled albumin passage across BAEC monolayers. This effect was markedly reduced by the TXA2 antagonist L655240 (10(-7) and 10(-6) M). Our results suggest that TXA2 may modulate the permeability of endothelial cells directly through activation of specific receptors.

Animals↗
PubMed1995

Dexamethasone and phosphoramidon inhibit endothelin release by cultured nonciliated bronchiolar epithelial (Clara) cells.

The release of immunoreactive endothelin (ir-ET) by cultured Clara cells isolated from guinea pig lung was investigated. Clara cells were cultured in DMEM-F12 with 10% fetal bovine serum for 4-5 days. The basal release of ir-ET, measured by radioimmunoassay, from cultured guinea pig Clara cells incubated for 2, 6, and 10 h was 59.6 +/- 8.6, 206.0 +/- 25.0, and 291.0 +/- 16.5 pg/ml, respectively. Treatment with phosphoramidon (1 mM) for 45 min decreased the release of ir-ET by 73% and 76% in 6- and 10-h incubation periods, respectively. In addition, treatment with dexamethasone (1 microM) for 24 h significantly attenuated the release of ir-ET by 62% and 71% during 6- and 10-h incubation periods, respectively. Our results show that Clara cells isolated from guinea pig can synthesize significant amounts of ir-ET and that a phosphoramidon-sensitive metalloprotease appears to be responsible for the generation of endothelin. This basal release of ir-ET was significantly attenuated by dexamethasone.

Animals↗
PubMed1995

[Infections on permanent endocavitary pacemaker leads: value of transesophageal echocardiography].

The prevalence of infection of permanent pacing material ranges from 0.13 to 19.9% of patients according to published series. The seriousness of this condition requires early diagnosis and treatment. Transesophageal echocardiography visualised vegetations on the intracardiac pacing lead in all of 11 patients studied, whereas transthoracic echocardiography and polynuclear leucocyte scintigraphy only provided positive diagnoses in 4 cases for each investigation. Three types of vegetation were visualised; no cases of tricuspid valve endocarditis were observed. Treatment was based on explantation of all implanted material by endovascular traction in 7 cases and by surgery in the other 4 cases according to the results of transesophageal echocardiography. There were no deaths or recurrence of infection. Transesophageal echocardiography is the investigation of choice for imaging a vegetation on an endocavitary pacing lead. Complete explanation is essential for a complete recovery of this infection.

Adult↗
PubMed1994

The vacuolar compartment is required for sulfur amino acid homeostasis in Saccharomyces cerevisiae.

In order to isolate new mutations impairing transcriptional regulation of sulfur metabolism in Saccharomyces cerevisiae, we used a potent genetic screen based on a gene fusion expressing XylE (from Pseudomonas putida) under the control of the promoter region of MET25. This selection yielded strains mutated in various different genes. We describe in this paper the properties of one of them, MET27. Mutation or disruption of MET27 leads to a methionine requirement and affects S-adenosylmethionine (AdoMet)-mediated transcriptional control of genes involved in sulfur metabolism. The cloning and sequencing of MET27 showed that it is identical to VPS33. Disruptions or mutations of gene VPS33 are well known to impair the biogenesis and inheritance of the vacuolar compartment. However, the methionine requirement of vps33 mutants has not been reported previously. We show here, moreover, that other vps mutants of class C (no apparent vacuoles) also require methionine for growth. Northern blotting experiments revealed that the met27-1 mutation delayed derepression of the transcription of genes involved in sulfur metabolism. By contrast, this delay was not observed in a met27 disrupted strain. Physiological and morphological analyses of met27-1 and met27 disrupted strains showed that these results could be explained by alterations in the ability of the vacuole to transport or store AdoMet, the physiological effector of the transcriptional regulation of sulfur metabolism.

Amino Acids, Sulfur↗
PubMed1994

Highly purified guinea pig type II pneumocytes have the leukotriene A4 hydrolase but do not express 5-lipoxygenase activity.

Guinea pig lung cells have been obtained by enzymatic digestion of lung tissue and type II pneumocytes have been purified by centrifugal elutriation and adherence on Petri dishes coated with guinea pig IgG. The cells have been characterized by histochemical staining of alkaline phosphatase and by electron microscopy. Arachidonic acid metabolism was studied by incubating purified type II pneumocytes with exogenous arachidonic acid in the presence or absence of calcium ionophore A23187 or with leukotriene A4. The reverse phase high performance liquid chromatography profiles of cells stimulated with calcium ionophore and/or arachidonic acid did not show peaks co-eluting with authentic leukotrienes, which suggested that these cells do not express 5-lipoxygenase activity. On the other hand, type II pneumocytes converted exogenous leukotriene A4 into leukotriene B4; a small amount of peptido-leukotrienes, accounting for less than 5% of total leukotrienes produced, was also detected. It is suggested that transcellular metabolism of leukotriene A4 between type II pneumocytes and other lung cells containing the 5-lipoxygenase may contribute to the previously reported LTB4 production by guinea pig lungs. The type II pneumocyte purification technique described represents a useful alternative to cell culture for studying arachidonic acid metabolism and other cell functions.

Animals↗