Performance of Laser Megajoule's x-ray streak camera.

A prototype of a picosecond x-ray streak camera has been developed and tested by Commissariat à l'Énergie Atomique et aux Énergies Alternatives to provide plasma-diagnostic support for the Laser Megajoule. We report on the measured performance of this streak camera, which almost fulfills the requirements: 50-µm spatial resolution over a 15-mm field in the photocathode plane, 17-ps temporal resolution in a 2-ns timebase, a detection threshold lower than 625 nJ/cm2 in the 0.05-15 keV spectral range, and a dynamic range greater than 100.

Overview of the ARGOS X-ray framing camera for Laser MegaJoule.

Commissariat à l'Énergie Atomique et aux Énergies Alternatives has developed the ARGOS X-ray framing camera to perform two-dimensional, high-timing resolution imaging of an imploding target on the French high-power laser facility Laser MegaJoule. The main features of this camera are: a microchannel plate gated X-ray detector, a spring-loaded CCD camera that maintains proximity focus in any orientation, and electronics packages that provide remotely-selectable high-voltages to modify the exposure-time of the camera. These components are integrated into an "air-box" that protects them from the harsh environmental conditions. A miniaturized X-ray generator is also part of the device for in situ self-testing purposes.

In vitro replication models for the hepatitis C virus.

Soon after the discovery of the hepatitis C virus (HCV), attention turned to the development of models whereby replication of the virus could be investigated. Among the HCV replication models developed, the HCV RNA replicon model and the newly discovered infectious cell culture systems have had an immediate impact on the study of HCV replication, and will continue to lead to important advances in our understanding of HCV replication. The aim of this study is to deal with developments in HCV replication models in a chronological order from the early 1990s to the recent infectious HCV cell culture systems.

Standardization of tritiated water by two improved methods.

Tritiated water has been standardized in the framework of a French-Romanian cooperation by two improved methods: liquid scintillation counting based on the triple to double coincidence ratio method and the internal gas proportional counting used in conjunction with a tritium generator for chemical reduction of water. The uncertainties of measurement for both methods were smaller than 0.6% and the two results were consistent within these uncertainties, indicating that either method is equally suited for standardizing tritiated water.

Analytical calculations of counting losses in internal gas proportional counting.

In internal gas proportional counting, the evaluation of counting losses is important in order to obtain high accuracy measurement results. In this paper, counting losses due to the wall effect and not counted beta particles with very low energy are evaluated by analytical calculations. The calculated and experimental results are compared and a very good agreement is found.

Comprehensive analysis of a large genomic sequence at the putative B-cell chronic lymphocytic leukaemia (B-CLL) tumour suppresser gene locus.

In many haematological diseases, and more particularly in B-cell chronic lymphocytic leukaemia (B-CLL), the existence of a tumour suppressor gene located within the frequently deleted region 13q14.3, has been put forward. A wide candidate region spanning from marker D13S273 to D13S25 has been proposed and an extensive physical map has been constructed by several teams. In this study, we sequenced a minimal core deleted region that we have previously defined and annotated it with flanking available public sequences. Our analysis shows that this region is gene-poor. Furthermore, our work allowed us to identify new alternative transcripts, spanning core regions, of the previously defined candidate genes DLEU1 and DLEU2. Since their putative involvement in B-CLL was controversial, our present study provide support for reconsidering the DLEU1 and DLEU2 genes as B-CLL candidate genes, with a new definition of their organisation and context.

Exclusion of Leu1 and Leu2 genes as tumor suppressor genes in 13q14.3-deleted B-CLL.

The chromosomal region 13q14.3 is frequently deleted in B cell chronic lymphocytic leukemia (B-CLL) and it is supposed that a tumor suppressor gene, involved in this leukemogenesis, is located in this area. The first exons of two genes, Leu1 and Leu2, mapped in a minimally deleted 13q14.3 region, are systematically lost in B-CLL sharing a 13q14.3 deletion. These two genes have been proposed as strong tumor suppressor gene candidates. However, in a study on 15 13q14.3 deleted B-CLL, we found three patients in which this critical region was not involved. Because of these results and that no mutations were detected on the two genes in a previous study, we think that Leu1 and Leu2 can be excluded as tumor suppressor genes.

[Fibromuscular dysplasia of the renal arteries]. / La dysplasie fibromusculaire des artères rénales.

Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory vascular disease that primary involves medium-sized and small arteries, most commonly the renal and carotid arteries. Dysplasic stenoses can be classified by angiography into three main subtypes, multifocal (multiple contiguous stenoses with the "string of beads" appearance), unifocal (single stenosis in a given renal artery), or tubular. The multifocal subtype is the most frequent and is usually associated with medial dysplasia, whereas unifocal and tubular stenoses are associated with intimal and perimedial dysplasia, respectively. Renovascular hypertension, mainly in women aged 30 to 50 years, is the most common manifestation of renal artery fibromuscular dysplasia. Its prevalence in hypertensive patients is estimated to less than 1 percent. The true prevalence of the disease is probably higher, however, because many cases can go undetected in normotensive or asymptomatic hypertensive patients. The first line treatment is percutaneous transluminal angioplasty that usually allows blood pressure improvement or normalization. Stenosis progression is slow and rarely leads to ischemic renal failure. Recognition of renal artery fibromuscular dysplasia should lead to screening for associated carotid artery lesions. Fibromuscular dysplasia can be a familial disease.

cDNA cloning, gene characterization and 13q14.3 chromosomal assignment of CHC1-L, a chromosome condensation regulator-like guanine nucleotide exchange factor.

We report the characterization of a new gene mapped at chromosome band 13q14.3 telomeric to the retinoblastoma gene. This gene, designated CHC1L (for chromosome condensation 1-like), is composed of 14 exons spanning 30 kb of genomic DNA and encodes a ubiquitously expressed 3-kb mRNA. The N-terminal half of the deduced amino acid sequence shows strong homology with the seven tandem repeat structure of the regulator of chromosome condensation RCC1, which acts as a guanine nucleotide exchange factor (GEF) protein for the Ras-related GTPase Ran. CHC1L appears to be a new member of the RCC1-related GEF family.

Assignment of 48 ESTs to chromosome 13 band q14.3 and expression pattern for ESTs located in the core region deleted in B-CLL.

An expression map containing 48 ESTs was constructed to identify a tumor-suppressor gene involved in B-cell chronic lymphocytic leukemia (B-CLL), which was previously assigned to chromosome band 13q14.3 close to genetic markers D13S25 and D13S319. Thirty-nine of these 48 ESTs, together with 11 additional ones listed in databases, were initially assigned to chromosome 13q14 between markers D13S168 and D13S176. Nine others have recently been located in the D13S319 region. Our results indicate that 48 of the 59 ESTs analyzed belong to a YAC contig of chromosome 13 band q14, and 22 are contained on YAC 933e9, which encompasses the B-CLL critical region. Ten of these 22 ESTs were accurately assigned on a PAC, BAC, and cosmid contig encompassing the smallest minimal deletion area described so far in B-CLL, and 20 were tested for their expression on 27 normal or tumor tissues. One EST appears to be a likely candidate for the tumor-suppressor gene involved in B-CLL.

[Genetic study of renal artery fibromuscular dysplasia]. / Etude génétique de la dysplasie fibromusculaire des artères rénales.

The aim of this study was to conduct a formal pedigree analysis of the involvement of the elastin gene in families. From 140 subjects with renal FMD documented on angiography, family cases with documented renal artery fibromuscular dysplasia (FMD) and to test pedigrees were constructed and familial cases defined by angiographic evidence of FMD in at least one sibling. Familial screening was made either by echodoppler for asymptomatic subjects or by digital intravenous angiography for hypertensive subjects. Linkage analysis at the elastin gene locus was performed in these families with two polymorphic markers: one diallelic RFLP located in exon 16 and one multiallelic CA repeat located in intron 17 of the elastin gene. Fourteen pedigrees (10%) were obtained including nine sibling pairs, four trios and one vertical transmission from a father to his daughter. Most affected subjects were females (84%) but familial cases were more frequently bilateral than sporadic cases (80% vs 49%, p = 0.07). Pedigrees analysis was compatible with an autosomal dominant mode of inheritance and suggested in these families an age and sex-dependent incomplete penetrance model. Linkage analysis resulted in a maximum two-point lod score of 0.06 at theta = 0.20 using the dinucleotide CA repeat. Analysis of the diallelic marker revealed similar frequencies in affected and non affected subjects. This study highlights the role of genetics factors in approximately 10% of FMD cases. The elastin gene does not seem to be involved in the pathogenesis of FMD.

[Reversible left intraventricular obstruction after treatment of pheochromocytoma and hyperthyroidism]. / Obstruction intraventriculaire gauche réversible après traitement d'un phéochromocytome et d'une hyperthyroïdie.

The authors report an original case of the association of three pathologies: pheochromocytoma, hyperthyroidism and cardiomyopathy with left ventricular outflow tract obstruction. This type of cardiac disease has occasionally been described in cases of pheochromocytoma and are usually induced by the endocrine disturbance because they regress with treatment of the pheochromocytoma. The associated hyperthyroidism observed in this case is very rare and may have increased the left ventricular pressure gradient. Medical treatment before surgery of the pheochromocytoma was unusual in that a triple therapy was used including betablockers, classically contra-indicated in pheochromocytoma alone. In this case, it provided excellent control of the blood pressure and decreased the left ventricular obstruction during the perioperative period.

Possible familial origin of multifocal renal artery fibromuscular dysplasia.

OBJECTIVE: To describe phenotypes and estimate the prevalence of familial cases of renal artery fibromuscular dysplasia (FMD). PATIENTS AND SETTING: One hundred and four unrelated hypertensive patients (94 women) with renal artery fibromuscular dysplasia documented on angiography and classified as having multifocal or unifocal lesions. Familial cases were defined as those with angiographic evidence of renal artery FMD in at least one sibling. RESULTS: Eighty-one patients had multifocal and 16 had unifocal FMD. Both types of stenosis were present in seven patients. Fifty-four patients had bilateral FMD, including the seven patients with both unifocal and multifocal lesions. The 16 patients with unifocal FMD were younger, more likely to be men, and more commonly had unilateral stenoses, stenoses exceeding 75% and a small ischemic kidney than the 81 patients with multifocal lesions. Eleven cases were identified as familial on the basis of FMD having been documented in at least one sibling (eight sibling pairs and three trios). All probands were women and exhibited multifocal lesions. FMD was more often bilateral in familial than it was in apparently sporadic cases. CONCLUSIONS: Multifocal FMD was mostly found in women and unifocal FMD in young men with more severe stenosis and kidney ischemia. The documented prevalence of familial cases was 11% in this series, the true prevalence being probably higher because only a few siblings were examined by angiography. Familial cases all exhibited the multifocal type and were more commonly bilateral than were sporadic cases.

Construction of a 780-kb PAC, BAC, and cosmid contig encompassing the minimal critical deletion involved in B cell chronic lymphocytic leukemia at 13q14.3.

A putative tumor suppressor gene involved in B cell chronic lymphocytic leukemia (B-CLL) was mapped to human chromosome 13q14.3 close to the genetic markers D13S25 and D13S319. We constructed a 780-kb-long contig composed of cosmids, bacterial artificial chromosomes, and bacteriophage P1-derived artificial chromosomes that provides essential information and tools for the positional cloning of this gene. The conting contains both flanking markers as well as several additional genetic markers, three ESTs, and one potential CpG island. In addition, using one B-CLL patient, we characterized a small internal deleted region of 550 kb. Comparing this deletion with other recently published deletions narrows the minimally deleted area to less than 100 kb in our physical map. This deletion core region should contain all or part of the disrupted in B cell malignancies tumor suppressor gene.

[Non-surgical treatments of renal artery stenoses]. / Traitements non chirurgicaux des sténoses de l'artère rénale.

Management of patients with renal artery stenoses is aimed at normalizing or reducing blood pressure and correcting or preventing reduced glomerular filtration. The results of renal revascularization have been documented mainly in retrospective, uncontrolled reports in which blood pressure improvement was overestimated due to the placebo effect and optimization of drug treatment, the latter being frequently required despite adequate revascularization. In an overview of 10 series reporting blood pressure outcome following percutaneous angioplasty, cure rates were 50% in patients with fibrodysplastic stenosis but only 19% in those with atherosclerotic stenosis. The literature on revascularization of atherosclerotic stenosis with progressive renal failure shows that 55% of patients have improved renal function following surgery and 41% following angioplasty. Mortality is 6 and 5% respectively. The first controlled trials comparing revascularization to medical treatment in renal artery stenosis have recently been published. In a prospective randomized trial, Weibull et al. compared percutaneous angioplasty and surgery in 58 patients with unilateral atherosclerotic stenosis. Although 17% of the patients initially treated with angioplasty required subsequent surgery, blood pressure, renal function and renal artery patency rate did not differ between angioplasty and surgery 24 months after treatment. A Scottish group reported a prospective randomized trial of percutaneous angioplasty vs. medical therapy in patients with bilateral or unilateral atherosclerotic stenosis. In the bilateral group (n = 28), the drop in systolic pressure was significantly larger following angioplasty than following medical therapy, but diastolic pressure and creatinine did not differ after 24 months. In the unilateral group (n = 27), there were no differences in blood pressure or creatinine levels following angioplasty or medical therapy. Several randomized trials comparing angioplasty and conservative treatment or angioplasty and stent placement in patients with renal artery stenosis and normal or reduced renal function are currently underway. They should provide additional information regarding the risk/benefit ratio of these procedures.

Growth inhibitory and agonistic signals of interleukin-7 (IL-7) can be mediated through the CDw127 IL-7 receptor.

The present study was aimed at identifying surface-membrane molecules involved in the regulation of human B-cell ontogeny. For this purpose, murine monoclonal antibodies (MoAbs) were generated against Pre-Alp, a pre-B acute lymphoblastic leukemia (ALL) cell line, and MoAb R34.34 was selected for further characterization. R34.34 recognized a molecule expressed on normal B-cell precursors (BCP) but not on mature B cells. The antibody also reacted with T lymphocytes, a subpopulation of monocytes from peripheral blood, and a subset of CD34+ cells. Immunoprecipitation analysis indicated that R34.34 recognizes an 80-kD molecular weight antigen. Antibody R34.34 was further found to be directed against an epitope interfering with binding of interleukin-7 (IL-7) to Pre-Alp cells. Expression cloning from a Pre-Alp cDNA library showed that R34.34 antigen is CDw127, the 75- to 80-kD IL-7 receptor. Proliferation of the B-lineage ALL cell lines Reh and Mieliki was inhibited by IL-7, and this effect was specifically reverted by MoAb R34.34. In addition, antibody R34.34 specifically inhibited IL-7-dependent proliferation of normal BCP, Pre-Alp cells, and peripheral T cells. These results imply that both inhibitory and proliferative effects of IL-7 can be mediated through the same receptor on various lineages. R34.34 antibody should be important for the analysis of signal transduction through CDw127.