Inv(X)(p21.1;q22.1) in a man with mental retardation,short stature,general muscle wasting,and facial dysmorphism: clinical study and mutation analysis of the NXF5 gene

We describe a 59-year-old male (patient A059) with moderate to severe mental retardation (MR) and a pericentric inversion of the X-chromosome: inv(X)(p21.1;q22.1). He had short stature, pectus excavatum, general muscle wasting, and facial dysmorphism. Until now, no other patients with similar clinical features have been described in the literature. Molecular analysis of both breakpoints led to the identification of a novel "Nuclear RNA export factor" (NXF) gene cluster on Xq22.1. Within this cluster, the NXF5 gene was interrupted with subsequent loss of gene expression. Hence, mutation analysis of the NXF5 and its neighboring homologue, the NXF2 gene was performed in 45 men with various forms of syndromic X-linked MR (XLMR) and in 70 patients with nonspecific XLMR. In the NXF5 gene four nucleotide changes: one intronic, two silent, and one missense (K23E), were identified. In the NXF2 gene two changes (one intronic and one silent) were found. Although none of these changes were causative mutations, we propose that NXF5 is a good candidate gene for this syndromic form of XLMR, given the suspected role of NXF proteins is within mRNA export/transport in neurons. Therefore, mutation screening of the NXF gene family in phenotypically identical patients is recommended.     

Up-regulation of tRNA biosynthesis affects translational readthrough in maf1-delta mutant of Saccharomyces cerevisiae

Maf1p is a negative effector of RNA polymerase III in yeast. The maf1-delta mutation caused an increase in the level of cellular tRNAs, but a decrease of translational readthrough at nonsense codons. Using the lacZ- luc dual gene reporter system, we detected an almost twofold diminution of UAA and UAG readthrough in maf1-delta compared with the parental strain. The maf1-delta mutation did not affect the rate of protein biosynthesis and growth at standard conditions, but resulted in temperature-sensitive growth on non-fermentable carbon sources. We examined the correlation of the temperature sensitive and antisuppression phenotypes of maf1- Delta using a colour phenotype assay in the ade2-1 SUP11 strain. Antisuppression, but not the temperature-sensitive growth defect, was compensated either by increased dosage of SUP11or by [PSI(+)], the prion form of the translation termination factor Sup35p. Summarizing, the elevated tRNA levels in maf1- Delta increase translational fidelity and, independently, affect growth under special conditions.     

Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes

While low avidity ligation of the T cell receptor (TCR) leads to positive selection and further maturation of developing thymocytes providing the immune system with mature CD4(+) and CD8(+) (single positive) T cells, high avidity ligation triggers negative selection by apoptotic cell death and therefore the TCR repertoire is purged of autoreactive T cells. On peripheral T cells, however, high avidity ligation of the TCR triggers activation and survival not death. In the present study we used concanavalin A (Con A) and alpha-CD3 epsilon antibody to investigate a possible survival mechanism in connection with TCR ligation. Con A and alpha-CD3 epsilon were used in the study for the following reasons: (1) they both mimic the effects of high avidity TCR ligation by activating peripheral T cells, and (2) they trigger distinctively different physiological changes in developing thymocytes. While Con A supports events associated with cellular survival, alpha-CD3 epsilon induces apoptotic cell death. In our experimental system the TCR was cross-linked by Con A and alpha-CD3 epsilon in thymocytes of major histocompatibility complex (MHC) deficient thymus organ cultures, where signals from the TCR can be triggered on zero background signal level. We have found that TCR cross-linking by Con A and not by alpha-CD3 epsilon decreases the gene and protein expression of the pro-apoptotic molecule, Bad; and that Con A is capable of the activation of the survival signalling pathway including protein kinase B (Akt/PKB) independently of phosphatidyl inositol kinase (PI3K).     

Bacteremia caused by an undescribed species of Janibacter

A yellow-pigmented rod- to coccoid-shaped coryneform microorganism was isolated from the blood of a patient with acute myeloid leukemia. It was identified by 16S rRNA gene sequencing as a previously undescribed species of Janibacter. The isolate was susceptible to penicillins, aminoglycosides, fluoroquinolones, and glycopeptides.     

Estimation of the parameters of the relationship between power and time to exhaustion from a single ramp test.

This study aimed to estimate the power/time relationship from a single ramp test (RT) assuming critical power (Pc) from ventilatory threshold (VT) and energy reserve (W') from total work during RT These estimates from single RT were compared to those from a series of 4 constant power exercises (CPT) and from a series of 4 RT. Only W' from CPT was higher than from the series of RT and from single RT using VT (p < 0.05).     

A new form of skeletal dysplasia with amelogenesis imperfecta and platyspondyly

We report two patients, born of consanguineous parents, affected by a disorder resulting in mild growth retardation. Hallmarks are amelogenesis imperfecta (absence of the enamel cap) associated with brachyolmia-like anomalies: platyspondyly with short pedicles, narrow intervertebral and interpedicular distances, rectangular-shaped vertebrae with posterior scalloping and herniation of the nuclei, and broad femoral necks. Inheritance appears to be autosomal recessive.     

Monomères acryliques à fonction carbonate cyclique, 2 Modification chimique de copolymères à groupements carbonate cyclique lateraux

Acrylic monomers with a cyclic carbonate function, their synthesis having been described previously, are used to synthesize copolymers with pendent cyclic carbonate side groups. Their chemical modification by ring opening addition reactions provides a convenient method for preparing functional polymers. The study of reactions with amines, on model compounds and on polymers, shows the possibility of obtaining a macromolecular network with crosslinking groups of carbamate type.     

A further mutation of the FGFR2 tyrosine kinase domain in mild Crouzon syndrome

We report a family heterozygous for a newly identified mutation in the tyrosine kinase I domain of the FGFR2 gene (1576A > G, encoding the missense substitution Lys526Glu), associated with variable expressivity of Crouzon syndrome, including clinical nonpenetrance. Our observations expand both the clinical and molecular spectrum of this unusual subset of FGFR2 mutations.     

Lack of selective Vβ deletion in peripheral CD4+ T cells of human immunodeficiency virus-infected infants

To investigate the possibility of superantigen-mediated deletions of T cells expressing particular T cell receptor Vβ (TcR Vβ) gene segments during human immunodeficiency virus (HIV) infection, TcR Vp usage in CD4⁺ and CD8⁺ subsets was analyzed in a cohort of infants maternally infected by HIV and in a group of healthy neonates. We used a semi-quantitative anchored polymerase chain reaction technique together with cytofluorographic analysis with anti-Vβ monoclonal antibodies. The representation of the 24 vβ families in CD4⁺ and CD8⁺ T cells from normal neonates was very similar to that in adults. Preferential expression of Vβ2 in the CD4⁺ subset was observed in both the neonates and in healthy adults. The representation of the 24 Vβ families in peripheral CD4⁺ T cells from the HIV-infected infants showed no selective vβ deletion, even when the CD4⁺ subset was globally depleted. Moreover, the main characteristics of the control group (predominance of certain Vβ families and Vβ2 skewing towards the CD4⁺ subset) were also present in all the HIV-infected infants.     

Mantle cell lymphoma, in leukaemic phase with prominent splenomegaly. A report of eight cases with similar clinical presentation and aggressive outcome

Mantle cell lymphoma (MCL) is a well-defined peripheral B-cell lymphoma usually diagnosed upon peripheral lymph node biopsy. We report eight cases of peripheral B-cell leukaemia that demonstrate presumptive evidence of mantle cell characteristics. The patients had a median age of 68.5 years, and five were male. All presented with an enlarged spleen without any peripheral lymphadenopathies, and they were leukaemic at presentation (median lymphocytosis, 38x10(9)/l). Morphological diagnosis of MCL was very difficult in five cases but easier in three because we were able to analyse either pre- or post-mortem lymph nodes and spleen. The immunophenotype of blood lymphocytosis using flow cytometry, the presence of a t(11;14)(q13;q32) and a cyclin D1 expression by leukaemic cells all fit with the diagnosis of MCL. All patients progressed and died with a median overall survival of 8 months. Multifocal areas of transformation in blastoid or large cell variants were observed in the three autopsied patients. In summary, one should consider the diagnosis of MCL at presentation in leukaemic phase even in the absence of peripheral adenopathies.