Angel Moreno

Mutations of CD40 ligand in two patients with hyper-IgM syndrome

Two patients with the X-linked form of the hyper-IgM syndrome have been studied. Both patients present: 1. Mutations in the CD40L gene (a nonsense point mutation that introduces a termination codon at the extracellular domain of the protein, and a deletion that eliminates exon 4 as consequence of an abnormal splicing). 2. Lack of CD40L expression on the lymphocyte surface after stimulation with ionomycin and PMA. 3. Altered lymphocytic proliferation in response to anti-CD3. 4. Hyper IgM, low IgG and IgA levels and neutropenia. One of the patients shows, in addition, low Natural Killer cell numbers and severe herpetic infections, which distinguishes this case from the common hyper-IgM syndrome phenotype. Finally, a hyper-IgM stable phenotype has been immortalized by Herpes virus Saimiri for the first time.

Novel mutations and defective protein kinase C activation of T‐lymphocytes in ataxia telangiectasia

Three ataxia telangiectasia (AT) patients have been characterized immunologically and molecularly. Patient 1 presents two nondescribed splicing mutations which affect exons 15 and 21 of the ATM gene. The maternal defect consists of a G > A transition in the first nucleotide of the intron 21 donor splicing site which results in a complete deletion of exon 21. The paternal mutation consists of an A > C transversion in the intron 14 acceptor splicing site which produces a partial skipping of exon 15. Two abnormal alternative transcripts were found, respectively, 17 and 41 nucleotides shorter. Patient 2 presents a homozygous genomic deletion of 28 nucleotides in the last exon of the gene. This deletion changes the normal reading frame after residue 3003 of the protein and introduces a premature stop codon at residue 3008 that could originate a truncated ATM protein. Patient 3, a compound heterozygote, presents a defect which consists of a G > A transition in the first nucleotide of intron 62 donor splicing site which results in a complete deletion of exon 62. The results obtained during a three year period in the proliferation assays show an impaired PMA (phorbol myristate acetate) activation in specific T lymphocyte activation pathways (CD69, CD26, CD28, CD3, PHA, PWM and Con A mediated) but not in others (CD2, ionomycin, and Ig surface receptor). The possible link among specific ATM mutations and abnormal immune responses is unknown.

The asymmetric synthesis of 2,3-benzocarbapenems by intramolecular aryl radical cyclizations

Abstract Racemic and enantiomerically pure 2,3-benzocarbapenems 1 are obtained in good yields by the tin-mediated, intramolecular aryl radical cyclizations of the readily available 4-alkenyl- N -(2-halogenophenyl)-β-lactams 2 .

A genetic study of cathepsin C gene in two families with Papillon–Lefèvre syndrome

Papillon-Lefèvre syndrome (PLS) is an inherited human disorder characterised by premature destruction of the periodontium of the deciduous and permanent teeth, palmoplantar hyperkeratosis, and increased susceptibility to bacterial infections during the first years of life. In this paper two PLS families have been studied. Family 1 presents a novel homozygous mutation (880T>C) in exon 6 causing Y294H amino acid substitution. Family 2 shows a previously described non-sense homozygous punctual change (72C>A) that introduces a termination codon at the extracellular domain of the protein (C24X).

Stability of neural firing in the trigeminal nuclei under mechanical whisker stimulation

Sensory information handling is an essentially nonstationary process even under a periodic stimulation. We show how the time evolution of ridges in the wavelet spectrum of spike trains can be used for quantification of the dynamical stability of the neuronal responses to a stimulus. We employ this method to study neuronal responses in trigeminal nuclei of the rat provoked by tactile whisker stimulation. Neurons from principalis (Pr5) and interpolaris (Sp5i) show the maximal stability at the intermediate (50 ms) stimulus duration, whereas Sp5o cells “prefer” shorter (10 ms) stimulation. We also show that neurons in all three nuclei can perform as stimulus frequency filters. The response stability of about 33% of cells exhibits low-pass frequency dynamics. About 57% of cells have band-pass dynamics with the optimal frequency at 5 Hz for Pr5 and Sp5i, and 4 Hz for Sp5o, and the remaining 10% show no prominent dependence on the stimulus frequency. This suggests that the neural coding scheme in trigeminal nuclei is not fixed, but instead it adapts to the stimulus characteristics.