Biomedical subjects

Gaetana Lanzi

Publications and source records attributed to Gaetana Lanzi.

4 recordsLinked to original sources

PubMed2006

Defects of class-switch recombination.

Shaping of the secondary antibody repertoire is generated by means of class-switch recombination (CSR), which replaces IgM with other isotypes, and somatic hypermutation (SHM), which allows production of high-affinity antibodies. However, the molecular mechanisms underlying these important processes have long remained obscure. Immunodeficiency with hyper-IgM comprises a group of genetically heterogeneous defects of CSR variably associated with defects of SHM. The study of these patients has allowed us to recognize that both T-cell-B-cell interaction (resulting in CD40-mediated signaling) and intrinsic B-cell mechanisms are involved in CSR and SHM. Elucidation of the molecular defects underlying these disorders has been essential to better understand the molecular basis of Ig diversification and has offered the opportunity to define the clinical spectrum of these diseases and to prompt more accurate diagnostic and therapeutic approaches.

B-Lymphocytes↗

PubMed2006

Omenn syndrome in an infant with IL7RA gene mutation.

Omenn syndrome (OS) is a rare combined immunodeficiency characterized by erythroderma, lymphadenopathy, and autoimmune manifestations. Most cases are due to mutations in the RAG genes. We report a case of OS due to mutations of IL7RA, thus defining Omenn syndrome as a genetically heterogeneous condition.

Amino Acid Substitution↗

PubMed2006

Molecular and biological characterization of deformed wing virus of honeybees (Apis mellifera L.).

Deformed wing virus (DWV) of honeybees (Apis mellifera) is closely associated with characteristic wing deformities, abdominal bloating, paralysis, and rapid mortality of emerging adult bees. The virus was purified from diseased insects, and its genome was cloned and sequenced. The genomic RNA of DWV is 10,140 nucleotides in length and contains a single large open reading frame encoding a 328-kDa polyprotein. The coding sequence is flanked by a 1,144-nucleotide 5' nontranslated leader sequence and a 317-nucleotide 3' nontranslated region, followed by a poly(A) tail. The three major structural proteins, VP1 (44 kDa), VP2 (32 kDa), and VP3 (28 kDa), were identified, and their genes were mapped to the N-terminal section of the polyprotein. The C-terminal part of the polyprotein contains sequence motifs typical of well-characterized picornavirus nonstructural proteins: an RNA helicase, a chymotrypsin-like 3C protease, and an RNA-dependent RNA polymerase. The genome organization, capsid morphology, and sequence comparison data indicate that DWV is a member of the recently established genus Iflavirus.

Amino Acid Sequence↗

PubMed2005

Damaging-agent sensitivity of Artemis-deficient cell lines.

Defects in repairing double-strand breaks can lead to genome instability and tumorigenesis. In humans, most T(-)B(-) severe combined immunodeficiencies (SCID) have a defect in either the RAG1 or RAG2 gene, are not radiosensitive and do not show genome instability. On the contrary, a minority of T(-)B(-) SCID patients have abnormalities in the Artemis gene and are moderately radiosensitive. Artemis-deficient cells are unable to process hairpin ends after RAG cleavage, but hairpin opening activity alone does not explain the moderate X-ray sensitivity of Artemis-deficient cells. We report here that, at variance with what has been described in mice, cell lines from Artemis(-/-) patients are moderately sensitive to mitomycin C and show only a low to moderate increase in genomic instability, both spontaneously and after exposure to ionizing radiations. There is some heterogeneity in the levels of DNA damage sensitivity and genome instability, which could in part be due to different effects of the specific mutation involved or to genetic background, which may not always represent null alleles. This data supports the hypothesis that, in addition to playing a role in hairpin opening during the V(D)J recombination process, Artemis is involved in the repair of a subset of DNA damage whose exact nature is still undefined.

Animals↗