Molecular characteristics of Machado-Joseph disease mutation in 25 newly described Brazilian families

Machado-Joseph disease (MJD) is a form of autosomal dominant spinocerebellar ataxia first described in North-American patients originating from the Portuguese islands of the Azores. Clinically this disorder is characterized by late onset progressive ataxia with associated features, such as: ophthalmoplegia, pyramidal and extrapyramidal signs and distal muscular atrophies. The causative mutation is an expansion of a CAG repeat in the coding region of the MJD1 gene. We have identified 25 unrelated families segregating the MJD mutation during a large collaborative study of spinocerebellar ataxias in Brazil. In the present study a total of 62 family members were genotyped for the CAG repeat in the MJD1 gene, as well as 63 non-MJD individuals (126 normal chromosomes), used as normal controls. We observed a wide gap between the size range of the normal and expanded CAG repeats: the normal allele had from 12 to 33 CAGs (mean = 23 CAGs), whereas the expanded alleles ranged from 66 to 78 CAGs (mean = 71.5 CAGs). There were no differences in CAG tract length according to gender of affected individuals or transmitting parent. We observed a significant negative correlation between age at onset of the disease and length of the CAG tract in the expended allele (r = -0.6, P = 0.00006); however, the size of the expanded CAG repeat could explain only about 40% of the variability in age at onset (r2 = 0.4). There was instability of the expanded CAG tract during transmission from parent to offspring, both expansions and contractions were observed; however, there was an overall tendency for expansion, with a mean increase of +2.4 CAGs. The tendency for expansion appeared to the greater in paternal (mean increase of +3.5 CAGs) than in maternal transmissions (mean increase of +1.3 CAGs). Anticipation was observed in all transmissions in which ages at onset for parent and offspring were known; however, anticipation was not always associated with an increase in the expanded CAG repeat length. Our results indicate that the molecular diagnosis of MJD can be confirmed or excluded in all suspected individuals, since alleles of intermediary size were not observed.

Comparative quantification of umbilical cord blood CD34+ and CD34+ bright cells using the ProCount™-BD and ISHAGE protocols

The total number of CD34+ cells is the most relevant clinical parameter when selecting human umbilical cord blood (HUCB) for transplantation. The objective of the present study was to compare the two most commonly used CD34+ cell quantification methods (ISHAGE protocol and ProCount™ - BD) and analyze the CD34+ bright cells whose 7-amino actinomycin D (7AAD) analysis suggests are apoptotic or dead cells. Twenty-six HUCB samples obtained at the Placental Blood Program of New York Blood Center were evaluated. The absolute numbers of CD34+ cells evaluated by the ISHAGE (with exclusion of 7AAD+ cells) and ProCount™ (with exclusion of CD34+ bright cells) were determined. Using the ISHAGE protocol we found 35.6 ± 19.4 CD34+ cells/µL and with the ProCount™ method we found 36.6 ± 23.2 CD34+ cells/µL. With the ProCount™ method, CD34+ bright cell counts were 9.3 ± 8.2 cells/µL. CD34+ bright and regular cells were individually analyzed by the ISHAGE protocol. Only about 1.8% of the bright CD34+ cells are alive, whereas a small part (19.0%) is undergoing apoptosis and most of them (79.2%) are dead cells. Our study showed that the two methods produced similar results and that 7AAD is important to exclude CD34 bright cells. These results will be of value to assist in the correct counting of CD34+ cells and to choose the best HUCB unit for transplantation, i.e., the unit with the greatest number of potentially viable stem cells for the reconstitution of bone marrow. This increases the likelihood of success of the transplant and, therefore, the survival of the patient.

Lettre du Roy, envoyée à Mgr l'abbé de Sainct Germain Desprez, ou à son vicaire général en son absence, pour l'exhorter de faire chommer la feste de sainct Joseph dans l'estendüe de sa jurisdiction

[Acte royal. 1661-03-16. Paris]

[Joseph] Guillemot gagnant du National anglais [épreuve de cross à Windsor, le 13 mars 1920] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58527

21-3-20, Bry-sur-Marne, [27e] championnat de France de cross-country, un passage de [Joseph] Guillemot et Vignaud : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58560

21/3/20, Bry-sur-Marne, [27e] championnat de France de cross-country, l'arrivée, [Joseph] Guillemot et Vignaud : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58561

21-3-20, Bry-sur-Marne [27e] championnat de France de cross-country, Vignaud et [Joseph] Guillemot après leur arrivée : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58562

21-3-20, Bry-sur-Marne, [27e] championnat de France de cross-country, [Joseph] Guillemot vainqueur : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58563

National anglais [épreuve de cross à Windsor], [Charles] Clibbon, [Joseph] Guillemot gagnant, [Christopher] Vose : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58529

[Joseph] Guillemot, [13-6-20, Croix Catelan, prix Blanchet, portrait du vainqueur du] 1500 m : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59678

Sénateur Joseph I. France, candidat à la présidence de la République des États-Unis, C.N. New York [cliché Central News] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59521