Hemoglobin Hakkari: an autosomal dominant form of beta thalassemia with inclusion bodies arising from de novo mutation in exon 2 of beta globin gene.

Certain beta globin gene mutations produce a thalassemia major phenotype in the heterozygous state. While most such patients have thalassemia intermedia, we describe a young Guatemalan child with a de novo mutation in the beta globin gene, codon 31 T --> G (Hemoglobin Hakkari), who developed severe anemia at the age of 10 months and remains transfusion-dependent. The substitution of B13 leucine with arginine in the beta globin results in alteration of a critical heme contact point resulting in an extremely unstable variant hemoglobin and a clinical picture that is characterized by ineffective erythropoiesis and numerous intracytoplasmic inclusions within the erythrocyte precursors of the bone marrow. .

Overexpression of the EphA2 tyrosine kinase in prostate cancer.

BACKGROUND: Molecules that are highly expressed by human prostate cancers may serve as therapeutically relevant targets or tumor markers. Tyrosine kinases are frequently overexpressed in metastatic tumor cells and this prompted us to screen for tyrosine kinases that are overexpressed in prostate cancer cells. METHODS: Expression levels of the EphA2 receptor tyrosine kinase were determined by Western blot analysis in canine and human prostate cancer cell lines and in immortalized and transformed variants of 267B1 prostatic epithelial cells. EphA2 levels in benign human prostate and prostate cancers were also determined in formalin-fixed, paraffin-embedded tissues using immunohistochemical staining. RESULTS: Metastatic prostate cancer cells overexpressed EphA2 by 10-100 fold as compared with non-invasive prostatic epithelial cells. EphA2 immunoreactivity in vivo was also significantly greater in human prostate cancers as compared with benign prostate epithelium. CONCLUSIONS: The EphA2 receptor tyrosine kinase is differentially expressed in human and canine prostate cancer cell lines and overexpressed in human prostate cancers as compared with benign prostate tissues. Metastasis-derived canine prostate carcinoma cell lines overexpress EphA2 and may provide pre-clinical models to further evaluate the role of EphA2 in prostate carcinogenesis. Further investigations are needed to determine the utility of EphA2 as a tumor marker and a novel target in human prostate cancer.

E-cadherin regulates the function of the EphA2 receptor tyrosine kinase.

EphA2 is a member of the Eph family of receptor tyrosine kinases, which are increasingly understood to play critical roles in disease and development. We report here the regulation of EphA2 by E-cadherin. In nonneoplastic epithelia, EphA2 was tyrosine-phosphorylated and localized to sites of cell-cell contact. These properties required the proper expression and functioning of E-cadherin. In breast cancer cells that lack E-cadherin, the phosphotyrosine content of EphA2 was decreased, and EphA2 was redistributed into membrane ruffles. Expression of E-cadherin in metastatic cells restored a more normal pattern of EphA2 phosphorylation and localization. Activation of EphA2, either by E-cadherin expression or antibody-mediated aggregation, decreased cell-extracellular matrix adhesion and cell growth. Altogether, this demonstrates that EphA2 function is dependent on E-cadherin and suggests that loss of E-cadherin function may alter neoplastic cell growth and adhesion via effects on EphA2.

[Surgery of aneurysm of the thoracic aorta. Operative results in 47 cases (author's transl)]. / Chirurgie des anévrysmes de l'aorte thoracique. Résultats opératoires à propos de 47 cas.

The authors report personal experience of surgical treatment of 47 aneurysms of the thoracic aorta, showing that the symptoms, the etiology, the treatment and the prognosis are variable depending on the site of the aneurysm. One may note regression of syphilis as a cause and an increase in the number of degenerative and traumatic aneurysms. In aneurysms of the ascending aorta, total replacement of the ascending aorta with reimplantation of the coronary arteries, according to a simplified technic, seems to give the best immediate and long term results.