Course of matrix metalloproteinase-9 isoforms after the administration of uric acid in patients with acute stroke

Abstract   Oxidative stress as well as expression and activity of matrix metalloproteinase 9 (MMP-9) are rapidly enhanced after cerebral ischemia. The magnitude of these effects is related to stroke outcome. In human stroke, the extent of oxidative stress correlates well with increased MMP-9 expression. The aim of this study was to evaluate whether treatment with the antioxidant molecule uric acid (UA) decreased the levels of MMP-9 in stroke patients treated with rtPA. The patients were part of a pilot, double-blind, randomized, vehiclecontrolled study of patients with acute stroke treated with rtPA (< 3 h) and randomized to receive an intravenous infusion of UA (n = 16) or vehicle (n = 8). Total matrix metalloproteinase (tMMP)-9 and active (aMMP-9) levels were measured in serum at baseline (< 3 h), at the end of study treatment infusion (< 5.5 h), and at 48 hours. Total MMP-9 and aMMP-9 increased very early after stroke onset in patients allocated vehicle after rtPA therapy. Lower increments of aMMP-9 were associated with better outcome at 3 months. UA treatment was associated with reduced levels of aMMP-9 at T1 (p < 0.02) in multivariate models adjusted for age, NIHSS score, and baseline aMMP-9 levels. The decline of aMMP-9 attained after UA administration supports further clinical assessment of UA therapy in patients with acute stroke.     

Paludism due to Plasmodium falciparum in visitors to the Dominican Republic

We present two cases of P. falciparum malaria in visitors to tourist resorts on the East Coast of the Dominican Republic, traditionally believed to be an area without risk of malaria. In both patients the malaria was severe (with 20% parasitization in one) and there was a long interval between the onset of symptoms and diagnosis. These cases are possibly related (along with a further 17 reports by the Centers for Disease Control and Prevention) to an increase in the population of Anopheles sp as a consequence of increased rainfall and floods provoked by a hurricane in September 2004, as well as to the presence of a semi-immune population (Haitian immigrants working in the construction and tourist sectors). Both physicians and patients should be aware of this outbreak so that adequate precautions can be taken and early diagnoses can be made.     

Aberrant DNA methylation profile of chronic and transformed classic Philadelphia-negative myeloproliferative neoplasms

Most DNA methylation studies in classic Philadelphia-negative myeloproliferative neoplasms have been performed on a gene-by-gene basis. Therefore, a more comprehensive methylation profiling is needed to study the implications of this epigenetic marker in myeloproliferative neoplasms. Here, we have analyzed 71 chronic (24 polycythemia vera, 23 essential thrombocythemia and 24 primary myelofibrosis) and 13 transformed myeloproliferative neoplasms using genome-wide DNA methylation arrays. The three types of chronic Philadelphia-negative myeloproliferative neoplasms showed a similar aberrant DNA methylation pattern when compared to control samples. Differentially methylated regions were enriched in a gene network centered on the NF-κB pathway, indicating that they may be involved in the pathogenesis of these diseases. In the case of transformed myeloproliferative neoplasms, we detected an increased number of differentially methylated regions with respect to chronic myeloproliferative neoplasms. Interestingly, these genes were enriched in a list of differentially methylated regions in primary acute myeloid leukemia and in a gene network centered around the IFN pathway. Our results suggest that alterations in the DNA methylation landscape play an important role in the pathogenesis and leukemic transformation of myeloproliferative neoplasms. The therapeutic modulation of epigenetically-deregulated pathways may allow us to design targeted therapies for these patients.     

Preneoplastic lesions in gallbladder cancer

BACKGROUND: Gallbladder cancer is an uncommon disease except in countries like Chile and areas of India and Japan. The knowledge regarding the etiology and mechanisms through which this neoplasia is developed is significantly less compared to other malignant tumors. RESULTS: The epithelial lesions involved in gallbladder carcinogenesis are dysplasia and adenomas that represent two biologically distinct carcinogenetic models. Dysplasia progresses to carcinoma in situ (CIS) and subsequently becomes invasive. Over 80% of invasive gallbladder cancers present areas adjacent to the CIS and epithelial dysplasia. Other authors have demonstrated adenomatous areas in carcinomas, or malignant transformation in an adenoma. The low incidence of gallbladder adenomas (0.14% of cholecystectomies) and the presence of adenomatous remnants in the neighboring mucosa to early carcinomas in less than 3% of the cases suggest the limited importance of this carcinogenic pathway. Epithelial dysplasia which is not associated with gallbladder cancer is observed in approximately 1% of cholecystectomies for symptomatic lithiasis. Metaplasia, dysplasia, and CIS are present in the mucosa adjacent to the cancer in 66%, 81.3%, and 69%, respectively. The average ages of patients with dysplasia not associated to cancer (51.9 years), early carcinomas (56.8 years), and advanced carcinomas (62.9 years) demonstrate a gradient which suggests the progression of these lesions. CONCLUSIONS: From the morphological point of view, the dysplasia-carcinoma sequence is the most plausible carcinogenic pathway for gallbladder cancer, a process which would require a period of approximately 10 years.     

Posttraumatic ectopic nail: case report

Ectopic nail, also known as onychoheterotopia or onychoheterotropia, is an extremely rare disorder. It is characterized by the growth of nail-like tissue in a different location other than the nail bed. Congenital and acquired deformities have been reported. We describe a case of posttraumatic ectopic nail and review the literature on this unusual condition.     

LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome

Background

LMO2 is highly expressed at the most immature stages of lymphopoiesis. In T-lymphocytes, aberrant LMO2 expression beyond those stages leads to T-cell acute lymphoblastic leukemia, while in B cells LMO2 is also expressed in germinal center lymphocytes and diffuse large B-cell lymphomas, where it predicts better clinical outcome. The implication of LMO2 in B-cell acute lymphoblastic leukemia must still be explored.

Design and Methods

We measured LMO2 expression by real time RT-PCR in 247 acute lymphoblastic leukemia patient samples with cytogenetic data (144 of them also with survival and immunophenotypical data) and in normal hematopoietic and lymphoid cells.

Results

B-cell acute lymphoblastic leukemia cases expressed variable levels of LMO2 depending on immunophenotypical and cytogenetic features. Thus, the most immature subtype, pro-B cells, displayed three-fold higher LMO2 expression than pre-B cells, common-CD10+ or mature subtypes. Additionally, cases with TEL-AML1 or MLL rearrangements exhibited two-fold higher LMO2 expression compared to cases with BCR-ABL rearrangements or hyperdyploid karyotype. Clinically, high LMO2 expression correlated with better overall survival in adult patients (5-year survival rate 64.8% (42.5%–87.1%) vs. 25.8% (10.9%–40.7%), P= 0.001) and constituted a favorable independent prognostic factor in B-ALL with normal karyotype: 5-year survival rate 80.3% (66.4%–94.2%) vs. 63.0% (46.1%–79.9%) (P= 0.043).

Conclusions

Our data indicate that LMO2 expression depends on the molecular features and the differentiation stage of B-cell acute lymphoblastic leukemia cells. Furthermore, assessment of LMO2 expression in adult patients with a normal karyotype, a group which lacks molecular prognostic factors, could be of clinical relevance.