Hernán García Rivello

Altered mRNA Expression of Telomere-Associated Genes in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

In this study, we explored changes in the expression of the telomere maintenance genes, TRF1, TRF2 and TANK1 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Results were correlated with human telomerase reverse transcriptase (hTERT) expression, telomere length (TL) and clinicopathological characteristics. Bone marrow (BM) samples from 132 patients, 64 with MGUS and 68 with MM, were studied. Real-time quantitative reverse transcription-polymerase chain reaction was used to quantify gene expression. TL was evaluated by terminal restriction fragment length analysis. MGUS patients showed increased TRF1 levels (P = 0.006) and lower expression of TRF2 (P = 0.005) and TANK1 (P = 0.003) compared with MM patients. For hTERT analysis, patients were divided into three groups by use of receiver operating characteristics: low (group I (GI)), intermediate (group II (GII)) and high (group III (GIII)) expression. We observed increasing expression of TRF2 and TANK1 from GI to GIII in MGUS and MM, with differences for both genes in MM (P < 0.01) and for TRF2 in MGUS (P > 0.01). GIII patients with the highest telomerase expression had the shortest TL. In both entities, a positive association between TRF2-TANK1, TRF2-hTERT and TANK1-hTERT (P ≤ 0.01) was observed. In MM, the percentage of BM infiltration and Ki-67 index were positively associated with TRF2, TANK1 and hTERT expression (P ≤ 0.03) and negatively with TL (P = 0.02), whereas lactate dehydrogenase was significantly correlated with TRF2 mRNA (P = 0.008). Our findings provide the first evidence of a modification in the expression of telomeric proteins in plasma cell disorders, and suggest that mechanisms other than telomerase activation are involved in TL maintenance in these pathologies.

Expression profile of shelterin components in plasma cell disorders. Clinical significance of POT1 overexpression

The core complex of telomere-associated proteins, named the shelterin complex, plays a critical role in telomere protection and telomere length (TL) homeostasis. In this study, we have explored changes in the expression of telomere-associated genes POT1, TIN2, RAP1 and TPP1, in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). A total of 154 patients: 70 with MGUS and 84 with MM were studied. Real-time quantitative PCR was used to quantify gene expression. TL was evaluated by Terminal Restriction Fragments. Our data showed increased expression of POT1, TPP1, TIN2 and RAP1 in MM with respect to MGUS patients, with significant differences for POT1 gene (p=0.002). In MM, the correlation of gene expression profiles with clinical characteristics highlighted POT1 for its significant association with advanced clinical stages, high calcium and β2-microglobulin levels (p=0.02) and bone lesions (p=0.009). In multivariate analysis, POT1 expression (p=0.04) was a significant independent prognostic factor for overall survival as well as the staging system (ISS) (p<0.02). Our findings suggest for the first time the participation of POT1 in the transformation process from MGUS to MM, and provide evidence of this gene as a useful prognostic factor in MM as well as a possible molecular target to design new therapeutic strategies.

Cardiac Fibroelastoma: Cardiovascular Magnetic Resonance Characteristics

Diego Perez de Arenaza,1 Marcelo Pietrani,2 James C. Moon, 3 Hernan Garcia Rivello,4 Nicolas Coccaro,2 Juan Krauss,1 Arturo Cagide,1 Ricardo Garcia Monaco2 Cardiology Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina1 Radiology Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina2 The Heart Hospital, London, UK 3 Pathology Departments, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina4

SOXC and MiR17-92 gene expression profiling defines two subgroups with different clinical outcome in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a heterogeneous B‐cell lymphoid malignancy where most patients follow an aggressive clinical course whereas others are associated with an indolent performance. SOX4, SOX11, and SOX12 belong to SOXC family of transcription factors involved in embryonic neurogenesis and tissue remodeling. Among them, SOX11 has been found aberrantly expressed in most aggressive MCL patients, being considered a reliable biomarker in the pathology. Several studies have revealed that microRNAs (miRs) from the miR‐17‐92 cluster are among the most deregulated miRNAs in human cancers, still little is known about this cluster in MCL. In this study we screened the transcriptional profiles of 70 MCL patients for SOXC cluster and miR17, miR18a, miR19b and miR92a, from the miR‐17‐92 cluster. Gene expression analysis showed higher SOX11 and SOX12 levels compared to SOX4 (P ≤ 0.0026). Moreover we found a negative correlation between the expression of SOX11 and SOX4 (P < 0.0001). miR17‐92 cluster analysis showed that miR19b and miR92a exhibited higher levels than miR17 and miR18a (P < 0.0001). Unsupervised hierarchical clustering revealed two subgroups with significant differences in relation to aggressive MCL features, such as blastoid morphological variant (P = 0.0412), nodal presentation (P = 0.0492), CD5+ (P = 0.0004) and shorter overall survival (P < 0.0001). Together, our findings show for the first time an association between the differential expression profiles of SOXC and miR17‐92 clusters in MCL and also relate them to different clinical subtypes of the disease adding new biological information that may contribute to a better understanding of this pathology.

Surgery for papillary fibroelastoma with uncommon location in left ventricle.

Cardiac papillary fibroelastoma is a rare tumor. Its location in the left ventricular wall is uncommon. A 59-year-old woman with 2 previous strokes presented with a tumor in the left ventricular apex. The patient underwent tumor resection through a left ventriculotomy. The histopathologic diagnosis was papillary fibroelastoma.

Efectos de la administración de glucocorticoides prenatales en el desarrollo de la enterocolitis necrosante en neonatos de rata wistar

INTRODUCTION Necrotizing enterocolitis (NEC) is a frequent problem in preterm infants. Prenatal treatment with steroids proved to be effective for lung maturation and it is thought to have a protective effect on the immature bowel. OBJECTIVES To study the effects of prenatal treatment with steroids at the onset, clinical course and histological pattern of NEC in an animal model. METHODS Pregnant rats received treatment with intraperitoneal hydrocortisone (5 mg/kg) 24 and 48 hrs prior to the expected date of delivery (group S). Control pregnant rats were injected with normal saline, at the same timing (group P). After term delivery by cesarean section, both groups were kept in identical conditions in a neonatal incubator at 35ºC, away from their mothers to prevent any exposure to breast milk. Pups were fed every three hours with neonatal formula via an orogastric tube. To further increase the susceptibility to NEC, pups were exposed to hypoxia followed by hypothermia three times a day for 72 hrs (H-H) or until development of clinical signs of NEC. At that point, each animal was anesthetized and euthanized. The intestine was fixed for histological analysis. Those animals which died before 72 hours were excluded to prevent false positive results in the histopathological exam. RESULTS The clinical signs of NEC include oral intolerance, gastric residuals, respiratory distress, abdominal distension, wall erythema and hematochezia; 60% of animals in group P (n= 16) presented with at least one clinical sign, vs. 40% of pups in group S (n= 15). The onset of clinical signs and clinical course in group S was more benign than in group P. Mortality rate was 40% for pups in group P vs. 20% for group S (NS). Histological analysis indicated that 80% of the animals from group P showed signs of NEC, of which 50% reached grade 3-4 (maximum score of damage), whereas only 40% of the animals in group S presented with signs of NEC (p<0.05), all were of grade 0-1 (minimum histological damage). CONCLUSIONS Prenatal treatment with steroids was effective for amelioration of the onset and clinical presentation in this model of experimental NEC.

Hypertrophic Cardiomyopathy, All Phenotypes in one

Hypertrophic cardiomyopathy (HCM) is an intrinsic myocardial disorder characterized by cardiac hypertrophy (wall thickness ≥ 15 mm), that is not explained by conditions of pressure overload (eg, hypertension, severe aortic stenosis).1 HCM is the most common genetic primary cardiomyopathy, with a prevalence estimated to be about one in 500 adults in the general population.2 More than 450 mutations have been identified in the 20 genes that cause different phenotypes. In most cases, HCM is associated with sarcomere protein gene mutations, and exhibits multiple phenotypic expressions. We present a case that combines all phenotypes.3

Linfoma de amígdala en niño con asimetría tonsilar. caso clínico

Tonsil malignancy is uncommon in children. Tonsillar asymmetry is usually secondary to a benign process, either inflammatory conditions, differences in the tonsillar fossa depth or anterior pillar asymmetry. However, it may indicate a serious underlying disorder such as lymphoma. Lymphoma is the most common childhood malignancy in the head and neck. Approximately, 15% of the cases affect the Waldeyers ring. The most common clinical manifestations of palatine tonsils lymphoma are unilateral tonsillar hypertrophy, alteration in the appearance of the mucosa and ipsilateral cervical lymphadenopathy. Early diagnosis and appropriate treatment are of great importance in the prognosis. We present a case of palatine tonsil lymphoma in a child with tonsillar asymmetry and we emphasize the importance of the examination of the oral cavity and the neck to identify suspicious alterations compatible with tonsillar lymphoma.