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The TRANSPLANTA collection of Arabidopsis lines: a resource for functional analysis of transcription factors based on their conditional overexpression. - The Plant journal : for cell and molecular biology
Transcription factors (TFs) are key regulators of gene expression in all organisms. In eukaryotes, TFs are often represented by functionally redundant members of large gene families. Overexpression might prove a means to unveil the biological functions of redundant TFs; however, constitutive overexpression of TFs frequently causes severe developmental defects, preventing their functional characterization. Conditional overexpression strategies help to overcome this problem. Here, we report on the TRANSPLANTA collection of Arabidopsis lines, each expressing one of 949 TFs under the control of a Î²-estradiol-inducible promoter. Thus far, 1636 independent homozygous lines, representing an average of 2.6 lines for every TF, have been produced for the inducible expression of 634 TFs. Along with a GUS-GFP reporter, randomly selected TRANSPLANTA lines were tested and confirmed for conditional transgene expression upon Î²-estradiol treatment. As a proof of concept for the exploitation of this resource, Î²-estradiol-induced proliferation of root hairs, dark-induced senescence, anthocyanin accumulation and dwarfism were observed in lines conditionally expressing full-length cDNAs encoding RHD6, WRKY22, MYB123/TT2 and MYB26, respectively, in agreement with previously reported phenotypes conferred by these TFs. Further screening performed with other TRANSPLANTA lines allowed the identification of TFs involved in different plant biological processes, illustrating that the collection is a powerful resource for the functional characterization of TFs. For instance, ANAC058 and a TINY/AP2 TF were identified as modulators of ABA-mediated germination potential, and RAP2.10/DEAR4 was identified as a regulator of cell death in the hypocotyl-root transition zone. Seeds of TRANSPLANTA lines have been deposited at the Nottingham Arabidopsis Stock Centre for further distribution.Â© 2014 The Authors The Plant Journal Â© 2014 John Wiley & Sons Ltd.
Radiological diagnosis and staging of hilar cholangiocarcinoma. - World journal of gastrointestinal oncology
Hilar cholangiocarcinoma is a rare malignant tumor arising from the epithelium of the bile ducts. Surgery is still the only chance of potentially curative treatment in patients with perihilar cholangiocarcinoma. However, radical resection requires aggressive surgical strategies that should be tailored optimally according to the location, size and vascular invasion of the tumors. Accurate diagnosis and staging of these tumors is therefore critical for optimal treatment planning and for determining a prognosis. Multidetector computed tomography (MDCT), magnetic resonance imaging (MRI) and MR cholangiography are useful tools, both to diagnose and stage hilar cholangiocarcinoma. Modern imaging techniques allow accurate detection of the level of obstruction and the longitudinal and radial spread of the tumor. In addition, high-resolution MDCT and MR provide specific radiographic features to determine vascular involvement of anatomic structures, such as the hepatic artery or the portal vein, which are critical to decide the surgical strategy. Finally, radiological staging allows detection of patients with distant metastasis in the liver or peritoneum who will not benefit from a surgical approach.
Children's Memory for Their Mother's Murder: Accuracy, Suggestibility, and Resistance to Suggestion. - Memory (Hove, England)
From its inception, child eyewitness memory research has been guided by dramatic legal cases that turn on the testimony of children. Decades of scientific research reveal that, under many conditions, children can provide veracious accounts of traumatic experiences. Scientific studies also document factors that lead children to make false statements. In this paper we describe a legal case in which children testified about their mother's murder. We discuss factors that may have influenced the accuracy of the children's eyewitness memory. Children's suggestibility and resistance to suggestion are illustrated. Expert testimony, based on scientific research, can aid the trier of fact when children provide crucial evidence in criminal investigations and courtroom trials about tragic events.
Executive function in Parkinson's disease: contributions of the dorsal frontostriatal pathways to action and motivation. - Cognitive, affective & behavioral neuroscience
Disruption of the dorsal frontostriatal pathways in Parkinson's disease (PD) is associated with impairments in motivation, as well as in executive function. The goal of this study was to investigate whether these impairments are related and, if so, whether the disruption of frontostriatal pathways compromises the ability to process the motivational aspects of feedback in such tasks. In Experiment 1, informative feedback improved the performance of young, healthy participants in a task-switching paradigm. This task-switching paradigm was then used in Experiment 2 to test whether feedback would improve the performance of 17 PD patients and age-matched controls. The PD group benefitted from feedback to the same degree as control participants; however, depression scores on the Beck Depression Inventory were significantly related to feedback usage, especially when response selection demands were high. Regardless of feedback, PD patients were more impaired when response demands were high than in an equally difficult condition with low action demands. These results suggest that response selection is a core impairment of insufficient dopamine to the dorsal frontal striatal pathways.
Preoperative staging of patients with liver metastases of colorectal carcinoma. Does PET/CT really add something to multidetector CT? - Annals of surgical oncology
This study was designed to determine prospectively whether the systematic use of PET/CT associated with conventional techniques could improve the accuracy of staging in patients with liver metastases of colorectal carcinoma. We also assessed the impact on the therapeutic strategy.Between 2006 and 2008, 97 patients who were evaluated for resection of LMCRC were prospectively enrolled. Preoperative workup included multidetector-CT (MDCT) and PET/CT. In 11 patients with liver steatosis or iodinated contrast allergy, MR also was performed. Sixty-eight patients underwent laparotomy. Sensitivity, specificity, positive predictive value (PPV), and negative predictive values for hepatic and extrahepatic staging of MDCT and PET-CT were calculated.In a lesion-by-lesion analysis of the hepatic staging, the sensitivity of MDCT/RM was superior to PET/CT (89.2 vs. 55%, pÂ <Â 0.001). On the extrahepatic staging, PET/CT was superior to MDCT/MR only for the detection of locoregional recurrence (pÂ =Â 0.03) and recurrence in uncommon sites (pÂ =Â 0.016). New findings in PET/CT resulted in a change in therapeutic strategy in 17 patients. However, additional information was correct only in eight cases and wrong in nine patients.PET/CT has a limited role in hepatic staging of LMCRC. Although PET-CT has higher sensitivity for the detection of extrahepatic disease in some anatomic locations, its results are hampered by its low PPV. PET/CT provided additional useful information in 8% of the cases but also incorrect and potentially harmful data in 9% of the staging. Our findings support a more selective use of PET/CT, basically in patients with high risk of local recurrence.
Left TPJ activity in verbal working memory: implications for storage- and sensory-specific models of short term memory. - NeuroImage
Patients with damage to the left temporoparietal junction (TPJ) have a low verbal span without concomitant deficits in speech perception. This pattern of cognitive impairment is taken as evidence for a dedicated phonological buffer that plays little role in perception (storage-specific account). In contrast, other research suggests that items are maintained and perceived in the same regions (sensory-specific account). In an fMRI study, we demonstrate that the left TPJ does not respond in a way predicted of a phonological buffer; that is, activity in this region is not sustained during encoding or maintenance. Instead, a region in the superior temporal gyrus that has been associated with both speech perception and production demonstrated the expected profile of a store: it was more active in the verbal condition than the object condition and was active during both encoding and maintenance. These results support the sensory-specific account of short term memory rather than the storage-specific account. Based on the pattern of activity in the left TPJ, we suggest that the impairment of verbal working memory observed in patients with TPJ damage may be due to diminished attentional processes rather than reduced storage capacity.Copyright Â© 2010 Elsevier Inc. All rights reserved.
Primary hepatic leiomyoma: case report. - Abdominal imaging
The patient is a previously healthy 28-year-old woman with incidentally detected focal liver lesion. On CT, the tumor showed brisk arterial enhancement and persistent hyperenhancement on portal and delayed phases. Histological study showed spindle cells without atypia and immunohistochemical study was consistent with leiomyoma.
[Use of PET-CT in pre-surgical staging of colorectal cancer hepatic metastases]. - CirugÃa espaÃ±ola
Unsuspected intrahepatic and extrahepatic metastases are frequently discovered at laparotomy in patients with resectable colorectal liver metastases (CLM), and 60% of these patients will develop a recurrent tumour within 3 years, after a "curative" liver resection. These findings strongly support the need for more effective preoperative staging. The combined positron emission tomography-computed tomography technique (PET-CT) has emerged as a promising diagnostic modality for determining whether patients with recurrent disease in the liver are suitable candidates for curative resection.The aim of this study was to assess the additional value of information provided by PET-CT compared to that of conventional radiological studies (CT and MR) in patients with resectable CLM.Between June 2006 and August 2007, 63 patients evaluated for a first resection of CLM were entered into a prospective database. Each patient received a CT-MR and a PET-CT. Forty-three patients underwent a laparotomy and 42 a hepatectomy. The main end point of the study was to assess the impact of the PET-CT findings on the therapeutic strategy.New findings in the PET-CT resulted in a change in the therapeutic strategy in 9 (14%) of the patients. However, PET-CT provided additional information was true positive by revealing abdominal extrahepatic metastases only in 4 (6.4%) patients, and falsely over-staged four patients and under staged one patient. Lesion-by-lesion sensitivity and predictive positive value for liver lesions were 78,4% and 96% for CT-MR alone, and 55% and 100% for PET-CT respectively. PET-CT was superior to CT-MR for the detection of local recurrence at the site of the initial colorectal surgery.In the selection of patients with CLM being considered for surgical therapy, PET-CT provided useful information only in 6.4% of cases. Possibly longer follow-up will increase this percentage. Our findings support the use of PET-CT mainly in patients with high risk of local recurrence.
Overexpression of urokinase receptor and cell surface urokinase-type plasminogen activator in the human vessel wall with different types of atherosclerotic lesions. - Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
Urokinase-type plasminogen activator (UPA) has been implicated in a broad spectrum of pathogenic processes involved in the formation and disruption of atherosclerotic lesions. Up to now, there is no consensus on the contribution of membrane-bound UPA and its receptor CD87 (UPAR) to the development of atherosclerosis. In this study, we determined comparatively the levels of UPAR and UPAR-bound UPA in segments of human coronary and aortic vessels with different degrees of atherosclerotic lesions (macroscopically normal areas, early atherosclerotic lesions, fibrous and calcified plaques). The UPAR content increased progressively with the severity of atherosclerosis. In aortic segments, in which intima and media layers were analyzed separately, the content of UPAR in the intima significantly exceeded the levels measured in the media. Using a detergent-phase separation method with a Triton X-114-containing buffer, we could demonstrate that the levels of membrane (glycosylphosphatidylinositol)-anchored UPAR were significantly higher in the intima of early atherosclerotic lesions as well as in the cap areas of fibrous plaques compared with macroscopically normal areas. However, only 20-25% of the intimal and 30-50% of the medial glycosylphosphatidylinositol-UPAR was occupied by UPA as determined on a molar basis. These data confirm that the overexpression of UPAR in advanced atherosclerotic lesions contributes to lesion development. Whether UPAR's excess over cell surface UPA provides an additional role for this receptor in atherogenesis besides UPA-mediated proteolysis remains to be elucidated.Copyright 2004 Lippincott Williams and Wilkins
Efficacy and safety of thalidomide in patients with acute myeloid leukemia. - Blood
Emerging data suggest an involvement of angiogenesis in the pathophysiology of acute myeloid leukemia (AML). Thus, antiangiogenic therapy could constitute a novel strategy for the treatment of AML. To test this hypothesis, a phase I/II dose-escalating trial was performed to study the safety and efficacy of thalidomide, a putative inhibitor of angiogenesis, in 20 patients with AML. Thirteen patients were assessable for both toxicity and response, tolerating a maximum dose of 200 to 400 mg daily for at least 1 month. Seven patients had to be prematurely withdrawn from drug administration owing to progressive disease and death (3 patients), personal decision (2 patients), or inability to tolerate thalidomide (2 patients). Overall, adverse events were fatigue, constipation, rash, and neuropathy (grade 1 to 2 in most patients). In 4 patients, a partial response, defined as reduction of at least 50% in the blast cell infiltration of the bone marrow accompanied by increases in platelet counts and hemoglobin values, was observed. One additional patient showed a hematologic improvement without fulfilling the criteria of a partial response. The responses lasted a median of 3 months (range, 1-8 months). In parallel, microvessel densities significantly decreased in these 5 patients during treatment with thalidomide (P <.05). This decrease was accompanied by declining plasma levels of basic fibroblast growth factor, one of the most potent angiogenic growth factors. In conclusion, single-agent thalidomide has antiangiogenic and antileukemic activity in AML, although a causal relationship between both effects has still to be proven.
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