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Papers by Roberto Diaz

Las reliquias del pasado que contiene el Palacio Yurrita, son las que hacen pensar que tiene un... more Las reliquias del pasado que contiene el Palacio Yurrita, son las que hacen pensar que tiene un interés mayor que todo lo que se haya podido contemplar en cualquier casa de habitación de principios de siglo, la diferencia está bien marcada con la utilización de un estilo único, parecido en cantidad con el Barroco, pero al mismo tiempo diferente en formas, figuras y elementos que tienen su origen en la mente excéntrica de su creador

Chordomas are rare malignant tumors arising in bone of the spheno-occiput, sacrum, and vertebral ... more Chordomas are rare malignant tumors arising in bone of the spheno-occiput, sacrum, and vertebral column which can cause neurological deficit. Current management of chordoma involves safe resection followed by radiation therapy. However, surgical resection is often subtotal and chordoma often recurs despite optimal therapy. Despite years of effort, effective adjuvant therapy for denovo, recurrent and metastatic chordoma are absent and 5-year survival is at best 65%. While no chemotherapeutic agent has been demonstrated to be effective against chordoma in vivo, a greater understanding of the genetics and molecular biology of chordoma is opening up avenues of investigation towards the rational development of targeted therapies. Although enthusiasm for the use of already established or new investigational agents will increase with greater understanding of chordoma biology, laboratory studies of these agents are important prior to incorporation into clinical human trials. The authors review the current state of knowledge regarding chordoma and offer insight into potential new therapies for this rare and challenging tumor.

International Journal of Cancer, 2005

Point mutations in ras genes have been found in a large number and wide variety of human tumors. ... more Point mutations in ras genes have been found in a large number and wide variety of human tumors. These oncogenic Ras mutants are locked in an active GTP-bound state that leads to a constitutive and deregulated activation of Ras function. The dogma that ras oncogenes are dominant, whereby the mutation of a single allele in a cell will predispose the host cell to transformation regardless of the presence of the normal allele, is being challenged. We have seen that increasing amounts of Ras protooncogenes are able to inhibit the activity of the N-Ras oncogene in the activation of Elk in NIH 3T3 cells and in the formation of foci. We have been able to determine that the inhibitory effect is by competition between Ras protooncogenes and the N-Ras oncogene that occurs first at the effector level at the membranes, then at the processing level and lastly at the effector level in the cytosol. In addition, coexpression of the N-Ras protooncogene in thymic lymphomas induced by the N-Ras oncogene is associated with increased levels of p107, p130 and cyclin A and decreased levels of Rb. In the present report, we have shown that the N-Ras oncogene is not truly dominant over Ras protooncogenes and their competing activities might be depending on cellular context.

Clinical Colorectal Cancer, 2005

Background: The objective of this study was to analyze prognostic factors for survival and to ass... more Background: The objective of this study was to analyze prognostic factors for survival and to assess the applicability of Köhne's classification in patients treated with irinotecan-or oxaliplatin-based first-line chemotherapy. Patients and Methods: One hundred forty-two consecutive cases from a single center were retrospectively reviewed. Median patient age was 62 years. Sixty percent were men. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0/1 in 88%. Primary tumor resection (PTR) was performed in 80.6% of patients who initially had stage IV disease. Chemotherapy consisted of fluoropyrimidines or raltitrexed plus irinotecan (50.5%), oxaliplatin (38.5%), or both (11%).Univariate and multivariate analyses for survival were performed using pretreatment patient characteristics. Results: Median follow-up was 33.9 months and median overall survival was 15.9 months. Significantly unfavorable prognostic factors were PTR not being performed, disease involvement of > 1 organ, liver metastases, undifferentiated histology, EGOG PS > 1, increased serum carcinoembryonic antigen and cancer antigen 19.9 levels, hypoalbuminemia, leucocytosis, and elevated alkaline phosphatase and lactate dehydrogenase (LDH) levels. Only ECOG PS, PTR, increased LDH level, no hypoalbuminemia, and number of organs involved retained prognostic value in the multivariate analysis.The incidence and median survival for Köhne's prognostic groups were as follows: good (54.2%; 20 months), intermediate (26.8%; 15.7 months), and poor (19%; 6.8 months). For patients with stage IV disease at presentation, PTR was associated with a significantly longer survival, mainly in patients with an ECOG PS of 0/1. Conclusion: Eastern Cooperative Oncology Group PS, PTR, serum albumin, increased LDH levels, and organ involvement were the main prognostic indicators in our series. Köhne's prognostic groups, developed in the era of 5-fluorouracil treatment, also seem to be applicable to patients treated with combination chemotherapy. Primary tumor resection should always be considered, especially in patients with an ECOG PS of 0/1. However, the benefit of PTR and multiple-agent chemotherapy is questionable in patients with an ECOG PS of > 1.

Clinical Colorectal Cancer, 2003

European Respiratory Journal, 2004

Central nervous system metastases of a pulmonary epitheloid haemangioendothelioma. R. Díaz, Á. Se... more Central nervous system metastases of a pulmonary epitheloid haemangioendothelioma. R. Díaz, Á. Segura, V. Calderero, I. Cervera, J. Aparicio, M.V. Jordá, L. Pellín. #ERS Journals Ltd 2004.

Digestive Diseases and Sciences, 1965

The records of 1258 patients with ulcerative colitis who were seen at the Cleveland Clinic in the... more The records of 1258 patients with ulcerative colitis who were seen at the Cleveland Clinic in the years 1950 through 1963 were reviewed. Twenty-four cases of carcinoma of the colon were found, an approximate overall incidence of 1.9%. Of these 24 patients, 15 died of the carcinoma; 1 patient died of an unrelated condition, and 8 patients are living and well. Carcinoma was found to occur in patients with ulcerative colitis at an age earlier than that at which colonic malignant lesions develop in persons without colitis. The mean age of diagnosis of colonic carcinoma was 40.7 years. The mean interval between the onset of colitis and the time of diagnosis of colonic carcinoma was 18.3 years. Ten of the 24 patients had multiple carcinomas, including 3 with multifocal lesions of carcinoma in situ. Of 29 separate carcinomas found, 14 were in the rectosigmoid. The most frequent symptoms of neoplasm simulated those of an exacerbation of the colitis, and included diarrhea, abdominal pain, rectal bleeding, and weight loss. The unreliability of roentgenographic diagnosis of colonic carcinoma in association with colitis was re-emphasized by our study, as 6 of 13 potentially diagnosable lesions were missed. Carcinoma of the colon arising in patients with long-standing ulcerative colitis is a serious hazard, but is not so frequent as has been suspected. However, the physician who treats the patient with ulcerative colitis should be wary of new symptoms and should manage them vigorously with appropriate diagnostic and therapeutic procedures. In this manner, carcinoma may be detected early, and survival rates may be improved.

Digestive Diseases and Sciences, 1962

Journal of Molecular and Cellular Cardiology, 2001

We have analyzed the time-dependent changes in the expression of IL-la and -B, IL-2, -3 ,-4, -5, ... more We have analyzed the time-dependent changes in the expression of IL-la and -B, IL-2, -3 ,-4, -5, -6, IFNy, and TNF-a and -8 mRNA in the infarct area (MI-A) and in the non-infarcted left ventricle (LV) by RF'A after myocardial infarction (MI) in rats. In both, the MI-A and the LV, IL-18 and IL-6 mRNA expression was strongly increased as early as 6 h after Ml. Both, IL-l!3 and IL-6 mRNA, were further increased in the MI-A 12 h after MI, while there was a decrease in the LV. From day 3 up to 12 weeks after MI, almost control levels were found. No signals were detected for the other cytokines at any time studied, except that TNF-a was slightly increased around day 1, Myocardial IL-6 protein was elevated from day I to day 4 as determined by western-blotting. These data were supported by immunohistochemistry in that strong signals for IL-6 were obtained in the MI-A and in the adjacent border zone from day 1 to day 4 after MI.

Journal of Molecular and Cellular Cardiology, 1997

The aim of the present study was to assess the participation of angiotensin II receptors in the t... more The aim of the present study was to assess the participation of angiotensin II receptors in the triggering mechanism of ischemic preconditioning. Isolated buffer-perfused rabbit hearts were subjected to 40 min of regional ischemia (37 degrees C) followed by 60 min of reperfusion. Ischemic preconditioning was induced with three cycles of 5-min ischemia and 10-min reperfusion given prior to the 40-min ischemic period. Infarct size and ventricular function were assessed. Ischemic preconditioning reduced infarct size to 5.2 +/- 1.2% of the area at risk (mean +/- S.E.M., P<0.001) when compared to controls (26.4 +/- 3.0%), but did not protect against ventricular dysfunction. Activation of angiotensin II receptors with angiotensin II (100 nM) also limited infarct size (9.6 +/- 2.2%, P<O.01 v control group). Inhibition of angiotensin II receptors with [Sar1, Val5, Ala8]-angiotensin II (saralasin, 1 microM) blocked the protection of ischemic preconditioning against necrosis (29.7 +/- 3.2%) while it did not increase infarct size in saralasin-treated control hearts (31.5 +/- 3.9%). Furthermore, inhibition of the AT1 subtype of the angiotensin II receptor with losartan (20 microM), but not inhibition of the AT2 subtype with PD-123,319 ditrifluoroacetate (10 microM), abolished the infarct size-limiting effect of ischemic preconditioning. We conclude that the AT1 angiotensin II receptor participates in ischemic preconditioning. Thus, in the isolated rabbit heart, activation of AT1 receptors must occur before prolonged ischemia for ischemic preconditioning to limit infarction.

Transplantation, 1994

Tyrosine phosphorylation is an early, critical event in lymphocyte signal transduction. We measur... more Tyrosine phosphorylation is an early, critical event in lymphocyte signal transduction. We measured tyrosine phosphorylation in a porcine experimental transplant model to evaluate its utility in monitoring the allograft immune response. Using flow cytometry, we demonstrate a biphasic increase in phosphotyrosine (ptyr) levels in peripheral blood mononuclear cells (PBMC), and that increases are detectable as early as 1 day posttransplantation in untreated transplanted animals (n = 4). This biphasic response is likely result from the sequestration of ptyr+ cells from the periphery into the graft as graft-infiltrating lymphocytic cells show increased ptyr levels. This suggests possible lymphocyte trafficking between the peripheral compartment and the allograft. A 5-day course of treatment with cyclosporine (CsA) at 20 mg/kg/day (n = 4), but not at 10 mg/kg/day (n = 4), prevents graft rejection in this allograft model. Strikingly, treatment with 20 mg/kg/day CsA, but not with 10 mg/kg/day, suppressed increases in ptyr levels in both PBMC and graft-infiltrating cells. Increases in ptyr levels in PBMC are detectable 2-5 days before histologic and electrocardiographic signs of graft rejection, suggesting a potential diagnostic utility for measuring tyrosine phosphorylation in monitoring and managing transplant rejection.

Isolated cardiomyocytes, obtained by enzymatic digestion of whole hearts, have multiple advantage... more Isolated cardiomyocytes, obtained by enzymatic digestion of whole hearts, have multiple advantages, most related to their accessibility to microscopic visualization, beyond the obvious elimination of other cell types that exist in the heart. Conversely, they cannot reproduce the mechanical disruption of reperfusion hypercontracture or the vascular phenomena of leukocyte plugging and compression from interstitial edema and contracture that can lead to the no-reflow phenomenon. Nevertheless, ischemic preconditioning has been consistently demonstrated to be a potent protective mechanism in freshly isolated and cultured cardiomyocytes across multiple species, indicating that much of the innate protection of ischemic preconditioning resides in cardiomyocytes. Centrifuging freshly isolated cardiomyocytes into a pellet with only a thin layer of supernatant covered by oil has proven to be an excellent model of simulated ischemia. In culture, cardiomyocytes may be exposed to severe hypoxia only or to various protocols for simulated ischemia in which an acid/lactate-rich, hyperkalemic extracellular environment with substrate deprivation (lacking glucose) is typically added. Reperfusion is simulated by welloxygenated media of normal ionic composition. Cardiomyocyte injury has been usually evaluated by cell membrane permeability to dyes, often under hypo-osmotic conditions (osmotic fragility) or enzyme release. A survey of the use of cardiomyocyte models to study preconditioning is presented with the emphasis on examples of the innovative measurements, increasingly involving molecular techniques, that point to an increasing future role for these models in preconditioning research and, more generally, in the mechanistic study of myocardial ischemia/reperfusion.

Journal of Molecular and Cellular Cardiology, 2001

Other by Roberto Diaz

OBJECTIVES AND FIRST RESULTS OF THE PROGRAM OF MOSAIC DOCUMENTATION IN THE QUIRIGUA ARCHAEOLOGICA... more OBJECTIVES AND FIRST RESULTS OF THE PROGRAM OF MOSAIC DOCUMENTATION IN THE QUIRIGUA ARCHAEOLOGICAL PARK Quirigua is renowned for the size and beauty of its stelae, zoomorphs, and altars. But the sculptural richness that this ancient city possesses is even greater than what is known. More than 1000 fragments of sculptures, most of which were attached to the walls of the structures that make up the Acropolis of the site, have been preserved in the storehouses at the site for many years. Unfortunately, almost all of these mosaics were stored without documentation or provenience. And so, in December of 2008, the task of ordering and cataloguing these pieces began. We hope to complete this study and reintegrate these works back into the architecture at the site. INTRODUCCIÓN Quirigua es reconocido dentro del área Maya por el tamaño y belleza de sus estelas, zoomorfos y altares. Sin embargo, la riqueza escultórica que posee es mucho más grande y casi desconocida, ya que por muchos años se han almacenado en las bodegas del parque más de 1000 fragmentos de esculturas que en su mayoría estaban adosadas a los muros de las estructuras del sitio. Estos fragmentos de escultura son denominados como mosaicos debido a que corresponden a bloques tallados individualmente y que posteriormente, se ensamblaban con otros para formar algún motivo. Desafortunadamente casi todos estos mosaicos fueron guardados sin documentación y procedencia. Por lo que en Diciembre del 2008, se inició su ordenamiento y catalogación con el objetivo de identificar los motivos representados y su posible ubicación. Se espera que al completar este estudio dichos mosaicos puedan ser reintegrados a la arquitectura del sitio. ANTECEDENTES En las Tierras Bajas Mayas del sureste, la ciudad de Copán inicia hacia finales del Clásico Temprano con la tradición de decorar sus edificios con mosaicos. Martin y Grube (2002:198-199) indican que el último edificio de Copán en donde se utilizó como decoración el estuco modelado, fue el famoso

Las reliquias del pasado que contiene el Palacio Yurrita, son las que hacen pensar que tiene un... more Las reliquias del pasado que contiene el Palacio Yurrita, son las que hacen pensar que tiene un interés mayor que todo lo que se haya podido contemplar en cualquier casa de habitación de principios de siglo, la diferencia está bien marcada con la utilización de un estilo único, parecido en cantidad con el Barroco, pero al mismo tiempo diferente en formas, figuras y elementos que tienen su origen en la mente excéntrica de su creador

Chordomas are rare malignant tumors arising in bone of the spheno-occiput, sacrum, and vertebral ... more Chordomas are rare malignant tumors arising in bone of the spheno-occiput, sacrum, and vertebral column which can cause neurological deficit. Current management of chordoma involves safe resection followed by radiation therapy. However, surgical resection is often subtotal and chordoma often recurs despite optimal therapy. Despite years of effort, effective adjuvant therapy for denovo, recurrent and metastatic chordoma are absent and 5-year survival is at best 65%. While no chemotherapeutic agent has been demonstrated to be effective against chordoma in vivo, a greater understanding of the genetics and molecular biology of chordoma is opening up avenues of investigation towards the rational development of targeted therapies. Although enthusiasm for the use of already established or new investigational agents will increase with greater understanding of chordoma biology, laboratory studies of these agents are important prior to incorporation into clinical human trials. The authors review the current state of knowledge regarding chordoma and offer insight into potential new therapies for this rare and challenging tumor.

International Journal of Cancer, 2005

Point mutations in ras genes have been found in a large number and wide variety of human tumors. ... more Point mutations in ras genes have been found in a large number and wide variety of human tumors. These oncogenic Ras mutants are locked in an active GTP-bound state that leads to a constitutive and deregulated activation of Ras function. The dogma that ras oncogenes are dominant, whereby the mutation of a single allele in a cell will predispose the host cell to transformation regardless of the presence of the normal allele, is being challenged. We have seen that increasing amounts of Ras protooncogenes are able to inhibit the activity of the N-Ras oncogene in the activation of Elk in NIH 3T3 cells and in the formation of foci. We have been able to determine that the inhibitory effect is by competition between Ras protooncogenes and the N-Ras oncogene that occurs first at the effector level at the membranes, then at the processing level and lastly at the effector level in the cytosol. In addition, coexpression of the N-Ras protooncogene in thymic lymphomas induced by the N-Ras oncogene is associated with increased levels of p107, p130 and cyclin A and decreased levels of Rb. In the present report, we have shown that the N-Ras oncogene is not truly dominant over Ras protooncogenes and their competing activities might be depending on cellular context.

Clinical Colorectal Cancer, 2005

Background: The objective of this study was to analyze prognostic factors for survival and to ass... more Background: The objective of this study was to analyze prognostic factors for survival and to assess the applicability of Köhne's classification in patients treated with irinotecan-or oxaliplatin-based first-line chemotherapy. Patients and Methods: One hundred forty-two consecutive cases from a single center were retrospectively reviewed. Median patient age was 62 years. Sixty percent were men. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0/1 in 88%. Primary tumor resection (PTR) was performed in 80.6% of patients who initially had stage IV disease. Chemotherapy consisted of fluoropyrimidines or raltitrexed plus irinotecan (50.5%), oxaliplatin (38.5%), or both (11%).Univariate and multivariate analyses for survival were performed using pretreatment patient characteristics. Results: Median follow-up was 33.9 months and median overall survival was 15.9 months. Significantly unfavorable prognostic factors were PTR not being performed, disease involvement of > 1 organ, liver metastases, undifferentiated histology, EGOG PS > 1, increased serum carcinoembryonic antigen and cancer antigen 19.9 levels, hypoalbuminemia, leucocytosis, and elevated alkaline phosphatase and lactate dehydrogenase (LDH) levels. Only ECOG PS, PTR, increased LDH level, no hypoalbuminemia, and number of organs involved retained prognostic value in the multivariate analysis.The incidence and median survival for Köhne's prognostic groups were as follows: good (54.2%; 20 months), intermediate (26.8%; 15.7 months), and poor (19%; 6.8 months). For patients with stage IV disease at presentation, PTR was associated with a significantly longer survival, mainly in patients with an ECOG PS of 0/1. Conclusion: Eastern Cooperative Oncology Group PS, PTR, serum albumin, increased LDH levels, and organ involvement were the main prognostic indicators in our series. Köhne's prognostic groups, developed in the era of 5-fluorouracil treatment, also seem to be applicable to patients treated with combination chemotherapy. Primary tumor resection should always be considered, especially in patients with an ECOG PS of 0/1. However, the benefit of PTR and multiple-agent chemotherapy is questionable in patients with an ECOG PS of > 1.

Clinical Colorectal Cancer, 2003

European Respiratory Journal, 2004

Central nervous system metastases of a pulmonary epitheloid haemangioendothelioma. R. Díaz, Á. Se... more Central nervous system metastases of a pulmonary epitheloid haemangioendothelioma. R. Díaz, Á. Segura, V. Calderero, I. Cervera, J. Aparicio, M.V. Jordá, L. Pellín. #ERS Journals Ltd 2004.

Digestive Diseases and Sciences, 1965

The records of 1258 patients with ulcerative colitis who were seen at the Cleveland Clinic in the... more The records of 1258 patients with ulcerative colitis who were seen at the Cleveland Clinic in the years 1950 through 1963 were reviewed. Twenty-four cases of carcinoma of the colon were found, an approximate overall incidence of 1.9%. Of these 24 patients, 15 died of the carcinoma; 1 patient died of an unrelated condition, and 8 patients are living and well. Carcinoma was found to occur in patients with ulcerative colitis at an age earlier than that at which colonic malignant lesions develop in persons without colitis. The mean age of diagnosis of colonic carcinoma was 40.7 years. The mean interval between the onset of colitis and the time of diagnosis of colonic carcinoma was 18.3 years. Ten of the 24 patients had multiple carcinomas, including 3 with multifocal lesions of carcinoma in situ. Of 29 separate carcinomas found, 14 were in the rectosigmoid. The most frequent symptoms of neoplasm simulated those of an exacerbation of the colitis, and included diarrhea, abdominal pain, rectal bleeding, and weight loss. The unreliability of roentgenographic diagnosis of colonic carcinoma in association with colitis was re-emphasized by our study, as 6 of 13 potentially diagnosable lesions were missed. Carcinoma of the colon arising in patients with long-standing ulcerative colitis is a serious hazard, but is not so frequent as has been suspected. However, the physician who treats the patient with ulcerative colitis should be wary of new symptoms and should manage them vigorously with appropriate diagnostic and therapeutic procedures. In this manner, carcinoma may be detected early, and survival rates may be improved.

Digestive Diseases and Sciences, 1962

Journal of Molecular and Cellular Cardiology, 2001

We have analyzed the time-dependent changes in the expression of IL-la and -B, IL-2, -3 ,-4, -5, ... more We have analyzed the time-dependent changes in the expression of IL-la and -B, IL-2, -3 ,-4, -5, -6, IFNy, and TNF-a and -8 mRNA in the infarct area (MI-A) and in the non-infarcted left ventricle (LV) by RF'A after myocardial infarction (MI) in rats. In both, the MI-A and the LV, IL-18 and IL-6 mRNA expression was strongly increased as early as 6 h after Ml. Both, IL-l!3 and IL-6 mRNA, were further increased in the MI-A 12 h after MI, while there was a decrease in the LV. From day 3 up to 12 weeks after MI, almost control levels were found. No signals were detected for the other cytokines at any time studied, except that TNF-a was slightly increased around day 1, Myocardial IL-6 protein was elevated from day I to day 4 as determined by western-blotting. These data were supported by immunohistochemistry in that strong signals for IL-6 were obtained in the MI-A and in the adjacent border zone from day 1 to day 4 after MI.

Journal of Molecular and Cellular Cardiology, 1997

The aim of the present study was to assess the participation of angiotensin II receptors in the t... more The aim of the present study was to assess the participation of angiotensin II receptors in the triggering mechanism of ischemic preconditioning. Isolated buffer-perfused rabbit hearts were subjected to 40 min of regional ischemia (37 degrees C) followed by 60 min of reperfusion. Ischemic preconditioning was induced with three cycles of 5-min ischemia and 10-min reperfusion given prior to the 40-min ischemic period. Infarct size and ventricular function were assessed. Ischemic preconditioning reduced infarct size to 5.2 +/- 1.2% of the area at risk (mean +/- S.E.M., P<0.001) when compared to controls (26.4 +/- 3.0%), but did not protect against ventricular dysfunction. Activation of angiotensin II receptors with angiotensin II (100 nM) also limited infarct size (9.6 +/- 2.2%, P<O.01 v control group). Inhibition of angiotensin II receptors with [Sar1, Val5, Ala8]-angiotensin II (saralasin, 1 microM) blocked the protection of ischemic preconditioning against necrosis (29.7 +/- 3.2%) while it did not increase infarct size in saralasin-treated control hearts (31.5 +/- 3.9%). Furthermore, inhibition of the AT1 subtype of the angiotensin II receptor with losartan (20 microM), but not inhibition of the AT2 subtype with PD-123,319 ditrifluoroacetate (10 microM), abolished the infarct size-limiting effect of ischemic preconditioning. We conclude that the AT1 angiotensin II receptor participates in ischemic preconditioning. Thus, in the isolated rabbit heart, activation of AT1 receptors must occur before prolonged ischemia for ischemic preconditioning to limit infarction.

Transplantation, 1994

Tyrosine phosphorylation is an early, critical event in lymphocyte signal transduction. We measur... more Tyrosine phosphorylation is an early, critical event in lymphocyte signal transduction. We measured tyrosine phosphorylation in a porcine experimental transplant model to evaluate its utility in monitoring the allograft immune response. Using flow cytometry, we demonstrate a biphasic increase in phosphotyrosine (ptyr) levels in peripheral blood mononuclear cells (PBMC), and that increases are detectable as early as 1 day posttransplantation in untreated transplanted animals (n = 4). This biphasic response is likely result from the sequestration of ptyr+ cells from the periphery into the graft as graft-infiltrating lymphocytic cells show increased ptyr levels. This suggests possible lymphocyte trafficking between the peripheral compartment and the allograft. A 5-day course of treatment with cyclosporine (CsA) at 20 mg/kg/day (n = 4), but not at 10 mg/kg/day (n = 4), prevents graft rejection in this allograft model. Strikingly, treatment with 20 mg/kg/day CsA, but not with 10 mg/kg/day, suppressed increases in ptyr levels in both PBMC and graft-infiltrating cells. Increases in ptyr levels in PBMC are detectable 2-5 days before histologic and electrocardiographic signs of graft rejection, suggesting a potential diagnostic utility for measuring tyrosine phosphorylation in monitoring and managing transplant rejection.

Isolated cardiomyocytes, obtained by enzymatic digestion of whole hearts, have multiple advantage... more Isolated cardiomyocytes, obtained by enzymatic digestion of whole hearts, have multiple advantages, most related to their accessibility to microscopic visualization, beyond the obvious elimination of other cell types that exist in the heart. Conversely, they cannot reproduce the mechanical disruption of reperfusion hypercontracture or the vascular phenomena of leukocyte plugging and compression from interstitial edema and contracture that can lead to the no-reflow phenomenon. Nevertheless, ischemic preconditioning has been consistently demonstrated to be a potent protective mechanism in freshly isolated and cultured cardiomyocytes across multiple species, indicating that much of the innate protection of ischemic preconditioning resides in cardiomyocytes. Centrifuging freshly isolated cardiomyocytes into a pellet with only a thin layer of supernatant covered by oil has proven to be an excellent model of simulated ischemia. In culture, cardiomyocytes may be exposed to severe hypoxia only or to various protocols for simulated ischemia in which an acid/lactate-rich, hyperkalemic extracellular environment with substrate deprivation (lacking glucose) is typically added. Reperfusion is simulated by welloxygenated media of normal ionic composition. Cardiomyocyte injury has been usually evaluated by cell membrane permeability to dyes, often under hypo-osmotic conditions (osmotic fragility) or enzyme release. A survey of the use of cardiomyocyte models to study preconditioning is presented with the emphasis on examples of the innovative measurements, increasingly involving molecular techniques, that point to an increasing future role for these models in preconditioning research and, more generally, in the mechanistic study of myocardial ischemia/reperfusion.

Journal of Molecular and Cellular Cardiology, 2001

OBJECTIVES AND FIRST RESULTS OF THE PROGRAM OF MOSAIC DOCUMENTATION IN THE QUIRIGUA ARCHAEOLOGICA... more OBJECTIVES AND FIRST RESULTS OF THE PROGRAM OF MOSAIC DOCUMENTATION IN THE QUIRIGUA ARCHAEOLOGICAL PARK Quirigua is renowned for the size and beauty of its stelae, zoomorphs, and altars. But the sculptural richness that this ancient city possesses is even greater than what is known. More than 1000 fragments of sculptures, most of which were attached to the walls of the structures that make up the Acropolis of the site, have been preserved in the storehouses at the site for many years. Unfortunately, almost all of these mosaics were stored without documentation or provenience. And so, in December of 2008, the task of ordering and cataloguing these pieces began. We hope to complete this study and reintegrate these works back into the architecture at the site. INTRODUCCIÓN Quirigua es reconocido dentro del área Maya por el tamaño y belleza de sus estelas, zoomorfos y altares. Sin embargo, la riqueza escultórica que posee es mucho más grande y casi desconocida, ya que por muchos años se han almacenado en las bodegas del parque más de 1000 fragmentos de esculturas que en su mayoría estaban adosadas a los muros de las estructuras del sitio. Estos fragmentos de escultura son denominados como mosaicos debido a que corresponden a bloques tallados individualmente y que posteriormente, se ensamblaban con otros para formar algún motivo. Desafortunadamente casi todos estos mosaicos fueron guardados sin documentación y procedencia. Por lo que en Diciembre del 2008, se inició su ordenamiento y catalogación con el objetivo de identificar los motivos representados y su posible ubicación. Se espera que al completar este estudio dichos mosaicos puedan ser reintegrados a la arquitectura del sitio. ANTECEDENTES En las Tierras Bajas Mayas del sureste, la ciudad de Copán inicia hacia finales del Clásico Temprano con la tradición de decorar sus edificios con mosaicos. Martin y Grube (2002:198-199) indican que el último edificio de Copán en donde se utilizó como decoración el estuco modelado, fue el famoso