Heregulin inhibits proliferation via ERKs and phosphatidyl-inositol 3-kinase activation but regulates urokinase plasminogen activator independently of these pathways in metastatic mammary tumor cells

Heregulin (HRG) and type I receptor tyrosine kinase (RTK) expression was investigated in the highly invasive and metastatic LM3 cell line, our previously described model of metastasis for mammary cancer (Bal de Kier Joffe et al. [1986] Invasion Metastasis 6:302-12; Urtreger et al. [1997] Int J Oncol 11:489-96). Although LM3 cells do not express HRG, they exhibit high levels of ErbB-2 and ErbB-3 as well as moderate expression of ErbB-4. Addition of exogenous HRGβ1 resulted in inhibition of both proliferation and migration of LM3 cells. HRGβ1 was also able to decrease the activity of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9), 2 key enzymes in the invasion and metastatic cascade. HRGβ1 treatment of LM3 cells induced tyrosine phosphorylation of ErbB-2, ErbB-3 and ErbB-4 as well as the formation of ErbB-2/ErbB-3 and ErbB-2/ErbB-4 heterodimers. Assessment of the signaling pathways involved in HRGβ1 action indicated that the addition of HRGβ1 to LM3 cells resulted in activation of phosphatidylinositol 3-kinase (PI-3K) and in strong induction of the association of the p85 subunit of PI-3K with ErbB-3. HRGβ1 also caused the rapid activation of ERKI/ERK2 and Stat3 and Stat5 (signal transducers and activators of transcription [STAT]). This is the first demonstration of the ability of HRGβ1 to activate STATs in mammary tumor cells. Blockage of PI-3K activity with its chemical inhibitor wortmannin, or of MEKI/ERKs activity with PD98059, resulted in suppression of the ability of HRGβ1 to inhibit LM3 cell growth. Notwithstanding the suppression of these 2 signaling pathways, HRGβ1 still proved capable of inhibiting uPA activity. Therefore, our results provide evidence that signaling pathways involved in HRGβ1-induced proliferation appear to be distinct from those involved in HRGβ1 regulation of uPA, a protease that plays a pivotal role in invasion and metastasis. © 2002 Wiley-Liss, Inc.Fil:Puricelli, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Labriola, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Salatino, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Balañá, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Pignataro, O.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Charreau, E.H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Elizalde, P.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

A new technique for mandibular osteotomy

Sagittal split osteotomy (SSO) is a surgical technique largely employed for mandibular mobilizations in orthognatic procedures. However, the traditional design of buccal osteotomy, located at the junction of mandibular ramus and body, may prevent more extensive sliding between the bone segments, particularly on the advance, laterality and verticality of the mandibular body. The author proposes a new technical and conceptual solution, in which osteotomy is performed in a more distal region, next to the mental formamen. Technically, the area of contact between medullary-cancellous bone surfaces is increased, resulting in larger sliding rates among bone segments; it also facilitates the use of rigid fixation systems, with miniplates and monocortical screws. Conceptually, it interferes with the resistance arm of the mandible, seen as an interpotent lever of the third gender

Available zinc levels in soils of Argentina

Adequate grain zinc (Zn) concentration is important because of its influence on human health. The Argentina Pampas region (APR) provides between 86% and 90% of total grain exports by the country. Soils of the Argentina Pampas region had high fertility under pristine condition but intensification of agriculture, increasing grain yields, and poor or no Zn fertilization could reduce soil available Zn. The objectives of this work were to determine the distribution of available Zn in agricultural and pristine soils of the Argentina Pampas region and its relationship with some chemical characteristics. Soil samples (0-20 cm depth) were collected and georeferenced (approximately 550 for each condition), and soil organic matter, pH, extractable phosphorus, cation exchange capacity, and available Zn by extraction with diethylenetriaminepentaacetic acid (DTPA-Zn) were measured. For geostatistical analysis, indicator kriging (non-parametric method) was utilized as interpolation method. Agriculture decreased soil organic matter, pH, extractable phosphorus and DTPA-Zn (26.9, 4.6, 57.8 and 69.5%, respectively). Relative decrease of DTPA-Zn was only significantly associated with the relative decrease of soil organic matter, although this association was low (r=0.41). Regionally, the DTPA-Zn distribution was very heterogeneous and soil organic matter, pH, extractable phosphorus and cation exchange capacity did not adequately predicted soil DTPA-Zn concentrations (r2=0.16 to 0.26). Agricultural soils of northern, northwestern and southwestern APR (approximately 12,150,000 ha) showed DTPA-Zn values below 1 mg kg-1 , and therefore would present some degree of Zn deficiency for sensitive crops.Fil: Sainz Rozas, Hernan Rene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Área de Investigación en Agronomía; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Puricelli, Marino Marcelo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Área de Investigación en Agronomía; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Eyherabide, Mercedes. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Área de Investigación en Agronomía; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Barbieri, Pablo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Área de Investigación en Agronomía; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Echeverria, Hernan Eduardo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Área de Investigación en Agronomía; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Reussi Calvo, Nahuel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Laboratorio Ferilab; ArgentinaFil: Martinez, Juan Pablo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Área de Investigación en Agronomía; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentin

Interruption of cancer screening services due to COVID-19 pandemic: lessons from previous disasters

Purpose: To review the scientific literature seeking lessons for the COVID-19 era that could be learned from previous health services interruptions that affected the delivery of cancer screening services. Methods: A systematic search was conducted up to April 17, 2020, with no restrictions on language or dates and resulted in 385 articles. Two researchers independently assessed the list and discussed any disagreements. Once a consensus was achieved for each paper, those selected were included in the review. Results: Eleven articles were included. Three studies were based in Japan, two in the United States, one in South Korea, one in Denmark, and the remaining four offered a global perspective on interruptions in health services due to natural or human-caused disasters. No articles covered an interruption due to a pandemic. The main themes identified in the reviewed studies were coordination, communication, resource availability and patient follow-up. Conclusion: Lessons learned applied to the context of COVID-19 are that coordination involving partners across the health sector is essential to optimize resources and resume services, making them more resilient while preparing for future interruptions. Communication with the general population about how COVID-19 has affected cancer screening, measures taken to mitigate it and safely re-establish screening services is recommended. Use of mobile health systems to reach patients who are not accessing services and the application of resource-stratified guidelines are important considerations. More research is needed to explore best strategies for suspending, resuming and sustaining cancer screening programs, and preparedness for future disruptions, adapted to diverse health care systems

Panorametry: suggestion of a method for mandibular measurements on panoramic radiographs

<p>Abstract</p> <p>Background</p> <p>Orthopantomography (panoramic radiography) has been used for the study of measurements involving particularly the prediction of the eruption of impacted lower third molars and analyses of measurements of the ramus and head of mandible. The discrepancies involved with the projection of this radiographic image has stimulated the search for further ways to use it, particularly in orthodontic treatments and oral and maxillofacial surgeries. The author proposes a graphimetric method for the mandible, based on panoramic radiography. The results are expressed in linear and angular measurements, aiming at bilateral comparisons as well as the determination of the proportion of skeletal and dental structures, individually and among themselves as a whole. The method has been named Panorametry, and allows measurement of the mandible (Mandibular Panorametry) or the posterior mandibular teeth (Dental Panorametry). When combining mandible and maxilla, it should be referred to as Total Panorametry. It may also be used, in the future, with Cone Beam computed tomography (CT) images, and in this case it may be mentioned as CT Panorametry.</p

Anti-atherogenic function of LPL in human and porcine coronary endothelial cells [abstract]

Abstract only availableMultiple epidemiological studies concluded that lipoprotein lipase (LPL) function is inversely related to the incidence and severity of coronary artery disease. There is debate, however, because those seeking to identify the responsible mechanisms have reported higher than normal levels of LPL in the arteries of diseased mouse models. This confusion could be clarified by beginning to identify the LPL responses in pigs as a large animal model and determining the phenotypic effects of experimentally altering LPL on cultured endothelial cells and isolated vascular tissue. PURPOSE: We tested the hypothesis that LPL activity regulates the expression of thrombospondin-1 (TSP-1), eNOS, VCAM1, and the PPAR promoter activity in endothelial cells. METHODS: LPL activity and protein were measured in the plasma and heart of pigs fed a normal or high fat diet. The cellular effects of changing LPL activity were determined in primary porcine and human endothelial cells. Studies of VCAM1 were performed in cultured cells and isolated aortic segments. Northern and Western blots were used for mRNA and protein measurements, respectively. RESULTS: LPL-dependent lipolysis of VLDL suppressed TSP-1 expression several fold in endothelial cells (PNational Institutes of Healt

Genetic immunization with the immunodominant antigen P48 of Mycoplasma agalactiae stimulates a mixed adaptive immune response in BALBc mice

A DNA vaccine against contagious agalactia was developed for the first time, encoding the P48 of Mycoplasma agalactiae. Specific immune responses elicited in BALB/c mice were evaluated. Both total IgG and IgG1 were detected in mice vaccinated with pVAX1/P48. Proliferation of mononuclear cells of the spleen, levels of gamma interferon, interleukin-12, and interleukin-2 mRNAs were enhanced in immunized animals. Results indicate that pVAX1/P48 vaccination induced both T(h)1 and T(h)2 immune responses. Nucleic acid immunization could be a new strategy against M. agalactiae infections and may be potentially used to develop vaccines for other Mycoplasma diseases

Clinical impact of videocapsule endoscopy and device-assisted enteroscopy in non-bleeding small bowel lesions

Background: Videocapsule endoscopy (VCE) and double-balloon enteroscopy (DBE) are part of the diagnostic and therapeutic work-up of indications other than suspected small bowel bleeding (OSBB). The literature is currently lacking studies describing these procedures in this particular setting. Objectives: We assessed the clinical impact of VCE and DBE in a large monocentric cohort of OSBB patients, as compared to a control group of suspected small bowel bleeding (SSBB) patients who underwent enteroscopy over the same period. Design: Monocentric, retrospective, cohort study. Methods: We collected the data of consecutive patients with OSBB undergoing VCE and/or DBE from March 2001 to July 2020. The demographic and clinical parameters of the patients, technical characteristics, and adverse events for each procedure were collected. The impact of VCE and DBE was defined in terms of diagnostic yield (DY). The patients were subdivided according to the main indication into four groups: celiac disease, Crohn’s disease (CD), neoplasia, and persistent gastrointestinal symptoms. Results: A total of 611 VCEs and 387 DBEs were performed for OSBB. The main indications were complicated celiac disease and CD. The DYs of VCE and DBE overall were 53 and 61.7%, respectively, with some variance among the four groups. We report no statistical differences in the DY of VCE and DBE in SSBB vs OSBB (57.7% vs 53%, p = 0.0859 and 68.8% vs 61.7%, p = 0.0582, respectively). OSBB patients were significantly younger than those with SSBB. However, similarly to SSBB (k = 0.059), poor agreement between the enteroscopic techniques was found in the OSBB population (k = 0.109). The safety of both procedures in OSBB was comparable to that in SSBB patients. Conclusion: VCE and DBE are effective and safe in suspected OSBB, where their role is similar to that in SSBB, their main indication