Publications by authors named "Pablo Lujan"

7 Publications

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Post-kidney donation glomerular filtration rate measurement and estimation.

Nefrologia 2020 Dec 15. Epub 2020 Dec 15.

Servicio de Nefrología, Hospital Privado Universitario de Córdoba y Carrera de posgrado de Nefrología, Universidad Católica de Córdoba, Córdoba, Argentina.

Background: Long-term consequences associated with kidney donation are controversial. Pre- and post-donation glomerular filtration rates (GFRs) are determinants of renal and cardiovascular risk weighting. In Latin America, there is limited experience in evaluating kidney function using GFR measurement techniques in kidney donors. The MDRD 4-variable and CKD-EPI equations are considered reasonable options. The objective of this study was to evaluate the performance of the MDRD and CKD-EPI equations in post-nephrectomy GFR dynamics in kidney donors.

Materials And Methods: A prospective cohort study with GFR measurement and estimation in 189 kidney donors who underwent nephrectomy between 2007 and 2016 at the Hospital Privado Universitario de Córdoba [Private University Hospital of Córdoba] in Córdoba, Argentina. GFRs were evaluated before and after nephrectomy by iothalamate clearance determined by HPLC and by the MDRD and CKD-EPI equations for estimating GFR. Two groups were formed for this study: Group 1 (n=107), with an evaluation time subsequent to GFR stabilization (3 months) of up to 5 years, and Group 2 (n=82), with an evaluation time of 5-10 years following donation. Measured GFR (mGFR) was assessed by iothalamate clearance determined by HPLC.

Results: Renal compensation values were 61.9% (52.0%-71.1%) and 75.6% (64.9%-84.4%) for Group 1 (n=107) and Group 2 (n=82), respectively. MDRD underestimated the GFR in 3.2% (90ml/min/1.73m) and 38.6% (60ml/min/1.73m) compared to the mGFR, and CKD-EPI underestimated the GFR in 2.6% (90ml/min/1.73 m) and 13.8% (60ml/min/1.73 m). Diagnostic performance was evaluated with a ROC curve (mGFR<60ml/min/1.73 m) for MDRD (ABC=0.66; CI: 0.59-0.73; sensitivity: 98.7%; specificity: 63.3%) and for CKD-EPI (ABC=0.79 CI: 0.73-0.85; sensitivity: 96.9%; specificity: 76.4%. Estimated GFR (eGFR) showed poor performance for estimating the glomerular filtration rate in the post-nephrectomy follow-up of donors over 50 years of age.

Conclusions: Equations for estimating GFRs showed poor performance for long-term follow-up of post-nephrectomy GFRs. Measuring GFRs to determine kidney function is recommended in the screening and follow-up of some donors under the current selection criteria.
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http://dx.doi.org/10.1016/j.nefro.2020.07.012DOI Listing
December 2020

Parvovirus B19 in HIV+ adult patients with different CD4+ lymphocyte counts.

J Med Microbiol 2017 Dec 2;66(12):1715-1721. Epub 2017 Nov 2.

Institutode Virología 'Dr J. M. Vanella', Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.

Purpose: Human parvovirus B19 (B19V) can cause anemia in immunocompromised patients. We aimed to investigate the presence of B19V in HIV+ adults with different CD4+ T cell counts, to recognise the frequency of B19V in these different conditions and its possible association with anemia.

Methodology: We studied B19V specific IgM, IgG and DNA in 98 HIV+ patients and in 52 healthy individuals. HIV load, CD4+ counts and haemoglobin level were also determined in the patients.

Results: No individual in the control group had detectable IgM, 41/52 (78.8 %) had IgG and 5/52 (9.6 %) had B19V DNA. Among HIV+ patients, we found 5/98 (5.1 %) IgM+, 66/98 (67.3 %) IgG+ and 15/98 (15.3 %) had B19V DNA (no significant differences between the two groups compared). Considering the CD4+ cell range in HIV patients, 37 had <200 CD4+ cells ml, 31 had 200-500, and 30 had >500. Anti-B19V IgG prevalence in patients with >500 CD4+ cells ml was significantly higher than in the rest (P=0.004) and compared to the control (P=0.046). B19V DNA concentration was always <10 IU ml, including 5 healthy individuals and 15 HIV+ patients. There was no significant association between B19V IgM or DNA and anemia nor between B19V DNA and HIV load.

Conclusions: The results indicate that B19V is not a high-risk factor for anemia in adult HIV+ patients under HAART treatment. Further studies will contribute to elucidate the mechanisms and significance of B19V DNA prevalence/persistence in adults, independently of the CD4+ cell status.
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http://dx.doi.org/10.1099/jmm.0.000629DOI Listing
December 2017

Keep it on the edge: The post-mitotic midbody as a polarity signal unit.

Commun Integr Biol 2017 5;10(4):e1338990. Epub 2017 Jul 5.

Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.

The maintenance of the epithelial architecture during tissue proliferation is achieved by apical positioning of the midbody after cell division. Consequently, midbody mislocalization contributes to epithelial architecture disruption, a fundamental event during epithelial tumorigenesis. Studies in 3D polarized epithelial MDCK or Caco2 cell models, where midbody misplacement leads to multiple ectopic but fully polarized lumen-containing cysts, revealed that this phenotype can be caused by 2 different scenarios: the loss of mitotic spindle orientation or the loss of asymmetric abscission. In addition, we have recently proposed a third cellular mechanism where the midbody mislocalization is achieved through cytokinesis acceleration driven by the cancer-promoting phosphatase of regenerating liver (PRL)-3. Here we critically review these findings, and we furthermore present new data indicating that midbodies themselves might act as signal unit for polarization since they can infer apical characteristics to a basal membrane.
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http://dx.doi.org/10.1080/19420889.2017.1338990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595415PMC
July 2017

PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position.

J Cell Sci 2016 11 21;129(21):4130-4142. Epub 2016 Sep 21.

European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany

Disruption of epithelial architecture is a fundamental event during epithelial tumorigenesis. We show that the expression of the cancer-promoting phosphatase PRL-3 (PTP4A3), which is overexpressed in several epithelial cancers, in polarized epithelial MDCK and Caco2 cells leads to invasion and the formation of multiple ectopic, fully polarized lumens in cysts. Both processes disrupt epithelial architecture and are hallmarks of cancer. The pathological relevance of these findings is supported by the knockdown of endogenous PRL-3 in MCF-7 breast cancer cells grown in three-dimensional branched structures, showing the rescue from multiple-lumen- to single-lumen-containing branch ends. Mechanistically, it has been previously shown that ectopic lumens can arise from midbodies that have been mislocalized through the loss of mitotic spindle orientation or through the loss of asymmetric abscission. Here, we show that PRL-3 triggers ectopic lumen formation through midbody mispositioning without altering the spindle orientation or asymmetric abscission, instead, PRL-3 accelerates cytokinesis, suggesting that this process is an alternative new mechanism for ectopic lumen formation in MDCK cysts. The disruption of epithelial architecture by PRL-3 revealed here is a newly recognized mechanism for PRL-3-promoted cancer progression.
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http://dx.doi.org/10.1242/jcs.190215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117205PMC
November 2016

Approaches to Study Phosphatases.

ACS Chem Biol 2016 11 4;11(11):2944-2961. Epub 2016 Oct 4.

European Molecular Biology Laboratory , Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany.

Phosphatases play key roles in normal physiology and diseases. Studying phosphatases has been both essential and challenging, and the application of conventional genetic and biochemical methods has led to crucial but still limited understanding of their mechanisms, substrates, and exclusive functions within highly intricate networks. With the advances in technologies such as cellular imaging and molecular and chemical biology in terms of sensitive tools and methods, the phosphatase field has thrived in the past years and has set new insights for cell signaling studies and for therapeutic development. In this review, we give an overview of the existing interdisciplinary tools for phosphatases, give examples on how they have been applied to increase our understanding of these enzymes, and suggest how they-and other tools yet barely used in the phosphatase field-might be adapted to address future questions and challenges.
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http://dx.doi.org/10.1021/acschembio.6b00570DOI Listing
November 2016

The laforin/malin E3-ubiquitin ligase complex ubiquitinates pyruvate kinase M1/M2.

BMC Biochem 2015 Oct 23;16:24. Epub 2015 Oct 23.

Instituto de Biomedicina de Valencia, CSIC, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Jaime Roig 11, 46010, Valencia, Spain.

Background: Lafora disease (LD, OMIM 254780) is a fatal neurodegenerative disorder produced mainly by mutations in two genes: EPM2A, encoding the dual specificity phosphatase laforin, and EPM2B, encoding the E3-ubiquitin ligase malin. Although it is known that laforin and malin may form a functional complex, the underlying molecular mechanisms of this pathology are still far from being understood.

Methods: In order to gain information about the substrates of the laforin/malin complex, we have carried out a yeast substrate-trapping screening, originally designed to identify substrates of protein tyrosine phosphatases.

Results: Our results identify the two muscular isoforms of pyruvate kinase (PKM1 and PKM2) as novel interaction partners of laforin.

Conclusions: We present evidence indicating that the laforin/malin complex is able to interact with and ubiquitinate both PKM1 and PKM2. This post-translational modification, although it does not affect the catalytic activity of PKM1, it impairs the nuclear localization of PKM2.
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http://dx.doi.org/10.1186/s12858-015-0053-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619252PMC
October 2015

CKD-EPI instead of MDRD for candidates to kidney donation.

Transplantation 2012 Sep;94(6):637-41

Clinical Chemistry Laboratory, Hospital Privado-Centro Médico de Córdoba, Córdoba, Argentina.

Background: The determination of the glomerular filtration rate (GFR) is critical for the selection of a potential kidney donor. The complex and impractical techniques for the measurement of GFR have led to the development of equations to estimate GFR. Modification of diet in renal disease (MDRD) formula is the most widely used but its performance is poor because it systematically underestimates GFR above 60 mL/min. A new formula called the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) seems to overcome this limitation but needs to be tested in healthy potential kidney donors.

Methods: From 2007 to 2011, a cross-sectional study was performed on 85 adults who were candidates for living-related kidney donation. GFR was measured by nonradiolabeled iothalamate clearance determined by high-performance liquid chromatography, and renal function was estimated by using CKD-EPI and MDRD equations. The overall performance of the equations was analyzed, and the estimation for GFR above 90 mL/min was studied by means of receiver operating characteristic curves.

Results: The mean (SD) (range) of the measured GFR was 116 (24) (64-160) mL/min per 1.73 m(2), estimated GFR with CKD-EPI was 108 (22) (64-153) mL/min per 1.73 m(2), and MDRD was 99 (28) (46-157) mL/min per 1.73 m(2). CKD-EPI presented lower bias (3.3 vs. 10.2 mL/min/1.73 m(2)), higher precision [interquartile range (minimum value-maximum value), 25 (53-140) vs. 32 (43-161) ml/min] and higher accuracy (100% vs. 89%) compared with MDRD.

Conclusion: The CKD-EPI equation showed a higher performance than the MDRD equation in the GFR estimation of healthy population. CKD-EPI is applicable instead of MDRD, to subjects or candidates for kidney donation to avoid wrong GFR underestimates, which may lead to an inappropriate exclusion of candidates.
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http://dx.doi.org/10.1097/TP.0b013e3182603260DOI Listing
September 2012