Ernie Esquivel - Academia.edu (original) (raw)
Papers by Ernie Esquivel
F1000 - Post-publication peer review of the biomedical literature, 2007
Autosomal dominant polycystic kidney disease is an important cause of end-stage renal disease, fo... more Autosomal dominant polycystic kidney disease is an important cause of end-stage renal disease, for which there is no proven therapy 1. Mutations in PKD1 (the gene encoding polycystin-1) are the principal cause of this disease. The disease begins in utero 2 and is slowly progressive, but it is not known whether cystogenesis is an ongoing process during adult life. We now show that inactivation of Pkd1 in mice before postnatal day 13 results in severely cystic kidneys within 3 weeks, whereas inactivation at day 14 and later results in cysts only after 5 months. We found that cellular proliferation was not appreciably higher in cystic specimens than in age-matched controls, but the abrupt change in response to Pkd1 inactivation corresponded to a previously unrecognized brake point during renal growth and significant changes in gene expression. These findings suggest that the effects of Pkd1 inactivation are defined by a developmental switch that signals the end of the terminal renal maturation process. Our studies show that Pkd1 regulates tubular morphology in both developing and adult kidney, but the pathologic consequences of inactivation are defined by the organ's developmental status. These results have important implications for clinical understanding of the disease and therapeutic approaches. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the gradual replacement of renal tubules by cysts, which results in end-stage renal disease in approximately 50% of affected individuals by the sixth decade of life 1. An unanswered question with important clinical implications is whether cyst initiation is an ongoing process throughout the lifetime of an individual, or whether it is restricted to the period of rapid growth during development and early childhood. A related question is whether PKD1 is required for maintenance of renal tubular structure in adult kidneys. To address these issues, we induced Correspondence should be addressed to G.G.G.
F1000 - Post-publication peer review of the biomedical literature, 2007
The American Journal of Human Genetics, 2002
Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disea... more Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease that presents primarily in infancy and childhood and that is characterized by enlarged kidneys and congenital hepatic fibrosis. We have identified PKHD1, the gene mutated in ARPKD. PKHD1 extends over у469 kb, is primarily expressed in human fetal and adult kidney, and includes a minimum of 86 exons that are variably assembled into a number of alternatively spliced transcripts. The longest continuous open reading frame encodes a 4,074-amino-acid protein, polyductin, that is predicted to have a single transmembrane (TM)-spanning domain near its carboxyl terminus, immunoglobulin-like plexin-transcription-factor domains, and parallel beta-helix 1 repeats in its amino terminus. Several transcripts encode truncated products that lack the TM and that may be secreted if translated. The PKHD1gene products are members of a novel class of proteins that share structural features with hepatocyte growth-factor receptor and plexins and that belong to a superfamily of proteins involved in regulation of cell proliferation and of cellular adhesion and repulsion.
The American Journal of Medicine
Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its... more Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its function causes cystogenesis in human autosomal dominant polycystic kidney disease. We have previously shown that recombinant human PC1 is cis-autoproteolytically cleaved at the G protein-coupled receptor proteolytic site domain. To investigate the role of cleavage in vivo, we generated by gene targeting a Pkd1 knockin mouse (Pkd1 V/V) that expresses noncleavable PC1. The Pkd1 V/V mice show a hypomorphic phenotype, characterized by a delayed onset and distal nephron segment involvement of cystogenesis at postnatal maturation stage. We show that PC1 is ubiquitously and incompletely cleaved in wildtype mice, so that uncleaved and cleaved PC1 molecules coexist. Our study establishes a critical but restricted role of cleavage for PC1 function and suggests a differential function of the two types of PC1 molecules in vivo. autosomal dominant polycystic kidney disease ͉ cis-autoproteolytic cleavage ͉ GPS ͉ knockin mouse ͉ tubulogenesis
Medical Education Online
The COVID-19 pandemic resulted in significant disruptions to medical education. The patient care ... more The COVID-19 pandemic resulted in significant disruptions to medical education. The patient care space was unavailable as a learning environment, which compounded the complexity of preparing students for clerkships with a traditional transition to clerkship (TTC) curriculum. We developed a multimodal, structured approach to reintroduce students to the clinical space prior to the start of clerkships. 105 second year medical students completed a 4-week clinical enhancement course. A modified Delphi method was used to select core topics, which were then anchored to key Entrustable Professional Activities (EPAs). Students participated in 9 virtual problem-based cases, workshops and multiple supervised patient encounters. Students were surveyed before, during, and after the course; responses were compared with paired t-tests. 25.9% rated the course as excellent, 44.2% as very good, and 19.5% as good. Compared to baseline, self-perceived efficacy grew significantly (P < 0.05) across all EPAs. Improvements in key competencies were sustained when students were surveyed 2 weeks into their first clerkship. This was a well-received, novel course, focused on helping students transition back into the clinical space through a multimodal teaching approach. This framework may be used by other institutions seeking to restructure their TTC initiatives.
The American Journal of Medicine
Medicine
Optimal antibiotic management of patients with osteomyelitis remains a challenge for many clinici... more Optimal antibiotic management of patients with osteomyelitis remains a challenge for many clinicians. Although image-guided bone biopsy (IGB) remains the gold standard, its role in confirming diagnosis and guiding antibiotic management is not clear in patients with non-vertebral osteomyelitis. To determine the diagnostic yield of IGB and its impact on antibiotic management in non-vertebral osteomyelitis. Retrospective cohort study. Urban academic medical center. Patients admitted for non-vertebral osteomyelitis who underwent image-guided bone biopsy. Primary outcomes were microbiologic and histopathological results. We evaluated the impact of IGB on clinician-initiated changes in antibiotic regimen before and after biopsy. We evaluated 203 bone biopsies in 185 patients with clinical suspicion of osteomyelitis. 79% of patient received antibiotics prior to biopsy. Bone cultures were positive in 28% and histopathology confirmed osteomyelitis in 29%, but concordance was poor. Furthermore, clinical suspicion of infection was much higher, given that 68% received empiric antibiotics. Leukocytosis was significantly associated with positive cultures in multivariate analysis. There was no statistically significant correlation between antibiotic management and bone culture results. When culture yielded an organism, empiric regimens were kept the same, broadened or narrowed with equal frequency; targeted regimens were chosen only in 4 cases. Despite negative cultures in 98/138 cases having received empiric treatment, antibiotics were discontinued in only 8 cases. Even when empiric treatment was not given, negative cultures did not dissuade clinicians from eventual antibiotic use in a significant number of cases (17/48). In 46/71 patients whose final regimen included vancomycin, there was no evidence of current or past infection with MRSA. In patients with non-vertebral osteomyelitis, the diagnostic yield of image-guided bone biopsy is low, and clinicians frequently make decisions regarding antibiotic management that are not aligned with culture results. Abbreviations: IGB = image-guided biopsy, MRSA = methicillin-resistant Staphylococcus aureus, WBC = white blood cell count.
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](Archives De Pediatrie, Jul 1, 2009
F1000 - Post-publication peer review of the biomedical literature, 2007
Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its... more Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its function causes cystogenesis in human autosomal dominant polycystic kidney disease. We have previously shown that recombinant human PC1 is cis-autoproteolytically cleaved at the G protein-coupled receptor proteolytic site domain. To investigate the role of cleavage in vivo, we generated by gene targeting a Pkd1 knockin mouse (Pkd1 V/V) that expresses noncleavable PC1. The Pkd1 V/V mice show a hypomorphic phenotype, characterized by a delayed onset and distal nephron segment involvement of cystogenesis at postnatal maturation stage. We show that PC1 is ubiquitously and incompletely cleaved in wildtype mice, so that uncleaved and cleaved PC1 molecules coexist. Our study establishes a critical but restricted role of cleavage for PC1 function and suggests a differential function of the two types of PC1 molecules in vivo. autosomal dominant polycystic kidney disease ͉ cis-autoproteolytic cleavage ͉ GPS ͉ knockin mouse ͉ tubulogenesis
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
Teaching and Learning in Medicine, 2015
F1000 - Post-publication peer review of the biomedical literature, 2008
F1000 - Post-publication peer review of the biomedical literature, 2007
Autosomal dominant polycystic kidney disease is an important cause of end-stage renal disease, fo... more Autosomal dominant polycystic kidney disease is an important cause of end-stage renal disease, for which there is no proven therapy 1. Mutations in PKD1 (the gene encoding polycystin-1) are the principal cause of this disease. The disease begins in utero 2 and is slowly progressive, but it is not known whether cystogenesis is an ongoing process during adult life. We now show that inactivation of Pkd1 in mice before postnatal day 13 results in severely cystic kidneys within 3 weeks, whereas inactivation at day 14 and later results in cysts only after 5 months. We found that cellular proliferation was not appreciably higher in cystic specimens than in age-matched controls, but the abrupt change in response to Pkd1 inactivation corresponded to a previously unrecognized brake point during renal growth and significant changes in gene expression. These findings suggest that the effects of Pkd1 inactivation are defined by a developmental switch that signals the end of the terminal renal maturation process. Our studies show that Pkd1 regulates tubular morphology in both developing and adult kidney, but the pathologic consequences of inactivation are defined by the organ's developmental status. These results have important implications for clinical understanding of the disease and therapeutic approaches. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the gradual replacement of renal tubules by cysts, which results in end-stage renal disease in approximately 50% of affected individuals by the sixth decade of life 1. An unanswered question with important clinical implications is whether cyst initiation is an ongoing process throughout the lifetime of an individual, or whether it is restricted to the period of rapid growth during development and early childhood. A related question is whether PKD1 is required for maintenance of renal tubular structure in adult kidneys. To address these issues, we induced Correspondence should be addressed to G.G.G.
F1000 - Post-publication peer review of the biomedical literature, 2007
The American Journal of Human Genetics, 2002
Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disea... more Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease that presents primarily in infancy and childhood and that is characterized by enlarged kidneys and congenital hepatic fibrosis. We have identified PKHD1, the gene mutated in ARPKD. PKHD1 extends over у469 kb, is primarily expressed in human fetal and adult kidney, and includes a minimum of 86 exons that are variably assembled into a number of alternatively spliced transcripts. The longest continuous open reading frame encodes a 4,074-amino-acid protein, polyductin, that is predicted to have a single transmembrane (TM)-spanning domain near its carboxyl terminus, immunoglobulin-like plexin-transcription-factor domains, and parallel beta-helix 1 repeats in its amino terminus. Several transcripts encode truncated products that lack the TM and that may be secreted if translated. The PKHD1gene products are members of a novel class of proteins that share structural features with hepatocyte growth-factor receptor and plexins and that belong to a superfamily of proteins involved in regulation of cell proliferation and of cellular adhesion and repulsion.
The American Journal of Medicine
Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its... more Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its function causes cystogenesis in human autosomal dominant polycystic kidney disease. We have previously shown that recombinant human PC1 is cis-autoproteolytically cleaved at the G protein-coupled receptor proteolytic site domain. To investigate the role of cleavage in vivo, we generated by gene targeting a Pkd1 knockin mouse (Pkd1 V/V) that expresses noncleavable PC1. The Pkd1 V/V mice show a hypomorphic phenotype, characterized by a delayed onset and distal nephron segment involvement of cystogenesis at postnatal maturation stage. We show that PC1 is ubiquitously and incompletely cleaved in wildtype mice, so that uncleaved and cleaved PC1 molecules coexist. Our study establishes a critical but restricted role of cleavage for PC1 function and suggests a differential function of the two types of PC1 molecules in vivo. autosomal dominant polycystic kidney disease ͉ cis-autoproteolytic cleavage ͉ GPS ͉ knockin mouse ͉ tubulogenesis
Medical Education Online
The COVID-19 pandemic resulted in significant disruptions to medical education. The patient care ... more The COVID-19 pandemic resulted in significant disruptions to medical education. The patient care space was unavailable as a learning environment, which compounded the complexity of preparing students for clerkships with a traditional transition to clerkship (TTC) curriculum. We developed a multimodal, structured approach to reintroduce students to the clinical space prior to the start of clerkships. 105 second year medical students completed a 4-week clinical enhancement course. A modified Delphi method was used to select core topics, which were then anchored to key Entrustable Professional Activities (EPAs). Students participated in 9 virtual problem-based cases, workshops and multiple supervised patient encounters. Students were surveyed before, during, and after the course; responses were compared with paired t-tests. 25.9% rated the course as excellent, 44.2% as very good, and 19.5% as good. Compared to baseline, self-perceived efficacy grew significantly (P < 0.05) across all EPAs. Improvements in key competencies were sustained when students were surveyed 2 weeks into their first clerkship. This was a well-received, novel course, focused on helping students transition back into the clinical space through a multimodal teaching approach. This framework may be used by other institutions seeking to restructure their TTC initiatives.
The American Journal of Medicine
Medicine
Optimal antibiotic management of patients with osteomyelitis remains a challenge for many clinici... more Optimal antibiotic management of patients with osteomyelitis remains a challenge for many clinicians. Although image-guided bone biopsy (IGB) remains the gold standard, its role in confirming diagnosis and guiding antibiotic management is not clear in patients with non-vertebral osteomyelitis. To determine the diagnostic yield of IGB and its impact on antibiotic management in non-vertebral osteomyelitis. Retrospective cohort study. Urban academic medical center. Patients admitted for non-vertebral osteomyelitis who underwent image-guided bone biopsy. Primary outcomes were microbiologic and histopathological results. We evaluated the impact of IGB on clinician-initiated changes in antibiotic regimen before and after biopsy. We evaluated 203 bone biopsies in 185 patients with clinical suspicion of osteomyelitis. 79% of patient received antibiotics prior to biopsy. Bone cultures were positive in 28% and histopathology confirmed osteomyelitis in 29%, but concordance was poor. Furthermore, clinical suspicion of infection was much higher, given that 68% received empiric antibiotics. Leukocytosis was significantly associated with positive cultures in multivariate analysis. There was no statistically significant correlation between antibiotic management and bone culture results. When culture yielded an organism, empiric regimens were kept the same, broadened or narrowed with equal frequency; targeted regimens were chosen only in 4 cases. Despite negative cultures in 98/138 cases having received empiric treatment, antibiotics were discontinued in only 8 cases. Even when empiric treatment was not given, negative cultures did not dissuade clinicians from eventual antibiotic use in a significant number of cases (17/48). In 46/71 patients whose final regimen included vancomycin, there was no evidence of current or past infection with MRSA. In patients with non-vertebral osteomyelitis, the diagnostic yield of image-guided bone biopsy is low, and clinicians frequently make decisions regarding antibiotic management that are not aligned with culture results. Abbreviations: IGB = image-guided biopsy, MRSA = methicillin-resistant Staphylococcus aureus, WBC = white blood cell count.
Archives De Pediatrie, Jul 1, 2009
F1000 - Post-publication peer review of the biomedical literature, 2007
Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its... more Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its function causes cystogenesis in human autosomal dominant polycystic kidney disease. We have previously shown that recombinant human PC1 is cis-autoproteolytically cleaved at the G protein-coupled receptor proteolytic site domain. To investigate the role of cleavage in vivo, we generated by gene targeting a Pkd1 knockin mouse (Pkd1 V/V) that expresses noncleavable PC1. The Pkd1 V/V mice show a hypomorphic phenotype, characterized by a delayed onset and distal nephron segment involvement of cystogenesis at postnatal maturation stage. We show that PC1 is ubiquitously and incompletely cleaved in wildtype mice, so that uncleaved and cleaved PC1 molecules coexist. Our study establishes a critical but restricted role of cleavage for PC1 function and suggests a differential function of the two types of PC1 molecules in vivo. autosomal dominant polycystic kidney disease ͉ cis-autoproteolytic cleavage ͉ GPS ͉ knockin mouse ͉ tubulogenesis
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
F1000 - Post-publication peer review of the biomedical literature, 2007
Teaching and Learning in Medicine, 2015
F1000 - Post-publication peer review of the biomedical literature, 2008