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Institutions training future healthcare professionals in healthcare and community engagement play a crucial role beyond traditional classroom settings. Recognizing their potential to support under-represented groups and minorities, institutions increasingly encourage engagement with schools and community organizations. However, work remains to advance meaningful and impactful educational outreach and service-learning programs. This manuscript synthesizes the perspectives of a group of medical school educators to discuss developing sustainable programs to engage youth in Science, Technology, Engineering, Math, and Medicine (STEMM) education with a focus on biomedical science. Through near-peer education and service-learning, healthcare students can impart knowledge, provide mentorship, promote enthusiasm for STEMM fields, and nurture health-related self-efficacy within individuals and communities. Collaborative efforts through student-as-teacher approaches bridge health-related disparities and cultivate healthier, more empowered futures for all. We advocate for community outreach strategies that target future health professionals early in their education and support the scholarship of teaching and learning and program evaluation. Successful long-term programs must ensure that results are systematically assessed, measured, and perpetuated. This perspective aims to highlight the role of service learning and community outreach in increasing individual health literacy and fostering an enduring interest in STEMM careers, thereby empowering the next generation of elementary and secondary school students.
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Relaciones Comunidad-Institución , Alfabetización en Salud , Humanos , EmpoderamientoRESUMEN
Informing parents that their child has a diagnosis of Down syndrome (DS) is a common example of the delivery of unexpected or difficult news. Expectations and life planning will change, and if detected prenatally, discussions might include the option of pregnancy termination. Medical school curricula currently include training in breaking unexpected news; however, it is difficult to teach and assess. We use the perspectives of clinicians, educators, and a medical student who is the parent of a child with DS to frame a discussion on teaching, practicing, and assessing communication of difficult news in human genetics during medical school.
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Estudiantes de Medicina , Niño , Humanos , Comunicación , Curriculum , Relaciones Médico-Paciente , Revelación de la VerdadRESUMEN
Recent advancements in genetic testing have revealed cases of mosaicism, demonstrating the phenomenon may be more common than once thought. Broadly defined, mosaicism describes the presence of two genotypically different cell lineages within the same organism. This can arise from small mutations or errors in chromosome segregation, as early as in gametes, before or after fertilization. Mosaicism is directly responsible for many conditions that present in a wide range of tissues, with the presence of the mutation or genetic abnormality following a tissue-dependent pattern. This makes it possible for patients to test negative for a condition using a standard tissue sample while harboring the variant in a different tissue. Understanding the timing and mechanisms of mosaic conditions will aid in targeted testing that is more appropriate to identify a pathogenic variant. This targeted testing should reduce the length of a patient's diagnostic odyssey and provide a better understanding of the chances of passing on their variant to their offspring, thereby allowing for more accurate genetic counseling. We illustrate this phenomenon with two cases: one of Pallister-Killian syndrome and the other of tuberous sclerosis complex. Both patients had increased time to diagnosis because of difficulties in identifying genetic variants in tested tissues. Beyond just increased time to diagnosis, we illustrate that mosaic conditions can present as less severe and more variable than the germline condition and how specific germ layers may be affected by the variant. Knowing which germ layers may be affected by the variant can give clinicians a clue as to which tissues may need to be tested to yield the most accurate result.
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PURPOSE: To investigate progress toward gender equality in academic medicine through a longitudinal analysis of gender parity among faculty at medical schools. METHOD: The authors conducted a retrospective analysis of Association of American Medical Colleges Faculty Roster data on gender, tenure status, and academic rank of faculty in basic science (BSc) and clinical science (CSc) departments from 1966 to 2019. They expressed data as whole numbers and percent female. A trend analysis projected time to gender parity across rank and tenure categories, and cross-tabulation analysis revealed the relative odds of females being in a rank and tenure position relative to males. RESULTS: A 12-fold increase in the number of faculty occurred from 1966 to 2019, driven largely by increases in non-tenure track faculty. Female tenured and tenure track numbers increased at consistent rates (121 and 174 per year; P < .001). Female non-tenure track rates mirrored those for males, both changing in 2000. Odds ratios in 2019 for BSc and CSc females to be in tenure track versus non-tenure track positions compared with males were 0.83/0.98 and to be tenured were 0.63/0.44. Odds ratios in 2019 for BSc and CSc females to be full professors versus assistant or associate professors compared with males were 0.55/0.42. BSc assistant and associate professor percent female rates increased linearly from 1966 to 2019, while full professor rates increased in 1986. Transition points between periods of linear change were seen later in CSc departments (1977, 1980, 1985, 1994). Best fit line models indicated gender parity will be reached for BSc/CSc faculty in 2034/2023, 2047/2033, and 2065/2053 for assistant, associate, and full professors, respectively. CONCLUSIONS: These findings suggest large historical changes in medical school expansion, medical education, and economics have shifted gender curves at all academic ranks. To achieve gender parity, additional national changes are needed.
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Docentes Médicos , Medicina , Centros Médicos Académicos , Movilidad Laboral , Femenino , Humanos , Masculino , Estudios Retrospectivos , Facultades de Medicina , Estados UnidosRESUMEN
PURPOSE: Advances in genetics have revolutionized disease surveillance and management. Understanding and integrating genetic principles clinically is becoming increasingly important for physician trainees. We developed an online, interactive, self-learning module/assessment to strengthen student proficiency in genetics. METHODS: Medical student knowledge of genetics during Internal Medicine Clerkship was assessed by an online, asynchronous quiz using simulated vignettes that included questions on (1) genetic red flags, (2) differential diagnoses, (3) pedigree drawing, (4) interpretation of inheritance patterns, (5) selection of diagnostic testing modalities, and (6) genetic counseling. Student self-assessment of genetics competencies was elicited with survey questions. RESULTS: A total of 592 medical students from classes of 2016 to 2020 successfully completed the "Genetics in Internal Medicine" module/assessment. In total, 91% of students correctly recognized genetic red flags in patient histories, 84% could accurately draw pedigrees, and 93% could accurately interpret inheritance patterns. In total, 92% of students felt that genetic proficiency would improve patient rapport and 91% felt that they could apply what they had learned clinically. Student narrative comments about the activity were positive. CONCLUSION: This online module was easily integrated into the IM Clerkship. Medical students were able to solidify scientific principles and interpret historical details, predict genetic patterns, and provide counseling. They had successful performances, and the module/assessment was well-received.
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Prácticas Clínicas , Educación de Pregrado en Medicina , Estudiantes de Medicina , Competencia Clínica , Curriculum , Humanos , Estudiantes de Medicina/psicologíaRESUMEN
Medical education has a role to play in responding to the global call for social justice. Medical educators can lead the global transformation by adopting culturally responsive teaching (CRT) practices. The ultimate objective must be the achievement of equitable learning and success outcomes for all students, especially those from underrepresented and international communities. The strategies outlined in this paper offer specific, actionable, evidence-based strategies that will empower educators to apply the CRT framework within the course design, delivery, and evaluation. As a result, more inclusive classroom environments will be created, ultimately closing the outcome gaps that exist between students.
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INTRODUCTION: Osteoporosis is the most common bone disease in the world. Approximately 50% of women and 20% of men over 50 will suffer an osteoporosis-related fracture. Future health care providers must be equipped to prevent, recognize, and treat osteoporosis-related fractures. METHODS: To supplement instruction on osteoporosis, we designed a case-based session. Groups of 10-12 second-year medical students worked with a single facilitator in a roundtable discussion. The 120-minute session integrated foundational sciences (pathology, physiology, pharmacology) and clinical disciplines (clinical skills, radiology, geriatrics, evidence-based medicine). Knowledge gains were assessed by performance on nine session-relevant multiple-choice questions (MCQs) on the final exam. Student satisfaction was assessed by an anonymous postsession survey. RESULTS: There were 121 students that participated, and their average performance on nine session-relevant final exam MCQs was 84%. After removal of a single outlier MCQ (15% correct), average performance on the remaining eight MCQs was 93%. A total of 107 students (88%) responded to the postsession survey. On a 5-point Likert scale, 101 of 107 students (94%) agreed or strongly agreed with the statement "The basic science-clinical combination lecture on osteoporosis followed by the small-group case discussion on osteoporosis prepared me adequately to understand the topic" (M = 4.56, SD = 0.63). DISCUSSION: We developed a case-based learning activity for preclinical medical students to enhance the clinical scaffolding of basic science and medical knowledge around osteoporosis. Students performed well on session-relevant exam questions, demonstrating competency in the educational objectives. Student satisfaction was high, with most students feeling well prepared.
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Educación de Pregrado en Medicina , Osteoporosis , Estudiantes de Medicina , Evaluación Educacional , Femenino , Humanos , Aprendizaje , MasculinoRESUMEN
Biochemistry is a core component of medical education as it contributes to the fundamental basis and understanding of molecular mechanisms in pathophysiological processes. The convergence of nutritional factors also gives insight to many chronic diseases. Topics of nutrition are often incorporated into biochemistry coursework and must be integrated in a way that makes sense within the overall curriculum. An important issue raised by this structure is determining which topics are most important to a student's understanding and what topics are most relevant to future clinical practice. Previous surveys show medical undergraduates feel that much of current medical biochemistry coursework lacks clinical relevance and pays too much attention to small details. Here we report the results of a survey that aims to determine the biochemical and nutritional topics that physicians and educators feel are most important to teach in medical school. This information is important for medical schools to better prepare their students for what they will see and apply in their future clinical practice. Physicians and medical educators were surveyed, asked demographic questions, and then requested to provide a prioritized list of the top 10 biochemistry and nutrition topics that they believed should be focused on in undergraduate medical education. Topics suggested by participants were normalized for spelling, acronyms, and abbreviations and given a weight from 10 to 1. A prioritized list was then created based on the suggested topics. This list provides insight into the topics that medical educators and physicians consider important to cover in undergraduate medical education.
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OBJECTIVES: Methotrexate (MTX) is the mainstay treatment for juvenile idiopathic arthritis (JIA), however approximately 30% of children will fail to respond to the drug. Identification of genetic predictors of response to MTX would be invaluable in developing optimal treatment strategies for JIA. Using a candidate gene approach, single nucleotide polymorphisms (SNPs) within genes in the metabolic pathway of MTX, were investigated for association with response to treatment in JIA cases. METHODS: Tagging SNPs were selected across 13 MTX metabolic pathway genes and were genotyped using Sequenom genotyping technology in subjects recruited from the Sparks Childhood Arthritis Response to Medication Study. Response to MTX was defined using the American College of Rheumatology (ACR) paediatric response criteria and SNP genotype frequencies were compared between the worst and best responders (ACR-Ped70) to MTX. An independent cohort of US JIA cases was available for validation of initial findings. RESULTS: One SNP within the inosine triphosphate pyrophosphatase gene (ITPA) and two SNPs within 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene (ATIC) were significantly associated with a poor response to MTX. One of the ATIC SNPs showed a trend towards association with MTX response in an independent cohort of US JIA cases. Meta-analysis of the two studies strengthened this association (combined p value=0.002). CONCLUSIONS: This study presents association of a SNP in the ATIC gene with response to MTX in JIA. There is now growing evidence to support a role of the ATIC gene with response to MTX treatment. These results could contribute towards a better understanding of and ability to predict MTX response in JIA.
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Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/genética , Transferasas de Hidroximetilo y Formilo/genética , Metotrexato/uso terapéutico , Complejos Multienzimáticos/genética , Nucleótido Desaminasas/genética , Adolescente , Antirreumáticos/farmacocinética , Niño , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética/métodos , Genotipo , Humanos , Masculino , Redes y Vías Metabólicas/genética , Metotrexato/farmacocinética , Polimorfismo de Nucleótido Simple , Pronóstico , Resultado del TratamientoRESUMEN
OBJECTIVES: Little is known about the mechanisms of efficacy of methotrexate (MTX) in childhood arthritis, or genetic influences upon response to MTX. The aims of this study were to use gene expression profiling to identify novel pathways/genes altered by MTX and then investigate these genes for genotype associations with response to MTX treatment. METHODS: Gene expression profiling before and after MTX treatment was performed on 11 children with juvenile idiopathic arthritis (JIA) treated with MTX, in whom response at 6 months of treatment was defined. Genes showing the most differential gene expression after the treatment were selected for single nucleotide polymorphism (SNP) genotyping. Genotype frequencies were compared between nonresponders and responders (ACR-Ped70). An independent cohort was available for validation. RESULTS: Gene expression profiling before and after MTX treatment revealed 1222 differentially expressed probes sets (fold change >1.7, P<0.05) and 1065 when restricted to full responder cases only. Six highly differentially expressed genes were analyzed for genetic association in response to MTX. Three SNPs in the SLC16A7 gene showed significant association with MTX response. One SNP showed validated association in an independent cohort. CONCLUSION: This study is the first, to our knowledge, to evaluate gene expression profiles in children with JIA before and after MTX, and to analyze genetic variation in differentially expressed genes. We have identified a gene, which may contribute to genetic variability in MTX response in JIA, and established as proof of principle that genes that are differentially expressed at mRNA level after drug administration may also be good candidates for genetic analysis.
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Antirreumáticos/uso terapéutico , Artritis Juvenil/genética , Expresión Génica , Metotrexato/uso terapéutico , Polimorfismo de Nucleótido Simple , Antirreumáticos/farmacocinética , Artritis Juvenil/tratamiento farmacológico , Estudios de Cohortes , Perfilación de la Expresión Génica , Frecuencia de los Genes , Genotipo , Humanos , Metotrexato/farmacocinética , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Farmacogenética , ARN Mensajero/metabolismoRESUMEN
OBJECTIVE: To test for associations between non-major histocompatibility complex susceptibility loci previously reported in autoimmune diseases and juvenile idiopathic arthritis (JIA). METHODS: Published autoimmune disease genome-wide association studies were reviewed, and 519 single-nucleotide polymorphisms (SNPs) were selected for association testing. The initial cohort included 809 JIA cases and 3,535 controls of non-Hispanic, European ancestry. Of the SNPs, 257 were successfully genotyped, while 168 were imputed with quality. Based on findings in the initial cohort, replication was sought for 21 SNPs in a second cohort of 1,015 JIA cases and 1,569 controls collected in the US and Germany. For the initial cohort, tests for association were adjusted for potential confounding effects of population structure by including principal components derived from a genome-wide association study as covariates in logistic regression models. Odds ratios (ORs) and 95% confidence intervals were calculated. RESULTS: Testing for association of previously reported autoimmune disease genetic associations in the initial cohort suggested associations with JIA in 13 distinct loci. Of these, 7 were validated in the replication cohort. Meta-analysis results for the replicating loci included PTPN22 (rs6679677 [OR 1.58, P = 1.98 × 10(-12) ], rs2476601 [OR 1.64, P = 1.90 × 10(-13) ], and rs2488457 [OR 1.32, P = 6.74 × 10(-8) ]), PTPN2 (rs1893217 [OR = 1.33, P = 1.60 × 10(-9) ] and rs7234029 [OR 1.35, P = 1.86 × 10(-10) ]), ADAD1-IL2-IL21 (rs17388568 [OR 1.24, P = 1.13 × 10(-6) ] and rs13143866 [OR 0.83, P = 1.95 × 10(-4) ]), STAT4 (rs3821236 [OR = 1.27, P = 2.36 × 10(-6) ] and rs7574865 [OR = 1.31, P = 2.21 × 10(-6) ]), C12orf30 (rs17696736 [OR = 1.19, P = 2.59 × 10(-5) ]), COG6 (rs7993214 [OR = 0.76, P = 1.10 × 10(-5) ]), and ANGPT1 (rs1010824 [OR = 0.79, P = 2.91 × 10(-4) ]). These polymorphisms have been reported in diseases such as rheumatoid arthritis, type 1 diabetes mellitus, Crohn's disease, and multiple sclerosis. CONCLUSION: General susceptibility loci for autoimmunity are shared across diseases, including JIA, suggesting the potential for common therapeutic targets and mechanisms.
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Proteínas Adaptadoras del Transporte Vesicular/genética , Angiopoyetina 1/genética , Artritis Juvenil/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 2/genética , Alelos , Niño , Preescolar , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Oportunidad Relativa , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: To determine the frequency of laboratory abnormalities with methotrexate (MTX) use in patients with juvenile idiopathic arthritis (JIA); to identify potential risk factors for MTX toxicity requiring medical interventions; and to compare the frequency of liver function abnormalities in patients treated with MTX to those not treated with MTX. METHODS: Results of MTX surveillance laboratory testing (SLT) available in clinical databases were reviewed for 588 children with JIA. Information on demographics, JIA features, and factors previously associated with increased frequency of SLT abnormalities was obtained. RESULTS: Results of SLT performed in at least 4-month intervals were available for 138 JIA patients whose JIA was not treated with MTX, and for 198 JIA patients treated with MTX plus folic acid. On SLT of the MTX-treated patients, there were 44 of 2650 (1.7%) AST tests and 90 of 2647 (3.4%) ALT tests that exceeded 2 times the upper limit of normal (> 2 ULN) in 30 children (15%). AST or ALT tests at > 2 ULN occurred more often with systemic JIA (p = 0.04), macrophage activation syndrome, during infections, in systemic antibiotic use, and after intensifying JIA drug regimens. AST or ALT results at > 2 ULN were as frequent among MTX-treated children as those not treated with MTX. Renal and hematological abnormalities with MTX were uncommon. CONCLUSION: Liver enzyme abnormalities > 2 ULN are rare in JIA, irrespective of MTX exposure. These data suggest that the adult standard of SLT every 4-8 weeks may not be necessary in children treated with MTX, especially if certain risk factors are absent.
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Antirreumáticos , Artritis Juvenil/tratamiento farmacológico , Metotrexato , Adolescente , Adulto , Antirreumáticos/uso terapéutico , Antirreumáticos/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Niño , Bases de Datos Factuales , Monitoreo de Drogas , Femenino , Humanos , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Metotrexato/uso terapéutico , Metotrexato/toxicidad , Factores de RiesgoRESUMEN
Joint inflammation and destruction have been linked to the deregulation of the highly synthetic fibroblast-like synoviocytes (FLSs), and much of our current understanding of the mechanisms that underlie synovitis has been collected from studies of FLSs. During a proteomic analysis of FLS cells, we identified a novel protein, c19orf10 (chromosome 19 open reading frame 10), that was produced in significant amounts by these cells. The present study provides a partial characterization of c19orf10 in FLSs, synovial fluid, and the synovium. Murine monoclonal and chicken polyclonal antibodies were produced against recombinant human c19orf10 protein and used to examine the distribution of c19orf10 in cultured FLSs and in synovial tissue sections from patients with rheumatoid arthritis or osteoarthritis. The intracellular staining pattern of c19orf10 is consistent with localization in the endoplasmic reticulum/Golgi distribution. Sections of rheumatoid arthritis and osteoarthritis synovia expressed similar patterns of c19orf10 distribution with perivascular and synovial lining staining. Double-staining in situ analysis suggests that fibroblast-like synovial cells produced c19orf10, whereas macrophages, B cells, or T cells produced little or none of this protein. There is evidence of secretion into the vascular space and the extracellular matrix surrounding the synovial lining. A competitive enzyme-linked immunosorbent assay confirmed the presence of microgram levels of c19orf10 in the synovial fluids of patients with one of various arthropathies. Collectively, these results suggest that c19orf10 is an FLS-derived protein that is secreted into the synovial fluid. However, the significance of this protein in synovial biology remains to be determined. The absence of known structural motifs or domains and its relatively late evolutionary appearance raise interesting questions about its function.
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Fibroblastos/metabolismo , Proteínas/genética , Membrana Sinovial/metabolismo , Secuencia de Aminoácidos , Animales , Artritis Reumatoide/metabolismo , Cromosomas Humanos Par 19 , Electroforesis en Gel Bidimensional , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Espectrometría de Masas , Datos de Secuencia Molecular , Osteoartritis/metabolismo , Reacción en Cadena de la Polimerasa , Proteínas/metabolismo , Proteómica , Homología de Secuencia de Aminoácido , Líquido Sinovial/química , Membrana Sinovial/citologíaRESUMEN
Our aim is to develop noninvasive tests to monitor the renal allograft posttransplant. Previously, we have reported that an unbiased proteomic-based approach can detect urine protein peaks associated with acute tubulointerstitial renal allograft rejection. Identification of these proteins peaks by mass spectrometry demonstrated that they all derive from nontryptic cleaved forms of beta2-microglobulin. In vitro experiments showed that cleavage of intact beta2-microglobulin requires a urine pH < 6 and the presence of aspartic proteases. Patients with acute tubulointerstitial rejection had lower urine pH than stable transplants and healthy individuals. In addition, they had higher amounts of aspartic proteases and intact beta2-microglobulin in urine. These factors ultimately lead to increased amounts of cleaved urinary beta2-microglobulin. Cleaved beta2-microglobulin as an indicator of acute tubular injury may become a useful tool for noninvasive monitoring of renal allografts.
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Trasplante de Riñón , Túbulos Renales/lesiones , Proteómica , Microglobulina beta-2/orina , Secuencia de Aminoácidos , Biomarcadores , Humanos , Túbulos Renales/metabolismo , Espectrometría de Masas , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/orina , Trasplante Homólogo , Microglobulina beta-2/químicaRESUMEN
BACKGROUND: In the last few years there has been an increasing interest in exploring the human proteome. In particular, efforts have focused on developing strategies to generate reproducible protein maps of normal cells, tissues, and biologic fluids, from which studies can then compare protein expression between different groups (e.g., healthy individuals vs. those with a specific pathologic state). METHODS: Various extrinsic factors (instrument settings, matrix composition, urine storage post void, freeze-thaw cycles) and intrinsic factors (blood in urine, urine dilution, first-void vs. midstream urine) were analyzed with respect to their impact on urine protein profiling using surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). RESULTS: Extrinsic factors that critically influenced reproducibility and peak detection of urine protein profiling were matrix composition and instrument settings, while freeze-thaw cycles had minimal impact. Midstream urines samples did not undergo changes in their protein profile when stored for three days at 4 degrees C. Intrinsic factors that influenced normal urine protein profiling were blood in the urine and urine dilution. Female first-void urine had a significantly different ratio of proteins present compared to a midstream urine sample. Limitations of the SELDI-TOF-MS technique included ion suppression and quantification of individual proteins when protein composition was complex. CONCLUSION: SELDI-TOF-MS offers a unique platform for high throughput urine protein profiling; however, standardization of analysis conditions is critical, and both extrinsic and intrinsic factors must be taken into account for accurate data interpretation.
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Análisis por Matrices de Proteínas/métodos , Proteómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Orina/química , Femenino , Humanos , Masculino , Análisis por Matrices de Proteínas/normas , Proteómica/instrumentación , Proteómica/normas , Reproducibilidad de los ResultadosRESUMEN
At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved by the development of non-invasive markers of rejection that can be measured frequently. This study sought to determine whether such candidate proteins can be detected in urine using mass spectrometry. Four patient groups were rigidly defined on the basis of allograft function, clinical course, and allograft biopsy result: acute clinical rejection group (n = 18), stable transplant group (n = 22), acute tubular necrosis group (n = 5), and recurrent (or de novo) glomerulopathy group (n = 5). Urines collected the day of the allograft biopsy were analyzed by mass spectrometry. As a normal control group, 28 urines from healthy individuals were analyzed the identical manner, as well as 5 urines from non-transplanted patients with lower urinary tract infection. Furthermore, sequential urine analysis was performed in patients in the acute clinical rejection and the stable transplant group. Three prominent peak clusters were found in 17 of 18 patients (94%) with acute rejection episodes, but only in 4 of 22 patients (18%) without clinical and histologic evidence for rejection and in 0 of 28 normal controls (P < 0.001). In addition, the presence or absence of these peak clusters correlated with the clinicopathologic course in most patients. Acute tubular necrosis, glomerulopathies, lower urinary tract infection, and cytomegalovirus viremia were not confounding variables. In conclusion, proteomic technology together with stringent definition of patient groups can detect urine proteins associated with acute renal allograft rejection. Identification of these proteins may prove useful as non-invasive diagnostic markers for rejection and the development of novel therapeutic agents.
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Rechazo de Injerto/orina , Trasplante de Riñón , Proteinuria/orina , Proteómica , Enfermedad Aguda , Adulto , Femenino , Rechazo de Injerto/diagnóstico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The determination of monoclonal antibody specificity is dependent upon the availability of purified antigen. Such material is not always available and this has proven to be one of the rate-limiting steps in monoclonal antibody production. The aim of the present study was to develop a generic approach to defining antibody specificity that bypassed the need for pure antigens through the use of proteomics. The scheme and its application to several biological mixtures are described. The results demonstrate the ability of the approach to identify antibodies against both the major components and the minor contaminants of a protein mixture. This approach should markedly enhance the characterization of antibodies to complex antigen mixtures.