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BACKGROUND: Obtaining reliable and valid information on resident performance is critical to patient safety and training program improvement. The goals were to characterize important anesthesia resident performance gaps that are not typically evaluated, and to further validate scores from a multiscenario simulation-based assessment. METHODS: Seven high-fidelity scenarios reflecting core anesthesiology skills were administered to 51 first-year residents (CA-1s) and 16 third-year residents (CA-3s) from three residency programs. Twenty trained attending anesthesiologists rated resident performances using a seven-point behaviorally anchored rating scale for five domains: (1) formulate a clear plan, (2) modify the plan under changing conditions, (3) communicate effectively, (4) identify performance improvement opportunities, and (5) recognize limits. A second rater assessed 10% of encounters. Scores and variances for each domain, each scenario, and the total were compared. Low domain ratings (1, 2) were examined in detail. RESULTS: Interrater agreement was 0.76; reliability of the seven-scenario assessment was r = 0.70. CA-3s had a significantly higher average total score (4.9 ± 1.1 vs. 4.6 ± 1.1, P = 0.01, effect size = 0.33). CA-3s significantly outscored CA-1s for five of seven scenarios and domains 1, 2, and 3. CA-1s had a significantly higher proportion of worrisome ratings than CA-3s (chi-square = 24.1, P < 0.01, effect size = 1.50). Ninety-eight percent of residents rated the simulations more educational than an average day in the operating room. CONCLUSIONS: Sensitivity of the assessment to CA-1 versus CA-3 performance differences for most scenarios and domains supports validity. No differences, by experience level, were detected for two domains associated with reflective practice. Smaller score variances for CA-3s likely reflect a training effect; however, worrisome performance scores for both CA-1s and CA-3s suggest room for improvement.
Assuntos
Anestesiologia/educação , Anestesiologia/normas , Competência Clínica/normas , Internato e Residência/normas , Manequins , Anestesiologia/métodos , Estudos Transversais , Feminino , Humanos , Internato e Residência/métodos , Masculino , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
Neurological complications after labor and delivery are most often caused by compressive trauma related to childbirth and rarely related to neuraxial anesthesia/analgesia. However, it is important for anesthesiologists to be able to recognize the common manifestations of these neuropathies in order to distinguish them from more ominous causes of neurologic disease. In this article, we review the anatomy and etiology of postpartum thoracolumbar spinal cord, lumbar nerve roots, plexus, and lower extremity peripheral nerve injuries. We will focus on a practical approach to their diagnosis, management, and treatment. Cases will be used to illustrate diagnosis and management.
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Extremidade Inferior/lesões , Traumatismos dos Nervos Periféricos/terapia , Período Pós-Parto , Traumatismos da Medula Espinal/terapia , Raízes Nervosas Espinhais/lesões , Adulto , Anestesia Obstétrica/efeitos adversos , Feminino , Humanos , Incidência , Recém-Nascido , Plexo Lombossacral/lesões , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/epidemiologia , Gravidez , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/epidemiologiaRESUMO
Harlequin ichthyosis is a rare congenital ichthyosis classified under the category of Autosomal Recessive Congenital Ichthyoses, which also include lamellar ichthyosis and congenital ichthyosiform erythroderma. It is caused by functional null mutations in the ABCA12 gene, a keratinocyte lipid transporter associated with lamellar granule formation. Patients have a classic clinical presentation at delivery and need neonatal intensive care treatment to maximize their chances of survival. Early oral retinoid therapy has been shown to increase survival in patients with harlequin ichthyosis, and we present a case of a 9-month-old male with this condition who has been treated with isotretinoin since day 7 of life.
Assuntos
Ictiose Lamelar/tratamento farmacológico , Isotretinoína/uso terapêutico , Ceratolíticos/uso terapêutico , Humanos , Ictiose Lamelar/terapia , Lactente , Recém-Nascido , MasculinoRESUMO
OBJECTIVE: To examine the role of depression and exposure to peer or family suicide and their interaction as risk factors for adolescent suicide attempts. METHODS: The study used the public-use data set of the National Longitudinal Study of Adolescent Health (Add Health), which is a nationally representative stratified sample of U.S. high school students. Sample size was 4,719. Analyses predicted suicide attempts from preexisting depression and exposure to suicide of a friend or family member, controlling for previous suicide attempts, exposure, and depression. RESULTS: The greatest risk for future suicide attempts (relative risk = 3.3), was attributable to an attempt in the preceding year, controlling for preexisting and current depression and exposure. There was a main effect of exposure with the next highest relative risk of 3.2. A similar risk ratio, 3.2, was found for the difference between no depression and current severe depression, controlling for past depression and attempts. There was no evidence of an interaction between exposure to a peer or family member suicide attempt and depression. Supplementary analyses found that exposure to a friend or family member suicide attempt or completed suicide each added significantly to risk for adolescents regardless of depression levels. CONCLUSION: Exposure to suicidal behavior in a friend or family member poses risk equivalent to the risk posed by becoming severely depressed. Attending to such risks could benefit clinical practice with adolescence and public health suicide prevention efforts.
Assuntos
Depressão/psicologia , Família , Acontecimentos que Mudam a Vida , Grupo Associado , Tentativa de Suicídio/psicologia , Suicídio/psicologia , Adolescente , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , National Longitudinal Study of Adolescent Health , Fatores de Risco , Índice de Gravidade de Doença , Estados UnidosRESUMO
The hormonal, physiologic, and anatomic changes of pregnancy have a number of significant anesthetic implications, including the potential for difficulties and failures in tracheal intubation. The American Society of Anesthesiology closed claims database in the 1970s observed that maternal deaths were involved in 30% of all obstetrics claims, most stemming from difficulty with intubation or ventilation. In the late 1970s, Dr. Sanjay Datta, MBBS, an obstetric anesthesiologist at Brigham and Women's Hospital (Boston, MA), observed a number of differences in the practice of obstetric anesthesia in the United States when compared with his prior experiences in the United Kingdom and Canada. Dr. Datta perceived that parturients within North America had a higher body mass index. In addition, he observed an increased rate of cesarean delivery and general anesthesia use. These differences led him to evaluate ways in which the laryngoscope itself could be altered to improve the ease of intubation of parturients; this led to the development of the short laryngoscope handle. The genesis of the Datta short laryngoscope handle, and the accompanying historical context, will be explored.
Assuntos
Anestesia Obstétrica/história , Intubação Intratraqueal/história , Laringoscópios/história , Anestesia Obstétrica/instrumentação , Índice de Massa Corporal , Desenho de Equipamento , Feminino , História do Século XX , Humanos , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/instrumentação , Gravidez , Aumento de PesoRESUMO
The rising popularity of regional anesthesia in the last several decades has greatly changed the experience of labor. Although the use of regional anesthesia has aided in decreasing maternal morbidity and mortality, a new dimension of neurologic issues, particularly headache and peripheral neuropathy, is apparent. Obstetric anesthesiologists frequently encounter patients with preexisting neurologic disease. Although very few of these disorders contraindicate the use of neuraxial technique, there are limited published data on specific neurologic and neuromuscular disorders in pregnancy. Neurologists are often consulted by anesthesiologists and obstetricians to evaluate pregnant patients for the feasibility of labor analgesia and when postpartum neurologic complications arise. Early consultation with an obstetric anesthesiologist, discussion with a neurologist, and communication with the obstetrician allows for the education and discussion of the risks and benefits of both the mode of delivery and anesthetic options. This multidisciplinary approach is crucial in forming reasonable expectations for the patient. The aim of this discussion is to provide an obstetric anesthesiologist's perspective on regional anesthesia and its implications in obstetrics, and to enhance communication between our specialties.
Assuntos
Anestesia Obstétrica/métodos , Doenças do Sistema Nervoso/terapia , Complicações na Gravidez/terapia , Anestesia Obstétrica/efeitos adversos , Dor nas Costas/etiologia , Dor nas Costas/prevenção & controle , Parto Obstétrico/efeitos adversos , Parto Obstétrico/métodos , Feminino , Humanos , Doenças do Sistema Nervoso/complicações , Cefaleia Pós-Punção Dural/etiologia , Cefaleia Pós-Punção Dural/prevenção & controle , GravidezRESUMO
BACKGROUND: The complexity of genome informatics is a recurring challenge for genome exploration and analysis by students and other non-experts. This complexity creates a barrier to wider implementation of experiential genomics education, even in settings with substantial computational resources and expertise. Reducing the need for specialized software tools will increase access to hands-on genomics pedagogy. RESULTS: MySeq is a React.js single-page web application for privacy-protecting interactive personal genome analysis. All analyses are performed entirely in the user's web browser eliminating the need to install and use specialized software tools or to upload sensitive data to an external web service. MySeq leverages Tabix-indexing to efficiently query whole genome-scale variant call format (VCF) files stored locally or available remotely via HTTP(s) without loading the entire file. MySeq currently implements variant querying and annotation, physical trait prediction, pharmacogenomic, polygenic disease risk and ancestry analyses to provide representative pedagogical examples; and can be readily extended with new analysis or visualization components. CONCLUSIONS: MySeq supports multiple pedagogical approaches including independent exploration and interactive online tutorials. MySeq has been successfully employed in an undergraduate human genome analysis course where it reduced the barriers-to-entry for hands-on human genome analysis.
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Genômica/educação , Genômica/métodos , Privacidade , Navegador , Genoma Humano/genética , HumanosRESUMO
Evidence regarding the effects of pet ownership and related variables on youth socioemotional development is mixed. Inconsistencies across studies may be due to a variety of factors, including the use of different outcomes measured across studies, small potential effect sizes, and use of selected samples. In addition, studies have not systematically controlled for demographic characteristics that may bias results, nor have studies systematically examined whether effects are consistent across different subgroups. The present study examined the impact of pet ownership and attitudes toward pets on four measures of youth socioemotional outcomes: delinquency, depressed mood, empathy, and prosocial behavior. Linear mixed-effect regression analyses were conducted on 342 youth (48.0% male) aged 9-19 (M = 14.05, SD = 1.77) from a racially, ethnically, and socioeconomically diverse sample. The majority (59.1%) of youth currently lived with a dog or cat and all participants completed the Pet Attitude Scale-Modified. Pet owners reported lower delinquency and higher empathy than non-owners; however, group differences became non-significant once demographic factors were controlled for. Attitudes toward pets was significantly associated with all four outcomes. More positive attitudes was modestly associated with lower delinquency (ß = -0.22, p < 0.001) and higher empathy (ß = 0.31, p < 0.001), with smaller effects for depressed mood (ß = -0.12, p = 0.04) and prosocial behavior (ß = 0.12, p = 0.02). For delinquency, empathy, and prosocial behavior, effects were only slightly attenuated and remained statistically significant after controlling for gender, age, race/ethnicity, family socioeconomic status, and pet ownership, although the effect for depressed mood became non-significant after inclusion of these demographic factors. While there was some variability in effect sizes across different subgroups, none of the interactions between attitudes toward pets and gender, race/ethnicity, age, family SES, or pet ownership was statistically significant, indicating that the effects may transcend individual differences in demographic characteristics. Overall, the study adds to a growing body of work supporting a positive relationship between emotional bonds with pets and youth socioemotional outcomes and offers potential explanations for inconsistencies across previous studies.
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The RHO family of small GTPases has multiple functions, including regulation of cytoskeletal organization, cell cycle progression and cell migration, among others. The key members of this family are RHO, RAC and CDC42. Active GTP-bound RHO proteins are down-regulated by RHO GTPase-activating proteins (RHOGAPs). Herein, we describe the identification, characterization and mutational analysis of a novel RHOGAP designated as ARHGAP8, which is located within a critical region of loss-of-heterozygosity on chromosome 22q13.31 in breast and colorectal carcinomas. ARHGAP8 shares an identical genomic organization with ARHGAP1/CDC42GAP/p50RHOGAP and the corresponding proteins share the same functional domains that distinguish them from other ARHGAP members. These domains include the C-terminal RHOGAP domain, a central SH3-binding motif, and an N-terminal BNIP-2/CDC42GAP homology (BCH)/Sec14p-like domain. Three alternatively spliced ARHGAP8 transcripts were expressed in normal mammary gland and colon, which differed in the size of the BCH/Sec14p-like domain only. PCR-SSCP analyses revealed a total of six germline missense variants in individuals with colorectal or breast cancer; however, somatic mutations were not identified. Surprisingly, ARHGAP8 expression was up-regulated in the majority of primary colorectal tumors analyzed. Taken together, ARHGAP8 encodes a novel RHOGAP with unique functional domains that is highly homologous to ARHGAP1/CDC42GAP/p50RHOGAP.
Assuntos
Neoplasias da Mama/genética , Neoplasias Colorretais/genética , Proteínas Ativadoras de GTPase/genética , Regulação Neoplásica da Expressão Gênica , Mutação , Processamento Alternativo , Sequência de Aminoácidos , Animais , Sequência de Bases , Neoplasias da Mama/patologia , Linhagem Celular , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Éxons , Feminino , Perfilação da Expressão Gênica , Genes/genética , Humanos , Íntrons , Masculino , Camundongos , Dados de Sequência Molecular , Células NIH 3T3 , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Proteína cdc42 de Ligação ao GTP/genética , Domínios de Homologia de src/genéticaRESUMO
Background. Significant decreases in p16 expression have been shown to occur in melanoma compared to Spitz tumors, and loss of p16 staining has been found to correlate with melanoma tumor progression. However, comparison of p16 between atypical cellular blue nevi (CBN) and melanoma has not been reported previously. Methods. p16 immunohistochemical staining was evaluated in 14 atypical CBN, 8 conventional and atypical melanocytic nevi, and 16 melanomas, including 4 malignant CBN. p16 staining intensity was graded on a scale of 0-3 and the percentage of melanocytes stained with p16 was determined. Results. p16 staining was significantly higher in all CBN as a group when compared to melanomas (P = 0.001) and malignant CBN (P = 0.00008). Higher p16 expression was also seen in mildly (P = 0.0002) and moderately atypical (P = 0.02), but not severely atypical, CBN compared to melanomas. Conclusions. p16 immunohistochemical expression is higher in mildly and moderately atypical CBN compared to severely atypical CBN and melanomas. In conjunction with additional markers and histology, p16 staining may be useful in confirming the benign nature of these tumors, but is not useful in distinguishing severely atypical CBN from malignant cases, consistent with the overlapping histologic features between these tumors.
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Ultraviolet (UV) light alters cutaneous structure and function. Prior work has shown loss of dermal hyaluronan after UV-irradiation of human skin, yet UV exposure increases total glycosaminoglycan (GAG) content in mouse models. To more fully describe UV-induced alterations to cutaneous GAG content, we subjected human volunteers to intermediate-term (5 doses/week for 4 weeks) or single-dose UV exposure. Total dermal uronyl-containing GAGs increased substantially with each of these regimens. We found that UV exposure substantially increased dermal content of chondroitin sulfate (CS), but not hyaluronan, heparan sulfate, or dermatan sulfate. UV induced the accumulation of both the 4-sulfated (C4S) and 6-sulfated (C6S) isoforms of CS, but in distinct distributions. Next, we examined several CS proteoglycan core proteins and found a significant accumulation of dermal and endothelial serglycin, but not of decorin or versican, after UV exposure. To examine regulation in vitro, we found that UVB in combination with IL-1α, a cytokine upregulated by UV radiation, induced serglycin mRNA in cultured dermal fibroblasts, but did not induce the chondroitin sulfate synthases. Overall, our data indicate that intermediate-term and single-dose UVB exposure induces specific GAGs and proteoglycan core proteins in human skin in vivo. These molecules have important biologic functions and contribute to the cutaneous response to UV.
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Sulfatos de Condroitina/metabolismo , Glicosaminoglicanos/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Células Cultivadas , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Pele/citologia , Pele/metabolismoRESUMO
Glycosaminoglycans (GAGs), also known histologically as dermal mucin, accumulate in several inflammatory skin conditions. Because different GAG species have distinct immunologic effects, the authors examined two GAGs, hyaluronan (HA) and chondroitin sulfate (CS), using specific stains in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). In the dermis of one CLE subtype, tumid LE (TLE), they found only increased HA, but both HA and CS were significantly elevated in another CLE subtype, discoid LE (DLE). DM lesional dermis accumulated mainly CS but not HA. The authors then used glycomic gene expression microarrays to assess the expression of HA- and CS-related genes in CLE skin. Real-time quantitative PCR confirmed significantly increased expression of HAS2, CHSY1, and C4ST1 in the combined groups of CLE lesions (n = 8) compared to healthy controls (n = 4). Thus, the increase in HA in CLE presumably results from upregulation of HAS2, whereas CHSY1 and C4ST1 appear to contribute to increased CS. Based on their known immunomodulatory effects in other systems, HA and CS may thus participate in the pathophysiology of these inflammatory skin conditions.
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Sulfatos de Condroitina/metabolismo , Dermatomiosite/metabolismo , Ácido Hialurônico/metabolismo , Lúpus Eritematoso Cutâneo/metabolismo , Complexo CD3/metabolismo , Estudos de Casos e Controles , Sulfatos de Condroitina/genética , Derme/metabolismo , Humanos , Ácido Hialurônico/genética , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/metabolismoRESUMO
BACKGROUND: Multidetector-row computed tomographic (MDCT) coronary angiography has been validated for noninvasive assessment of coronary anatomy. However, we have less experience in diagnosing children with congenital or acquired coronary artery abnormalities by MDCT. We compared the results of MDCT with invasive coronary angiography (ICA) on identifying coronary abnormalities in infants, children, and adolescents with coronary artery abnormalities, including aneurysm, coronary fistula, or anomalous left coronary artery from pulmonary artery (ALCAPA). METHODS: From January 2002 to December 2009, patients with congenital or acquired coronary abnormalities underwent either ICA, MDCT, or both studies for assessment of coronary anatomy. We reviewed all patients' clinical diagnosis, coronary abnormalities identified by MDCT or ICA, and analyzed the advantages and disadvantages between those two methods. RESULTS: Thirty-three patients (20 males and 13 females) with a mean age of 10.3 years (range: 18 days to 25 years) had coronary abnormalities, including coronary artery aneurysm in Kawasaki disease (n=15), coronary artery fistula (n=12), myocardial bridge (n=2), and ALCAPA (n=4). In 17 patients only referred for ICA, 5 coronary aneurysms (3 on left main coronary artery, 1 on left anterior descending artery segment proximal, 1 on right coronary artery segment proximal), 11 coronary artery fistulas, and 2 ALCAPAs were detected. Sixteen patients received MDCT study, and 14 coronary artery aneurysms (4 on right coronary artery, 5 on left main coronary artery, 4 on left anterior descending artery, 1 on left circumflex artery), 3 myocardial bridges, 1 coronary artery fistulas, and 2 ALCAPAs were assessed. Ten patients with Kawasaki disease-related coronary lesions received MDCT study, and totally 102 (78.5%) segments permitted visualization with accurate diagnostic image quality. In this study, there were 11 patients with indication for conventional ICA spared invasive angiography after precise assessment by MDCT. CONCLUSION: We conclude that MDCT is a good and useful modality for assessment of congenital or acquired coronary abnormalities in pediatric patients. However, MDCT cannot replace invasive cardiac catheterization and ICA because of lack of therapeutic role.
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Angiografia Coronária/métodos , Anomalias dos Vasos Coronários/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagem , Ponte Miocárdica/diagnóstico por imagemRESUMO
PURPOSE: To determine the degree of knowledge that medical students applying to the St. Luke's-Roosevelt Hospital Center anesthesiology residency program had regarding the core physician competencies mandated by the Accreditation Council for Graduate Medical Education. METHOD: As a part of the department's annual resident-selection process, in the fall of 2008, 193 interviewed fourth-year U.S. MD-degree medical students applying to the St. Luke's-Roosevelt Hospital Center anesthesiology program were given a brief, written questionnaire to determine their knowledge of the six core physician competencies. The instructions for completing the instrument were standardized and delivered to the applicants by one of the program directors. RESULTS: A total of 193 applicants completed the interview questionnaire. Seventy-six had no knowledge of any of the physician competencies, and only three were able to correctly identify all six. CONCLUSIONS: While this research is an observation of only one set of applicants to one residency program, if the findings are applicable to other programs and specialties, that suggests that medical schools and residency program directors should develop methods for increasing competency awareness among medical students.
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Competência Clínica/normas , Estudantes de Medicina , Acreditação , Anestesiologia/educação , Educação de Pós-Graduação em Medicina/normas , Humanos , Internato e Residência , Inquéritos e Questionários , Estados UnidosRESUMO
Balloon valvuloplasty became the treatment of choice for valvular pulmonary stenosis following its first description in 1982 by Kan et al, and has almost replaced surgical pulmonary valvotomy in the present day. It is a safe and effective method for children for relief of right ventricular obstruction. The results of the procedure are excellent, without significant complications. This report describes the case of a 12-year-old boy who received successful balloon valvuloplasty for critical pulmonary valve stenosis complicated by an episode of acute pulmonary hemorrhage. Because of cyanosis, hypotension and bradycardia, he received emergent endotracheal intubation with 100% oxygen supplement and the highest infusion rate of inotropic agents. Venoarterial mode extracorporeal membrane oxygenation was indicated for life support due to the persistent high oxygenation index. Extracorporeal membrane oxygenation played a key role in the survival of this patient during the course of treatment.
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Cateterismo/efeitos adversos , Hemorragia/etiologia , Pneumopatias/etiologia , Estenose da Valva Pulmonar/terapia , Doença Aguda , Criança , Oxigenação por Membrana Extracorpórea , Humanos , MasculinoAssuntos
Bacteriemia/complicações , Staphylococcus aureus Resistente à Meticilina , Dermatopatias Vesiculobolhosas/microbiologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Criança , Humanos , Masculino , Dermatopatias Vesiculobolhosas/tratamento farmacológico , Vancomicina/uso terapêuticoRESUMO
A major mechanism for apical peptide absorption by small intestine is via the proton-coupled transporter PepT1. PepT1 is expressed at a high level in proximal small intestine, but it is not expressed in the healthy colon. However, in chronic states of intestinal inflammation, such as in Crohn's disease and ulcerative colitis, PepT1 expression in colonic epithelia is increased, serving as a pathway for entry of bacteria-derived molecules such as muramyl dipeptide (MDP) and fMet-Leu-Phe (fMLP). As little is known of how inflammation induces PepT1, we investigated whether or not inflammatory cytokines and mediators such as interleukins (IL)-1beta, IL-2, IL-8, IL-10, tumor necrosis factor-alpha, (TNF-alpha) and interferon-gamma (IFN-gamma ) up-regulate PepT1 activity and expression. Uptake of the PepT1 substrate glycylsarcosine [(3)H]-Gly-Sar was studied in vitro in the human colon carcinoma cell line Caco2/bbe monolayers as well as in vivo in mice injected with cytokines. TNF-alpha and IFN-gamma increased the activity, and total and apical membrane protein expression of PepT1 protein in a concentration- and time-dependent fashion. No changes in PepT1 mRNA were observed, suggesting post-transcriptional regulation. All three cytokines increased PepT1 protein expression in mouse proximal and distal colon but not in jejunum or ileum. TNF-alpha and IFN-gamma, but not IL-1beta, increased Gly-Sar uptake in mouse proximal and distal colon; however, no changes were observed in the small intestine with any cytokine treatment. Whereas neither TNF-alpha nor IFN-gamma increased PepT1 mRNA expression in any segment of the intestine, treatment with IL-1beta increased PepT1 mRNA expression in mouse proximal and distal colon and decreased PepT1 mRNA expression in jejunum and ileum. Since PepT1 transports bacteria-derived peptides, the up-regulation of protein expression and activity observed after treatment with TNF-alpha or IFN-gamma may play a role in activating host responses in involved colon.
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Interferon gama/fisiologia , Mucosa Intestinal/metabolismo , Simportadores/metabolismo , Fator de Necrose Tumoral alfa/fisiologia , Animais , Células CACO-2 , Citocinas/fisiologia , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transportador 1 de PeptídeosRESUMO
Loss of heterozygosity on chromosome 22q13.31 is a frequent event during human breast and colorectal carcinogenesis. Herein we characterize a novel gene at chromosome 22q13.31 designated PRR5. Alternative promoter usage and splicing converge to generate five PRR5 transcript variants with maximum mRNA expression in kidney. In vitro transcription/translation demonstrated that the five variants generate three protein isoforms differing in their N-terminal length. Mutational analysis of PRR5 in human breast and colorectal tumors did not reveal somatic mutations. However, mRNA expression analyses revealed PRR5 overexpression in a majority of colorectal tumors but substantial downregulation of PRR5 expression in a subset of breast tumors and reduced expression in two breast cancer cell lines. Treatment with trichostatin A increased PRR5 mRNA levels in BT549 and MDA-MB-231 cells, whereas 5'-aza-2'-deoxycytidine induced expression in MDA-MB-231 cells only. Thus, PRR5 may represent a potential candidate tumor suppressor gene in breast cancer.