RESUMEN
Introduction: Cochlear implants (CIs) restore hearing to deafened patients. The foreign body response (FBR) following cochlear implantation (post-CI) comprises an infiltration of macrophages, other immune and non-immune cells, and fibrosis into the scala tympani; a space that is normally devoid of cells. This FBR is associated with negative effects on CI outcomes including increased electrode impedances and loss of residual acoustic hearing. This study investigates the extent to which macrophage depletion by an orally administered CSF-1R specific kinase (c-FMS) inhibitor, PLX-5622, modulates the tissue response to CI and neural health. Materials and methods: 10-12-week-old CX3CR1+/GFP Thy1+/YFP mice on C57Bl6 background with normal hearing were fed chow containing 1200 mg/kg PLX5622 or control chow for the duration of the study. 7-days after starting the diet, 3-channel cochlear implants were implanted ear via the round window. Serial impedance and neural response telemetry (NRT) measurements were acquired throughout the study. Electric stimulation began 7 days post-CI until 28- days post-CI for 5 hrs/day, 5 days/week, with programming guided by NRT and behavioral responses. Cochleae harvested at 10-, 28- or 56-days post-CI were cryosectioned and labeled with antibody against α-smooth muscle actin (α-SMA) to identify myofibroblasts and quantify the fibrotic response. Using IMARIS image analysis software, the outlines of scala tympani, Rosenthal canal, modiolus and lateral wall for each turn were traced manually to measure region volume. Density of nuclei, CX3CR1+ macrophages, Thy1+ spiral ganglion neuron (SGN) numbers and ratio of volume of α-SMA+ space/volume of scala tympani were calculated. Results: Cochlear implantation in control diet subjects caused infiltration of cells, including macrophages, into the cochlea: this response was initially diffuse throughout the cochlea and later localized to the scala tympani of the basal turn by 56-days post-CI. Fibrosis was evident in the scala tympani adjacent to the electrode array. Mice fed PLX5622 chow showed reduced macrophage infiltration throughout the implanted cochleae across all timepoints. However, scala tympani fibrosis was not reduced relative to control diet subjects. Further, mice treated with PLX5622 showed increased electrode impedances compared to controls. Finally, treatment with PLX5622 decreased SGN survival in implanted and contralateral cochleae. Discussion: The data suggest that macrophages play an important role in modulating the intracochlear tissue response following CI and neural survival.
RESUMEN
Objective: This narrative review aims to detail the indications, technique, and published outcomes of the bridge in slot technique for lateral meniscus allograft transplantation (LMAT) and to serve as a concise reference for orthopaedists looking to incorporate this method into their practice. Background: The menisci are crucial to normal knee function but are commonly injured; partial and subtotal meniscectomy are frequently performed to address meniscal pathology. Following these procedures, a substantial number of patients go on to develop degenerative joint changes accompanied by pain and disability. LMAT is an attractive option for young, active, lateral meniscal-deficient patients who seek pain relief and improved function but who are not yet prepared to undergo arthroplasty. In the properly indicated patient, the bridge in slot technique is a reliable and effective method for LMAT. Methods: Using a narrative style, this review outlines the indications and preoperative assessment for LMAT, the detailed technical steps for the bridge in slot technique, postoperative considerations, and trends in the surgical outcomes literature. The presented technique is consistent with the senior author's clinical experience and with published literature and the discussed outcomes are elicited from a focused review of recent peer-reviewed sources. Conclusions: The bridge in slot technique is a reliable and effective method for LMAT and is supported by the literature. This technique may confidently be used in patients with severe lateral meniscal pathology who are not yet candidates for arthroplasty.
RESUMEN
A dendritic cell-based, Type 1 Helper T cell (Th1)-polarizing anti-Human Epidermal Growth Factor Receptor-2 (HER-2) vaccine supplied in the neoadjuvant setting eliminates disease in up to 30% of recipients with HER-2-positive (HER-2pos) ductal carcinoma in situ (DCIS). We hypothesized that drugs with low toxicity profiles that target signaling pathways critical for oncogenesis may work in conjunction with vaccine-induced immune effector mechanisms to improve efficacy while minimizing side effects. In this study, a panel of four phenotypically diverse human breast cancer lines were exposed in vitro to the combination of Th1 cytokines Interferon-gamma (IFN-γ) and Tumor Necrosis Factor-alpha (TNF-α) and lipophilic statins. This combination was shown to potentiate multiple markers of apoptotic cell death. The combination of statin drugs and Th1 cytokines minimized membrane K-Ras localization while maximizing levels in the cytoplasm, suggesting a possible means by which cytokines and statin drugs might cooperate to maximize cell death. A combined therapy was also tested in vivo through an orthotopic murine model using the neu-transgenic TUBO mammary carcinoma line. We showed that the combination of HER-2 peptide-pulsed dendritic cell (DC)-based immunotherapy and simvastatin, but not single agents, significantly suppressed tumor growth. Consistent with a Th1 cytokine-dependent mechanism, parenterally administered recombinant IFN-γ could substitute for DC-based immunotherapy, likewise inhibiting tumor growth when combined with simvastatin. These studies show that statin drugs can amplify a DC-induced effector mechanism to improve anti-tumor activity.
RESUMEN
BACKGROUND: Sex differences in youth's posttraumatic stress disorder (PTSD) symptomatology have not been well studied. METHODS: Based on a recently burgeoning theory of psychopathology networks, this study conducted sex comparisons of global and local connectivity of PTSD symptoms in a sample of 868 disaster-exposed adolescents (57.0% girls; a mean age of 13.4 ± 0.8 years) with significant PTSD symptomatology evaluated by the UCLA PTSD Reaction Index for DSM-IV. RESULTS: The results revealed that global connectivity was stronger in girls' network than in boys', and individual symptoms' connectivity and its rankings differed by sex. Intrusive recollections, flashbacks, avoiding activities/people, and detachment were the most strongly connected symptoms in girls, whereas flashbacks, physiological cue reactivity, diminished interest, and foreshortened future were the most strongly connected symptoms in boys. Several symptoms were identified as featuring large connectivity differences across sex. CONCLUSIONS: These findings provide novel insights into sex differential risk and features of youth's PTSD symptomatology. Sex differences reflected in the co-occurrence of PTSD symptoms may merit more consideration in research and clinical practice.
Asunto(s)
Caracteres Sexuales , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/fisiopatología , Adolescente , China/epidemiología , Terremotos , Femenino , Humanos , Masculino , Trastornos por Estrés Postraumático/etiologíaRESUMEN
It has been well-documented that posttraumatic stress symptoms cause impairments in health-related quality of life (HRQoL). Until now we have little data on how DSM-5 PTSD symptom dimensions relate to different aspects of HRQoL. Clarifying this question would be informative to improve the quality of life of PTSD patients. This study aimed to investigate the effects of dimensions of a well-supported seven-factor model of DSM-5 PTSD symptoms on physical and psychosocial HRQoL. A total of 1063 adult survivors of the 2008 Wenchuan earthquake took part in this study nine years after the disaster. PTSD symptoms were measured by the PTSD Checklist for DSM-5 (PCL-5). HRQoL was measured by the Medical Outcomes Survey Short Form-36 (SF-36). The associations between PTSD symptom dimensions and HRQoL were examined using structural equation models. Dysphoric arousal symptoms were found to significantly relate to physical HRQoL. Other symptom dimensions were not associated with HRQoL. Our findings contribute to the relationship between DSM-5 PTSD and HRQoL, and carry implications for further clinical practice and research on trauma-exposed individuals.
La evidencia previa indica que los síntomas de estrés postraumático causan déficits en la calidad de vida relacionada con la salud (CVRS). Hasta ahora, tenemos pocos datos sobre cómo las dimensiones de los síntomas del TEPT del DSM-5 se relacionan con diferentes aspectos de la CVRS. Aclarar esta pregunta ayudaría a mejorar clínicamente la calidad de vida de los pacientes con TEPT. Este estudio tuvo como objetivo investigar los efectos de las dimensiones de un modelo bien respaldado de siete factores de los síntomas del TEPT según el DSM-5 sobre la CVRS física y psicosocial. En este estudio participaron mil sesenta y tres supervivientes adultos del terremoto de Wenchuan en 2008, nueve años después del desastre. Los síntomas del TEPT se midieron mediante el Lista de Evaluación del TEPT para el DSM-5 (PCL-5), y la CVRS se midió mediante el Cuestionario de Salud en formato abreviado-36 (SF-36). Las asociaciones entre las dimensiones de los síntomas de TEPT y la CVRS se examinaron utilizando modelos de ecuaciones estructurales. Los síntomas de alerta disfórica se relacionaron significativamente con la CVRS física, mientras que las otras dimensiones de síntomas no se relacionaron con la CVRS.Conclusiones: Nuestros hallazgos aportan conocimiento sobre las relaciones entre el TEPT según el DSM-5 y CVRS, y tienen implicaciones para la práctica clínica y la investigación en individuos expuestos al trauma.
RESUMEN
The thalamus has recently received renewed interest in systems-neuroscience and schizophrenia (ScZ) research because of emerging evidence highlighting its important role in coordinating functional interactions in cortical-subcortical circuits. Moreover, higher cognitive functions, such as working memory and attention, have been related to thalamo-cortical interactions, providing a novel perspective for the understanding of the neural substrate of cognition. The current review will support this perspective by summarizing evidence on the crucial role of neural oscillations in facilitating thalamo-cortical (TC) interactions during normal brain functioning and their potential impairment in ScZ. Specifically, we will focus on the relationship between NMDA-R mediated (glutamatergic) neurotransmission in TC-interactions. To this end, we will first review the functional anatomy and neurotransmitters in thalamic circuits, followed by a review of the oscillatory signatures and cognitive processes supported by TC-circuits. In the second part of the paper, data from preclinical research as well as human studies will be summarized that have implicated TC-interactions as a crucial target for NMDA-receptor hypofunctioning. Finally, we will compare these neural signatures with current evidence from ScZ-research, suggesting a potential overlap between alterations in TC-circuits as the result of NMDA-R deficits and stage-specific alterations in large-scale networks in ScZ.
Asunto(s)
Corteza Cerebral/fisiopatología , Ácido Glutámico/metabolismo , Esquizofrenia/fisiopatología , Transmisión Sináptica/fisiología , Tálamo/fisiopatología , Animales , Ondas Encefálicas/fisiología , Corteza Cerebral/patología , Humanos , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Receptores de N-Metil-D-Aspartato/metabolismo , Esquizofrenia/patología , Tálamo/patologíaAsunto(s)
Hernia Umbilical/diagnóstico , Preescolar , Femenino , Hernia Umbilical/cirugía , Humanos , Remisión EspontáneaRESUMEN
Biliary epithelial cells (BEC) are important targets in some liver diseases, including acute allograft rejection. Although some injured BEC die, many can survive in function compromised states of senescence or phenotypic de-differentiation. This study was performed to examine changes in the phenotype of BEC during acute liver allograft rejection and the mechanism driving these changes. Liver allograft sections showed a positive correlation (p < 0.0013) between increasing T cell mediated acute rejection and the number of BEC expressing the senescence marker p21(WAF1/Cip) or the mesenchymal marker S100A4. This was modeled in vitro by examination of primary or immortalized BEC after acute oxidative stress. During the first 48 h, the expression of p21(WAF1/Cip) was increased transiently before returning to baseline. After this time BEC showed increased expression of mesenchymal proteins with a decrease in epithelial markers. Analysis of TGF-ß expression at mRNA and protein levels also showed a rapid increase in TGF-ß2 (p < 0.006) following oxidative stress. The epithelial de-differentiation observed in vitro was abrogated by pharmacological blockade of the ALK-5 component of the TGF-ß receptor. These data suggest that stress induced production of TGF-ß2 by BEC can modify liver allograft function by enhancing the de-differentiation of local epithelial cells.
Asunto(s)
Conductos Biliares Intrahepáticos/patología , Senescencia Celular , Células Epiteliales/patología , Rechazo de Injerto/patología , Trasplante de Hígado/patología , Enfermedad Aguda , Conductos Biliares Intrahepáticos/metabolismo , Biopsia , Western Blotting , Células Cultivadas , Densitometría , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales/metabolismo , Regulación de la Expresión Génica , Rechazo de Injerto/genética , Rechazo de Injerto/metabolismo , Humanos , Inmunohistoquímica , Estrés Oxidativo/genética , ARN/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Crecimiento Transformador beta2/biosíntesis , Factor de Crecimiento Transformador beta2/genética , Trasplante HomólogoRESUMEN
Osteosarcoma is the most common primary cancer of bone and one that predominantly affects children and adolescents. Osteoblastic osteosarcoma represents the major subtype of this tumor, with approximately equal representation of fibroblastic and chondroblastic subtypes. We and others have previously described murine models of osteosarcoma based on osteoblast-restricted Cre:lox deletion of Trp53 (p53) and Rb1 (Rb), resulting in a phenotype most similar to fibroblastic osteosarcoma in humans. We now report a model of the most prevalent form of human osteosarcoma, the osteoblastic subtype. In contrast to other osteosarcoma models that have used Cre:lox mediated gene deletion, this model was generated through shRNA-based knockdown of p53. As is the case with the human disease the shRNA tumors most frequently present in the long bones and preferentially disseminate to the lungs; feature less consistently modeled using Cre:lox approaches. Our approach allowed direct comparison of the in vivo consequences of targeting the same genetic drivers using two different technologies, Cre:lox and shRNA. This demonstrated that the effects of Cre:lox and shRNA mediated knock-down are qualitatively different, at least in the context of osteosarcoma, and yielded distinct subtypes of osteosarcoma. Through the use of complementary genetic modification strategies we have established a model of the most common clinical subtype of osteosarcoma that was not previously represented and more fully recapitulated the clinical spectrum of this cancer.
Asunto(s)
Linaje de la Célula/genética , Integrasas/metabolismo , Modelos Biológicos , Osteosarcoma/clasificación , Osteosarcoma/genética , ARN Interferente Pequeño/metabolismo , Transgenes/genética , Animales , Biomarcadores de Tumor/metabolismo , Diferenciación Celular , Membrana Celular/metabolismo , Cromosomas de los Mamíferos/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Cariotipificación , Ratones , Ratones Transgénicos , Osteoblastos/metabolismo , Osteoblastos/patología , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/patología , Penetrancia , Fenotipo , Radiografía , Transducción de Señal , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The past decade has seen significant increases in combustion-generated ambient particles, which contain a nanosized fraction (less than 100 nm), and even greater increases have occurred in engineered nanoparticles (NPs) propelled by the booming nanotechnology industry. Although inhalation of these particulates has become a public health concern, human health effects and mechanisms of action for NPs are not well understood. Focusing on the human airway smooth muscle cell, here we show that the cellular mechanical function is altered by particulate exposure in a manner that is dependent upon particle material, size and dose. We used Alamar Blue assay to measure cell viability and optical magnetic twisting cytometry to measure cell stiffness and agonist-induced contractility. The eight particle species fell into four categories, based on their respective effect on cell viability and on mechanical function. Cell viability was impaired and cell contractility was decreased by (i) zinc oxide (40-100 nm and less than 44 microm) and copper(II) oxide (less than 50 nm); cell contractility was decreased by (ii) fluorescent polystyrene spheres (40 nm), increased by (iii) welding fumes and unchanged by (iv) diesel exhaust particles, titanium dioxide (25 nm) and copper(II) oxide (less than 5 microm), although in none of these cases was cell viability impaired. Treatment with hydrogen peroxide up to 500 microM did not alter viability or cell mechanics, suggesting that the particle effects are unlikely to be mediated by particle-generated reactive oxygen species. Our results highlight the susceptibility of cellular mechanical function to particulate exposures and suggest that direct exposure of the airway smooth muscle cells to particulates may initiate or aggravate respiratory diseases.
Asunto(s)
Supervivencia Celular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Nanopartículas/efectos adversos , Sistema Respiratorio/citología , Emisiones de Vehículos/toxicidad , Análisis de Varianza , Fenómenos Biomecánicos , Línea Celular , Cobre/toxicidad , Humanos , Peróxido de Hidrógeno , Miocitos del Músculo Liso/fisiología , Oxazinas , Poliestirenos/toxicidad , Titanio/toxicidad , Xantenos , Óxido de Zinc/toxicidadRESUMEN
BACKGROUND: The reported high incidence of 30-60% postoperative pain after an elective day surgical orchidopexy is undesirable. We evaluated the efficacy of our analgesic regimen for unilateral orchidopexy in preschool children performed as a day surgical procedure. METHODS: Between January 2004 and December 2006, 247 children (mean age: 3.3 +/- 1.6 years) underwent a unilateral orchidopexy as a day surgical procedure. They were prospectively analyzed for postoperative pain during a period of 48 h by using the Visual Analogue Scale (VAS). After standardized general anesthesia, all children had a 0.25% levo-bupivacaine hydrochloride ilio-inguinal block and a rectal diclofenac sodium suppository. Orchidopexy was performed through transverse inguinal and scrotal incisions. The wounds were infiltrated with 0.25% levo-bupivacaine hydrochloride at the end of the operation. Postoperatively acetaminophen and ibuprofen were given orally at regular intervals for 48 h. RESULTS: On first assessment in the recovery room, 148 out of 247 (60%) patients were pain-free, and 99 of 247 (40%) patients had pain: VAS score ranged from 3 to 10. By 3 h, 27 (11%) had mild-to-moderate pain, with VAS scores between 3 and 7. All children were discharged home at 4 h with no pain. At home, 95% were pain-free at 10 h and 97% by 24 h, with a declining pain score. All children were pain-free at 32, 40, and 48 h. Pain scores were unrelated to the duration of surgery (r (s) = 0.54). CONCLUSION: Clinical effectiveness of our institution analgesic regime justifies the performance of unilateral orchidopexy as a day-case procedure.
Asunto(s)
Analgesia/métodos , Criptorquidismo/cirugía , Dolor Postoperatorio/prevención & control , Procedimientos Quirúrgicos Ambulatorios/métodos , Preescolar , Humanos , Masculino , Dimensión del Dolor , Estudios ProspectivosAsunto(s)
Enfermedades en Gemelos , Hernias Diafragmáticas Congénitas , Complicaciones Intraoperatorias , Hígado/lesiones , Derrame Pleural/etiología , Infecciones Bacterianas/complicaciones , Tubos Torácicos , Drenaje , Femenino , Hernia Diafragmática/complicaciones , Hernia Diafragmática/cirugía , Humanos , Recién Nacido , Masculino , Gemelos DicigóticosRESUMEN
The experiences of chronic pain among children and adolescents with cerebral palsy (CP) were examined in this survey-based study. Perspective of both the individual and the parent were solicited in a preliminary sample of 20 youths with CP, ages 6 to 17 years from a metropolitan area. Selected participants completed in-person, structured interviews that focused on quality of life with attention to pain experiences. Quantitative data were analyzed descriptively. Seventy percent of participants (n = 14) experienced recurrent chronic pain of moderate intensity on a daily or weekly basis. Greater than half of those participants (n = 9) reported that pain presented a problem for them and especially interfered with self-care and with sleep. Pain appears to be a problem for many youths with CP, and may create additional interference with routine activities of daily living and participation. Further exploration regarding pain experiences and the nature of pain interference is warranted in order to address development and maintenance of routine activities and participation by children and adolescents with CP.
Asunto(s)
Parálisis Cerebral/psicología , Dolor/clasificación , Calidad de Vida , Adolescente , Parálisis Cerebral/complicaciones , Niño , Enfermedad Crónica , Evaluación de la Discapacidad , Femenino , Humanos , Entrevistas como Asunto , Masculino , Dolor/etiologíaRESUMEN
The Cbl ubiquitin ligase has emerged as a negative regulator of receptor and non-receptor tyrosine kinases. Cbl is known to associate with the proto-oncogene product Vav, a hematopoietic-restricted Rac guanine nucleotide exchange factor, but the consequences of this interaction remain to be elucidated. Using immortalized T cell lines from Cbl(+/+) and Cbl(-/-) mice, and transfection analyses in 293T cells, we demonstrate that Vav undergoes Cbl-dependent ubiquitinylation under conditions that promote Cbl and Vav phosphorylation. Interaction with Cbl also induced the loss of phosphorylated Vav. In addition, we show that an activated Vav mutant (Vav-Y174F) is more sensitive to Cbl-dependent ubiquitinylation. We demonstrate that the Cbl-dependent ubiquitinylation of Vav requires Cbl/Vav association through phosphorylated Tyr-700 on Cbl, and also requires an intact Cbl RING finger domain. Finally, using transfection analyses in the Jurkat T cell line, we show that Cbl, but not its ubiquitin ligase mutant, can inhibit Vav-dependent signaling. Thus, our findings strongly support the role of Cbl, via its ubiquitin ligase activity, as a negative regulator of activated Vav.
Asunto(s)
Regulación de la Expresión Génica , Proteínas Oncogénicas/metabolismo , Proteínas Oncogénicas de Retroviridae/fisiología , Ubiquitina/metabolismo , Animales , Línea Celular , Electroforesis en Gel de Poliacrilamida , Humanos , Immunoblotting , Células Jurkat , Luciferasas/metabolismo , Ratones , Ratones Transgénicos , Modelos Genéticos , Mutación , Proteína Oncogénica v-cbl , Fosforilación , Plásmidos/metabolismo , Pruebas de Precipitina , Unión Proteica , Estructura Terciaria de Proteína , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-vav , Proteínas Oncogénicas de Retroviridae/metabolismo , Transducción de Señal , Factores de Tiempo , Transfección , Tirosina/química , Vanadatos/farmacologíaRESUMEN
Fibrinogen is a soluble protein produced by hepatocytes and secreted into plasma, where it functions in hemostasis. During inflammation, the hepatic synthesis of fibrinogen is induced 2-10 fold. Recent studies demonstrate that after an inflammatory stimulus, fibrinogen gene expression and protein production is upregulated in lung epithelial cells, where it is secreted basolaterally and consequently deposited into the extracellular matrix in fibrils that extensively colocalize with fibronectin fibrils. In this study, we show that the deposition of fibrinogen into the matrix of fibroblasts occurred rapidly and in a Rho-dependent manner in response to serum or lysophosphatidic acid; RhoA GTPase signaling is also required for fibronectin matrix assembly. Using mouse embryonic fibronectin-null cells, we show that incorporation of exogenous fibrinogen into matrix fibrils occurred only in the presence of exogenous fibronectin, which is also assembled into matrix fibrils. Furthermore, treatment of fibroblasts and fibronectin-null cells with an antibody that inhibits fibronectin matrix assembly impaired incorporation of fibrinogen into matrix fibrils. Collectively, these data suggest that incorporation of fibrinogen into the extracellular matrix requires active fibronectin polymer elongation into matrix fibrils. From these data, we hypothesize that fibrinogen deposition rapidly changes the topology of the extracellular matrix to provide a surface for cell migration and matrix remodeling during tissue repair.
Asunto(s)
Matriz Extracelular/metabolismo , Fibrinógeno/metabolismo , Fibronectinas/metabolismo , ADP Ribosa Transferasas/metabolismo , Animales , Anticuerpos Monoclonales/metabolismo , Toxinas Botulínicas/metabolismo , Adhesión Celular/fisiología , Células Cultivadas , Medio de Cultivo Libre de Suero , Activación Enzimática , Fibrinógeno/genética , Fibroblastos , Proteoglicanos de Heparán Sulfato/metabolismo , Humanos , Radioisótopos de Yodo/metabolismo , Lisofosfolípidos/metabolismo , Ratones , Proteínas de Unión al GTP rho/metabolismoRESUMEN
Ozone (O(3)), a major component of urban air pollution, is a strong oxidizing agent that can cause lung injury and inflammation. In the present study, we investigated the effect of inhalation of O(3) on levels of F(2)-isoprostanes in bronchoalveolar lavage fluid (BALF) and on levels of antioxidants in the BALF and plasma of hamsters. Because antioxidants, including urate, ascorbate, GSH, and vitamin E, defend the lungs by reacting with oxidizing agents, we expected to find a decrease in antioxidant levels after O(3) exposure. Similarly, we expected an increase in the levels of F(2)-isoprostanes, which are lipid peroxidation products. Exposure to 1.0 or 3.0 parts/million (ppm) O(3) for 6 h resulted in an increase in BALF neutrophil numbers, an indicator of acute inflammation, as well as elevation of BALF F(2)-isoprostanes. The higher dose of O(3) caused an increase in the BALF level of urate and a decrease in the plasma level of ascorbate, but 1.0 ppm O(3) had no effect on BALF or plasma antioxidant levels. Exposure to 0.12 ppm O(3) had no effect on BALF neutrophils or F(2)-isoprostanes nor on BALF and plasma antioxidants. We also investigated the effect of O(3) exposure of hamsters during exercise on F(2)-isoprostane and antioxidant levels. We found that exposure to 1.0 ppm O(3) during 1 h of exercise on a laddermill increased BALF levels of F(2)-isoprostanes but had no effect on BALF neutrophils or on BALF and plasma antioxidants. These results indicate that O(3) induces inflammation and biomolecule oxidation in the lungs, whereas extracellular antioxidant levels are relatively unchanged.
Asunto(s)
Peroxidación de Lípido/efectos de los fármacos , Oxidantes Fotoquímicos/toxicidad , Ozono/toxicidad , Esfuerzo Físico/fisiología , Animales , Antioxidantes/metabolismo , Líquido del Lavado Bronquioalveolar/citología , Cricetinae , Masculino , Mesocricetus , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismoRESUMEN
BACKGROUND/PURPOSE: The aim of this study was to determine the normal position of the umbilicus and hence improve the cosmetic result of exomphalos major repair. METHODS: The position of the umbilicus was determined in 50 neonates with respect to the xiphisternum and pubis. RESULTS: The normal umbilical position is 60% of the way from the inferior border of the xiphisternum to the superior border of the pubis in the midline. CONCLUSION: In the repair of exomphalos major, the most aesthetically pleasing result is obtained if the umbilicus is placed 60% of the way from the xiphisternum to the pubis.
Asunto(s)
Hernia Umbilical/cirugía , Ombligo/anatomía & histología , Estética , Femenino , Humanos , Recién Nacido , Masculino , Valores de Referencia , Ombligo/cirugíaRESUMEN
Mice transgenic for a p190bcr/abl construct develop pre-B cell leukemia/lymphoma, providing a model of Ph+ ALL. To investigate events in tumorigenesis, immunofluorescence labeling, flow cytometry and a short-term culture assay were used to quantitate precursor B cells and their apoptotic rates in bone marrow of p190bcr/abl transgenic mice over a wide age range. Malignancies appeared rapidly at 8-12 weeks of age, followed by slower tumor onset. At 8-12 weeks in normal mice, the apoptotic rate fell among pro-B cells but increased steeply among pre-B cells, while the total number of B lineage cells declined. In contrast, in p190bcr/abl transgenic mice over the same time period, while pro-B cells remained normal in apoptotic rate and number, apoptosis of pre-B cells was markedly inhibited and the number of B lymphocytes increased. At later ages (14-30 weeks), B cell precursors in control mice remained constant in apoptotic activity and number, while in the few surviving transgenic mice B cell populations were expanded. The results reveal characteristic changes in apoptotic activity among B cell precursors in bone marrow during early life, severely perturbed in preleukemic p190bcr/abl transgenic mice by a preferential suppression of pre-B cell apoptosis. p190bcr/abl may thus promote leukemogenesis by permitting aberrant cells generated during early B cell development to evade a normal quality checkpoint and negative selection.
Asunto(s)
Apoptosis , Linfocitos B/fisiología , Células de la Médula Ósea/fisiología , Proteínas de Fusión bcr-abl/fisiología , Células Madre Hematopoyéticas/fisiología , Preleucemia/patología , Factores de Edad , Animales , Daño del ADN , Ratones , Ratones TransgénicosRESUMEN
Some colonic and neuronal cells which are CD4- but galactosyl ceramide-positive are susceptible to infection with HIV-1. We have previously shown that the T-cell tropic V3 loop of HIV-1 gp120 serves as a primary viral determinant for infectivity of CD4- neuronal cells. However, the nature of the V3 loop of HIV-1 needed for infection and the V3 loop's interaction with coreceptors on colonic epithelial cells have not been fully analyzed. By using HIV-1 molecular clones, we show that the T-cell tropic V3 domain is critical for HIV-1 infection of colonic HT-29 epithelial cells. Because T-cell tropic HIV-1 can use CXCR4 as a coreceptor in T cells, we set out to determine the role of CXCR4 during infection of HT-29 cells. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining, we show that these epithelial cells of colonic origin express the chemokine receptor CXCR4. Importantly, antibody against CXCR4 or a neutralizing antibody against HIV-1 gp120 V3 loop blocks T-cell tropic HIV-1 entry into HT-29 cells. These data indicate that the V3 loop of HIV-1 and the chemokine receptor CXCR4 are both critical for HIV-1 infection of colonic HT-29 epithelial cells. An HIV-1 T-tropic virus may be responsible for the infection of human colonic epithelial cells in vivo.