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1.
Nat Immunol ; 15(7): 687-94, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24908390

RESUMEN

The catalytic activity of Zap70 is crucial for T cell antigen receptor (TCR) signaling, but the quantitative and temporal requirements for its function in thymocyte development are not known. Using a chemical-genetic system to selectively and reversibly inhibit Zap70 catalytic activity in a model of synchronized thymic selection, we showed that CD4(+)CD8(+) thymocytes integrate multiple, transient, Zap70-dependent signals over more than 36 h to reach a cumulative threshold for positive selection, whereas 1 h of signaling was sufficient for negative selection. Titration of Zap70 activity resulted in graded reductions in positive and negative selection but did not decrease the cumulative TCR signals integrated by positively selected OT-I cells, which revealed heterogeneity, even among CD4(+)CD8(+) thymocytes expressing identical TCRs undergoing positive selection.


Asunto(s)
Linfocitos T/fisiología , Proteína Tirosina Quinasa ZAP-70/fisiología , Animales , Calcio/metabolismo , Catálisis , Diferenciación Celular , Péptidos y Proteínas de Señalización Intracelular/fisiología , Ratones , Ratones Endogámicos C57BL , Proteínas Tirosina Quinasas/fisiología , Receptores de Antígenos de Linfocitos T/fisiología , Transducción de Señal , Quinasa Syk
2.
J Extra Corpor Technol ; 54(2): 142-147, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35928341

RESUMEN

Nitric oxide (NO) incorporation into the sweep gas of the extracorporeal life support (ECLS) circuit has been proposed as a strategy to ameliorate the insults caused by the systemic inflammatory response. This technical study describes circuit modifications allowing nitric oxide to be incorporated into the circuit and describing and validating the oxygenator sweep flow rates necessary to achieve consistent safe delivery of the therapy. For patients requiring sweep rates less than 2 L/min, a simplified setup, incorporating a pressure relief valve/low flow meter in the gas delivery line, was placed in line between the blender/NO injector module and the NO sampling port/oxygenator. This setup allows titration of sweep to low flows without the need to blend in CO2 while maintaining the manufacturer recommendation of a minimum 2 L/min of sweep gas to safely deliver NO without nitric dioxide (NO2) buildup. This setup was tested three times at three different FiO2 rates and eleven different desired low sweep flows to test for reproducibility and safety to build an easy-to-follow chart for making gas flow changes. For patients requiring oxygenator sweep rates greater than 2 L/min, the pressure relief valve/low flow meter apparatus is not needed. Maintaining consistent sweep rate and nitric oxide delivery is required in order to utilize this therapy in ECLS. We demonstrated gas delivery across all flow rates. There were no issues delivering 20 parts per million of NO and negligible NO2 detection. The results from testing this setup were used to provide the specialist a chart at which to set the low flow meter to produce the desired flow rate at which the patient needs. This has been used clinically on 15 ECLS patients with success.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Oxigenación por Membrana Extracorpórea/métodos , Humanos , Óxido Nítrico , Dióxido de Nitrógeno , Oxigenadores , Reproducibilidad de los Resultados
3.
Ann Diagn Pathol ; 50: 151661, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33197866

RESUMEN

As peripheral vascular disease and diabetes mellitus are increasingly common, chronic wounds are often seen. Bone biopsies, with imaging and microbial cultures, are often obtained to evaluate for osteomyelitis. Because much of the historical literature describing the histology of osteomyelitis pertains to primary osteomyelitis, this study characterizes the histologic findings and provides correlation with culture results in secondary osteomyelitis. The histologic features of bone biopsies were assessed over a 5 year period. Concurrent laboratory and radiographic data were obtained and these data were compared with culture results. This study included 163 cases, of which 104 were culture-positive osteomyelitis. All culture-positive cases had been present longer than 28 days and had at least one of the following histologic features: neutrophilic inflammation, plasmacytic inflammation, or eosinophilic fibrosis. However, none of these findings were restricted to culture-positive cases. Overall, plasmacytic and neutrophilic inflammation provided similar specificity, and positive predictive values for osteomyelitis. Medullary fibrosis gave a sensitivity of 95%, the highest for any single feature, and the combination of fibrosis and neutrophilic inflammation had the greatest specificity of 96%. Additionally, neutrophilic inflammation correlated often with isolation of Staphylococcus aureus, while plasma cell predominance was found more frequently with other infectious agents. This study describes histologic features in secondary osteomyelitis, which may challenge the widespread inclination to equate a neutrophilic inflammation with 'acute osteomyelitis' and 'chronic osteomyelitis' with one rich in plasma cells. We report an early correlation between common histopathologic findings and specific culture isolates, which can be further refined with additional research.


Asunto(s)
Biopsia/métodos , Cultivo de Sangre/métodos , Inflamación/patología , Osteomielitis/microbiología , Osteomielitis/patología , Enfermedad Aguda , Médula Ósea/patología , Huesos/patología , Enfermedad Crónica , Eosinófilos/patología , Femenino , Fibrosis/diagnóstico , Fibrosis/patología , Humanos , Inflamación/inmunología , Masculino , Persona de Mediana Edad , Neutrófilos/patología , Osteomielitis/diagnóstico , Células Plasmáticas/patología , Valor Predictivo de las Pruebas , Staphylococcus aureus/aislamiento & purificación
4.
J Immunol ; 194(3): 1057-1061, 2015 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-25520400

RESUMEN

Negative selection is one of the primary mechanisms that render T cells tolerant to self. Thymic dendritic cells play an important role in negative selection, in line with their ability to induce migratory arrest and sustained TCR signals. Thymocytes themselves display self-peptide/MHC class I complexes, and although there is evidence that they can support clonal deletion, it is not clear whether they do so directly via stable cell-cell contacts and sustained TCR signals. In this study, we show that murine thymocytes can support surprisingly efficient negative selection of Ag-specific thymocytes. Furthermore, we observe that agonist-dependent thymocyte-thymocyte interactions occurred as stable, motile conjugates led by the peptide-presenting thymocyte and in which the trailing peptide-specific thymocyte exhibited persistent elevations in intracellular calcium concentration. These data confirm that self-Ag presentation by thymocytes is an additional mechanism to ensure T cell tolerance and further strengthen the correlation between stable cellular contacts, sustained TCR signals, and efficient negative selection.


Asunto(s)
Comunicación Celular , Supresión Clonal , Selección Clonal Mediada por Antígenos , Receptores de Antígenos de Linfocitos T/metabolismo , Transducción de Señal , Timocitos/inmunología , Timocitos/metabolismo , Animales , Presentación de Antígeno/inmunología , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/metabolismo , Células Dendríticas , Humanos , Ratones , Ratones Transgénicos , Péptidos/inmunología , Unión Proteica , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo
5.
Proc Natl Acad Sci U S A ; 111(25): E2550-8, 2014 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-24927565

RESUMEN

Positive selection of CD8 T cells in the thymus is thought to be a multistep process lasting 3-4 d; however, the discrete steps involved are poorly understood. Here, we examine phenotypic changes, calcium signaling, and intrathymic migration in a synchronized cohort of MHC class I-specific thymocytes undergoing positive selection in situ. Transient elevations in intracellular calcium concentration ([Ca(2+)]i) and migratory pauses occurred throughout the first 24 h of positive selection, becoming progressively briefer and accompanied by a gradual shift in basal [Ca(2+)]i over time. Changes in chemokine-receptor expression and relocalization from the cortex to medulla occurred between 12 and 24 h after the initial encounter with positive-selecting ligands, a time frame at which the majority of thymocytes retain CD4 and CD8 expression and still require T-cell receptor (TCR) signaling to efficiently complete positive selection. Our results identify distinct phases in the positive selection of MHC class I-specific thymocytes that are distinguished by their TCR-signaling pattern and intrathymic location and provide a framework for understanding the multistep process of positive selection in the thymus.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Señalización del Calcio/inmunología , Movimiento Celular/inmunología , Selección Clonal Mediada por Antígenos/inmunología , Timo/inmunología , Animales , Linfocitos T CD8-positivos/citología , Señalización del Calcio/genética , Movimiento Celular/genética , Selección Clonal Mediada por Antígenos/genética , Ratones , Ratones Noqueados , Timo/citología
6.
J Strength Cond Res ; 28(6): 1739-50, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24276295

RESUMEN

Whole body vibration (WBV) is widely promoted as a means of improving muscle strength, but the evidence of a performance benefit is unclear with some reporting improvements and others finding none. The objective of this study was to analyze the current evidence for the effectiveness of WBV on jump height. We included randomized controlled trials or matched design studies comparing the effect of WBV training on countermovement and squat jump (SJ) height, which were gathered from MEDLINE, Web of Knowledge, Sciencedirect, Proquest, Scopus, Google Scholar, and SPORTDiscus databases. The overall effect of WBV training (from the 15 studies included) compared with having no additional exercise on countermovement jump height yielded a positive standardized mean difference of 0.77 (95% confidence interval, 0.55-0.99). The effect of WBV training on SJ height was 0.68 (0.08-1.11). Vibration exercise consisting of a higher frequency (>30 Hz, 0.86, 0.62-1.10), higher amplitude (>3 mm, 0.84, 0.52-1.17), longer exposure duration (>10 minutes per session, 0.92, 0.48-1.36), longer training period (>12 weeks, 0.87, 0.56-1.19) and among nonathletes (0.96, 0.63-1.30) had greater benefit for jump height improvement than a lower frequency (≤ 30 Hz, 0.56, 0.13-0.99), lower amplitude (≤ 3 mm, 0.66, 0.35-0.98), shorter exposure duration (≤ 10 minutes per session, 0.68, 0.45-0.92), intermediate training period (4-12 weeks, 0.72, 0.35-1.09), shorter training period (<4 weeks, 0.58, -0.08 to -1.23) and in athletes (0.59, 0.31-0.88). The effect of WBV training compared with a standard cardiovascular-type exercise group from 4 studies was 0.63 (0.10-1.15). In conclusion, WBV training produces a moderate-to-large effect on jump height. Vibration training protocols with higher frequencies, higher amplitudes, longer exposures per session, and longer training periods are more likely to enhance muscle power.


Asunto(s)
Movimiento/fisiología , Fuerza Muscular/fisiología , Músculo Esquelético/fisiología , Vibración , Rendimiento Atlético/fisiología , Humanos
7.
Hum Mol Genet ; 19(21): 4216-28, 2010 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-20705736

RESUMEN

Reduced expression of the survival motor neuron (SMN) gene causes the childhood motor neuron disease spinal muscular atrophy (SMA). Low levels of ubiquitously expressed SMN protein result in the degeneration of lower motor neurons, but it remains unclear whether other regions of the nervous system are also affected. Here we show that reduced levels of SMN lead to impaired perinatal brain development in a mouse model of severe SMA. Regionally selective changes in brain morphology were apparent in areas normally associated with higher SMN levels in the healthy postnatal brain, including the hippocampus, and were associated with decreased cell density, reduced cell proliferation and impaired hippocampal neurogenesis. A comparative proteomics analysis of the hippocampus from SMA and wild-type littermate mice revealed widespread modifications in expression levels of proteins regulating cellular proliferation, migration and development when SMN levels were reduced. This study reveals novel roles for SMN protein in brain development and maintenance and provides the first insights into cellular and molecular pathways disrupted in the brain in a severe form of SMA.


Asunto(s)
Modelos Animales de Enfermedad , Hipocampo/crecimiento & desarrollo , Atrofia Muscular Espinal/genética , Proteína 1 para la Supervivencia de la Neurona Motora/genética , Animales , Movimiento Celular , Proliferación Celular , Ratones , Ratones Noqueados , Proteómica
8.
Nat Genet ; 54(5): 670-683, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35468964

RESUMEN

HOXB13, a homeodomain transcription factor, critically regulates androgen receptor (AR) activities and androgen-dependent prostate cancer (PCa) growth. However, its functions in AR-independent contexts remain elusive. Here we report HOXB13 interaction with histone deacetylase HDAC3, which is disrupted by the HOXB13 G84E mutation that has been associated with early-onset PCa. Independently of AR, HOXB13 recruits HDAC3 to lipogenic enhancers to catalyze histone deacetylation and suppress lipogenic regulators such as fatty acid synthase. Analysis of human tissues reveals that the HOXB13 gene is hypermethylated and downregulated in approximately 30% of metastatic castration-resistant PCa. HOXB13 loss or G84E mutation leads to lipid accumulation in PCa cells, thereby promoting cell motility and xenograft tumor metastasis, which is mitigated by pharmaceutical inhibition of fatty acid synthase. In summary, we present evidence that HOXB13 recruits HDAC3 to suppress de novo lipogenesis and inhibit tumor metastasis and that lipogenic pathway inhibitors may be useful to treat HOXB13-low PCa.


Asunto(s)
Histona Desacetilasas , Proteínas de Homeodominio , Lipogénesis , Neoplasias de la Próstata , Andrógenos , Línea Celular Tumoral , Epigénesis Genética , Histona Desacetilasas/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Factores de Transcripción/genética
9.
J Neurosci ; 29(31): 9903-17, 2009 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-19657041

RESUMEN

Retrograde axonal transport of cellular signals driven by dynein is vital for neuronal survival. Mouse models with defects in the retrograde transport machinery, including the Loa mouse (point mutation in dynein) and the Tg(dynamitin) mouse (overexpression of dynamitin), exhibit mild neurodegenerative disease. Transport defects have also been observed in more rapidly progressive neurodegeneration, such as that observed in the SOD1(G93A) transgenic mouse model for familial amyotrophic lateral sclerosis (ALS). Here, we test the hypothesis that alterations in retrograde signaling lead to neurodegeneration. In vivo, in vitro, and live-cell imaging motility assays show misregulation of transport and inhibition of retrograde signaling in the SOD1(G93A) model. However, similar inhibition is also seen in the Loa and Tg(dynamitin) mouse models. Thus, slowing of retrograde signaling leads only to mild degeneration and cannot explain ALS etiology. To further pursue this question, we used a proteomics approach to investigate dynein-associated retrograde signaling. These data indicate a significant decrease in retrograde survival factors, including P-Trk (phospho-Trk) and P-Erk1/2, and an increase in retrograde stress factor signaling, including P-JNK (phosphorylated c-Jun N-terminal kinase), caspase-8, and p75(NTR) cleavage fragment in the SOD1(G93A) model; similar changes are not seen in the Loa mouse. Cocultures of motor neurons and glia expressing mutant SOD1 (mSOD1) in compartmentalized chambers indicate that inhibition of retrograde stress signaling is sufficient to block activation of cellular stress pathways and to rescue motor neurons from mSOD1-induced toxicity. Hence, a shift from survival-promoting to death-promoting retrograde signaling may be key to the rapid onset of neurodegeneration seen in ALS.


Asunto(s)
Transporte Axonal/fisiología , Degeneración Nerviosa/fisiopatología , Enfermedades Neurodegenerativas/fisiopatología , Animales , Supervivencia Celular/fisiología , Células Cultivadas , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Complejo Dinactina , Dineínas/genética , Dineínas/metabolismo , Ganglios Espinales/fisiología , Ratones , Ratones Transgénicos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Neuronas Motoras/fisiología , Neuroglía/fisiología , Neuronas/fisiología , Ratas , Transducción de Señal , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1 , Factores de Tiempo
10.
Cochrane Database Syst Rev ; (7): CD003436, 2010 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-20614434

RESUMEN

BACKGROUND: Brain arteriovenous malformations (AVMs) are the single most common cause of intracerebral haemorrhage in young adults. Brain AVMs also cause seizure(s) and focal neurological deficits (in the absence of haemorrhage, migraine or an epileptic seizure); approximately one fifth are incidental discoveries. Various interventions are used in an attempt to eradicate brain AVMs: neurosurgical excision, stereotactic radiotherapy/'radiosurgery' (using gamma knife, linear accelerator, proton beam, or 'Cyber Knife'), endovascular embolisation (using glues, particles, fibres, coils, or balloons), and staged combinations of these interventions. This is an update of a Cochrane review first published in 2006. OBJECTIVES: To assess the clinical effects of interventions to treat brain AVMs in adults (with the aim of either partial obliteration or total eradication), using data published in randomised controlled trials (RCTs). SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched November 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2009), MEDLINE (1966 to November 2009) and EMBASE (1980 to November 2009). We searched international registers of clinical trials, the contents pages of relevant journals, and bibliographies of relevant articles (November 2009). We also contacted manufacturers of interventional treatments for brain AVMs (March 2005). SELECTION CRITERIA: We sought randomised trials of any or all of the interventions for brain AVMs, compared against each other or against usual medical therapy, with relevant clinical outcome measures. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria and reviewed the relevant studies. MAIN RESULTS: One ongoing RCT fulfils the selection criteria for this review: A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA, www.arubastudy.org), comparing interventional treatment versus medical management for brain AVMs that have never bled. We also found two RCTs which tested the equivalence of two embolic agents for the pre-operative embolisation of brain AVMs (one published, one unpublished), but none of the primary or secondary outcome measures in these trials met our desired criteria. We also excluded a third RCT which studied three different blood pressure lowering treatments to induce deliberate hypotension during surgical resection of brain AVMs because the intervention was not the focus of this review. AUTHORS' CONCLUSIONS: There is no evidence from randomised trials with clear clinical outcomes comparing different interventional treatments for brain AVMs against each other or against usual medical therapy to guide the interventional treatment of brain AVMs in adults. One such trial (ARUBA) is ongoing.


Asunto(s)
Malformaciones Arteriovenosas Intracraneales/terapia , Adulto , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto Joven
11.
Rural Remote Health ; 10(2): 1336, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20572744

RESUMEN

INTRODUCTION: Concerns have been raised about childhood obesity and its long-term impact on the health of children. The objective of this study was to investigate rural-urban differences in body composition, energy intake, physical activity and screen time in New Zealand children. METHODS: This study reports on data collected in a large national cross-sectional population survey of 5-15 year-old New Zealanders (the 2002 National Children's Nutrition Survey, CNS02). Schools were randomly selected to participate, as were pupils from the selected schools. Measurements of body composition were taken at school. Energy intake, physical activity and screen time information were taken from interviews and questionnaires undertaken by the child and parent/guardian. Means and standard deviations were calculated in the Statistical Analysis System (SAS Inst; Cary, NC, USA). Differences between groups were analysed using Proc Mixed after adjusting for socio-economic status and ethnicity. Data indicating differences between groups were presented as least square means +/- 95% confidence limits (CL); unless otherwise stated, and the alpha was set at p< 0.05. RESULTS: Rural children had a significantly lower BMI, smaller waist circumferences and thinner skinfold measurements than urban children. The differences in skinfold thicknesses remained after controlling for ethnicity and socioeconomic status. Furthermore, urban boys were 1.3 times more likely to be overweight or obese than rural boys (95% confidence limits 1.1-1.6, p <0.01) and urban girls were 1.4 times more likely to be overweight or obese than rural girls (95% CL 1.2-1.7, p <0.01).There was no significant difference in the energy intake per day of rural and urban children. Similarly, there was no significant difference in the frequency of bouts of physical activity undertaken by rural and urban children. CONCLUSION: Differences were found in body composition with rural children being leaner than urban children. This finding is different from other Western countries and may be due to differences in the physical and social environment in New Zealand. More research is required to understand these potential environmental rural-urban differences.


Asunto(s)
Ingestión de Energía , Ejercicio Físico , Obesidad/epidemiología , Población Rural , Población Urbana , Adolescente , Composición Corporal , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Nueva Zelanda/epidemiología , Encuestas Nutricionales
12.
Arch Pathol Lab Med ; 144(3): 290-304, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32101059

RESUMEN

CONTEXT.­: Immunohistochemistry (IHC) has become increasingly important in the evaluation of pathologic conditions in the genitourinary (GU) organs. In addition to careful evaluation of hematoxylin-eosin sections and generation of a differential diagnosis, choosing the optimal panel of IHC markers becomes even more important when the biopsy material is very limited. The following summary of our experience supplemented with relevant literature review exemplifies how to use IHC to facilitate pathologic diagnosis in the GU system. OBJECTIVE.­: To describe our experience with the most common immunohistochemical markers used in GU pathology. DATA SOURCES.­: Institutional experience and literature search comprise our data sources. CONCLUSIONS.­: Application of IHC provides enormous benefits to the interpretation of GU pathologic conditions, including benign and malignant lesions. However, both insufficient and excessive types of use of IHC, as well as incorrect interpretations in common and rare GU conditions, could present pitfalls in diagnosis.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Inmunohistoquímica/métodos , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias Testiculares/diagnóstico , Neoplasias Urogenitales/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/metabolismo , Neoplasias de la Próstata/metabolismo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Neoplasias Testiculares/metabolismo , Neoplasias Urogenitales/metabolismo
13.
J Manipulative Physiol Ther ; 32(7): 556-63, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19748407

RESUMEN

OBJECTIVE: This study investigated the reliability of experienced physiotherapists in classifying patients in McKenzie nonspecific mechanical syndromes from extremity McKenzie assessment forms. METHODS: Real patient vignettes (N = 25) were collected during clinical practice; all identifying information was removed to make the assessment form anonymous, and the mechanical classification chosen by the treating therapist was also deleted. The forms were saved in an electronic format. Forms and a sheet to be filled in for classification for each vignette and demographic details were sent electronically to McKenzie Institute International Diploma holders worldwide. Three repeat mailings were undertaken to maximize response rates. RESULTS: Of a sample frame of 126 therapists, 97 responded and provided classification for the patient vignettes. Overall agreement was 92% and the kappa value was 0.83. CONCLUSION: This reliability analysis of McKenzie extremity assessment forms showed a good level of reliability among the participating experienced therapists.


Asunto(s)
Extremidades/fisiopatología , Dimensión del Dolor/métodos , Dolor/clasificación , Modalidades de Fisioterapia/normas , Intervalos de Confianza , Femenino , Humanos , Extremidad Inferior/fisiopatología , Masculino , Variaciones Dependientes del Observador , Registros , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Extremidad Superior/fisiopatología
14.
BMJ Case Rep ; 12(8)2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31371277

RESUMEN

A 70-year-old man presented with 1 month of haematuria and mild right-sided flank pain with no other symptoms. Diagnostic workup included serum studies which showed the presence of antimyeloperoxidase antibodies, a kidney biopsy which demonstrated necrotising crescentic glomerulonephritis with linear immunofluorescence of the basement membrane, and electron microscopy which exhibited thickening of the glomerular basement membrane. Incidentally, the patient was discovered to have a latent hepatitis B infection, which complicated immunosuppressive therapy. He was treated with a course of plasmapheresis and methylprednisolone, followed by entecavir for hepatitis B prophylaxis, and finally by rituximab. This case of glomerulonephritis was notable for its resemblance to the better known Goodpasture's disease. Typically, Goodpasture's syndrome exists on a spectrum from seronegative disease to double-positive disease that presents with both anti-glomerular basement membrane (anti-GBM) and cytoplasmic-antineutrophil cytoplasmic antibodies/antiproteinase 3 antibodies (c-ANCA/anti-PR3). However, this patient's glomerulonephritis was unique because he presented negative for anti-GBM antibodies and positive for perinuclear-antineutrophil cytoplasmic antibodies/antimyeloperoxidase antibodies (p-ANCA/anti-MPO).


Asunto(s)
Glomerulonefritis/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , Peroxidasa/inmunología , Anciano , Anticuerpos Anticitoplasma de Neutrófilos/metabolismo , Autoanticuerpos/metabolismo , Diagnóstico Diferencial , Glomerulonefritis/inmunología , Glomerulonefritis/terapia , Guanina/análogos & derivados , Guanina/uso terapéutico , Humanos , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/terapia , Masculino , Metilprednisolona/uso terapéutico , Microscopía Electrónica , Plasmaféresis , Rituximab/uso terapéutico , Resultado del Tratamiento
15.
Health Promot J Austr ; 18(1): 73-6, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17501715

RESUMEN

ISSUE ADDRESSED: Indigenous populations have disparities in health along with disparities in modifiable risk factors, including low participation in physical activity. Given the importance of physical activity in moderating ill health, do all indigenous peoples exhibit low activity prevalence in concert with ill health? If an indigenous population is relatively active, what can be learned about physical activity development that has underlined this activity and could this be transferred to practice in other countries? METHODS: A review of national surveys undertaken since 1997 reporting physical activity prevalence of New Zealanders of different ethnicities, including Maori, was conducted. This was compared with prevalence data from other countries gained from searches of databases including PubMed, MEDLINE, Sports Discus and government websites. Socio-economic and environmental influences were examined with a view to understanding Maori physical activity prevalence. RESULTS: The proportion of active adult Maoris, the indigenous population of New Zealand, is similar to European New Zealanders. For example, the Ministry of Health has reported that 60% and 51% of Maori males and females respectively, and 58% and 50% of European men and women respectively, undertake at least 30 minutes of physical activity on at least five days per week. These findings are at odds with other indigenous populations, with the possible exception of Canada. The prevalence of undertaking no leisure-time physical activity is 48.7% for American Indian/Alaskan Native American women compared with 30.7% of white American women; 37.2% for American Indian/Alaskan Native American older adults compared with 29.3% of white American older adults; and 12% for Maori compared with 10% for all New Zealanders. CONCLUSIONS: Despite health disparities, Maori are at least as active as European New Zealanders. The reasons for this lack of disparity in physical activity prevalence between Maori and European New Zealanders could be due to environmental influences, including those in the socio-cultural and policy environment.


Asunto(s)
Nativos de Hawái y Otras Islas del Pacífico , Aptitud Física , Factores de Edad , Comparación Transcultural , Femenino , Estado de Salud , Humanos , Masculino , Nueva Zelanda , Factores Sexuales
16.
J Radiol Case Rep ; 11(9): 10-21, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29299105

RESUMEN

Pulmonary blastomas are rare malignancies, representing 0.25% to 0.5% of all primary lung neoplasms with often aggressive progression and poor prognosis. Clinical management of pulmonary blastomas depends on histologic subtype, staging, and presentation, and may consist of surgery, chemotherapy, and radiation. Biphasic pulmonary blastoma is a subtype of pulmonary blastoma that exhibits biphasic histology, with both epithelial and mesenchymal malignant elements. We report a case of biphasic pulmonary blastoma in a 33-year-old female with 1 pack per day history of smoking for approximately 16 years, who presented with left-sided pleuritic chest pain on deep inspiration without otherwise significant pat medical history. Imaging evaluation using chest radiography, computed tomography, and magnetic resonance imaging identified a heterogenous, well-circumscribed, left lower lobe mass with extensive necrosis and hemorrhage. No lymphadenopathy or distant metastasis was detected through imaging evaluation. Surgical resection of the tumor followed by histopathological analysis confirmed a biphasic pulmonary blastoma.


Asunto(s)
Neoplasias Pulmonares/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Blastoma Pulmonar/diagnóstico por imagen , Adulto , Femenino , Humanos , Pulmón/patología , Pulmón/cirugía , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Imagen por Resonancia Magnética , Imagen de Perfusión , Blastoma Pulmonar/etiología , Blastoma Pulmonar/patología , Blastoma Pulmonar/cirugía , Fumar/efectos adversos , Tomografía Computarizada por Rayos X
17.
Methods Mol Biol ; 1323: 131-40, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26294404

RESUMEN

Recently, tissue slices have been adapted to study both mouse and human T cell development. Thymic slices combine and complement the strengths of existing organotypic culture systems to study thymocyte differentiation. Specifically, the thymic slice system allows for high throughput experiments and the ability to introduce homogenous developmental intermediate populations into an environment with a well-established cortex and medulla. These qualities make thymic slices a highly versatile and technically accessible model to study thymocyte development. Here we describe methods to prepare, embed, and slice thymic lobes to study T cell development in situ.


Asunto(s)
Diferenciación Celular , Linfocitos T/citología , Timocitos/citología , Timo/citología , Timo/fisiología , Animales , Citometría de Flujo , Técnicas de Preparación Histocitológica , Técnicas In Vitro , Ratones , Linfocitos T/metabolismo , Timocitos/metabolismo
18.
Int J Sports Physiol Perform ; 10(3): 388-95, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25229836

RESUMEN

PURPOSE: To compare whole-body vibration (WBV) with traditional recovery protocols after a high-intensity training bout. METHODS: In a randomized crossover study, 16 athletes performed 6 × 30-s Wingate sprints before completing either an active recovery (10 min of cycling and stretching) or WBV for 10 min in a series of exercises on a vibration platform. Muscle hemodynamics (assessed via near-infrared spectroscopy) were measured before and during exercise and into the 10-min recovery period. Blood lactate concentration, vertical jump, quadriceps strength, flexibility, rating of perceived exertion (RPE), muscle soreness, and performance during a single 30-s Wingate test were assessed at baseline and 30 and 60 min postexercise. A subset of participants (n = 6) completed a 3rd identical trial (1 wk later) using a passive 10-min recovery period (sitting). RESULTS: There were no clear effects between the recovery protocols for blood lactate concentration, quadriceps strength, jump height, flexibility, RPE, muscle soreness, or single Wingate performance across all measured recovery time points. However, the WBV recovery protocol substantially increased the tissue-oxygenation index compared with the active (11.2% ± 2.4% [mean ± 95% CI], effect size [ES] = 3.1, and -7.3% ± 4.1%, ES = -2.1 for the 10 min postexercise and postrecovery, respectively) and passive recovery conditions (4.1% ± 2.2%, ES = 1.3, 10 min postexercise only). CONCLUSION: Although WBV during recovery increased muscle oxygenation, it had little effect in improving subsequent performance compared with a normal active recovery.


Asunto(s)
Ejercicio Físico/fisiología , Músculo Esquelético/fisiología , Adulto , Umbral Anaerobio/fisiología , Estudios Cruzados , Prueba de Esfuerzo , Hemodinámica , Humanos , Ácido Láctico/sangre , Fatiga Muscular/fisiología , Fuerza Muscular/fisiología , Ejercicios de Estiramiento Muscular , Mialgia/fisiopatología , Consumo de Oxígeno , Percepción/fisiología , Esfuerzo Físico/fisiología , Vibración , Ejercicio de Calentamiento , Adulto Joven
19.
J Sci Med Sport ; 16(4): 337-42, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22999393

RESUMEN

OBJECTIVES: To investigate the effect of blood flow restriction or normobaric hypoxic exposure combined with low-load resistant exercise (LRE), on muscular strength and endurance. DESIGN: A randomised controlled trial. METHODS: Well-trained netball players (n=30) took part in a 5 weeks training of knee flexor and extensor muscles in which LRE (20% of one repetition maximum) was combined with (1) an occlusion pressure of approximately 230mmHg around the upper thigh (KT, n=10), (2) hypoxic air to generate blood oxyhaemoglobin levels of approximately 80% (HT, n=10) or (3) with no additional stimulus (CT, n=10). The training was of the same intensity and amount in all groups. One to five days before and after training, participants performed a series of strength and endurance tests of the lower limbs (3-s maximal voluntary contraction [MVC3], area under 30-s force curve [MVC30], number of repetitions at 20% 1RM [Reps201RM]). In addition, the cross-sectional area (CSA) of the quadriceps and hamstrings were measured. RESULTS: Relative to CT, KT and HT increased MVC3 (11.0±11.9% and 15.0±13.1%), MVC30 (10.2±9.0% and 18.3±17.4%) and Reps201RM (28.9±23.7% and 23.3±24.0%, mean±90% confidence interval) after training. CSA increased by 6.6±4.5%, 6.1±5.1% and 2.9±2.7% in the KT, HT and CT groups respectively. CONCLUSIONS: LRE in conjunction with KT or HT can provide substantial improvements in muscle strength and endurance and may be useful alternatives to traditional training practices.


Asunto(s)
Rendimiento Atlético/fisiología , Hipoxia , Pierna/irrigación sanguínea , Fuerza Muscular , Entrenamiento de Fuerza , Adolescente , Atletas , Femenino , Voluntarios Sanos , Humanos , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/fisiología , Deportes/fisiología , Adulto Joven
20.
Man Ther ; 18(2): 169-71, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22728212

RESUMEN

Current guidelines advise against the use of routine imaging for low back pain. Positional MRI can provide enhanced assessment of the lumbar spine in functionally loaded positions which are often relevant to the presenting clinical symptoms. The purpose of this case report is to highlight the use of positional MRI in the assessment and classification of a subject with low back pain. A low back pain subject underwent a Mechanical Diagnosis and Therapy (MDT) assessment and positional MRI scan of the lumbar spine. The MDT assessment classified the subject as "other" since the subjective history indicated a possible posterior derangement whilst the objective assessment indicated a possible anterior derangement. Positional MRI scanning in flexed, upright and extended sitting postures confirmed the MDT assessment findings to reveal a dynamic spinal stenosis which reduced in flexion and increased in extension.


Asunto(s)
Dolor de la Región Lumbar/diagnóstico , Imagen por Resonancia Magnética , Examen Físico/métodos , Estenosis Espinal/diagnóstico , Adulto , Diagnóstico Diferencial , Evaluación de la Discapacidad , Humanos , Dolor de la Región Lumbar/fisiopatología , Dimensión del Dolor , Postura/fisiología , Estenosis Espinal/fisiopatología , Encuestas y Cuestionarios
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