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1.
Eur J Neurol ; 28(1): 40-47, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32918317

RESUMEN

BACKGROUND AND PURPOSE: Functional neurological disorder (FND) is a common diagnosis within neurology. Effective communication of the diagnosis is known to be an important part of treatment and can result in reduction or cessation of symptoms, as well as decreased healthcare utilisation. A single group education session, facilitated by professionals commonly involved in the care of patients with FND, was developed to further enhance patients' and relatives' understanding and acceptance of diagnosis. METHODS: Patients and relatives attending a single education session were asked to complete self-report ratings of understanding of diagnosis, acceptance of diagnosis, belief in treatability and hopefulness regarding recovery, at the beginning and end of the session. Satisfaction data were also collected. RESULTS: Data were obtained from 193 patients and 153 relatives. Patients had experienced a median duration of symptoms of 4 years, and more than 80% of patients reported more than one functional neurological symptom. There were significant increases in terms of understanding, acceptance, belief in treatability and hopefulness for patients and relatives. Effect sizes ranged from large for improved understanding of FND to small-to-medium for increased agreement with FND diagnosis. High levels of satisfaction were also reported. CONCLUSIONS: A multidisciplinary, single group education session is an effective and acceptable method of increasing understanding and acceptance of an FND diagnosis, even for patients with a long duration of symptoms and high symptom burden. It could help improve readiness for further treatment.


Asunto(s)
Enfermedades del Sistema Nervioso , Comunicación , Humanos , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/terapia
2.
J Neurol Neurosurg Psychiatry ; 88(6): 484-490, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-27694498

RESUMEN

OBJECTIVE: To determine the feasibility of conducting a randomised controlled trial of a specialist physiotherapy intervention for functional motor symptoms (FMS). METHODS: A randomised feasibility study was conducted recruiting patients with a clinically established diagnosis of FMS from a tertiary neurology clinic in London, UK. Participants were randomised to the intervention or a treatment as usual control. Measures of feasibility and clinical outcome were collected and assessed at 6 months. RESULTS: 60 individuals were recruited over a 9-month period. Three withdrew, leaving 29 intervention and 28 controls participants in the final analysis. 32% of patients with FMS met the inclusion criteria, of which 90% enrolled. Acceptability of the intervention was high and there were no adverse events. At 6 months, 72% of the intervention group rated their symptoms as improved, compared to 18% in the control group. There was a moderate to large treatment effect across a range of outcomes, including three of eight Short Form 36 (SF36) domains (d=0.46-0.79). The SF36 Physical function was found to be a suitable primary outcome measure for a future trial; adjusted mean difference 19.8 (95% CI 10.2 to 29.5). The additional quality adjusted life years (QALY) with intervention was 0.08 (95% CI 0.03 to 0.13), the mean incremental cost per QALY gained was £12 087. CONCLUSIONS: This feasibility study demonstrated high rates of recruitment, retention and acceptability. Clinical effect size was moderate to large with high probability of being cost-effective. A randomised controlled trial is needed. TRIAL REGISTRATION NUMBER: NCT02275000; Results.


Asunto(s)
Trastornos de Conversión/rehabilitación , Trastornos Motores/rehabilitación , Modalidades de Fisioterapia , Adulto , Terapia Cognitivo-Conductual , Terapia Combinada , Trastornos de Conversión/diagnóstico , Trastornos de Conversión/psicología , Evaluación de la Discapacidad , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Comunicación Interdisciplinaria , Colaboración Intersectorial , Masculino , Persona de Mediana Edad , Trastornos Motores/diagnóstico , Trastornos Motores/psicología , Evaluación de Resultado en la Atención de Salud , Aceptación de la Atención de Salud/psicología , Calidad de Vida/psicología , Años de Vida Ajustados por Calidad de Vida
3.
Epidemiol Infect ; 145(14): 2980-2990, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28903784

RESUMEN

Each year in the United States, an estimated 525 000 infections, 2900 hospitalizations, and 82 deaths are attributed to consumption of pork. We analyzed the epidemiology of outbreaks attributed to pork in the United States reported to the Centers for Disease Control and Prevention (CDC) 1998-2015. During that period, 288 outbreaks were attributed to pork, resulting in 6372 illnesses, 443 hospitalizations, and four deaths. The frequency of outbreaks attributed to pork decreased by 37% during this period, consistent with a decline in total foodborne outbreaks. However, outbreaks attributed to pork increased by 73% in 2015 (19 outbreaks) compared with the previous 3 years (average of 11 outbreaks per year), without a similar increase in total foodborne outbreaks. Most (>99%) of these outbreaks occurred among people exposed in the same state. The most frequent etiology shifted from Staphylococcus aureus toxin during 1998-2001 (19%) to Salmonella during 2012-2015 (46%). Outbreaks associated with ham decreased from eight outbreaks per year during 1998-2001, to one per year during 2012-2015 (P < 0·01). Additional efforts are necessary to reduce outbreaks and sporadic illnesses associated with pork products.


Asunto(s)
Brotes de Enfermedades , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/epidemiología , Carne Roja/microbiología , Animales , Enfermedades Transmitidas por los Alimentos/microbiología , Enfermedades Transmitidas por los Alimentos/mortalidad , Incidencia , Sus scrofa , Estados Unidos/epidemiología
4.
Psychooncology ; 25(6): 691-8, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26449611

RESUMEN

OBJECTIVE: We hypothesised that being diagnosed with gynaecological cancer influences adult attachment and occurrence of depression and post-traumatic stress disorder (PTSD). The main aim of the study was to assess changes in the attachment dimensions, PTSD and depression from baseline to 5-month post-treatment. Further, we evaluated the association between attachment avoidance/anxiety dimensions and PTSD/depression among women newly diagnosed with ovarian, endometrial, or cervical cancer. METHODS: Consecutive Danish-speaking women aged 20 to 75 years and treated surgically for primary gynaecological cancer were eligible. All patients were offered a rehabilitation programme consisting of two face-to-face sessions and two phone calls carried out by a nurse. Patients were asked to complete the Revised Adult Attachment Scale, the Harvard Trauma Questionnaire and the Major Depression Inventory at baseline and at 5-month follow-up. In all, 151 women consent to participate in the sessions where 51 fulfilled Revised Adult Attachment Scale questionnaire and contribute with socio-demographic data. RESULTS: We found significant positive changes within the attachment anxiety dimension among women with ovarian cancer, a significant reduction of PTSD among endometrial cancer patients and insignificant changes in depression among all cancer types. The attachment anxiety dimension significantly increased the odds for PTSD and depression. CONCLUSIONS: Depression and PTSD were prevalent among ovarian and cervical cancer patients. The adjustment of rehabilitation according to patients' attachment anxiety dimension contains possibilities for indirect impact on PTSD and depression symptoms. Copyright © 2015 John Wiley & Sons, Ltd.


Asunto(s)
Depresión/psicología , Neoplasias de los Genitales Femeninos/psicología , Relaciones Interpersonales , Índice de Severidad de la Enfermedad , Trastornos por Estrés Postraumático/psicología , Adulto , Anciano , Ansiedad/psicología , Dinamarca , Depresión/etiología , Femenino , Neoplasias de los Genitales Femeninos/complicaciones , Neoplasias de los Genitales Femeninos/terapia , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Apoyo Social , Trastornos por Estrés Postraumático/etiología , Encuestas y Cuestionarios
5.
Epidemiol Infect ; 143(9): 2003-13, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25427978

RESUMEN

Non-typhoidal Salmonella is estimated to be the most common bacterial cause of foodborne illness in the United States, causing an estimated one million domestically acquired foodborne illnesses annually. Recent, large outbreaks have highlighted the importance of ground beef as an important source of multidrug-resistant Salmonella. We analysed the epidemiology of salmonellosis outbreaks that were attributed to beef in the United States reported to the Centers for Disease Control and Prevention (CDC) from 1973 to 2011. During 1973-2011, of the 1965 outbreaks of Salmonella where a food vehicle was implicated, 96 were attributed to beef, accounting for 3684 illnesses. We observed a shift in the type of beef implicated in salmonellosis outbreaks, from roast to ground beef. Delicatessen-style roast beef cooked in commercial processing establishments was the predominant type during the 1970s and early 1980s; regulations on cooking and processing essentially eliminated this problem by 1987. Ground beef emerged as an important vehicle in the 2000s; it was implicated in 17 (45%) of the 38 beef-attributed outbreaks reported during 2002-2011. Although this emergence was likely due in part to increased participation in CDC's PulseNet, which was established in 1996, and proactive decisions by the United States Department of Agriculture's Food Safety and Inspection Service, stronger measures are needed to decrease contamination of ground beef with Salmonella.


Asunto(s)
Brotes de Enfermedades , Carne/microbiología , Intoxicación Alimentaria por Salmonella/epidemiología , Adulto , Anciano , Animales , Bovinos , Centers for Disease Control and Prevention, U.S. , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Intoxicación Alimentaria por Salmonella/microbiología , Estados Unidos/epidemiología , Adulto Joven
6.
New Phytol ; 203(3): 735-42, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25180326

RESUMEN

Pollen grains are microscopic so their identification and quantification has, for decades, depended upon human observers using light microscopes: a labour-intensive approach. Modern improvements in computing and imaging hardware and software now bring automation of pollen analyses within reach. In this paper, we provide the first review in over 15 yr of progress towards automation of the part of palynology concerned with counting and classifying pollen, bringing together literature published from a wide spectrum of sources. We consider which attempts offer the most potential for an automated palynology system for universal application across all fields of research concerned with pollen classification and counting. We discuss what is required to make the datasets of these automated systems as acceptable as those produced by human palynologists, and present suggestions for how automation will generate novel approaches to counting and classifying pollen that have hitherto been unthinkable.


Asunto(s)
Automatización/métodos , Botánica/métodos , Polen/fisiología , Estándares de Referencia
7.
Case Rep Infect Dis ; 2021: 6638780, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34007495

RESUMEN

BACKGROUND: Hypervirulent Klebsiella pneumoniae causes severe disseminated infections, typically with hepatic and central nervous system involvement including endophthalmitis. Case Presentation. We report a fatal case of an undocumented Chinese migrant in her 60s who presented to the emergency department with abdominal pain, lethargy, and headache over the preceding two weeks. She had a new diagnosis of diabetes mellitus on admission. Computed tomography scan of the thorax, abdomen, and pelvis showed bilateral pneumonia with liver abscesses. The patient was treated with empirical broad-spectrum antibiotics before K. pneumoniae was isolated from cerebrospinal fluid and blood cultures. The isolate was further characterised as a ST23 (ST: sequence type), serotype K1 hypervirulent strain using Nanopore sequencing. Despite admission to the intensive care unit, the patient died within 48 hrs of admission. CONCLUSIONS: This case demonstrates the need for increased awareness of hypervirulent K. pneumoniae, even in countries where it occurs infrequently. Novel, rapid, sequencing technologies can support diagnosis in unusual presentations.

8.
J Cell Biol ; 145(1): 153-65, 1999 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-10189375

RESUMEN

The dystrophin-glycoprotein complex (DGC) is a multisubunit complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix. The proteins of the DGC are structurally organized into distinct subcomplexes, and genetic mutations in many individual components are manifested as muscular dystrophy. We recently identified a unique tetraspan-like dystrophin-associated protein, which we have named sarcospan (SPN) for its multiple sarcolemma spanning domains (Crosbie, R.H., J. Heighway, D.P. Venzke, J.C. Lee, and K.P. Campbell. 1997. J. Biol. Chem. 272:31221-31224). To probe molecular associations of SPN within the DGC, we investigated SPN expression in normal muscle as a baseline for comparison to SPN's expression in animal models of muscular dystrophy. We show that, in addition to its sarcolemma localization, SPN is enriched at the myotendinous junction (MTJ) and neuromuscular junction (NMJ), where it is a component of both the dystrophin- and utrophin-glycoprotein complexes. We demonstrate that SPN is preferentially associated with the sarcoglycan (SG) subcomplex, and this interaction is critical for stable localization of SPN to the sarcolemma, NMJ, and MTJ. Our experiments indicate that assembly of the SG subcomplex is a prerequisite for targeting SPN to the sarcolemma. In addition, the SG- SPN subcomplex functions to stabilize alpha-dystroglycan to the muscle plasma membrane. Taken together, our data provide important information about assembly and function of the SG-SPN subcomplex.


Asunto(s)
Proteínas Portadoras/metabolismo , Proteínas del Citoesqueleto/fisiología , Distrofina/fisiología , Glicoproteínas de Membrana/fisiología , Proteínas de la Membrana/metabolismo , Distrofia Muscular Animal/metabolismo , Proteínas de Neoplasias , Secuencia de Aminoácidos , Animales , Transporte Biológico , Células CHO , Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/metabolismo , Cardiomiopatía Hipertrófica/patología , Cricetinae , Proteínas del Citoesqueleto/deficiencia , Proteínas del Citoesqueleto/genética , Distroglicanos , Distrofina/deficiencia , Distrofina/genética , Humanos , Concentración de Iones de Hidrógeno , Sustancias Macromoleculares , Masculino , Glicoproteínas de Membrana/deficiencia , Glicoproteínas de Membrana/genética , Proteínas de la Membrana/deficiencia , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Ratones , Ratones Noqueados , Ratones Transgénicos , Modelos Moleculares , Datos de Secuencia Molecular , Músculo Esquelético/metabolismo , Distrofia Muscular Animal/genética , Unión Neuromuscular/metabolismo , Conejos , Sarcoglicanos , Sarcolema/metabolismo , Sarcolema/ultraestructura , Alineación de Secuencia , Especificidad de la Especie , Tendones/metabolismo , Transfección , Utrofina
9.
J Cell Biol ; 142(6): 1461-71, 1998 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-9744877

RESUMEN

Limb-girdle muscular dystrophy type 2D (LGMD 2D) is an autosomal recessive disorder caused by mutations in the alpha-sarcoglycan gene. To determine how alpha-sarcoglycan deficiency leads to muscle fiber degeneration, we generated and analyzed alpha-sarcoglycan- deficient mice. Sgca-null mice developed progressive muscular dystrophy and, in contrast to other animal models for muscular dystrophy, showed ongoing muscle necrosis with age, a hallmark of the human disease. Sgca-null mice also revealed loss of sarcolemmal integrity, elevated serum levels of muscle enzymes, increased muscle masses, and changes in the generation of absolute force. Molecular analysis of Sgca-null mice demonstrated that the absence of alpha-sarcoglycan resulted in the complete loss of the sarcoglycan complex, sarcospan, and a disruption of alpha-dystroglycan association with membranes. In contrast, no change in the expression of epsilon-sarcoglycan (alpha-sarcoglycan homologue) was observed. Recombinant alpha-sarcoglycan adenovirus injection into Sgca-deficient muscles restored the sarcoglycan complex and sarcospan to the membrane. We propose that the sarcoglycan-sarcospan complex is requisite for stable association of alpha-dystroglycan with the sarcolemma. The Sgca-deficient mice will be a valuable model for elucidating the pathogenesis of sarcoglycan deficient limb-girdle muscular dystrophies and for the development of therapeutic strategies for this disease.


Asunto(s)
Proteínas del Citoesqueleto/deficiencia , Glicoproteínas de Membrana/deficiencia , Distrofia Muscular Animal/etiología , Proteínas de Neoplasias , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/fisiología , Proteínas del Citoesqueleto/genética , ADN Complementario , Progresión de la Enfermedad , Distrofina/metabolismo , Técnicas de Transferencia de Gen , Glicoproteínas/metabolismo , Glicoproteínas de Membrana/genética , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Datos de Secuencia Molecular , Contracción Muscular , Distrofia Muscular Animal/fisiopatología , Sarcoglicanos , Sarcolema/metabolismo
10.
Am J Surg ; 218(3): 648-652, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30826007

RESUMEN

BACKGROUND: There is limited data on deliberate teaching of residents in the clinic setting; we sought to investigate the clinic experience at our institution and improve education through creation of a novel "Resident-Optimized Clinic" (ROC). METHODS: An online survey was sent separately to residents and faculty. Based on the results of this survey a modified ROC was developed to try to improve the obstacles to learning in clinic. RESULTS: Qualitative analysis revealed the barriers in clinic were inconsistencies in expectations, lack of autonomy, time, and facility limitations. The modified ROC was rated positively with 100% of participants expressing they had sufficient time and autonomy; and 90% felt the environment was optimized for teaching. CONCLUSIONS: Multiple themes have been identified as problematic for the clinic education experience. The ROC was rated positively by trainees suggesting thoughtful intervention to improve clinic results in a better clinic experience and more educational gain from the clinic environment.


Asunto(s)
Cirugía General/educación , Internado y Residencia , Evaluación de Necesidades , Humanos , Internado y Residencia/organización & administración
11.
J Biomech ; 41(5): 968-76, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18304555

RESUMEN

This study examined the transverse plane kinematics of the pelvis, thorax and head while participants walked at a range of speeds on a treadmill under three load conditions: no load, with a loaded backpack with no hip belt and with a loaded backpack with a hip belt. Research has suggested that one mechanism for adapting to heavy loads carried with no hip belt is to reduce the amplitudes and relative phase of transverse plane pelvic and thoracic rotations, in order to minimize rotational torque on the loaded upper body. Transverse plane rotation amplitudes of the pelvis, thorax, backpack and head were calculated from 3D kinematic data for 12 healthy subjects, walking at speeds of 0.5, 0.9, 1.3 and 1.7 ms(-1). Relative phase relation and its variability were also computed for pelvis-thorax rotations and backpack-thorax rotations. Stability of the coordination pattern was estimated as an inverse function of the variability in relative phase. The backpack with the hip belt allowed significantly larger transverse plane rotation amplitudes, along with increased stability of the coordination pattern, than the backpack with no hip belt. Motion patterns of the backpack and thorax suggested that the backpack frame was used to assist with the deceleration and reversal of the loaded thorax, driven by the pelvis through the hip belt connection. Use of the frame in this way may have required less trunk muscle activation and allowed for improved pattern stability.


Asunto(s)
Pelvis/fisiología , Tórax/fisiología , Caminata/fisiología , Soporte de Peso/fisiología , Adolescente , Adulto , Fenómenos Biomecánicos , Femenino , Humanos , Imagenología Tridimensional/estadística & datos numéricos , Masculino , Rotación , Torque
12.
Cardiovasc Res ; 76(2): 311-22, 2007 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-17658497

RESUMEN

OBJECTIVE: Myocardial hypertrophy often develops in response to hypertension, and it is causal to and an independent predictor of heart failure. Several risk factors modify the progression of hypertrophy, the associated progressive impairment of myocardial function, and eventually the transition to overt congestive heart failure. The aim of the present study was to investigate the effects of smoking on the progression of pressure-dependent myocardial hypertrophy. METHODS: Spontaneously hypertensive rats (SHR) were used as a model for pressure-dependent hypertrophy. SHR were exposed to mainstream smoke from the Kentucky reference cigarette 2R4F (450 microg total particulate matter/l) or to fresh air (control), 5 days a week, twice for 1 h per day with a 30-minute fresh air exposure break for 30, 60, or 90 days. Endpoints for hypertrophy-associated changes were heart weight to body weight ratio, ventricular expression of hypertrophy-associated genes, ischemic tolerance, and inotropic responsiveness to isoprenaline in post-ischemic hearts. RESULTS: Smoke-exposed SHR showed a significant elevation in heart weight to body weight ratio, increased mRNA expression of atrial natriuretic factor (ANF), transforming growth factor (TGF)-beta(1), ornithine decarboxylase (ODC), and parathyroid hormone-related protein in both ventricles compared to controls. Hearts from smoke-exposed SHR showed a reduced recovery after 30 min global ischemia during the first 5 min of reperfusion and loss of inotropic stimulation after 30 min reperfusion. Smoke cessation was sufficient to reverse most of these alterations. WKY exposed to smoke did not develop similar changes. CONCLUSION: Our data indicate that several aspects of myocardial hypertrophy are accelerated by smoking.


Asunto(s)
Cardiomegalia/complicaciones , Insuficiencia Cardíaca/etiología , Hipertensión/complicaciones , Fumar/efectos adversos , Animales , Progresión de la Enfermedad , Técnicas In Vitro , Masculino , Isquemia Miocárdica/fisiopatología , Proteína Relacionada con la Hormona Paratiroidea/genética , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptores Adrenérgicos beta/fisiología , Factor de Crecimiento Transformador beta1/fisiología , Función Ventricular Izquierda
13.
Clin Microbiol Infect ; 24(4): 428.e1-428.e7, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28736074

RESUMEN

OBJECTIVES: As part of annual cross-sectional Streptococcus pneumoniae carriage surveys in Fiji (2012-2015), we detected pneumococci in over 100 nasopharyngeal swabs that serotyped as '11F-like' by microarray. We examined the genetic basis of this divergence in the 11F-like capsular polysaccharide (cps) locus compared to the reference 11F cps sequence. The impact of this diversity on capsule phenotype, and serotype results using genetic and serologic methods were determined. METHODS: Genomic DNA from representative 11F-like S. pneumoniae isolates obtained from the nasopharynx of Fijian children was extracted and subject to whole genome sequencing. Genetic and phylogenetic analyses were used to identify genetic changes in the cps locus. Capsular phenotypes were evaluated using the Quellung reaction and latex agglutination. RESULTS: Compared to published 11F sequences, the wcwC and wcrL genes of the 11F-like cps locus are phylogenetically divergent, and the gct gene contains a single nucleotide insertion within a homopolymeric region. These changes within the DNA sequence of the 11F-like cps locus have modified the antigenic properties of the capsule, such that 11F-like isolates serotype as 11A by Quellung reaction and latex agglutination. CONCLUSIONS: This study demonstrates the ability of molecular serotyping by microarray to identify genetic variants of S. pneumoniae and highlights the potential for discrepant results between phenotypic and genotypic serotyping methods. We propose that 11F-like isolates are not a new serotype but rather are a novel genetic variant of serotype 11A. These findings have implications for invasive pneumococcal disease surveillance as well as studies investigating vaccine impact.


Asunto(s)
Portador Sano/microbiología , Genotipo , Infecciones Neumocócicas/microbiología , Serogrupo , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/genética , Adulto , Niño , Preescolar , Estudios Transversales , Fiji , Humanos , Lactante , Masculino , Análisis por Micromatrices , Nasofaringe/microbiología , Análisis de Secuencia de ADN , Serotipificación , Streptococcus pneumoniae/aislamiento & purificación , Secuenciación Completa del Genoma
14.
J Clin Invest ; 59(3): 426-31, 1977 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14173

RESUMEN

Since monosodium urate (NaU) may play an important etiologic role in the formation of renal stones containing Ca in patients with hyperuricosuria, the current studies were undertaken to define some of the physiocochemical factors which determine the formation of NaU. In solutions containing Na, uric acid was rapidly transformed to NaU at pH greater than 6. The results indicated that NaU, and not uric acid, was the stable phase above this pH. A reliable and simple method for the calculation of the state of saturation of urine with respect to NaU was developed from the ratio of concentration products of Na and total dissolved urate (Upi) in the ambient fluid before and after incubation of urine with synthetic NaU. The concentration product ratio closely approximated the ratio of activity products of Na+ and acid urate ion. In contrast, the relative saturation ratio, or the ratio of activity product of original sample and the thermodynamic solubility product of NaU, often differed from the activity product ratio in the individual urine samples. With the concentration product rate, it was found in 45 urine samples that a critical determinant for the supersaturated state with respect to NaU was the high concentration of UT. At UT greater than 300 mg/liter, urine samples were invariably supersaturated with respect to NaU. These results suggest that the nidus of NaU could potentially form in the urine of patients with hyperuricosuria and Ca stones.


Asunto(s)
Calcio , Ácido Úrico/orina , Cálculos Urinarios/etiología , Humanos , Concentración de Iones de Hidrógeno , Sodio/orina
15.
Mol Cell Biol ; 16(2): 577-83, 1996 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8552085

RESUMEN

The Ras guanylnucleotide exchange protein SOS undergoes feedback phosphorylation and dissociation from Grb2 following insulin receptor kinase activation of Ras. To determine the serine/threonine kinase(s) responsible for SOS phosphorylation in vivo, we assessed the role of mitogen-activated, extracellular-signal-regulated protein kinase kinase (MEK), extracellular-signal-regulated protein kinase (ERK), and the c-JUN protein kinase (JNK) in this phosphorylation event. Expression of a dominant-interfering MEK mutant, in which lysine 97 was replaced with arginine (MEK/K97R), resulted in an inhibition of insulin-stimulated SOS and ERK phosphorylation, whereas expression of a constitutively active MEK mutant, in which serines 218 and 222 were replaced with glutamic acid (MEK/EE), induced basal phosphorylation of both SOS and ERK. Although expression of the mitogen-activated protein kinase-specific phosphatase (MKP-1) completely inhibited the insulin stimulation of ERK activity both in vitro and in vivo, SOS phosphorylation and the dissociation of the Grb2-SOS complex were unaffected. In addition, insulin did not activate the related protein kinase JNK, demonstrating the specificity of insulin for the ERK pathway. The insulin-stimulated and MKP-1-insensitive SOS-phosphorylating activity was reconstituted in whole-cell extracts and did not bind to a MonoQ anion-exchange column. In contrast, ERK1/2 protein was retained by the MonoQ column, eluted with approximately 200 mM NaCl, and was MKP-1 sensitive. Although MEK also does not bind to MonoQ, immunodepletion analysis demonstrated that MEK is not the insulin-stimulated SOS-phosphorylating activity. Together, these data demonstrate that at least one of the kinases responsible for SOS phosphorylation and functional dissociation of the Grb2-SOS complex is an ERK-independent but MEK-dependent insulin-stimulated protein kinase.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Proteínas de Ciclo Celular , Insulina/farmacología , Quinasa 1 de Quinasa de Quinasa MAP , Proteínas de la Membrana/metabolismo , Fosfoproteínas Fosfatasas , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Animales , Células CHO , Cricetinae , Fosfatasa 1 de Especificidad Dual , Proteína Adaptadora GRB2 , Humanos , Proteínas Inmediatas-Precoces/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Modelos Biológicos , Proteínas del Tejido Nervioso/metabolismo , Fosforilación , Proteína Fosfatasa 1 , Proteínas Tirosina Fosfatasas/metabolismo , Proteínas/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Son Of Sevenless
16.
Mol Cell Biol ; 14(1): 42-9, 1994 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8264609

RESUMEN

Domains of interaction between the p85 and p110 subunits of phosphatidylinositol 3-kinase (PI 3-kinase) were studied with the yeast two-hybrid expression system. A gene fusion between the GAL4 transactivation domain and p85 activated transcription from a GAL1-lacZ reporter gene when complemented with a gene fusion between the GAL4 DNA binding domain and p110. To define subdomains responsible for this interaction, a series of p85 deletion mutants were analyzed. A 192-amino-acid inter-SH2 (IS) fragment (residues 429 to 621) was the smallest determinant identified that specifically associated with p110. In analogous experiments, the subdomain within p110 responsible for interaction with p85 was localized to an EcoRI fragment encoding the amino-terminal 127 residues. Expression of these two subdomains [p85(IS) with p110RI] resulted in 100-fold greater reporter activity than that obtained with full-length p85 and p110. Although the p85(IS) domain conferred a strong interaction with the p110 catalytic subunit, this region was not sufficient to impart phosphotyrosine peptide stimulation of PI 3-kinase activity. In contrast, coexpression of the p110 subunit with full-length p85 or with constructs containing the IS sequences flanked by both SH2 domains of p85 [p85(n/cSH2)] or either of the individual SH2 domains [p85(nSH2+IS) or p85(IS+cSH2)] resulted in PI 3-kinase activity that was activated by a phosphotyrosine peptide. These data suggest that phosphotyrosine peptide binding to either SH2 domain generates an intramolecular signal propagated through the IS region to allosterically activate p110.


Asunto(s)
Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Secuencia de Aminoácidos , ADN de Hongos/genética , Activación Enzimática , Expresión Génica , Genes Fúngicos , Genes Reporteros , Datos de Secuencia Molecular , Fosfatidilinositol 3-Quinasas , Fosfotransferasas (Aceptor de Grupo Alcohol)/química , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Conformación Proteica , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética , Eliminación de Secuencia , beta-Galactosidasa/genética , beta-Galactosidasa/metabolismo
17.
Chem Commun (Camb) ; 53(15): 2351-2354, 2017 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-28164180

RESUMEN

In situ IR spectroscopy is used to monitor electrolyte composition and acid protonation state at the interface of graphene nanoflake electrodes. Deprotonation of both electrode-immobilised and solution acids is driven by a local increase in cation activity at the electrode surface on application of a negative electrode potential.

18.
Lancet ; 365(9454): 142-9, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15639296

RESUMEN

BACKGROUND: Increasing evidence suggests that patterns of T-cell immunity to inhalant allergens in genetically diverse human populations are more heterogeneous than previously assumed, and that covert differences in expression patterns might underlie variations in airway disease phenotypes. We tested this proposition in a community sample of children. METHODS: We analysed data from 172 individuals who had been recruited antenatally to a longitudinal birth cohort study. Of the 194 birth cohort participants, data from the 147 probands (age range 8.6-13.5 years) who consented to blood collection were included along with data from 25 consenting siblings (mean age 11 years [range 7.4-17.4]). We ascertained clinical phenotypes related to asthma and allergy. We measured T-cell responses to allergens and mitogens, together with blood eosinophils and IgE/IgG antibodies, and assessed associations between these indices and clinical phenotypes. FINDINGS: Atopy was associated with allergen-specific T-helper (Th)2 responses dominated by interleukin 4, interleukin 5, interleukin 9, interleukin 13, whereas interleukin 10, tumour necrosis factor alpha, and interferon gamma responses were common to both atopics and non-atopics. The wheal size from skin prick with allergen was positively associated with in-vitro interleukin 5 and interferon gamma responses, and negatively associated with interleukin 10. Asthma, especially in atopics, was strongly associated with eosinophilia/interleukin 5, and bronchial hyper-responsiveness (BHR) was associated with eosinophilia plus polyclonal interferon gamma production. BHR in non-atopics was associated with elevated allergen-specific and polyclonal interleukin 10 production. INTERPRETATION: Parallel immunological and clinical profiling of children identified distinctive immune response patterns related to asthma and wheeze compared with BHR, in atopics non-atopics. Immunological hyper-responsiveness, including within the Th1 cytokine compartment, is identified as a hallmark of BHR. RELEVANCE TO PRACTICE: These findings highlight the heterogeneity of immune response patterns in asthmatic children, including those with seemingly homogeneous Th2-driven atopic asthma. Further elucidation of the covert relationships between wheezing phenotypes and underlying immunophenotypes in this age group will potentially lead to more effective treatments for what is an unexpectedly heterogeneous collection of disease subtypes.


Asunto(s)
Asma/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Adolescente , Animales , Asma/fisiopatología , Hiperreactividad Bronquial , Niño , Eosinofilia , Humanos , Hipersensibilidad Inmediata/inmunología , Interleucinas/metabolismo , Fenotipo , Pyroglyphidae/inmunología , Ruidos Respiratorios , Pruebas Cutáneas
19.
Phys Ther Sport ; 21: 75-81, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27500450

RESUMEN

OBJECTIVES: To investigate inter and intra-rater reliability of hand held (HHD) and externally fixed (EFD) dynamometry for shoulder internal (IR) and external rotation (ER) strength and their correlation to isokinetic testing. DESIGN: Within participant, inter and intra-rater reliability study. PARTICIPANTS: Twenty active, healthy male and female participants underwent testing by two examiners. OUTCOME MEASURES: Intra-class coefficients (ICC), percentage standard error of measurement (%SEM), and percentage minimal detectable change (%MDC) were calculated for inter-rater, intra-day and intra-rater, inter-week reliability. Maximum and average of three repetitions were compared to the isokinetic results at three speeds (60°/sec, 180°/sec, 240°/sec) for both concentric and eccentric contractions. RESULTS: Inter and intra-tester values demonstrated good to high agreement (HHD, ICC range = 0.89-0.97, %SEM = 4.80-8.60%, %MDC = 13.29-23.70%; EFD, ICC = 0.88-0.96, %SEM = 6.60-11.00%, %MDC = 18.40-30.04%). HHD and EFD showed moderate to very strong correlations to the isokinetic testing (HHD, r = 0.45-0.86; EFD, r = 0.49-0.83). CONCLUSIONS: The results of this study indicate that both EFD and HHD are suitable for clinical practice and research. Hand-held dynamometry is preferred due to its higher intra- and inter-rater reliability and smaller MDC and lower SEM.


Asunto(s)
Dinamómetro de Fuerza Muscular , Hombro/fisiología , Adulto , Femenino , Voluntarios Sanos , Humanos , Masculino , Reproducibilidad de los Resultados , Rotación
20.
Plant Physiol ; 117(3): 1047-58, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9662548

RESUMEN

Tomato (Lycopersicon esculentum) plants were transformed with gene constructs containing a tomato alcohol dehydrogenase (ADH) cDNA (ADH 2) coupled in a sense orientation with either the constitutive cauliflower mosaic virus 35S promoter or the fruit-specific tomato polygalacturonase promoter. Ripening fruit from plants transformed with the constitutively expressed transgene(s) had a range of ADH activities; some plants had no detectable activity, whereas others had significantly higher ADH activity, up to twice that of controls. Transformed plants with fruit-specific expression of the transgene(s) also displayed a range of enhanced ADH activities in the ripening fruit, but no suppression was observed. Modified ADH levels in the ripening fruit influenced the balance between some of the aldehydes and the corresponding alcohols associated with flavor production. Hexanol and Z-3-hexenol levels were increased in fruit with increased ADH activity and reduced in fruit with low ADH activity. Concentrations of the respective aldehydes were generally unaltered. The phenotypes of modified fruit ADH activity and volatile abundance were transmitted to second-generation plants in accordance with the patterns of inheritance of the transgenes. In a preliminary taste trial, fruit with elevated ADH activity and higher levels of alcohols were identified as having a more intense "ripe fruit" flavor.

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