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1.
BMC Public Health ; 24(1): 657, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38429629

RESUMEN

BACKGROUND: Environmentally sustainable food initiatives accompanying nutrition education, such as the Food Education and Sustainability Training (FEAST) program, have gained traction in school settings. The aim of this trial was to conduct an impact and process evaluation of FEAST, to evaluate its effect on children's fruit and vegetable (F&V) intakes, and secondary outcomes: F&V variety consumed, nutrition knowledge, food preparation/cooking skills, self-efficacy and behaviours, food waste knowledge and behaviours, and food production knowledge. METHODS: FEAST was a 10-week curriculum-aligned program, designed to educate children about healthy eating, food waste, and sustainability, while teaching cooking skills. It was implemented by classroom teachers, face-to-face and online, during COVID-19 school closures, in Australia in 2021. A custom designed survey was used to collect baseline and post-intervention data from students. Generalised linear mixed models (GLMM) estimated group differences in pre-post changes for primary and secondary outcomes. Surveys were also administered to students and teachers to evaluate intervention implementation. RESULTS: Twenty schools participated and self-selected to be either intervention schools (n = 10) or wait-list control (WLC) schools (n = 10). A total of 977, 5th and 6th grade children participated in the trial with a mean age of 11.1 years (SD ± 0.7). The FEAST intervention, compared to WLC, did not result in significant increases in primary outcomes nor secondary outcomes. The process evaluation revealed FEAST was well-received by students and teachers, but COVID-19 school closures hindered implementation fidelity with a less intense program delivered under the constraints of pandemic lockdowns. CONCLUSIONS: This is the first cluster non-randomized controlled trial designed to independently evaluate FEAST in the primary-school setting. No evidence was found for improved F&V intakes in children, nor secondary outcomes. However, the positive process evaluation results suggest that further trials of the program are warranted. If implemented as originally designed (pre-pandemic), with increased duration and complemented by supporting school policies, such programs have the potential to improve children's daily F&V intakes, cooking skills and food waste behaviours. This would support the Australian curriculum and contribute to: health promotion within schools and sustainable schools initiatives, the national agenda to reduce food waste and sustainable development goals. AUSTRALIAN AND NEW ZEALAND CLINICAL TRIALS REGISTRY: [ACTRN12620001347954]- Registered prospectively on 14/12/2020.


Asunto(s)
COVID-19 , Eliminación de Residuos , Niño , Humanos , Alimentos , Australia , Instituciones Académicas , COVID-19/prevención & control
2.
BMC Public Health ; 21(1): 967, 2021 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-34022839

RESUMEN

BACKGROUND: The promotion of healthy eating is a public health priority. Poor dietary behaviours, including low fruit and vegetable (F&V) consumption are of particular concern among children. Novel nutrition promotion strategies are needed to improve F&V consumption. Sustainability education could be used to support nutrition education within the school context. The purpose of this paper is to report the protocol for impact and process evaluation of the school-based Food Education and Sustainability Training (FEAST) program, designed to educate children about sustainability, food waste and nutrition, using hands-on cooking activities. METHODS: A pragmatic, parallel, cluster non-randomized controlled trial with pre- and post-measures, will be implemented among 20 primary schools (10 intervention vs 10 wait-list-control) within NSW, Australia, involving children in Grades 5-6. FEAST is a curriculum-aligned program, delivered as a 1.5-h lesson/week, for a 10-week unit of inquiry, incorporating theory and cooking. FEAST was developed using theoretical frameworks which included Social Cognitive Theory and the Precede-Proceed Planning model. Primary outcomes include children's self-reported F&V intakes (serves/day). Food literacy constructs such as: nutrition knowledge, food preparation and cooking skills, self-efficacy and behaviours, food waste knowledge and behaviours and food production knowledge, will be assessed as secondary outcomes. Process evaluation will assess program reach, adoption, implementation, maintenance, satisfaction and perceived benefits by teachers and students. An online survey (including quantitative and qualitative questions) was developed for administration at baseline (impact evaluation) and immediately post-intervention (impact and process evaluation). Intervention effects on quantitative study outcomes will be estimated with ​generalised linear mixed models, including random effects and will follow the intention-to-treat principles. Open-ended questions embedded within the surveys will be analysed qualitatively using content and thematic analyses. DISCUSSION: Results from this trial will provide valuable information on the value of adding environmental sustainability strategies to nutrition education in schools. Results will inform the design of future research and programs focused on primary-school children's nutrition, sustainability-related behaviours and experiential school-based interventions. TRIAL REGISTRATION: Trial registered 14th December 2020 with the Australian and New Zealand Clinical Trials Registry ( ACTRN12620001347954 ).


Asunto(s)
Eliminación de Residuos , Servicios de Salud Escolar , Australia , Niño , Promoción de la Salud , Humanos , Nueva Zelanda , Evaluación de Programas y Proyectos de Salud , Instituciones Académicas
3.
Mult Scler ; 20(5): 577-87, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24009164

RESUMEN

BACKGROUND: Neutralizing antibodies (NAb) affect efficacy of interferon-beta (IFN-b) treatment in multiple sclerosis (MS) patients. NAbs evolve in up to 44% of treated patients, usually between 6-18 months on therapy. OBJECTIVES: To investigate whether early binding antibody (BAb) titers or different IFN-b biomarkers predict NAb evolution. METHODS: We included patients with MS or clinically isolated syndrome (CIS) receiving de novo IFN-b treatment in this prospective European multicenter study. Blood samples were collected at baseline, before and after the first IFN-b administration, and again after 3, 12 and 24 months on that therapy; for determination of NAbs, BAbs, gene expression of MxA and protein concentrations of MMP-9, TIMP-1, sTRAIL, CXCL-10 and CCL-2. RESULTS: We found that 22 of 164 (13.4%) patients developed NAbs during a median time of 23.8 months on IFN-b treatment. Of these patients, 78.9% were BAb-positive after 3 months. BAb titers ≥ 1:2400 predicted NAb evolution with a sensitivity of 74.7% and a specificity of 98.5%. Cross-sectionally, MxA levels were significantly diminished in the BAb/NAb-positive samples; similarly, CXCL-10 and sTRAIL concentrations in BAb/NAb-positive and BAb-positive/NAb-negative samples, respectively, were also diminished compared to BAb/NAb-negative samples. CONCLUSIONS: BAb titers reliably predict NAbs. CXCL-10 is a promising sensitive biomarker for IFN-b response and its abrogation by anti-IFN-b antibodies.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Enfermedades Desmielinizantes/tratamiento farmacológico , Enfermedades Desmielinizantes/inmunología , Factores Inmunológicos/inmunología , Factores Inmunológicos/uso terapéutico , Interferón beta/inmunología , Interferón beta/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/inmunología , Adulto , Biomarcadores/sangre , Quimiocina CXCL10/sangre , Enfermedades Desmielinizantes/sangre , Enfermedades Desmielinizantes/diagnóstico , Diagnóstico Precoz , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/genética , Proteínas de Resistencia a Mixovirus/genética , Valor Predictivo de las Pruebas , Estudios Prospectivos , Ligando Inductor de Apoptosis Relacionado con TNF/sangre , Factores de Tiempo , Resultado del Tratamiento
4.
Nat Genet ; 12(2): 195-9, 1996 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8563760

RESUMEN

Acute intermittent porphyria (AIP) is a human disease resulting from a dominantly inherited partial deficiency of the heme biosynthetic enzyme, porphobilinogen deaminase (PBGD). The frequency of the trait for AIP is 1/10,000 in most populations, but may be markedly higher (1/500) in psychiatric patients. The clinical expression of the disease is characterized by acute, life-threatening attacks of 'porphyric neuropathy' that include abdominal pain, motor and sensory neurological deficits and psychiatric symptoms. Attacks are frequently precipitated by drugs, alcohol and low caloric intake. Identical symptoms occur in other hepatic porphyrias. To study the pathogenesis of the neurologic symptoms of AIP we have generated Pbgd-deficient mice by gene targeting. These mice exhibit the typical biochemical characteristics of human AIP, notably, decreased hepatic Pbgd activity, increased delta-aminolevulinic acid synthase activity and massively increased urinary excretion of the heme precursor, delta-aminolevulinic acid after treatment with drugs such as phenobarbital. Behavioural tests reveal decreased motor function and histopathological findings include axonal neuropathy and neurologic muscle atrophy.


Asunto(s)
Enfermedades del Sistema Nervioso/etiología , Porfiria Intermitente Aguda , Porfiria Intermitente Aguda/metabolismo , Ácido Aminolevulínico/orina , Animales , Atrofia , Axones/patología , Secuencia de Bases , Quimera , Modelos Animales de Enfermedad , Femenino , Marcación de Gen , Humanos , Hidroximetilbilano Sintasa/genética , Riñón/efectos de los fármacos , Hígado/química , Masculino , Ratones , Datos de Secuencia Molecular , Actividad Motora , Músculo Esquelético/patología , Enfermedades del Sistema Nervioso/enzimología , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/patología , Fenobarbital/farmacología , Porfiria Intermitente Aguda/enzimología , Porfiria Intermitente Aguda/genética , Porfiria Intermitente Aguda/patología , ARN Mensajero/análisis
5.
Phys Rev Lett ; 106(11): 114801, 2011 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-21469866

RESUMEN

Generation of short-wavelength radiation by a free-electron laser using up-frequency conversion of an electron bunch density modulation is currently an area of active research. We propose a new scheme for producing the longitudinal electron bunch density modulation similar to the recently proposed echo-enabled harmonic generation but based on an emittance exchange beam line and a multislit mask. Beam line analysis and start-to-end simulation are presented.

6.
Artículo en Inglés | MEDLINE | ID: mdl-33626402

RESUMEN

INTRODUCTION: Preterm labor is a common clinical problem in obstetrics. Since the majority of women with preterm labor eventually deliver at full term, biomarkers are needed to more accurately predict who will deliver preterm. Oxylipins, given their importance in inflammation regulation, are highly interesting in this respect since labor is an inflammatory process. METHODS: Eighty women with preterm labor before 34 weeks of gestation were enrolled in a prospective observational multi-center cohort study. Oxylipin levels of 67 analytes in plasma samples were analyzed by liquid chromatography coupled to tandem mass spectrometry. RESULTS: Twenty-one (26%) of the women delivered before 34 weeks of gestation, and of those women, fourteen delivered within 48 h of admission. Logistic multivariate regression showed that lower levels of 9,10-DiHODE were associated with delivery before 34 weeks of gestation (aOR 0.12 (0.024-0.62)) and within 48 h ((aOR 0.13 (0.019-0.93)). Furthermore, higher levels of 11,12-DiHETrE were associated with delivery before 34 weeks of gestation ((aOR 6.19 (1.17-32.7)) and higher levels of 8-HETE were associated with delivery within 48 h ((aOR 5.01 (1.13-22.14)). CONCLUSIONS: The oxylipin 9,10-DiHODE may be protective in preterm labor, both for delivery after 34 weeks of gestation and for delivery later than 48 h of admission, whereas 11,12-DiHETrE and 8-HETE display the opposite effect. Larger studies are needed to validate these mediators as biomarkers for prediction of preterm birth following preterm labor.


Asunto(s)
Oxilipinas/sangre , Nacimiento Prematuro/sangre , Adulto , Biomarcadores/sangre , Cromatografía Liquida/métodos , Femenino , Edad Gestacional , Humanos , Recién Nacido , Oxilipinas/análisis , Admisión del Paciente , Embarazo , Pronóstico , Estudios Prospectivos , Espectrometría de Masas en Tándem/métodos
7.
Equine Vet J ; 52(2): 298-304, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31397916

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) is a well-recognised but poorly understood disease complex in the horse. Clinical signs may vary but often include weight loss, diarrhoea and colic. The effect this disease process may have on the gastrointestinal pacemaker cells (the interstitial cells of Cajal), enteric neurons and glial cells has not been previously evaluated in the horse. OBJECTIVES: To compare the density of the interstitial cells of Cajal (ICC), enteric neurons and glial cells in horses with IBD to those of normal horses using immunohistochemical markers. STUDY DESIGN: Retrospective, quantitative immunohistochemical study. METHODS: Ileal samples were collected during post-mortem examinations from 14 horses with a clinical and histopathological diagnosis of IBD and from eight normal controls. All horses were Standardbreds 1-15 years of age. Six of the IBD cases had eosinophilic gastroenteritis (EG) while the remaining eight had granulomatous enteritis (GE). Tissue sections were labelled with anti-CD117 (c-Kit), anti-TMEM16 (TMEM16), anti-protein gene product (PGP9.5) and anti-glial fibrillary acidic protein (GFAP) using standard immunohistochemical labelling techniques. Image analysis was performed to quantify the presence of ICC (CD117, TMEM16) as well as neuronal (PGP9.5) and enteroglial (GFAP) networks. RESULTS: Interstitial cells of Cajal networks were significantly reduced in the myenteric plexus (MP) region in IBD horses compared with the controls for both markers (P<0.05). There was no significant difference in the density of the neuronal or glial cell markers between the two groups (P>0.05). MAIN LIMITATIONS: The number of horses included in the study. CONCLUSIONS: Disruption to ICC networks may contribute to the clinical signs of colic in some horses with IBD. Further studies are needed to establish the pathophysiological mechanisms involved and the functional effects of the reduced ICC networks.


Asunto(s)
Cólico/veterinaria , Enfermedades Inflamatorias del Intestino/veterinaria , Células Intersticiales de Cajal , Animales , Enfermedades de los Caballos , Caballos , Plexo Mientérico , Estudios Retrospectivos
8.
Science ; 164(3885): 1288-9, 1969 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-4388907

RESUMEN

A 24-hour cycle of pressure (1.0 to 1.09 atmospheres) can act as a zeitgeber to entrain the endogenous circadian rhythm of body temperature in pocket mice (Perognathus longimembris) under constant conditions of environmental temperature and light.


Asunto(s)
Presión Atmosférica , Temperatura Corporal , Ritmo Circadiano , Animales , Sistemas Ecológicos Cerrados , Percepción del Tiempo
9.
Science ; 225(4665): 925-7, 1984 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-17779866

RESUMEN

Computer modeling of 611 high-quality analyses of normal ground waters from diverse geographic areas reveals that aqueous oxidation-reduction reactions are generally not at equilibrium. Multiple redox couples present in individual samples yield computed Nernstian Eh (redox potential) values spanning as much as 1000 millivolts. The computed Eh values do not agree with each other, nor do they agree with the single "master" value measured in the field with a platinum electrode. Because of internal disequilibrium, the use of any measured Eh value as input to equilibrium hydrogeochemical computer models will generally yield misleading results for normal ground waters.

10.
Eur J Neurol ; 16(6): 771-4, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19236470

RESUMEN

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS. METHODS: We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1beta (MIP-1beta), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients. RESULTS: MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum (P < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis (r = -0.407; P = 0.075). CONCLUSIONS: We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease.


Asunto(s)
Esclerosis Amiotrófica Lateral/diagnóstico , Quimiocinas/análisis , Inflamación/diagnóstico , Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Biomarcadores/análisis , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Quimiocina CCL2/análisis , Quimiocina CCL2/sangre , Quimiocina CCL2/líquido cefalorraquídeo , Quimiocinas/sangre , Quimiocinas/líquido cefalorraquídeo , Progresión de la Enfermedad , Diagnóstico Precoz , Gliosis/sangre , Gliosis/líquido cefalorraquídeo , Gliosis/diagnóstico , Humanos , Inflamación/sangre , Inflamación/líquido cefalorraquídeo , Interleucina-8/análisis , Interleucina-8/sangre , Interleucina-8/líquido cefalorraquídeo , Microglía/inmunología , Microglía/metabolismo , Valor Predictivo de las Pruebas , Pronóstico , Sensibilidad y Especificidad , Factores de Tiempo , Regulación hacia Arriba/inmunología
11.
Res Vet Sci ; 86(3): 472-8, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19027127

RESUMEN

This study explored host immune responses and their possible relationship to the anti-fecundity phenomenon in Schistosoma bovis-infected goats. The design comprised a primary infection with or without treatment at week (wk) 13, and with or without challenge at wk 36. Necropsy was performed at 36 or 52wk. Serum levels of anti-egg IgG, and anti-worm IgG and IgM, were measured by ELISA. In chronic infection, anti-worm antibodies stayed high, reflecting persisting worm burdens, whereas anti-egg IgG remained high despite minimized egg excretion. After treatment, anti-worm IgM and anti-egg IgG were minimized, but anti-worm IgG remained above the values of the uninfected controls. Histopathology showed lowered numbers of perioval granulomas in chronic infection and resolution of liver fibrosis with time, but intestinal lymphoplasmacytic perivasculitis and hepatic eosinophilic infiltrates were maintained at wk 52. Significant splenic plasmacytosis persisted after treatment. The results indicated that persistent immune responses, in chronically infected and in treated goats, may explain sustained worm fecundity depression at challenge infection.


Asunto(s)
Enfermedades de las Cabras/parasitología , Schistosoma/inmunología , Esquistosomiasis/inmunología , Esquistosomiasis/veterinaria , Animales , Antihelmínticos/uso terapéutico , Anticuerpos Antihelmínticos/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Enfermedades de las Cabras/tratamiento farmacológico , Enfermedades de las Cabras/inmunología , Enfermedades de las Cabras/patología , Cabras , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Intestino Delgado/parasitología , Intestino Delgado/patología , Hígado/parasitología , Hígado/patología , Mebendazol/inmunología , Mebendazol/uso terapéutico , Óvulo , Praziquantel/uso terapéutico , Schistosoma/aislamiento & purificación , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/patología
12.
Trends Biochem Sci ; 17(3): 114-9, 1992 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1412695

RESUMEN

Protein kinases are classified by the target amino acid in their substrates. Those protein kinases that phosphorylate hydroxyamino acids comprise two groups, the protein-tyrosine and protein-serine/threonine kinases, which, until recently, had been thought to be mutually exclusive. However, several new protein kinases have been discovered that, by the criterion of primary structure, would be classified as protein-serine/threonine kinases but which, surprisingly, are able to phosphorylate tyrosine residues. Even more surprising, there are reports of protein kinases that are capable of phosphorylating both tyrosine and serine/threonine residues. We review and discuss recent developments concerning these 'dal-specificity' protein kinases.


Asunto(s)
Proteínas Serina-Treonina Quinasas/fisiología , Proteínas Tirosina Quinasas/fisiología , Secuencia de Aminoácidos , Animales , Humanos , Hidroxilación , Datos de Secuencia Molecular , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , Proteínas Tirosina Quinasas/genética , Saccharomyces cerevisiae , Serina/metabolismo , Especificidad por Sustrato , Treonina/metabolismo , Tirosina/metabolismo
13.
Obes Sci Pract ; 4(2): 119-128, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29670749

RESUMEN

Objective: Excess body weight negatively impacts health, but there are few evaluations of low-intensity weight management challenge programs in defined populations. This study examined weight change in adults who participated in the LOSE IT to WIN IT (LIWI) health challenge in a US community. The community-level impact on body mass index was also explored. Methods: Body weight was analysed over 1 year in the cohort of LIWI enrolees, stratified by participants who were healthy weight or overweight/obese at baseline. Secondarily, a multiple cross-sectional analysis compared the 2.5-year trends in body mass index between community adults who did vs. did not participate in LIWI. Results: LOSE IT to WIN IT participants who were overweight/obese lost a mean (95% confidence interval) 1.6 (1.2, 2.0) kg (~2%) over 1 year (p < 0.001), whereas healthy weight participants lost 0.7 (0.3, 1.1) kg. Across the community, LIWI participants and non-participants both gained 0.4 kg m-2 over the 2.5-year study period (p = 0.884). Conclusions: LOSE IT to WIN IT was modestly effective among enrolees, resulting in a small weight loss of 2% over 1 year among those who were overweight/obese. However, LIWI did not impact weight gain in the community. To slow such community-level weight gain trends, weight management challenges must reach larger fractions of the populations that they target.

14.
Sci Rep ; 8(1): 11918, 2018 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-30093728

RESUMEN

Novel features of the longitudinal instability of a single electron bunch circulating in a low-emittance electron storage ring are discussed. Measurements and numerical simulations, performed both in time and frequency domain, show a non-monotonic increase of the electron beam energy spread as a function of single bunch current, characterized by the presence of local minima and maxima, where a local minimum of the energy spread is interpreted as a higher-order microwave instability threshold. It is also shown that thresholds related to the same zero-intensity bunch length depend linearly on the accelerating radio frequency voltage. The observed intensity-dependent features of the energy spread, confirmed by measurements with two independent diagnostics methods, i.e. horizontal beam profile measurements by a synchrotron light monitor and photon energy spectrum measurements of undulator radiation, are given a theoretical interpretation by applying a novel eigenvalue analysis based on the linearized Vlasov equation.

15.
Curr Biol ; 5(9): 986-9, 1995 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-8542290

RESUMEN

A family of ligands has been identified for the largest group of receptor protein-tyrosine kinases--the hitherto 'orphan' EPH receptor subfamily--and the functions of these receptors and ligands are starting to be elucidated.


Asunto(s)
Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptores de Superficie Celular/metabolismo , Secuencia de Aminoácidos , Animales , Humanos , Ligandos , Datos de Secuencia Molecular , Proteínas Tirosina Quinasas Receptoras/química , Receptores de Superficie Celular/química
16.
J Clin Invest ; 103(8): 1127-34, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10207164

RESUMEN

Acute porphyrias are inherited disorders caused by partial deficiency of specific heme biosynthesis enzymes. Clinically, porphyrias are manifested by a neuropsychiatric syndrome that includes peripheral neuropathy. Although much is known about the porphyrias' enzyme defects and their biochemical consequences, the cause of the neurological manifestations remains unresolved. We have studied porphyric neuropathy in mice with a partial deficiency of porphobilinogen deaminase (PBGD). PBGD-deficient mice (PBGD-/-) imitate acute porphyria through massive induction of hepatic delta-aminolevulinic acid synthase by drugs such as phenobarbital. Here we show that PBGD-/- mice develop impairment of motor coordination and muscle weakness. Histologically femoral nerves of PBGD-/- mice exhibit a marked decrease in large-caliber (>8 microm) axons and ultrastructural changes consistent with primary motor axon degeneration, secondary Schwann cell reactions, and axonal regeneration. These findings resemble those found in studies of affected nerves of patients with acute porphyria and thus provide strong evidence that PBGD deficiency causes degeneration of motor axons without signs of primary demyelination, thereby resolving a long-standing controversy. Interestingly, the neuropathy in PBGD-/- mice developed chronically and progressively and in the presence of normal or only slightly (twofold) increased plasma and urinary levels of the putative neurotoxic heme precursor delta-aminolevulinic acid. These data suggest that heme deficiency and consequent dysfunction of hemeproteins can cause porphyric neuropathy.


Asunto(s)
Hidroximetilbilano Sintasa/fisiología , Neuronas Motoras/patología , Nervios Periféricos/fisiopatología , Porfirias/fisiopatología , Enfermedad Aguda , Ácido Aminolevulínico/sangre , Ácido Aminolevulínico/orina , Animales , Modelos Animales de Enfermedad , Electrofisiología , Nervio Femoral/patología , Nervio Femoral/fisiopatología , Nervio Femoral/ultraestructura , Humanos , Hidroximetilbilano Sintasa/genética , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Actividad Motora , Neuronas Motoras/ultraestructura , Nervios Periféricos/patología , Nervios Periféricos/ultraestructura , Porfirias/patología
17.
Mol Cell Biol ; 10(12): 6316-24, 1990 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2174105

RESUMEN

A human epithelial (HeLa) cDNA library was screened with degenerate oligonucleotides designed to hybridize to highly conserved regions of protein-tyrosine kinases. One cDNA from this screen was shown to contain a putative protein-tyrosine kinase catalytic domain and subsequently used to isolate another cDNA from a human keratinocyte library that encompasses the entire coding region of a 976-amino-acid polypeptide. The predicted protein has an external domain of 534 amino acids with a presumptive N-terminal signal peptide, a transmembrane domain, and a cytoplasmic domain of 418 amino acids that includes a canonical protein-tyrosine kinase catalytic domain. Molecular phylogeny indicates that this protein kinase is closely related to eph and elk and that this receptor family is more closely related to the non-receptor protein-tyrosine kinase families than to other receptor protein-tyrosine kinases. Antibodies raised against a TrpE fusion protein immunoprecipitated a 130-kDa protein that became phosphorylated on tyrosine in immune complex kinase assays, indicating that this protein is a bona fide protein-tyrosine kinase. Analysis of RNA from 13 adult rat organs showed that the eck gene is expressed most highly in tissues that contain a high proportion of epithelial cells, e.g., skin, intestine, lung, and ovary. Several cell lines of epithelial origin were found to express the eck protein kinase at the protein and RNA levels. Immunohistochemical analysis of several rat organs also showed staining in epithelial cells. These observations prompted us to name this protein kinase eck, for epithelial cell kinase.


Asunto(s)
Familia de Multigenes , Proteínas Tirosina Quinasas/genética , Receptores de Superficie Celular/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN de Neoplasias/genética , Epitelio/enzimología , Biblioteca de Genes , Células HeLa/enzimología , Humanos , Riñón/enzimología , Pulmón/enzimología , Datos de Secuencia Molecular , Sondas de Oligonucleótidos , Filogenia , Homología de Secuencia de Ácido Nucleico
18.
Mol Cell Biol ; 9(1): 232-40, 1989 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-2467187

RESUMEN

p36 and p35 are distinct but related proteins that share many structural and biochemical features which were first identified as major substrates for protein-tyrosine kinases. Subsequently, both proteins have been shown to be Ca2+-, phospholipid-, and F-actin-binding proteins that underlie the plasma membrane and are associated with the cortical cytoskeleton. Recent reports have claimed that these proteins function as lipocortins, i.e., phospholipase A2 inhibitors that mediate the anti-inflammatory action of glucocorticoids. To investigate this possibility and to learn more about the functions of p36 and p35, we used human-specific anti-p36 and anti-p35 monoclonal antibodies to determine whether the expression or secretion of either protein was inducible by dexamethasone in the human U-937 myeloid cell line and in other human cell types. Additionally, we examined the levels of mRNA for both proteins. No effect of dexamethasone was observed on p36 or p35 expression at either the mRNA or protein level, nor were these proteins secreted under any of the culture conditions investigated. However, it was observed that in these cells the rate of synthesis and accumulation of both proteins was increased when the U-937 cells were induced to differentiate in culture to adherent macrophagelike cells. This offers a model system with which to study the control of p36 and p35 expression.


Asunto(s)
Proteínas de Unión al Calcio/biosíntesis , Regulación de la Expresión Génica/efectos de los fármacos , Glucocorticoides/farmacología , Animales , Anexinas , Anticuerpos Monoclonales/biosíntesis , Northern Blotting , Proteínas de Unión al Calcio/genética , Diferenciación Celular/efectos de los fármacos , Dexametasona/farmacología , Humanos , Leucemia Mieloide/metabolismo , Ratones , Biosíntesis de Proteínas/efectos de los fármacos , ARN/análisis , Células Tumorales Cultivadas
19.
Mol Cell Biol ; 11(1): 143-53, 1991 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-1846020

RESUMEN

We have screened an adult rat cerebellar cDNA library in search of novel protein tyrosine-kinase (PTK) cDNAs. A cDNA for a putative PTK, trkB, was cloned, and its sequence indicates that it is likely to be derived from a gene for a ligand-regulated receptor closely related to the human trk oncogene. Northern (RNA) analysis showed that the trkB gene is expressed predominantly in the brain and that trkB expresses multiple mRNAs, ranging from 0.7 to 9 kb. Hybridization of cerebral mRNAs with a variety of probes indicates that there are mRNAs encoding truncated trkB receptors. Two additional types of cDNA were isolated, and their sequences are predicted to encode two distinct C-terminally truncated receptors which have the complete extracellular region and transmembrane domain, but which differ in their short cytoplasmic tails.


Asunto(s)
Glicoproteínas de Membrana/genética , Proteínas Tirosina Quinasas/genética , Receptores de Superficie Celular/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Clonación Molecular , ADN/genética , Expresión Génica , Datos de Secuencia Molecular , Fenómenos Fisiológicos del Sistema Nervioso , Sondas de Oligonucleótidos , ARN Mensajero/genética , Ratas
20.
Mol Cell Biol ; 18(6): 3357-67, 1998 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9584176

RESUMEN

Oncostatin M (OSM) is a member of a family of cytokines that includes ciliary neurotrophic factor, interleukin-6, interleukin-11, cardiotrophin-1, and leukemia inhibitory factor (LIF). The receptors for these cytokines consist of a common signaling subunit, gp130, to which other subunits are added to modify ligand specificity. We report here the isolation and characterization of a cDNA encoding a subunit of the mouse OSM receptor. In NIH 3T3 cells (which endogenously express gp130, LIF receptor beta [LIFRbeta], and the protein product, c12, of the cDNA described here), mouse LIF, human LIF, and human OSM signaled through receptors containing the LIFRbeta and gp130 but not through the mouse OSM receptor. Mouse OSM, however, signaled only through a c12-gp130 complex; it did not use the LIF receptor. Binding studies demonstrated that mouse OSM associated directly with either the c12 protein or gp130. These data highlight the species-specific differences in receptor utilization and signal transduction between mouse and human OSM. In mouse cells, only mouse OSM is capable of activating the mouse OSM receptor; human OSM instead activates the LIF receptor. Therefore, these data suggest that all previous studies with human OSM in mouse systems did not elucidate the biology of OSM but, rather, reflected the biological actions of LIF.


Asunto(s)
Interleucina-6 , Linfocinas , Péptidos/metabolismo , Precursores de Proteínas/genética , Receptores de Citocinas/genética , Células 3T3 , Secuencia de Aminoácidos , Animales , Antígenos CD/metabolismo , Secuencia de Bases , Células COS , Clonación Molecular , Receptor gp130 de Citocinas , Inhibidores de Crecimiento/metabolismo , Humanos , Factor Inhibidor de Leucemia , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia , Glicoproteínas de Membrana/metabolismo , Ratones , Datos de Secuencia Molecular , Peso Molecular , Oncostatina M , Precursores de Proteínas/metabolismo , Receptores de Citocinas/metabolismo , Receptores OSM-LIF , Receptores de Oncostatina M , Alineación de Secuencia , Transducción de Señal , Especificidad de la Especie
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