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1.
Pulmonology ; 28(1): 28-33, 2022.
Article in English | MEDLINE | ID: mdl-32507497

ABSTRACT

INTRODUCTION: Cytological samples obtained by endobronchial ultrasound (EBUS) are capital for diagnosis, staging and molecular profile in non-small cell lung carcinoma (NSCLC). OBJECTIVE: To assess the success rate of complete, partial and individual of molecular analysis in samples obtained by EBUS-guided transbronchial needle aspiration (TBNA) and/or by oesophageal ultrasound-guided fine needle aspiration with an echobronchoscope (EUS-B-FNA) in patients with NSCLC. METHODS: Prospective study including 90 patients with non-squamous NSCLC, or non-smoking squamous. Cytological samples were classified into two groups. Group 1: PEN membrane slide and/or cell blocks for the determination of mutations of EGFR, KRAS, ERBB2 and BRAF. Group 2: silane coated slides or cell blocks for rearrangements of ALK, ROS1 and MET amplification. RESULTS: The success rate was 78.6% for 4 molecular alterations (EGFR, KRAS, ALK and ROS1), and 44% for 7 determinations. The individual success rate for EGFR was 97%, KRAS 96.3%, ALK 85%, ROS1 82.3%, ERBB2 71.4%, BRAF 67.7% and MET 81.1%. There were no significant differences (p=0.489) in the number of molecular analyses (1-3 vs. 4) in group 1, depending on the types of samples (cell block vs. PEN membrane slide vs. cell block and PEN membrane slide). CONCLUSIONS: In patients with NSCLC, the cytological material obtained by ultrasound-guided needle aspiration is sufficient for individual and partial molecular analysis in the vast majority of cases. Membrane slides such as cell blocks are valid samples for molecular analysis.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Lung Neoplasms/genetics , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/pathology , DNA Mutational Analysis/methods , ErbB Receptors , Female , Gene Amplification , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Male , Middle Aged , Polymerase Chain Reaction , Prevalence , Prospective Studies , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins B-raf , Proto-Oncogene Proteins p21(ras) , Receptor Protein-Tyrosine Kinases
2.
Rev. int. med. cienc. act. fis. deporte ; 17(68): 677-692, dic. 2017. tab, graf
Article in Spanish | IBECS | ID: ibc-168955

ABSTRACT

Esta investigación pretende estudiar los niveles de violencia percibida y sufrida en centros escolares, analizar la satisfacción con la autoimagen corporal y la relación entre estas variables. Es un estudio descriptivo cuya muestra está compuesta por 284 escolares de la Región de Murcia con edades comprendidas entre los 12 y 17 años. Se han administrado los cuestionarios BODY SHAPE self-perceived de Stunkard, Sorensen y Schulsinger (1983) para el análisis de la autoimagen corporal y el CUVECO de Fernández-Baenal et al. (2011) para la violencia escolar. Los resultados muestran, sobre la imagen corporal, que existe un elevado porcentaje de adolescentes que están insatisfechos, especialmente las chicas, mientras que sobre la violencia escolar se observa una estabilidad en la evolución de violencia percibida mientras que se produce una disminución de la violencia sufrida. Por último, se ha registrado el mayor riesgo de formar parte de los grupos que más violencia sufren entre quienes mayor descontento muestran con su autoimagen (AU)


This investigation aims to study perceived violence and suffered violence levels in school settings, to analyze satisfaction with body self-image and to explore the relationship among these variables. It is a descriptive study whose sample is made up of 284 secondary students from the Region of Murcia aged 12 to 17. BODY SHAPE self-perceived questionnaire by Stunkard, Sorensen and Schulsinger (1983) and CUVECO questionnaire by Fernández-Baenal et al. (2011) were administered to analyze body self-image and school violence respectively. With regard to their body image the results show that there is a high percentage of students who are dissatisfied, especially girls. Regarding school violence levels, students' perceived violence is stable while suffered violence decreases progressively. Finally, if students are dissatisfied there is a higher chance of belonging to groups who suffered more violence (AU)


Subject(s)
Humans , Male , Female , Child , Adolescent , Violence/prevention & control , Body Image , Adolescent Behavior/psychology , Psychology, Adolescent/methods , Bullying , Adolescent Health/trends , Adolescent Development/physiology , 28599 , Logistic Models
3.
Rev. int. med. cienc. act. fis. deporte ; 17(67): 467-479, sept. 2017. tab, ilus
Article in Spanish | IBECS | ID: ibc-166525

ABSTRACT

El objetivo del presente estudio es conocer los efectos en la cantidad y eficacia de golpeos y la percepción de satisfacción/diversión, aburrimiento y esfuerzo a través de cuatro formas de organización diferentes de sesiones de pádel. Los participantes del estudio fueron 48 estudiantes del Ciclo Formativo de Técnico en Animación y Actividades Físico Deportivas (33 chicos y 15 chicas), con edades comprendidas entre los 18 y los 26 años. Se evaluó la cantidad y eficacia de los golpeos a través de una hoja de observación directa. La percepción de diversión y aburrimiento fue evaluada a través del Sport Satisfaction Instrument y la percepción de esfuerzo a través de la Pictorial Children's Effort Rating Table. Los resultados obtenidos muestran que la forma de organización basada en el peloteo entre los alumnos se plantea como la más eficaz en la enseñanza del pádel, obteniendo un número significativamente mayor y más eficaz de golpeos, así como valores significativamente superiores de diversión/satisfacción y esfuerzo e inferiores de aburrimiento (AU)


The aim of this study was to determine the effects on the quantity and effectiveness of strokes and perceived satisfaction / fun, boredom and effort through four different organizational forms of paddle sessions. Study participants were 48 students from the Technical Training Course in Animation and Sports Physical Activities (33 boys and 15 girls) with ages between 18 and 26 years. The amount and effectiveness of beatings through direct observation of a sheet was evaluated. The perception of fun and boredom was evaluated through the Sport Satisfaction Instrument and perception of effort through the Pictorial Children's Effort Rating Table. The results show that the form of organization based on the rally among students is seen as the most effective in teaching paddle. A significantly greater and more effective number of strokes and significantly higher values ​​of amusement / satisfaction and effort and lower boredom have been proved as a result of this form of organization (AU)


Subject(s)
Humans , Male , Female , Adolescent , Young Adult , Adult , Motor Activity/physiology , Boredom , Learning , Exercise/physiology , Athletic Performance/education , Students/psychology , Students/statistics & numerical data , Psychology, Sports/education , Psychology, Sports/statistics & numerical data , Data Analysis/methods
4.
Ars pharm ; 51(supl.3): 447-451, jul. 2010.
Article in Spanish | IBECS | ID: ibc-99503

ABSTRACT

Dentro de las actividades del farmacéutico de atención primaria se encuentra el análisis del perfil de prescripción farmacológica, la identificación de áreas de mejora y la puesta en marcha de estrategias para mejorar el uso de los medicamentos dentro del Distrito. En octubre de 2008, la prescripción de antibióticos en el Distrito se caracterizaba por una alta variabilidad en la selección de antibióticos por parte de los pediatras, que daba como resultado un global del indicador de calidad del Contrato Programa del Servicio Andaluz de Salud peor que el de la media de Andalucía. Todo esto junto con la alta frecuentación de población pediátrica a los servicios de urgencias y la discrepancia entre criterios de prescripción en servicios de urgencias y pediatras del Equipo Básico de Atención Primaria (EBAP), motivó el desarrollo del presente trabajo. Nuestro objetivo fue mejorar el perfil de utilización de antibióticos en pediatría en Atención Primaria. Para ello se diseño un plan de mejora consistente en a)la formación de un grupo de mejora constituido por pediatras, farmacéuticos y coordinador de urgencias, b) elaboración de una “Guía empírica sobre antibioterapia pediátrica en AP”, adaptada y consensuada en el ámbito del Distrito, c) difusión de la guía a todos los pediatras, médicos de Dispositivo de Cuidados Críticos y Urgencias (DCCU) y Dirección Médica del Hospital de referencia, d) sesiones formativas a los médicos de DCCU impartidas por un pediatra del grupo, e) para la evaluación del plan se midieron indicadores de calidad en la prescripción pediátrica durante los meses enero-abril 2009 respecto al año anterior y se elaboró una encuesta dirigida a los pediatras de EBAP de valoración del plan(AU)


La selección de un antibiótico debe basarse en criterios de eficacia, seguridad, adecuación y coste. En este sentido, la intervención produjo una mejora en la selección de antibióticos en pediatría a nivel de Atención Primaria, disminuyendo la variabilidad de la prescripción. En concreto, se incrementó la descripción de antibióticos de primera elección, bajo criterios de práctica clínica (amoxicilina, ampicilina, penicilinas frente a Gram positivo y cloxacilina) frente a macrólidos y cefalosporinas de 2ª y 3ª generación. Este aumento debe traducirse en un aumento de la eficiencia terapéutica y disminución de la aparición de resistencias bacterianas y efectos adversos. La aceptación del plan de mejora entre los profesionales fue bueno debido, entre otras causas, a la participación activa de los mismos(AU)


Among the activities of Primary Care Pharmacist we have drug prescription profiles analysis. In October 2008, antibiotics prescription at Distrito Costa del Sol was characterized by a high variability in the selection of antibiotics by paediatricians, which resulted in an overall quality indicator worse than the regional mean value. All this together with the high frequency of paediatric emergency services and discrepancy in prescription criteria with Primary Care Services prompted the development of this work. We designed an improvement plan consisting on establishing a multidisciplinary group that generateda “Guide on empirical antibiotic therapy”. This guide was distributed to all paediatricians and Emergency Services along with training sessions. Quality indicators in paediatric prescription were measured from January to April 2009 and compared to same period 2008 along with a satisfaction survey. We observed an increased prescription of antibiotics of choice that may lead to an improved therapeutic efficiency and decreased bacterial resistances and adverse effects. Acceptance of the plan by professionals was high based on, among other reasons, their active participation(AU)


Subject(s)
Humans , Male , Female , Child , Pharmaceutical Services , Drug Prescriptions/statistics & numerical data , Drug Prescriptions/standards , Emergency Medicine
5.
J Thromb Haemost ; 8(4): 808-16, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20088932

ABSTRACT

BACKGROUND: The fibrinolytic system has been implicated in the pathogenesis of pulmonary hypertension (PH). Thrombin-activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis and therefore its absence would be expected to increase fibrinolysis and ameliorate PH. OBJECTIVE: The objective of the present study was to evaluate the effect of TAFI deficiency on pulmonary hypertension in the mouse. METHODS AND RESULTS: PH was induced in C57/Bl6 wild-type (WT) or TAFI-deficient (KO) mice by weekly subcutaneous treatment with 600 mg kg(-1) monocrotaline (MCT) for 8 weeks. PH was inferred from right heart hypertrophy measured using the ratio of right ventricle-to-left ventricle-plus-septum weight [RV/(LV+S)]. Pulmonary vascular remodeling was analyzed by morphometry. TAFI-deficient MCT-treated and wild-type MCT-treated mice suffered similar weight loss. TAFI-deficient MCT-treated mice had reduced levels of total protein and tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), transforming growth factor-beta (TGF-beta) and monocyte chemoattractant protein-1 (MCP-1) in bronchial alveolar lavage compared with wild-type MCT-treated mice. The ratio of RV to (LV+S) weight was significantly higher in WT/MCT than in KO/MCT mice. The pulmonary artery wall area and vascular stenosis were both greater in MCT-treated WT mice compared with MCT-treated TAFI-deficient mice. CONCLUSIONS: TAFI-deficient MCT-treated mice had less pulmonary hypertension, vascular remodeling and reduced levels of cytokines compared with MCT-treated WT animals, possibly as a result of reduced coagulation activation.


Subject(s)
Carboxypeptidase B2/deficiency , Fibrinolysis , Hypertension, Pulmonary/prevention & control , Lung/metabolism , Animals , Biomarkers/metabolism , Bronchoalveolar Lavage Fluid/immunology , Capillary Permeability , Carboxypeptidase B2/genetics , Chemokine CCL2/metabolism , Disease Models, Animal , Fibrinolysis/genetics , Hypertension, Pulmonary/blood , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/immunology , Hypertension, Pulmonary/pathology , Hypertrophy, Right Ventricular/blood , Hypertrophy, Right Ventricular/prevention & control , Inflammation Mediators/metabolism , Interleukin-6/metabolism , Lung/blood supply , Lung/immunology , Lung/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Monocrotaline , Platelet-Derived Growth Factor/metabolism , Pulmonary Artery/metabolism , Pulmonary Artery/pathology , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/metabolism , Weight Loss
6.
Transplant Proc ; 41(8): 3505-6, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19857781

ABSTRACT

Kidney transplantation has been performed in Cuba since 1970. In 1979, compatible living-related donors were introduced into our renal transplantation program. There are 43 hospitals distributed around the country with a multidisciplinary group that attends cadaveric donors with encephalic death. The donor rate in Cuba oscillates between 15 and 18 per million; 90% of them are from cadaveric donors. This program includes 47 dialysis centers throughout the country with 2300 patients as supported by a National Coordinating Center at The Nephrology Institute. Cuba is one of the first countries in our region with this experience.


Subject(s)
Kidney Transplantation/statistics & numerical data , Cadaver , Cause of Death , Cuba/epidemiology , Humans , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/surgery , Tissue Donors
7.
Med Intensiva ; 30(9): 432-9, 2006 Dec.
Article in Spanish | MEDLINE | ID: mdl-17194400

ABSTRACT

OBJECTIVE: Describe the frequency of high degree atrioventricular block (HDAVB) in patients with unstable angina (UA), analyze the variables associated with their appearance and evaluate whether HDAVB is independently associated with increased mortality or increased length of ICU stay. DESIGN: Retrospective descriptive study of patients with UA included in the ARIAM registry. SETTING: ICUs from 129 hospitals in Spain. PATIENTS: From June 1996 to December 2003 a total of 14,096 patients were included in the ARIAM registry with a diagnosis of UA. MAIN VARIABLES OF INTEREST: Variables associated with the development of HDAVB, variables associated with the mortality of patients with UA, variables associated with the length of ICU stay of patients with UA. RESULTS: HDAVB frequency was 1%. Development of HDAVB was independently associated with the Killip classification and the presence of sustained ventricular tachycardia or ventricular fibrillation. Crude mortality of patients was significantly increased when HDAVB was present (9% versus 1%, p < 0,001). When adjusted for other variables, HDAVB was not associated with increased mortality. Development of HDAVB in patients with UA was independently associated with an increase in the length of ICU stay (adjusted odds ratio 1.89: 95% confidence interval: 1.33-5.69). CONCLUSIONS: Patients with UA complicated with HDAVB represent a high-risk population with an increased ICU stay.


Subject(s)
Angina, Unstable/complications , Heart Block/complications , Aged , Aged, 80 and over , Angina, Unstable/drug therapy , Angina, Unstable/epidemiology , Cardiovascular Agents/therapeutic use , Female , Heart Block/drug therapy , Heart Block/epidemiology , Humans , Male , Middle Aged , Registries , Retrospective Studies , Risk Factors , Spain/epidemiology
8.
Med. intensiva (Madr., Ed. impr.) ; 30(9): 432-439, dic. 2006. tab
Article in Es | IBECS | ID: ibc-050721

ABSTRACT

Objetivo. Describir la frecuencia de bloqueo auriculoventricular (BAVAG) en los pacientes con angina inestable (AI), analizar las variables asociadas al desarrollo del mismo y evaluar si el BAVAG se asocia de manera independiente con aumento de la mortalidad o de la estancia en Unidades de Cuidados Intensivos (UCI). Diseño. Estudio descriptivo retrospectivo de los pacientes con AI incluidos en el estudio ARIAM. Ámbito. UCI de 129 hospitales españoles. Pacientes. Desde junio de 1996 a diciembre de 2003 se incluyeron en el proyecto ARIAM 14.096 pacientes con diagnóstico de AI. Variables de interés principales. Variables asociadas con el desarrollo de BAVAG, con la mortalidad de los pacientes con AI y con la duración de la estancia en UCI de los pacientes con AI. Resultados. La frecuencia de BAVAG durante el ingreso en UCI fue del 1%. El desarrollo de BAVAG se asoció de manera independiente con el grado en la clasificación de Killip y la presencia de taquicardia ventricular sostenida o de fibrilación ventricular. La mortalidad cruda de los pacientes con AI aumentó significativamente en presencia de BAVAG (9% frente a 1%, p < 0,001). Cuando se ajustó para otras variables no se observó un aumento de la mortalidad asociada al BAVAG. El desarrollo de BAVAG en los pacientes con AI se asocia de manera independiente con un aumento de la estancia media (odds ratio ajustada 1,89; intervalo de confianza del 95%: 1,33-5,69). Conclusiones. Los pacientes con AI que desarrollan BAVAG representan una población de alto riesgo. El BAVAG se asocia con un incremento de la estancia media


Objective. Describe the frequency of high degree atrioventricular block (HDAVB) in patients with unstable angina (UA), analyze the variables associated with their appearance and evaluate whether HDAVB is independently associated with increased mortality or increased length of ICU stay. Design. Retrospective descriptive study of patients with UA included in the ARIAM registry. Setting. ICUs from 129 hospitals in Spain. Patients. From June 1996 to December 2003 a total of 14,096 patients were included in the ARIAM registry with a diagnosis of UA. Main variables of interest. Variables associated with the development of HDAVB, variables associated with the mortality of patients with UA, variables associated with the length of ICU stay of patients with UA. Results. HDAVB frequency was 1%. Development of HDAVB was independently associated with the Killip classification and the presence of sustained ventricular tachycardia or ventricular fibrillation. Crude mortality of patients was significantly increased when HDAVB was present (9% versus 1%, p < 0,001). When adjusted for other variables, HDAVB was not associated with increased mortality. Development of HDAVB in patients with UA was independently associated with an increase in the length of ICU stay (adjusted odds ratio 1.89: 95% confidence interval: 1.33-5.69). Conclusions. Patients with UA complicated with HDAVB represent a high-risk population with an increased ICU stay


Subject(s)
Male , Female , Middle Aged , Aged , Humans , Intensive Care Units , Heart Block/complications , Angina, Unstable/complications , Angina, Unstable/mortality , Retrospective Studies , Hospital Mortality , Length of Stay , Cohort Studies , Risk Factors , Severity of Illness Index
9.
Neuropathol Appl Neurobiol ; 32(2): 131-40, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16599942

ABSTRACT

JC virus (JCV), the agent of progressive multifocal leucoencephalopathy (PML), exerts an oncogenic effect in several laboratory animal models. Moreover, JCV genomic DNA and early viral protein T-antigen have been detected in various types of human central nervous system (CNS) neoplasms. To further explore this association we have studied paraffin-embedded brain biopsy tissue from 60 neoplasms (55 gliomas and five medulloblastomas) and 15 reactive gliosis cases for the presence of JCV DNA sequences and proteins. Four post mortem cases of HIV-associated PML were used as positive controls. Samples were assessed by polymerase chain reaction (PCR) amplification of early (large T antigen) and late (virion protein 3) sequences and immunohistochemistry (IHC) with both PAb 2024 and anti-SV40 large T antigen monoclonal antibodies. Five cases (three neoplasms and two reactive gliosis instances) showed low viral DNA levels when PCR-tested for VP3 or large T, while no case was immunoreactive for any of the two antibodies used. The four PML cases yielded positive results with both PCR and IHC. Additionally, IHC with both antibodies was applied to a tissue micro-array including 109 CNS tumours and 21 reactive gliosis samples. No immunoreactivity was detected in any of these tissue micro-array samples. The rarity of JCV DNA sequences and early proteins in our brain tumours enriches the controversy over the role of JCV in human neurooncogenesis, whose clarification is in need of further molecular and epidemiologic studies.


Subject(s)
Brain Neoplasms/virology , DNA, Viral/isolation & purification , Glioma/virology , JC Virus/genetics , Medulloblastoma/virology , Adult , Animals , Antigens, Viral, Tumor/isolation & purification , Cell Transformation, Neoplastic , Child , Female , Humans , Immunohistochemistry , Male , Middle Aged , Polymerase Chain Reaction
17.
Proc Natl Acad Sci U S A ; 96(2): 558-63, 1999 Jan 19.
Article in English | MEDLINE | ID: mdl-9892672

ABSTRACT

The Pax-6 gene encodes a transcription factor containing both a paired and a homeodomain and is highly conserved among Metazoa. In both vertebrates and invertebrates, Pax-6 is required for eye morphogenesis, development of parts of the central nervous system, and, in some phyla, for the development of olfactory sense organs. Ectopic expression of Pax-6 from insects, mammals, cephalopods, and ascidians induces ectopic eyes in Drosophila, suggesting that Pax-6 may be a universal master control gene for eye morphogenesis. Platyhelminthes are an ancient phylum, originating from the base of spiralian protostomes, that bear primitive eyes, consisting of a group of rhabdomeric photoreceptor cells enclosed in a cup of pigment cells. The analysis of Pax-6 and its expression pattern should provide insights into the ancestral function of Pax-6 in eye morphogenesis. We have identified the Pax-6 gene of the planarian Dugesia(G)tigrina (Platyhelminthes; Turbellaria; Tricladida). This gene shares significant sequence identity and conserved genomic organization with Pax-6 proteins from other phyla. Phylogenetic analysis indicates that it clusters with the other Pax-6 genes, but in the most basal position. DtPax-6 is expressed as a single transcript in both regenerating and fully grown eyes, and electron microscopy studies show strong expression in the perykarion of both photoreceptor and pigment cells. Very low levels of expression also are detectable in other body regions. Because a bona fide Pax-6 homolog so far has not been detected in diploblastic animals, we speculate that Pax-6 may be typical for triploblasts and that the appearance of additional Pax genes may have coincided with increasingly complex body plans.


Subject(s)
DNA-Binding Proteins/genetics , Gene Expression Regulation, Developmental/genetics , Homeodomain Proteins , Planarians/genetics , Regeneration/genetics , Amino Acid Sequence , Animals , Eye/growth & development , Eye Proteins , In Situ Hybridization , Molecular Sequence Data , PAX6 Transcription Factor , Paired Box Transcription Factors , Phylogeny , RNA, Messenger/genetics , Repressor Proteins , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Transcription Factors/genetics
18.
Mech Dev ; 76(1-2): 127-40, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9767147

ABSTRACT

POU domain proteins are a large family of transcription factors that have been identified in a variety of metazoans, from freshwater sponges, planarians and nematodes to arthropods, echinoderms and vertebrates. Many of these proteins are implicated in the development and establishment of the nervous system. In this paper we describe the identification of the planarian genes GtPOU-1, GtPOU-3 and GtPOU-4, which belong to the subclasses III and IV of POU-domain genes. Their similarity with other members of the POU family is restricted to the POU and homeo domains, plus some peptide sequences scattered in the linker and flanking regions. As with other subclass III POU genes, GtPOU-1 is devoid of introns. Axial transcript distribution by RT-PCR and immunohistochemical assays, performed with a polyclonal antibody raised against the GtPOU-1 fusion protein, indicate that both the GtPOU-1 transcript and protein are continuously expressed along the antero-posterior axis. A monoclonal antibody raised against the same fusion protein indicates that a GtPOU-1-specific epitope, probably obtained by post-translational modification, is present in neural cells from both the central and peripheral nerve systems of the adult planarian's anterior third. Moreover, the GtPOU-1-specific epitope shows a dynamic expression pattern during regeneration, always marking the most anterior region of the planarian nervous system. Both the rapid and general GtPOU-1-specific epitope modification, during posterior regeneration, indicate that regeneration is a global process involving all planarian regions, including those that are far from the wound, by a combination of morphallactic and epimorphic mechanisms.


Subject(s)
Helminth Proteins/genetics , Helminth Proteins/metabolism , Homeodomain Proteins/genetics , Planarians/genetics , Transcription Factors/genetics , Amino Acid Sequence , Animals , Antibodies, Monoclonal , Base Sequence , Helminth Proteins/immunology , Homeodomain Proteins/immunology , Homeodomain Proteins/metabolism , Molecular Sequence Data , Organ Specificity , Phylogeny , Planarians/physiology , Protein Processing, Post-Translational , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Recombinant Fusion Proteins/metabolism , Regeneration , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis , Sequence Homology, Amino Acid , Transcription Factors/immunology , Transcription Factors/metabolism , Transcription, Genetic
19.
Proc Natl Acad Sci U S A ; 95(19): 11312-7, 1998 Sep 15.
Article in English | MEDLINE | ID: mdl-9736733

ABSTRACT

Mice lacking desmin produce muscle fibers with Z disks and normal sarcomeric organization. However, the muscles are mechanically fragile and degenerate upon repeated contractions. We report here a human patient with severe generalized myopathy and aberrant intrasarcoplasmic accumulation of desmin intermediate filaments. Muscle tissue from this patient lacks the wild-type desmin allele and has a desmin gene mutation encoding a 7-aa deletion within the coiled-coil segment of the protein. We show that recombinant desmin harboring this deletion cannot form proper desmin intermediate filament networks in cultured cells, nor is it able to assemble into 10-nm filaments in vitro. These findings provide direct evidence that a mutation in desmin can cause human myopathies.


Subject(s)
Desmin/genetics , Muscle Proteins/genetics , Amino Acid Sequence , DNA Mutational Analysis , Female , Humans , Immunohistochemistry , Intermediate Filaments/metabolism , Male , Microscopy, Fluorescence , Molecular Sequence Data , Muscle Proteins/analysis , Muscles/pathology , Muscles/ultrastructure , Mutation/genetics , Pedigree , Protein Structure, Secondary , Recombinant Proteins/metabolism , Sequence Deletion/genetics
20.
Am J Pathol ; 153(1): 183-90, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9665479

ABSTRACT

The repertoire of distinct CD44 protein isoforms is generated by means of alternative pre-mRNA splicing of 10 variable exons located in the central region of the CD44 gene. We have used human breast ductal carcinoma as a model to identify two alternative splicing pathways of the CD44 pre-mRNA variable region that account for the generation of all of the CD44 isoforms described in breast tissue. An alternative splicing pathway that reflects inclusion of variable exons in a gradual 3'-to-5' fashion is evidenced in breast ductal carcinoma and its lymph node metastases. This pathway is compatible with a mechanism that generates the standard form of CD44 (devoid of variable exons) and is distinguishable from an alternative splicing pathway that involves exclusively variant exon 3 and is observable in both normal and carcinoma breast tissue. We show that both pathways are detectable in the same cell type in the breast and provide a speculative model by which these splicing routes could take place.


Subject(s)
Alternative Splicing , Breast Neoplasms/immunology , Breast/immunology , Hyaluronan Receptors/genetics , Hyaluronan Receptors/metabolism , Cloning, Molecular , Female , Glycoproteins/genetics , Glycoproteins/metabolism , Humans , Immunoenzyme Techniques , Polymerase Chain Reaction , Transcription, Genetic
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