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PURPOSE: The Government of India offers various schemes for various classes of citizens. Most of the application forms of schemes to be filled are in English and it is observed that monolingual individuals find it difficult to access and fill the forms. This paper addresses the challenges faced by monolingual individuals in India, particularly the elderly, people with impairments, and those from marginalized communities. The proposed work is to create an interactive system called "Dhvani" voicebot, specifically designed for the Kannada language. It helps users in identifying suitable government schemes and fills forms in English. MATERIALS AND METHODS: The proposed system is developed using the RASA chatbot framework and NLP techniques to comprehend user utterances. RNN and SVM algorithms are employed to ensure smooth conversation flow and interaction with the users. To enhance scheme suggestion accuracy, a knowledge graph is created, containing relevant data on government schemes. RESULTS: The intent classification model achieves an accuracy of 97%, indicating its ability to accurately understand user intentions. The integration of a knowledge graph improves the accuracy of scheme identification and suggestion to users. The system automates the process of filling out government scheme forms based on user inputs. CONCLUSION: Dhvani voicebot system presents a practical solution to address the challenges faced by monolingual individuals in accessing government schemes in India. The high accuracy of intent classification and the use of a knowledge graph contribute to the system's effectiveness. The study suggests that this system can be extended to other languages.
An automated tool called "Dhvani" will solve the problem of aged, illiterate and physically challenged persons filling forms in post offices and banks. Most of the schemes, pension funds, cash withdrawal, cash deposit is through these organizations. So. the tool makes the process easier for the above mention persons without the help of others.An intent recognition and interactive tool developed in Kannada Language which is widely spoken in Karnataka, India. The digital resources available in Kannada Language is very sparce.Use of technology like interactive tool, Knowledge graph, RNN and SVM are used in the development of the tool.Government scheme recommendation interactively makes the users to choose the scheme faster in an interactive way.The form is filled automatically and can be edited to rectify mistakes.
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OBJECTIVE: The quantitative measurement of handgrip strength is important in assessing and charting the progress of patients with neuromuscular diseases. The aim of this research was to determine the intra-rater and inter-rater reliability and the validity of the Squegg digital dynamometer. SUBJECTS AND METHODS: Twenty-one females and nine male participants with an age range between 18 and 40 years volunteered for the study. Three testers each took three measurements with a Squegg device and a Jamar dynamometer using standardized measurement techniques. Intra- and inter-tester reliability were calculated using the intra-class correlation coefficient (ICC). To investigate the relationship between hand measures and isometric handgrip strength, the Pearson correlation coefficient test was used. To determine the agreement between the two devices, a Bland Altman plot was constructed, and the concurrent validity of Squegg was calculated. RESULTS: The intra-rater reliability coefficients for both Jamar and Squegg were greater than 0.99 for all three testers, indicating excellent intra-rater reliability. The inter-rater reliability of Jamar (ICC=0.93) and Squegg (ICC=0.87) was excellent. With an ICC of 0.844 and an r-value of 0.720, Squegg with Jamar demonstrates good validity and statistical significance (p=0.001). CONCLUSIONS: The isometric handgrip strength and hand measures showed a moderate correlation in the study population. The Squegg isometric handgrip dynamometer has good concurrent validity and great intra- and inter-rater reliability in healthy individuals. The validity of Squegg in patients with neuromuscular diseases that affect hand function has to be investigated further.
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Fuerza de la Mano , Enfermedades Neuromusculares , Femenino , Humanos , Masculino , Adolescente , Adulto Joven , Adulto , Reproducibilidad de los Resultados , Dinamómetro de Fuerza Muscular , Estado de SaludRESUMEN
Background: Vestibular Disorders Activities of Daily Living Scale (VADL) is a self-reported survey for assessing functions of individuals affected by vestibular disorders, and this survey has been translated and cross-culturally adapted into many languages. Objective: : Kannada is one of the most-spoken languages in India, with approximately 64 million speakers. We aimed to develop the Kannada version of VADL and to assess its psychometric properties. Materials and Methods: The translation and adaptation of the English version of VADL into Kannada were accomplished with the input of medical professional language experts. Pretesting of the Kannada VADL (VADL-K) was conducted on 30 patients with vestibular disorders. Six professional experts with medical background provided their opinion during the content validation process of VADL-K, and 50 subjects aged between 30 and 70 years with variant vestibular disorders were administered VADL-K and the Dizziness Handicap Inventory to determine the internal consistency, test-retest reliability, and concurrent validity of this assessment. Results: This study effectively translated, adapted, and pretested VADL-K. The scale's content validity was 0.95, its internal consistency (Cronbach's alpha = α) was 0.94, its test-retest reliability with Intra Class- Correlation Coefficient was 0.97, and its concurrent validity in comparison with DHI was significant, with a moderate correlation r-value of 0.58. Conclusion: The English version of VADL was successfully translated and adapted into the Kannada language. VADL-K is a valid and reliable measure for patients with vestibular disorders in the state of Karnataka to report their functional performance.
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Lenguaje , Enfermedades Vestibulares , Actividades Cotidianas , Adulto , Anciano , Comparación Transcultural , Humanos , India , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Enfermedades Vestibulares/diagnósticoRESUMEN
Prediction of soil depth for larger areas provides primary information on soil depth and its spatial distribution that becomes vital for land resource management, crop, nutrient, and ecosystem modeling. The present study assessed the spatial distribution of soil depth over 160,205 km2 of Andhra Pradesh, India, using 20 covariables by quantile regression forest (QRF). An aggregate of 2854 soil datasets compiled from various physiographic units were randomly partitioned into 80:20 ratio for calibration (2283 samples) and validation (571 samples). Landsat imagery, terrain datasets (8), and bioclimatic factors (11) were utilized as covariates. The QRF model outputs signified that precipitation, multi-resolution index of valley bottom flatness (MrVBF), mean diurnal range, isothermality, and elevation were the most important variables influencing soil depth variability across the landscape. Spatial prediction of soil depth by QRF model yielded a ME of - 1.81 cm, RMSE of 34 cm, PICP of 90.2, and a R2 value of 42% as compared to ordinary kriging which results in a ME of - 0.14 cm, a RMSE of 37 cm, and a R2 value of 32%. As soil depth is spatially dynamic and has significant correlation with terrain and environmental covariates, better prediction was possible by the QRF model. However, high-density bioclimatic variables could be utilized along with high-resolution terrain variables to improve the predictive accuracy.
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Ecosistema , Suelo , Monitoreo del Ambiente , India , Análisis EspacialRESUMEN
BACKGROUND: Segmental Assessment of Trunk Control (SATCo) is a scientific evaluation measure used to assess trunk control in subjects with cerebral palsy (CP). AIMS: The present study aimed at assessing the psychometric properties of SATCo in children with spastic quadriplegic CP. METHODOLOGY: This was an observational study in which we validated a test instrument in 31 children (aged 1-5 years) with spastic quadriplegic CP. Children were assessed for trunk control by principal rater (R1) using SATCo. Each assessment was video recorded, scored retrospectively, and independently by principal rater (R2) and secondary rater (R3) for intra-rater and inter-rater reliability, respectively. Concurrent validity was assessed by comparing the SATCo scores with sitting component scores of Gross Motor Functional Measure -88. RESULTS: Intra-class correlation coefficient values for intra-rater and inter-rater reliability for various components of the scale ranged from 0.82 to 0.98. The concurrent validity was calculated for various components of the scale using the Pearson correlation coefficient and they ranged from 0.72 to 0.77. CONCLUSION/RECOMMENDATION: SATCo is a reliable and valid scale that can be used for examining trunk control in children with spastic quadriplegic CP aged 1-5 years.
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Parálisis Cerebral , Parálisis Cerebral/complicaciones , Niño , Humanos , Espasticidad Muscular/diagnóstico , Psicometría , Reproducibilidad de los Resultados , Estudios Retrospectivos , TorsoRESUMEN
BACKGROUND: The timed up-and-go test (TUGT) is a quick, reliable, and valid assessment tool for evaluating functional mobility or dynamic balance. AIMS: The purpose of this study was to establish the normative values for TUGT in children aged 4 to 11 years old in Surat, India. METHODS: A total of 420 children (210 boys and 210 girls) were included. Subjects were divided into seven age groups. In each age group, 60 (30 males and 30 females) subjects were included. Subjects were randomly recruited from primary schools and underwent three trials of the TUGT. Then, the mean of the three TUGT trials was calculated for each participant. RESULTS: We formulated normative reference values for each of the seven age groups. The mean and standard deviation of the TUGT score across the total population was 6.00 ± 1.15 seconds. TUGT scores were compared between age groups and genders. Between boys and girls, we found no significant differences. Among the age groups, however, we found significant differences, with a P value of less than 0.001. Thus, only age showed a moderate negative correlation with TUGT score. CONCLUSIONS: This study provides normative reference values for the TUGT among Indian children aged four to 11 years old. We found that no differences existed between the TUGT results according to genders. Conversely, age had a moderate negative correlation: a comparison of TUGT scores among the ages revealed significant differences between the age groups.
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Tamizaje Masivo , Niño , Preescolar , Estudios Transversales , Demografía , Femenino , Humanos , India , Masculino , Valores de ReferenciaRESUMEN
AIMS: To establish normative values for functional, lateral, and Oblique Direction Reach Tests (ODRT) and to assess the validity and reliability of the ODRT in Saudi children of age 6-15 years. METHODS: Three hundred Saudi children of age 6-15 years children were recruited by using snowball sampling. Children were measured for distance reached in forward, lateral, and oblique direction on a graph paper, which was mounted on a wall/cardboard. RESULTS: The Mean ± SD for forward, lateral and oblique direction reach was 25.63 ± 6.95, 18.91 ± 5.66, 22.08 ± 5.98 cm respectively. The Intraclass Correlation Coefficient values of intra and inter-rater reliability of ODRT shown to be 0.94 and 0.91, respectively. Concurrent validity of ODRT with forward and lateral reach test is 0.87 and 0.84, respectively. CONCLUSION: : We established the normal values for functional, lateral, and ODRT in 6-15 years of Saudi children. We found that ODRT is a valid and reliable for measuring limits of stability in oblique direction.
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Movimiento , Psicometría , Adolescente , Niño , Humanos , Valores de Referencia , Reproducibilidad de los Resultados , Arabia SauditaRESUMEN
AIMS: This study establishes the reliability and validity of pain pressure threshold (PPT) in evaluating pain for older adults with knee arthritis, and explores the importance of using a standard tool to measure pain in older adults. METHODS: The study consisted of a group of 31 older adult patients with bilateral symptomatic knee osteoarthritis, intra- and inter-rater reliability, and concurrent validity that were assessed for PPT and were compared with standard visual analogue scale (VAS). Physical therapy intervention was provided to combat the pain. RESULTS: The PPT showed excellent intra-assessor reliability by not only meeting acceptable standards but also representing very high values. The intra-assessor reliability between test sessions was excellent. The inter-assessor agreement was also very high before treatment. The highest ICC showed very good agreement (0.860) during the initial treatment for pain pressure measurement. The study also established concurrent validity of VAS and PPT (before treatment and after treatment), where the rho correlation was high (-0.708 and -0.625) and significant, indicating that PPT is adequately sensitive for detecting changes over time. CONCLUSION: PPT is a reliable and valid tool for measuring pain, and it helps clinicians understand the prognostic effect of the intervention, especially in older adults. The tool is consistent at measuring pain and is a valid tool compared to subjective pain scoring.
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Osteoartritis de la Rodilla , Dimensión del Dolor/métodos , Umbral del Dolor , Dolor , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Osteoartritis de la Rodilla/fisiopatología , Dimensión del Dolor/normas , Modalidades de Fisioterapia , Reproducibilidad de los Resultados , Arabia Saudita , Escala Visual AnalógicaRESUMEN
BACKGROUND: Prolapsed lumbar intervertebral disc is one of the most prevalent causes of low back pain and traction is one of the most common physical therapy treatments offered to affected patients. Advancements in traction equipment are needed to ensure their effectiveness in clinical situations. AIMS: The objective of the study was to find out the effect of patient-specific three-dimensional lumbar traction on pain and functional disability in individuals with lumbar intervertebral disc prolapse. SUBJECTS AND METHODS: Original article and Experimental design. Twenty-five participants (age range: 34-67 years) diagnosed with lumbar intervertebral disc prolapse were included in this study. Patient-specific three-dimensional lumbar traction was given as three sessions per week for the duration of one month. All participants completed a 10-cm visual analog pain scale and pain pressure threshold to assess pain and the Oswestry disability index to assess the functional disability. RESULTS: On pre to post interventions, a significant change in mean values were found for visual analog scale pain score, pain pressure threshold, and Oswestry disability index (P < 0.001). The pain intensity was reduced from 8.5 to 3.2, pain pressure threshold increased from 0.7 to 1.6 kg/cm2, and functional disability was reduced from 53.5% to 31.3%. CONCLUSION: Twelve sessions of patient-specific three-dimensional lumbar traction promoted a reduction in pain and improvement in functional disability among subjects with lumbar intervertebral disc prolapse.
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Degeneración del Disco Intervertebral/terapia , Desplazamiento del Disco Intervertebral/terapia , Dolor de la Región Lumbar/terapia , Tracción/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modalidades de Fisioterapia , Prolapso , Resultado del Tratamiento , Escala Visual AnalógicaRESUMEN
AIMS: The study aimed to assess the percentage difference of hand dimensions and their correlation with grip and pinch strength among school children in Saudi Arabia. MATERIALS AND METHODS: Anthropometric measurements, hand dimensions, grip, and pinch strength measurements were obtained from 200 healthy schoolchildren in both genders aged 6-16 years. A Jamar electronic handgrip dynamometer was used to measure handgrip strength in kg. Pinch dynamometer was used to measure the two-point pinch strength, three-point pinch strength and lateral pinch strength in kg. Hand circumference was measured following hand arch at the maximum palm level. Hand span from the tip of the thumb to the tip of the little finger with the hand opened as broad as possible. Hand length from the tip of the middle finger to the midline of the distal wrist crease. Palm length from the distal wrist crease to the base of the middle finger. RESULTS: The percentage of difference of hand dimensions between both the genders was statistically significant. Both handgrip and pinch strength were significantly correlated with anthropometric measurements and hand dimensions. Body mass index had mild correlation with both handgrip strength and pinch strength (P < 0.05). Age, hand circumference, hand span, hand length and palm length had moderate to strong correlation with both grip and pinch strength (P < 0.01). CONCLUSION: The current study provides a source of perspective reference values in clinical settings for hand dimensions. The present study showed significant correlations with handgrip and pinch grip strengths among schoolchildren in Saudi Arabia.
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Fuerza de la Mano/fisiología , Mano/anatomía & histología , Fuerza de Pellizco/fisiología , Adolescente , Factores de Edad , Antropometría , Estatura , Índice de Masa Corporal , Niño , Femenino , Dedos/fisiología , Humanos , Masculino , Valores de Referencia , Arabia SauditaRESUMEN
Primary intraosseous mucoepidermoid carcinoma (PIOC) is an infrequent malignancy of the head and neck that exhibits diverse biological behavior. The rareness of the location for a salivary gland tumor and the clinical and radiographic manifestations, suggestive of an odontogenic lesion often pose a diagnostic challenge. We hereby report such a unique case of central mucoepidermoid carcinoma that presented in an ambiguous manner, developing in the maxilla and intruding into the adjacent vital structures, adding a literature review.
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Carcinoma Mucoepidermoide/mortalidad , Carcinoma Mucoepidermoide/patología , Maxilar/diagnóstico por imagen , Neoplasias de las Glándulas Salivales/mortalidad , Neoplasias de las Glándulas Salivales/patología , Adulto , Biopsia , Humanos , Masculino , Tasa de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
The present paper describes the development of a reversed phase liquid chromatographic (RPLC) analytical method for duloxetine HCl in the presence of its impurities and degradation products generated from forced decomposition studies. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation of duloxetine HCl was observed under acid hydrolysis. The drug was found to be stable in other stress conditions studied. Successful separation of the drug from the synthetic impurities and degradation products formed under stress conditions was achieved on a Zorabax XDB C18, 50 mm x 4.6 mm, 5.0 micron column using a mixture of aqueous 0.1% trifluroacetic acid, methanol, tetrahydrofuran (60:20:20, v/v/v) as mobile phase. The HPLC method developed was validated with respect to linearity, accuracy, precisions, specificity and ruggedness. To our knowledge, a rapid stability indicating LC method for duloxetine HCl has not been published elsewhere.
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Nootrópicos/análisis , Tiofenos/análisis , Calibración , Cromatografía Líquida de Alta Presión , Clorhidrato de Duloxetina , Calor , Hidrólisis , Indicadores y Reactivos , Oxidación-Reducción , Fotólisis , Estándares de Referencia , Reproducibilidad de los Resultados , SolucionesRESUMEN
BACKGROUND: Regulation of actin structures is instrumental in maintaining proper cytoarchitecture in many tissues. In the follicular epithelium of Drosophila ovaries, a system of actin filaments is coordinated across the basal surface of cells encircling the oocyte. These filaments have been postulated to regulate oocyte elongation; however, the molecular components that control this cytoskeletal array are not yet understood. RESULTS: We find that the receptor tyrosine phosphatase (RPTP) Dlar and integrins are involved in organizing basal actin filaments in follicle cells. Mutations in Dlar and the common beta-integrin subunit mys cause a failure in oocyte elongation, which is correlated with a loss of proper actin filament organization. Immunolocalization shows that early in oogenesis Dlar is polarized to membranes where filaments terminate but becomes generally distributed late in development, at which time beta-integrin and Enabled specifically associate with actin filament terminals. Rescue experiments point to the early period of polar Dlar localization as critical for its function. Furthermore, clonal analysis shows that loss of Dlar or mys influences actin filament polarity in wild-type cells that surround mutant tissues, suggesting that communication between neighboring cells regulates cytoskeletal organization. Finally, we find that two integrin alpha subunits encoded by mew and if are required for proper oocyte elongation, implying that multiple components of the ECM are instructive in coordinating actin fiber polarity. CONCLUSIONS: Dlar cooperates with integrins to coordinate actin filaments at the basal surface of the follicular epithelium. To our knowledge, this is the first direct demonstration of an RPTP's influence on the actin cytoskeleton.
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Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Integrinas/metabolismo , Folículo Ovárico/metabolismo , Proteínas Tirosina Fosfatasas/metabolismo , Animales , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila , Epitelio/metabolismo , Femenino , Integrinas/genética , Mutagénesis , Oocitos/citología , Oocitos/crecimiento & desarrollo , Proteínas Tirosina Fosfatasas/genética , Proteínas Tirosina Fosfatasas/fisiología , Proteínas Tirosina Fosfatasas Similares a ReceptoresRESUMEN
Sustained high output release of Nitric oxide (NO) as result of activation of inducible nitric oxide synthase (iNOS), and increased production of the antiproliferative/profibrotic cytokine transforming growth factor-beta1 (TGF-beta1) are well documented in glomerulonephritis. Modulation of iNOS activity and of TGF-beta1 production can therefore be viewed as anti-inflammatory strategies. The present study employed all-trans retinoic acid (atRA) which is known to have anti-inflammatory effects and to modulate expression of iNOS and TGF-beta1, in order to explore its effect on iNOS enzyme activity and TGF-beta1 production in anti-GBM antibody induced glomerulonephritis. Glomerulonephritis was induced in Lewis rats by injection of anti-GBM antibody. A group of nephritic rats were given daily administration of atRA for 14-16 days. Extent of proteinuria was assessed by measuring urine protein and creatinine excretion. iNOS enzyme activity was measured by calculating conversion of L[14C]arginine to L-[14C]citrulline in glomerular protein lysates. Levels of TGF-beta1 in glomerular protein lysates were measured by quantitative ELISA. Levels of proliferating nuclear antigen (PCNA), TGF-beta receptor II (TGFbeta-RII), and fibronectin were assessed by Western blot analysis. Glomerular iNOS activity in atRA treated nephritic animals was attenuated in comparison to that in nephritic controls that were not. Glomerular expression of PCNA was also reduced. Levels of TGF-beta1 were increased in glomeruli of atRA treated nephritic animals. In these animals, there was no change in glomerular levels of TGF-beta receptor II (TGFbeta-RII) or fibronectin. and there was no reduction in urine protein excretion. These results suggest that atRA attenuates iNOS activity and proliferation in glomeruli of nephritic animals. The failure of atRA treatment to reduce proteinuria could be due to the increase in TGF-beta1 levels and to inhibition of iNOS-driven NO production.
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Glomerulonefritis/tratamiento farmacológico , Óxido Nítrico Sintasa/efectos de los fármacos , Factor de Crecimiento Transformador beta/efectos de los fármacos , Tretinoina/farmacología , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Anticuerpos , Autoanticuerpos , División Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Glomerulonefritis/metabolismo , Glomerulonefritis/patología , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II , Antígeno Nuclear de Célula en Proliferación/efectos de los fármacos , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteinuria/inducido químicamente , Ratas , Ratas Endogámicas Lew , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Crecimiento Transformador beta1 , Tretinoina/administración & dosificaciónRESUMEN
Four different forms of a non-receptor type protein-tyrosine phosphatase are generated by alternative splicing; two of these forms (PTP-S2 and PTP-S4) are major forms, which are expressed in rat as well as human cells. Here we report that PTP-S2 binds to nonspecific DNA in vitro and localizes in the nucleus upon transfection in HeLa cells. PTP-S4 does not bind to nonspecific DNA and shows perinuclear and cytoplasmic localization. Removal of the C-terminal 34 amino acids of PTP-S4 gives rise to a truncated protein, which binds to nonspecific DNA and localizes to the nucleus. PTP-S4, but not PTP-S2, interacts strongly with the isolated nuclear matrix. The two forms of this tyrosine phosphatase show different substrate specificity in vitro, a feature novel to splice variants of tyrosine phosphatases. Mitogenic stimulation induces mRNAs for PTP-S2 as well as for PTP-S4 in the G1 phase during liver regeneration. These results suggest that alternative splicing gives rise to two protein-tyrosine phosphatases with distinct substrate specificities and subcellular locations. The 34 amino acids at the C terminus of PTP-S4 play a critical role in determining substrate specificity, subcellular location, and interaction with nuclear matrix and DNA.
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Empalme Alternativo , Proteínas de Unión al ADN/metabolismo , Isoenzimas/metabolismo , Proteínas Tirosina Fosfatasas/metabolismo , Fracciones Subcelulares/metabolismo , Animales , Proteínas de Unión al ADN/genética , Humanos , Isoenzimas/genética , Mitógenos/farmacología , Matriz Nuclear/metabolismo , Proteínas Tirosina Fosfatasas/genética , Ratas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidad por Sustrato , TransfecciónRESUMEN
PTP-S is a widely expressed non-transmembrane protein tyrosine phosphatase (PTPase), which binds to DNA in vitro. The cellular PTP-S gene product is present mainly in the nucleus in association with chromatin. cDNAs related to PTP-S have been described from human and mouse cells. To establish the origin of molecular diversity in these cDNAs, genomic clones of rat PTP-S were isolated that span over 40 kb of the gene and contain 7 axons. The exon-intron splice sites in the catalytic domain are conserved between PTP-S and human PTP1B. Sequences specific to and homologous to human T-cell PTPase (TC-PTP) were found in the genomic clones of PTP-S, which are expressed in rat cells, as determined by using a specific probe and Northern blot analysis. Analysis of RNA from different rat tissues by reverse transcription-polymerase chain reaction (RT-PCR) showed the presence of four different forms of PTP-S mRNA (named PTP-S1, PTP-S2, PTP-S3, and PTP-S4). PTP-S1 is same as PTP-S reported previously by us. PTP-S2, which is the major form, differs from PTP-S1 in having additional 19 amino acids corresponding to exon E1. PTP-S4 is similar to human T-cell phosphatase. PTP-S3 differs from PTP-S4 in having a deletion of 19 amino acids corresponding to exon E1. Our results suggest that four different forms of PTP-S mRNA arise from a single gene by differential splicing. Two of these forms, PTP-S1 and PTP-S3, were not found in human cells, possibly due to the loss of an internal splice acceptor site in one of the exons, suggesting the occurrence of species-specific splicing in this gene.
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Empalme Alternativo , Proteínas Tirosina Fosfatasas/genética , ARN Mensajero/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Membrana Celular/enzimología , Clonación Molecular , Cartilla de ADN , ADN Complementario , Células HeLa , Humanos , Ratones , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Especificidad de la EspecieRESUMEN
BACKGROUND: Prompted by the results of CAST results, attention has shifted from class I agents that primarily block sodium channels to class III agents that primarily block potassium channels for pharmacological management of certain cardiac arrhythmias. Recent studies demonstrated that sodium channel blockade, while antiarrhythmic at the cellular level, was inherently proarrhythmic in the setting of a propagating wave front as a result of prolongation of the vulnerable period during which premature stimulation can initiate reentrant activation. From a theoretical perspective, sodium (depolarizing) and potassium (repolarizing) currents are complementary so that if antiarrhythmic and proarrhythmic properties are coupled to modulation of sodium currents, then antiarrhythmic and proarrhythmic properties might similarly be coupled to modulation of potassium currents. The purpose of the present study was to explore the role of repolarization currents during reentrant excitation. METHODS AND RESULTS: To assess the generic role of repolarizing currents during reentry, we studied the responses of a two-dimensional array of identical excitable cells based on the FitzHugh-Nagumo model, consisting of a single excitation (sodium-like) current and a single recovery (potassium-like) current. Spiral wave reentry was initiated by use of S1S2 stimulation, with the delay timed to occur within the vulnerable period (VP). While holding the sodium conductance constant, the potassium conductance (gK) was reduced from 1.13 to 0.70 (arbitrary units), producing a prolongation of the action potential duration (APD). When gK was 1.13, the tip of the spiral wave rotated around a small, stationary, unexcited region and the computed ECG was monomorphic. As gK was reduced, the APD was prolonged and the unexcited region became mobile (nonstationary), such that the tip of the spiral wave inscribed an outline similar to a multipetaled flower; concomitantly, the computed ECG became progressively more polymorphic. The degree of polymorphism was related to the APD and the configuration of the nonstationary spiral core. CONCLUSIONS: Torsadelike (polymorphic) ECGs can be derived from spiral wave reentry in a medium of identical cells. Under normal conditions, the spiral core around which a reentrant wave front rotates is stationary. As the balance of repolarizing currents becomes less outward (eg, secondary to potassium channel blockade), the APD is prolonged. When the wavelength (APD.velocity) exceeds the perimeter of the stationary unexcited core, the core will become unstable, causing spiral core drift. Large repolarizing currents shorten the APD and result in a monomorphic reentrant process (stationary core), whereas smaller currents prolong the APD and amplify spiral core instability, resulting in a polymorphic process. We conclude that, similar to sodium channel blockade, the proarrhythmic potential of potassium channel blockade in the setting of propagation may be directly linked to its cellular antiarrhythmic potential, ie, arrhythmia suppression resulting from a prolonged APD may, on initiation of a reentrant wave front, destabilize the core of a rotating spiral, resulting in complex motion (precession) of the spiral tip around a nonstationary region of unexcited cells. In tissue with inhomogeneities, core instability alters the activation sequence from one reentry cycle to the next and can lead to spiral wave fractination as the wave front collides with inhomogeneous regions. Depending on the nature of the inhomogeneities, wave front fragments may annihilate one another, producing a nonsustained arrhythmia, or may spawn new spirals (multiple wavelets), producing fibrillation and sudden cardiac death.