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Introducción El método Kabat sostiene que el sincronismo normal se produce de distal a proximal, lo cual requiere evidencia electromiográfica. Objetivo Describir el sincronismo muscular de patrones motores de miembros superiores descritos por Kabat, en posiciones sedente y supina, a partir de la medición de la latencia al inicio del pico de la máxima activación electromiográfica (IPMA-EMG) de músculos seleccionados. Material y métodos Se realizó un estudio analítico comparativo. Se evaluó a 20 hombres y 20 mujeres entre 19 y 26 años. Cada participante realizó 3repeticiones activas sin resistencia externa de cada uno de los patrones de movimiento (flexor y extensor) de las 2diagonales. Se registró la latencia del IPMA-EMG para cada uno de los 8músculos evaluados en los 4patrones de movimiento, tanto en supino como en sedente. Estos se promediaron y se ordenaron de menor a mayor para obtener la secuencia de contracciones musculares en cada patrón de movimiento. Se compararon las secuencias obtenidas para cada patrón en sedente y supino y se valoró la existencia de correlaciones entre ellas. Resultados Se observó correlación significativa en las secuencias del IPMA-EMG entre posiciones supina y sedente, en todos los patrones de movimiento (p<0,05), excepto en el patrón extensor de la primera diagonal (p=0,139). No hubo diferencias estadísticamente significativas entre posiciones en ninguno de los patrones (p>0,05). Conclusiones Aunque con variaciones en la IPMA-EMG, se halló, en general, un sincronismo muscular de proximal a distal, más evidenciado en la posición sedente y en los patrones flexores (AU)
Introduction The Kabat method argues that normal synchronism occurs from distal to proximal, which requires electromyographic evidence. Objective To describe the muscular timing of motor patterns of the upper limbs described by Kabat, in seated and supine positions, from the measurement of the latency at the beginning of the peak of the maximum electromyographic activation (BPM-EMG-A) of selected muscles. Material and methods A comparative analytical study was carried out. Twenty men and 20 women between 19 and 26 years old were evaluated. Each participant performed 3active repetitions without external resistance of each of the movement patterns (flexor and extensor) of the 2diagonals. BPM-EMG-A latency was recorded for each of the 8muscles tested in the 4movement patterns, both supine and seated. These were averaged and ordered from lowest to highest to obtain the sequence of muscle contractions in each movement pattern. The sequences obtained for each pattern in seated and supine were compared and the existence of correlations between them was assessed. Results Significant correlation was observed in the BPM-EMG-A sequences between supine and seated positions, in all movement patterns (P<0.05), except in the extensor pattern of the first diagonal (P=0.139). There were no statistically significant differences between positions in any of the patterns (P>0.05). Conclusion Although with variations in BPM-EMG-A, muscle timing was generally found from proximal to distal, more evident in the sitting position and in flexor patterns (AU)
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Humanos , Masculino , Femenino , Adulto Joven , Adulto , Técnicas de Ejercicio con Movimientos/métodos , Contracción Muscular/fisiología , Propiocepción/fisiología , Brazo/fisiología , ElectromiografíaRESUMEN
BACKGROUND: Preclinical Alzheimer's disease (AD) provides an opportunity for the study and implementation of interventions and strategies aimed at delaying, mitigating, and preventing AD. While this preclinical state is an ideal target, it is difficult to identify efficiently and cost-effectively. Recent findings have suggested that cognitive-motor dual task paradigms may provide additional inference. OBJECTIVES: Investigate the relationship between dual task performance and amyloidosis, suggestive of preclinical Alzheimer's disease and whether dual task performance provides additional information beyond a cognitive composite, to help in the identification of amyloidosis. DESIGN: Cross-sectional. SETTING: Outpatient specialty brain health clinical research institution in the United States. PARTICIPANTS: 52 cognitively healthy adults. MEASUREMENTS: The data included demographics, amyloid standardized uptake value ratio obtained via florbetapir-PET, neuropsychological testing, apolipoprotien E genotype, and dual task performance measures. Data were analyzed via hierarchal multiple linear regression or logistic regression, controlling for age, education, and apolipoprotien E genotype. Receiver operating characteristic curves were plotted, and sensitivity and specificity calculated via 2x2 contingency tables. RESULTS: There was a moderate relationship (rs>.30) between motor and cognitive dual task effects and amyloid standardized uptake value ratio (ps<.042). A strong relationship (r=.58) was found between combined dual task effect, a measure of automaticity derived from dual task performance, and amyloid standardized uptake value ratio (p<.001). Additionally, combined dual task effect showed promise in its unique contributions to amyloid standardized uptake value ratio, accounting for 7.8% of amyloid standardized uptake value ratio variance beyond cognitive composite scores (p=.018). Additionally, when incorporated into the cognitive composite, combined dual task effect resulted in improved diagnostic accuracy for determining elevated amyloid standardized uptake value ratio, and increased the sensitivity and specificity of the cognitive composite. CONCLUSSION: Dual task performance using the combined dual task effect, a measure of automaticity, was a moderate predictor of cerebral amyloidosis, which suggests that it has utility in the screening and diagnosis of individuals for preclinical AD. Additionally, when combined with the cognitive composite, the combined dual task effect improves diagnostic accuracy. Further research is warranted.
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Enfermedad de Alzheimer , Amiloidosis , Adulto , Enfermedad de Alzheimer/diagnóstico por imagen , Amiloide , Péptidos beta-Amiloides , Amiloidosis/diagnóstico por imagen , Estudios Transversales , Humanos , Tomografía de Emisión de Positrones , Análisis y Desempeño de TareasRESUMEN
Background: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. Patients and methods: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24 h with poly-ICLC (Hiltonol), TNF-α and IFN-α. On days +8 and +10 of each cycle, patients received intratumoral image-guided 0.25 mg injections of the dsRNA-analogue Hiltonol. Cyclophosphamide 600 mg/m2 was administered 1 week before. Six patients received stereotactic ablative radiotherapy (SABR) on selected tumor lesions, including those injected with Hiltonol. Expression of 25 immune-relevant genes was sequentially monitored by RT-PCR on circulating peripheral blood mononuclear cell (PBMCs) and serum concentrations of a cytokine panel were sequentially determined before and during treatment. Pre- and post-treatment PBMC from patients achieving durable stable disease (SD) were studied by IFNγ ELISPOT-assays responding to tumor-lysate loaded DC and by TCRß sequencing. Results: Combined treatment was, safe and well tolerated. One heavily pretreated castration-resistant prostate cancer patient experienced a remarkable mixed abscopal response to SABR+ immunotherapy. No objective responses were observed, while nine patients presented SD (five of them in the six-patient radiotherapy cohort). Intratumoral Hiltonol increased IFN-ß and IFN-α mRNA in circulating PBMC. DC vaccination increased serum IL-12 and IL-1ß concentrations, especially in patients presenting SD. IFNγ-ELISPOT reactivity to tumor lysates was observed in two patients experiencing durable SD. Conclusions: This radio-immunotherapy combination strategy, aimed at resembling viral infection in tumor tissue in combination with a dendritic-cell vaccine and SABR, is safe and shows immune-associated activity and signs of preliminary clinical efficacy.
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Vacunas contra el Cáncer/administración & dosificación , Inmunoterapia/métodos , Neoplasias/terapia , Radiocirugia/métodos , Adulto , Anciano , Antígenos de Neoplasias/administración & dosificación , Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Carboximetilcelulosa de Sodio/administración & dosificación , Carboximetilcelulosa de Sodio/análogos & derivados , Terapia Combinada/métodos , Ciclofosfamida/administración & dosificación , Citocinas/inmunología , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/trasplante , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Inyecciones Intralesiones , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Poli I-C/administración & dosificación , Polilisina/administración & dosificación , Polilisina/análogos & derivados , Criterios de Evaluación de Respuesta en Tumores SólidosRESUMEN
Temephos is an organophosphorus pesticide that is used in control campaigns against Aedes aegypti mosquitoes, which transmit dengue. In spite of the widespread use of temephos, few studies have examined its genotoxic potential. The aim of this study was to evaluate the cytotoxic, cytostatic and genotoxic effects of temephos in human lymphocytes and hepatoma cells (HepG2). The cytotoxicity was evaluated with simultaneous staining (FDA/EtBr). The cytostatic and genotoxic effects were evaluated using comet assays and the micronucleus technique. We found that temephos was not cytotoxic in either lymphocytes or HepG2 cells. Regarding the cytostatic effect in human lymphocytes, temephos (10 µM) caused a significant decrease in the percentage of binucleated cells and in the nuclear division index as well as an increase in the apoptotic cell frequency, which was not the case for HepG2 cells. The comet assay showed that temephos increased the DNA damage levels in human lymphocytes, but it did not increase the MN frequency. In contrast, in HepG2 cells, temephos increased the tail length, tail moment and MN frequency in HepG2 cells compared to control cells. In conclusion, temephos causes stable DNA damage in HepG2 cells but not in human lymphocytes. These findings suggest the importance of temephos biotransformation in its genotoxic effect.
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Linfocitos/efectos de los fármacos , Mutágenos/toxicidad , Temefós/toxicidad , Adolescente , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ensayo Cometa , Citocinesis/efectos de los fármacos , Células Hep G2 , Humanos , Insecticidas/toxicidad , Masculino , Pruebas de Micronúcleos , Adulto JovenRESUMEN
A mouse model was established to reproduce the haemorrhagic syndrome which occurs in humans after accidental contact with the hairs of the caterpillar Lonomia achelous (LA) and measures the haemostatic and inflammatory alterations that occur as a result of this contact. Mice were injected intradermally with different doses (0.4, 0.8 and 1.6 mg/animal) of L. achelous haemolymph (LAH). Haematological (haemoglobin, haematocrit, platelet count, differential leukocyte count), haemostatic (fibrinogen, plasminogen, factor XIII [FXIII], fibrinolytic activity) and inflammatory parameters (tumour necrosis factor alpha [TNF-α], nitric oxide [NO]) were measured at different times up to 48 h. C57BL/6 mice responded to LAH injection, in terms of these parameters, in a manner similar to that seen in humans, whereas the BALB/c mice were unresponsive. In C57BL/6 mice injected with LAH, time course measurements showed: a) a reduction in the haemoglobin, haematocrit, fibrinogen, FXIII and plasminogen levels, b) no effect on the platelet count and c) immediate leukocytosis and an increase in the fibrinolytic activity in plasma. An inflammatory response (TNF-α) was observed within 1 h post-injection, followed by a more persistent increase in serum NO. These findings suggest that C57BL/6 mice represent a useful model of the haemorrhagic syndrome observed in humans who have suffered contact with the caterpillar, permitting a deeper understanding of the role of the inflammatory response in the haematological and haemostatic manifestations of this syndrome.
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Venenos de Artrópodos/toxicidad , Hemolinfa , Hemostasis/efectos de los fármacos , Inflamación/etiología , Mariposas Nocturnas , Animales , Fibrinógeno/análisis , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Modelos Animales , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Little is known concerning the seroprevalence of Toxoplasma gondii infection in chickens (Gallus domesticus) in Mexico. Antibodies to T. gondii were determined in 519 chickens in Durango, Mexico using the modified agglutination test (MAT). Two groups (A, B) of chickens were sampled. Group A chickens (n â=â 51) were raised in backyards in 7 municipalities in 3 geographical regions in Durango State. Group B chickens were raised in farms in the Mexican States of Sinaloa (n â=â 289) and Nayarit (n â=â 179) but slaughtered in 2 abattoirs in Durango City. Overall, antibodies to T. gondii were found in 36 (6.9%) of 519 chickens, with MAT titers of 1â¶25 in 22, 1â¶50 in 8, 1â¶100 in 2, 1â¶200 in 3, and 1â¶400 in 1. Seroprevalence of T. gondii increased significantly with age and was significantly higher in Group A chickens than in Group B chickens. In Group A chickens, a 25.5% seroprevalence of T. gondii infection was found. Seropositive chickens were found in all 7 municipalities sampled. In Group B chickens, the seroprevalence of T. gondii infection was 4.9%. This is the first report of T. gondii infection in chickens in Durango State, Mexico.
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Anticuerpos Antiprotozoarios/sangre , Pollos/parasitología , Enfermedades de las Aves de Corral/epidemiología , Toxoplasma/inmunología , Toxoplasmosis Animal/epidemiología , Mataderos , Animales , Femenino , Masculino , México/epidemiología , Enfermedades de las Aves de Corral/parasitología , Estudios SeroepidemiológicosRESUMEN
Little is known concerning the prevalence of Toxoplasma gondii infection in pigs in Mexico. Accordingly, antibodies to T. gondii were determined in 1,074 domestic pigs in Durango, Mexico using the modified agglutination test. Two groups (A, B) of pigs were sampled: Group A pigs (n â=â 555) were raised in 3 geographical regions in Durango State and Group B pigs (n â=â 519) were from Sonora State but slaughtered in Durango City. Overall, antibodies to T. gondii were found in 136 (12.7%) of 1,074 pigs with titers of 1â¶25 in 29, 1â¶50 in 23, 1â¶100 in 18, 1â¶200 in 22, 1â¶400 in 12, 1â¶800 in 8, 1â¶1,600 in 2, and 1â¶3,200 or higher in 22. Of the pigs raised in Durango State, seroprevalence varied with age, management, and the geographic region; pigs raised in backyards in the mountainous region had a significantly higher seroprevalence (32.1%) than those raised in the valley (13.0%) and the semi-desert regions (14.0%). In Group A pigs from Durango, seroprevalence of T. gondii infection was significantly higher in pigs older than 8 mo (19.5%) than in younger pigs (10.9%). In the whole pig population (Groups A and B together), seroprevalence was higher in pigs raised in Durango (16.0%) than in those raised in Sonora (9.1%) and higher in mixed-breed pigs (15.7%) than in pure-bred pigs (10.3%). This is the first, in-depth study on the seroprevalence of T. gondii infection of pigs in Mexico and the first report on pigs from Durango State, Mexico. Results indicate that infected pork is likely an important source of T. gondii infection for humans in Durango State.
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Anticuerpos Antiprotozoarios/sangre , Enfermedades de los Porcinos/epidemiología , Toxoplasma/inmunología , Toxoplasmosis Animal/epidemiología , Mataderos , Pruebas de Aglutinación/veterinaria , Animales , Animales Domésticos , Femenino , Masculino , México/epidemiología , Estudios Seroepidemiológicos , Porcinos , Enfermedades de los Porcinos/parasitologíaRESUMEN
BACKGROUND: The Vietnam Head Injury Study (VHIS) is a prospective, longitudinal follow-up of 1,221 Vietnam War veterans with mostly penetrating head injuries (PHIs). The high prevalence (45%-53%) of posttraumatic epilepsy (PTE) in this unique cohort makes it valuable for study. METHODS: A standardized multidisciplinary neurologic, cognitive, behavioral, and brain imaging evaluation was conducted on 199 VHIS veterans plus uninjured controls, some 30 to 35 years after injury, as part of phase 3 of this study. RESULTS: The prevalence of seizures (87 patients, 43.7%) was similar to that found during phase 2 evaluations 20 years earlier, but 11 of 87 (12.6%) reported very late onset of PTE after phase 2 (more than 14 years after injury). Those patients were not different from patients with earlier-onset PTE in any of the measures studied. Within the phase 3 cohort, the most common seizure type last experienced was complex partial seizures (31.0%), with increasing frequency after injury. Of subjects with PTE, 88% were receiving anticonvulsants. Left parietal lobe lesions and retained ferric metal fragments were associated with PTE in a logistic regression model. Total brain volume loss predicted seizure frequency. CONCLUSIONS: Patients with PHI carry a high risk of PTE decades after their injury, and so require long-term medical follow-up. Lesion location, lesion size, and lesion type were predictors of PTE.
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Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/epidemiología , Epilepsia Postraumática/epidemiología , Epilepsia Postraumática/etiología , Guerra de Vietnam , Apolipoproteína E4/genética , Lesiones Encefálicas/genética , Lesiones Encefálicas/patología , Catecol O-Metiltransferasa/genética , Trastornos del Conocimiento/etiología , Epilepsia Postraumática/genética , Estudio de Asociación del Genoma Completo , Glutamato Descarboxilasa/genética , Hospitales Militares , Humanos , Inteligencia/fisiología , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Examen Neurológico/métodos , Pruebas Neuropsicológicas , Receptores de N-Metil-D-Aspartato/genética , Factores de Tiempo , Tomografía Computarizada por Rayos X/métodosRESUMEN
The divergence and antigenic shifts in influenza viruses represent significant challenges for the development of effective vaccines and antiviral drugs against influenza viruses. In view of current challenges and/or deficiencies in the influenza pandemic influenza preparedness, novel antiviral strategies which are robust and can respond to constant viral mutations, are particularly needed to combat future pandemic threats. Toll-like receptor-3 (TLR-3) is an integral part of the host's innate immune system and serves as an important signaling pathway for the recognition of dsRNA for the triggering of antiviral and inflammatory responses to combat viral infections. This review examines dsRNA including Poly ICLC and liposome-encapsulated Poly ICLC (LE Poly ICLC) as TLR-3 agonists for their antiviral activity against seasonal and highly pathogenic avian influenza (HPAI) viruses. Furthermore, their roles in attenuating the antiviral and inflammatory cytokines in the host will also be explored. Preclinical studies in experimental animals suggest Poly ICLC and liposome-encapsulated Poly ICLC are safe and offer broad-spectrum protection against both seasonal and HPAI viruses, as well as other respiratory viruses including respiratory syncytial virus and SARS. Preliminary results from recent studies suggest these drugs up-regulate the production of interferons (-alpha, -beta, and -gamma), and tumor necrosis factor (TNF-alpha) but downregulate some proinflammatory cytokines including IL-2 and IL-4. Taken together, these results suggest these TLR-3 agonists have a promising role to play as safe, effective and broad-spectrum anti-influenza drugs that could complement other antiviral drugs to combat seasonal, zoonotic and pandemic influenza viruses. The clinical safety of these drugs and their efficacy in pre-clinical studies may provide sufficient justification for regulatory agencies to consider their fast track development for use in future outbreaks of pandemic influenza or of other emerging respiratory pathogens.
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Antivirales/farmacología , Antivirales/uso terapéutico , Gripe Humana/tratamiento farmacológico , Orthomyxoviridae/efectos de los fármacos , Receptor Toll-Like 3/agonistas , Animales , Citocinas/fisiología , Humanos , Subtipo H5N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/fisiopatología , Receptor Toll-Like 3/fisiologíaRESUMEN
This study aims to evaluate the antiviral role of nucleic acid-based agonists for the activation of toll-like receptor (TLR) signaling pathways, and its protective role in respiratory influenza A virus infections. TLR-3 is expressed on myeloid dendritic cells, respiratory epithelium, and macrophages, and appears to play a central role in mediating both the antiviral and inflammatory responses of the innate immunity in combating viral infections. Influenza viruses can effectively inhibit the host's ability to produce interferons, and thereby suppress the immune system's antiviral defence mechanisms. Poly ICLC is a synthetic double stranded RNA comprising of polyriboinosinic-poly ribocytidylic acid (Poly IC) stabilized with l-lysine (L) and carboxymethylcellulose (C). Poly ICLC and liposome-encapsulated Poly ICLC (LE Poly ICLC) are TLR-3 agonists and are potent inducer of interferons and natural killer cells. Intranasal pre-treatment of mice with Poly ICLC and LE Poly ICLC provided high level of protection against lethal challenge with a highly lethal avian H5N1 influenza (HPAI) strain (A/H5N1/chicken/Henan clade 2), and against lethal seasonal influenza A/PR/8/34 [H1N1] and A/Aichi/2 [H3N2] virus strains. The duration of protective antiviral immunity to multiple lethal doses of influenza virus A/PR/8/34 virus had been previously found to persist for up to 3 weeks in mice for LE Poly ICLC and 2 weeks for Poly ICLC. Similarly, pre-treatment of mice with CpG oligonucleotides (TLR-9 agonist) was also found to provide complete protection against influenza A/PR/8/34 infection in mice. RT-PCR analysis of lung tissues of mice treated with Poly ICLC and LE Poly ICLC revealed upregulation of TLR-3 mRNAs gene expression. Taken together, these results do support the potential role of TLR-3 and TLR-9 agonists such as Poly ICLC and LE Poly ICLC in protection against lethal seasonal and HPAI virus infection.
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Antivirales/farmacología , Carboximetilcelulosa de Sodio/análogos & derivados , Infecciones por Orthomyxoviridae/prevención & control , Poli I-C/farmacología , Polilisina/análogos & derivados , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 3/fisiología , Animales , Carboximetilcelulosa de Sodio/administración & dosificación , Carboximetilcelulosa de Sodio/farmacología , Femenino , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H5N1 del Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A , Liposomas , Ratones , Ratones Endogámicos BALB C , Oligodesoxirribonucleótidos/farmacología , Poli I-C/administración & dosificación , Polilisina/administración & dosificación , Polilisina/farmacología , ARN Mensajero/análisis , Receptor Toll-Like 3/genéticaRESUMEN
Influenza viruses are etiological agents of deadly flu that continue to pose global health threats, and have caused global pandemics that killed millions of people worldwide. The availability of neuraminidase inhibitors and attenuated vaccines improves our ability to defend against influenza, but their benefits can be significantly limited by drug-resistance and virus mutations. Nucleic acid-based drugs may represent a promising class of antiviral agents that could play a role in the prevention and treatment of influenza. Efficacy studies in animals have shown that ds RNA, such as poly ICLC can provide effective and broad-spectrum prophylaxis against lethal challenges against various strains of influenza A virus. Furthermore, similar level of antiviral protection in mice can be provided by using short fragments of oligonucleotides that induce antiviral immunity. Finally, influenza virus expression can also be specifically inhibited or suppressed using antisense oligonucleotides that bind to viral mRNA encoding key viral proteins. The versatility and potency of nucleic acid-based drugs make them potential drug candidates for used in seasonal or pandemic influenza situations.
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Antivirales/uso terapéutico , Carboximetilcelulosa de Sodio/análogos & derivados , Virus de la Influenza A/efectos de los fármacos , Gripe Humana/prevención & control , Poli I-C/uso terapéutico , Polilisina/análogos & derivados , Animales , Aves , Carboximetilcelulosa de Sodio/administración & dosificación , Carboximetilcelulosa de Sodio/uso terapéutico , Humanos , Gripe Aviar/tratamiento farmacológico , Gripe Aviar/prevención & control , Gripe Humana/complicaciones , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Liposomas , Ratones , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/uso terapéutico , Poli I-C/administración & dosificación , Polilisina/administración & dosificación , Polilisina/uso terapéuticoAsunto(s)
Traumatismos Craneocerebrales/terapia , Adulto , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/etiología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Traumatismos Craneocerebrales/complicaciones , Traumatismos Craneocerebrales/psicología , Escala de Coma de Glasgow , Humanos , Pruebas Neuropsicológicas , Educación del Paciente como Asunto , Calidad de Vida , Ajuste Social , Factores de Tiempo , Resultado del TratamientoRESUMEN
Arsenic (As), a human carcinogen, represents a worldwide health problem due to the high number of people exposed to this element in their drinking water. Previously our group has demonstrated that As can impair lymphocyte cell proliferation in vitro and in vivo and can increase the level of P53 protein, with different responses to these effects between individuals. Recently it has been shown that ATM protein, responsible for the autosomal recessive disorder ataxia telangiectasia (AT), regulates P53. In this study the induced response of P53 was evaluated following exposure to As in human lymphoblastoid cell lines normal (+/+), heterozygous (+/-) or homozygous (-/-) for the mutant ATM gene. After 24 h As treatment we found a dose-dependent induction of P53 in normal and heterozygous cell lines, although differences between cell lines were observed. An increase in P21(WAF) protein, a main effector of P53 activation, was also observed in the same cell lines. In contrast, neither P53 nor P21 induction was detected in homozygous cells. The ATM (+/-) and (-/-) genotypes confer more sensitivity to As cytotoxic effects than the normal allelic condition. Paradoxically, ATM heterozygous cells were more sensitive to As, leading us to propose that this might be related to activation of apoptosis and removal of non-repairable cells. In contrast, in AT cells in which ATM is absent or mutated activation of P53 and its target genes is abrogated, allowing cells to replicate with damage in the presence of As, with cell death ensuing by a pathway different from P53.
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Arsénico/toxicidad , Ataxia Telangiectasia/metabolismo , Carcinógenos/toxicidad , Proteínas Serina-Treonina Quinasas/fisiología , Ataxia Telangiectasia/genética , Proteínas de la Ataxia Telangiectasia Mutada , Proteínas de Ciclo Celular , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/biosíntesis , Ciclinas/metabolismo , Ciclinas/fisiología , Proteínas de Unión al ADN , Humanos , Activación de Linfocitos/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/fisiología , Proteínas Supresoras de TumorRESUMEN
Biased responding on the Sternberg Recognition Memory Test was observed in four patients with traumatic brain injury. None of these individuals met the Diagnostic and Statistical Manual's (DSM-IV) criteria for malingering. Individual recognition memory scores were high shortly after injury, declined to chance or below at the 6- and 12-month evaluations, and then showed substantial recovery by the 24-month evaluation. Recall memory performance actually declined slightly across this same 2-year period. Recognition memory scores were related to the extent to which the patients endorsed somatic items on the Hamilton Rating Scale for Depression (HAM-D). Poor performance was associated with high somatic scores. The relationship between memory and somatic scores on the HAM-D in this case series suggests that unconscious processes can influence memory performance and, because of this, that clinicians should not use such performance as a primary indicator of malingering. More importantly, biased responding and actual memory deficits may coexist. This is indicated in the current cases by the failure of recall memory to improve during the 2 years these patients were followed.
Asunto(s)
Daño Encefálico Crónico/diagnóstico , Lesiones Encefálicas/diagnóstico , Recuerdo Mental , Pruebas Neuropsicológicas/estadística & datos numéricos , Trastornos Somatomorfos/diagnóstico , Adulto , Anciano , Sesgo , Daño Encefálico Crónico/psicología , Lesiones Encefálicas/psicología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Simulación de Enfermedad/diagnóstico , Simulación de Enfermedad/psicología , Persona de Mediana Edad , Psicometría , Trastornos Somatomorfos/psicología , Inconsciente en Psicología , Aprendizaje VerbalRESUMEN
A DNA-binding domain (DBD) was identified on simian virus 40 (SV40) major capsid protein Vp1, and the domain's function in the SV40 life cycle was examined. The DBD was mapped by assaying various recombinant Vp1 proteins for DNA binding in vitro. The carboxy-terminal 58-residue truncated Vp1DeltaC58 pentamer bound DNA with a K(d) of 1.8 x 10(-9) M in terms of the protein pentamer, while full-length Vp1 and carboxy-terminal-17-truncated Vp1DeltaC17 had comparable apparent K(d)s of 5.3 x 10(-9) to 7.3 x 10(-9) M in terms of the protein monomers. Previously identified on Vp1 was a nuclear localization signal (NLS) consisting of two N-terminal basic clusters, NLS1 (4-KRK-6) and NLS2 (15-KKPK-18). Vp1DeltaC58 pentamers harboring multiple-point mutations in NLS1 (NLSm1), NLS2 (NLSm2), or both basic clusters (NLSm1. 2) had progressively decreased DNA-binding activity, down to 0.7% of the Vp1DeltaC58 level for NLSm1. 2 Vp1. These data, along with those of N-terminally truncated proteins, placed the DBD in overlap with the bipartite NLS. The role of the Vp1 DBD during infection was investigated by taking advantage of NLS phenotypic complementation (N. Ishii, A. Nakanishi, M. Yamada, M. H. Macalalad, and H. Kasamatsu, J. Virol. 68:8209-8216, 1994), in which an NLS-defective Vp1 could localize to the nucleus in the presence of wild-type minor capsid proteins Vp2 and Vp3. This approach made it possible to dissect the role of the bifunctional Vp1 NLS-DBD in virion assembly in the nucleus. Mutants of the viable nonoverlapping SV40 (NO-SV40) DNA NLSm1, NLSm2, and NLSm1. 2 replicated normally following transfection into host cells and produced capsid proteins at normal levels. All mutant Vp1s were able to interact with Vp3 in vitro. The mutants NLSm1 and NLSm1. 2 were nonviable, and the mutant Vp1s unexpectedly failed to localize to the nucleus though Vp2 and Vp3 did, suggesting that the mutated NLS1 acted as a dominant signal for the cytoplasmic localization of Vp1. Mutant NLSm2, for which the mutant Vp1's nuclear localization defect was complemented by Vp2 and Vp3, displayed a 5,000-fold reduced viability. Analysis of NLSm2 DNA-transfected cell lysate revealed a 10-fold reduction in the level of DNase I-protected viral DNA, and yet virion-like particles were found among the DNase I-resistant material. Collective results support a role for Vp1 NLS2-DBD2 in the assembly of virion particles. The results also suggest that this determinant can function in the infection of new cells.
Asunto(s)
Proteínas de la Cápside , Cápside/fisiología , Virus 40 de los Simios/fisiología , Ensamble de Virus , Animales , Mutación , Proteínas Recombinantes/genéticaRESUMEN
CVLT and WMS-R Digit Span variables were used to calculate indexes of seven specific short- and long-term memory processes: working memory span and central executive functions, and long-term memory encoding, consolidation, retention, retrieval, control abilities. Scores on these indexes were then cluster-analyzed to determine whether subtypes of memory performance exist that correspond to deficits in these theoretical memory constructs. Parallel analyses were conducted with two large samples (N = 150 and N = 151) of individuals who had sustained a traumatic brain injury (TBI). Findings showed that TBI results in subgroups of memory disorders with specific deficits in consolidation, retention, and retrieval processes. Control problems (keeping track of list versus non-list items) only appeared in conjunction with retrieval deficits. Working memory span and central executive functioning (i.e., the ability to manipulate information in working memory) do not appear to be deficits characteristic of TBI as no such clusters emerged in the analyses. By using specific indexes of memory processes, and in contrast to previous studies, patterns of memory dysfunction were found that correspond to deficits in theoretically meaningful memory constructs.
Asunto(s)
Amnesia/diagnóstico , Conmoción Encefálica/diagnóstico , Daño Encefálico Crónico/diagnóstico , Lesión Encefálica Crónica/diagnóstico , Pruebas Neuropsicológicas , Adulto , Amnesia/psicología , Conmoción Encefálica/psicología , Daño Encefálico Crónico/psicología , Lesión Encefálica Crónica/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Retención en Psicología , Aprendizaje Seriado , Aprendizaje Verbal , Escalas de WechslerAsunto(s)
Adenocarcinoma/cirugía , Neoplasias Pulmonares/cirugía , Complicaciones Posoperatorias/diagnóstico por imagen , Arteria Pulmonar/diagnóstico por imagen , Embolia Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Femenino , Humanos , Arteria Pulmonar/cirugíaRESUMEN
Congenital bronchial atresia (CBA) is a rare disorder, first reported in 1953. Less than 100 cases are reported in the literature, mostly in young, asymptomatic male patients with involvement of the apical-posterior segment of the left upper lobe. Patients may complain of fever, cough, or shortness of breath, symptoms that result from post-obstructive, sometimes recurrent, infections. Chest radiography and computed tomography reveal a tubular branching density representing mucus impaction or mucocele with surrounding focal hyperinflation. Surgical excision is reserved for symptomatic cases. We report an unusual case of CBA in a middle-aged man with a history of relapsing infections, who was found to have an atretic superior segment of the left lower lobe, with surrounding areas of organizing pneumonia.
Asunto(s)
Bronquios/anomalías , Absceso Pulmonar/etiología , Neumonía/etiología , Actividades Cotidianas , Adulto , Antibacterianos/uso terapéutico , Biopsia , Bronquios/patología , Bronquios/cirugía , Fatiga/etiología , Fiebre/etiología , Humanos , Absceso Pulmonar/tratamiento farmacológico , Masculino , Neumonía/tratamiento farmacológico , Recurrencia , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos XRESUMEN
Progesterone receptor (PR) isoforms expression was determined in several regions of the prepuberal and adult male rat brain by using reverse transcription coupled to polymerase chain reaction. Rats under a 14:10-h light-dark cycle, with lights on at 0600 h were used. We found that in the hypothalamus of prepuberal animals the expression of both PR isoforms was similar, whereas PR-A expression was higher than that of PR-B in adults. In the cerebellum PR-B expression was predominant in both prepuberal and adult rats. In both ages PR-A and PR-B exhibited a non-significant tendency to be predominant in the hippocampus and the preoptic area respectively. In the frontal cortex and the olfactory bulb PR isoforms were expressed at a similar level. These results indicate a differential expression pattern of PR isoforms in the male rat brain and suggest that the tissue-specific expression of PR-A and PR-B is important for the appropriate response of each cerebral region to progesterone.
Asunto(s)
Química Encefálica/genética , Encéfalo/crecimiento & desarrollo , Receptores de Progesterona/genética , Maduración Sexual/fisiología , Factores de Edad , Animales , Regulación del Desarrollo de la Expresión Génica , Hipocampo/química , Hipocampo/crecimiento & desarrollo , Hipocampo/fisiología , Hipotálamo/química , Hipotálamo/crecimiento & desarrollo , Hipotálamo/fisiología , Isomerismo , Masculino , Bulbo Olfatorio/química , Bulbo Olfatorio/crecimiento & desarrollo , Bulbo Olfatorio/fisiología , Área Preóptica/química , Área Preóptica/crecimiento & desarrollo , Área Preóptica/fisiología , Ratas , Ratas Wistar , Receptores de Progesterona/química , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
EEG spectral analyses were conducted from 19 scalp locations for patients with mild (n=40), moderate (n=25), and severe (n=43) traumatic brain injury (TBI), 15 days to 4 years after injury. Severity of TBI was judged by emergency hospital admission records (Glasgow Coma Score and duration of coma and amnesia). Highest-loading EEG variables on each factor that differed significantly between severe and mild TBI by univariate t-test were entered into a multivariate discriminant analysis, yielding 16 variables. Discriminant analysis between mild and severe TBI groups showed classification accuracy of 96.39%, sensitivity 95.45%, and specificity 97.44%. The EEG discriminant score also measured intermediate severity in moderate TBI patients. Results were cross-validated in 503 VA patients. Significant correlations between EEG discriminant scores, emergency admission measures, and post-trauma neuropsychological test scores validated the discriminant function as an index of severity of injury and a classifier of the extremes of severity.