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1.
Cell ; 184(13): 3426-3437.e8, 2021 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-33991487

RESUMEN

We identified an emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the western United States. Named B.1.427/B.1.429 to denote its two lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6%-24% increased transmissibility relative to wild-type circulating strains. The variant carries three mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 4.0- to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California exhibiting decreased antibody neutralization warrants further investigation.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , COVID-19/inmunología , COVID-19/transmisión , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Humanos , Mutación/genética , Secuenciación Completa del Genoma/métodos
2.
MMWR Morb Mortal Wkly Rep ; 73(40): 903-905, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39388389

RESUMEN

The antiviral drug tecovirimat* has been used extensively to treat U.S. mpox cases since the start of a global outbreak in 2022. Mutations in the mpox viral protein target (F13 or VP37) that occur during treatment can result in resistance to tecovirimat† (1,2). CDC and public health partners have conducted genetic surveillance of monkeypox virus (MPXV) for F13 mutations through sequencing and monitoring of public databases. MPXV F13 mutations associated with resistance have been reported since 2022, typically among severely immunocompromised mpox patients who required prolonged courses of tecovirimat (3-5). A majority of patients with infections caused by MPXV with resistant mutations had a history of tecovirimat treatment; however, spread of tecovirimat-resistant MPXV was reported in California during late 2022 to early 2023 among persons with no previous tecovirimat treatment (3). This report describes a second, unrelated cluster of tecovirimat-resistant MPXV among 18 persons with no previous history of tecovirimat treatment in multiple states.


Asunto(s)
Antivirales , Brotes de Enfermedades , Farmacorresistencia Viral , Monkeypox virus , Mpox , Humanos , Estados Unidos/epidemiología , Antivirales/farmacología , Antivirales/uso terapéutico , Mpox/epidemiología , Mpox/tratamiento farmacológico , Monkeypox virus/aislamiento & purificación , Monkeypox virus/genética , Monkeypox virus/efectos de los fármacos , Adulto , Masculino , Femenino , Persona de Mediana Edad , Adolescente , Adulto Joven , Anciano , Niño , Mutación , Dibenzotiepinas , Benzamidas/uso terapéutico , Benzamidas/farmacología , Ftalimidas
3.
J Infect Dis ; 224(6): 1015-1023, 2021 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-33528506

RESUMEN

In 2019, the United States (US) experienced the highest number of measles importations and cases in the postelimination era. More than a quarter of imported cases entered the US through California. Measles surveillance efforts in California resulted in the identification of 26 importations, 6 outbreaks, and 72 cases in 2019. Only genotype B3 and D8 measles strains were detected. Genotype-specific differences were noted in the incidence of vaccine failures, hospitalizations, and severe complications among cases. A targeted whole genome sequencing approach provided higher-resolution discrimination between epidemiologically linked and sporadically introduced strains than conventional N450 sequencing. Our report underscores the importance of ensuring appropriate measles vaccination status, especially prior to international travel to measles-endemic regions, and highlights the value of a strong measles surveillance system in minimizing outbreaks and preserving measles elimination status in the US.


Asunto(s)
Brotes de Enfermedades , Vacuna Antisarampión/administración & dosificación , Virus del Sarampión , Sarampión/epidemiología , Adolescente , Adulto , Anciano , California/epidemiología , Niño , ARN Polimerasas Dirigidas por ADN , Femenino , Genotipo , Humanos , Masculino , Virus del Sarampión/genética , Virus del Sarampión/inmunología , Virus del Sarampión/aislamiento & purificación , Persona de Mediana Edad , Epidemiología Molecular , Filogenia , Análisis de Secuencia de ADN , Estados Unidos/epidemiología , Adulto Joven
4.
Emerg Infect Dis ; 25(8): 1594-1596, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31310213

RESUMEN

We implemented subgenomic and whole-genome sequencing to support the investigation of a large hepatitis A virus outbreak among persons experiencing homelessness, users of illicit drugs, or both in California, USA, during 2017-2018. Genotyping data helped confirm case-patients, track chains of transmission, and monitor the effectiveness of public health control measures.


Asunto(s)
Virus de la Hepatitis A/clasificación , Virus de la Hepatitis A/genética , Hepatitis A/epidemiología , Hepatitis A/virología , Tipificación Molecular , California/epidemiología , Brotes de Enfermedades , Genotipo , Hepatitis A/historia , Hepatitis A/transmisión , Virus de la Hepatitis A/inmunología , Virus de la Hepatitis A/aislamiento & purificación , Historia del Siglo XXI , Humanos , Vigilancia en Salud Pública , Proteínas Virales/genética , Secuenciación Completa del Genoma
5.
J Clin Microbiol ; 58(1)2019 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-31666366

RESUMEN

Pacific Coast tick fever is a febrile illness associated with the bite of Dermacentor occidentalis and results from an infection due to the intracellular pathogen Rickettsia 364D (also known by the proposed name "Rickettsia philipii"). Current molecular methods for the detection of this pathogen rely on the amplification of a conserved spotted fever group rickettsial gene (ompA) followed by DNA sequencing of the amplicon to identify the species. This work describes the development of a Rickettsia 364D-specific TaqMan assay to simplify and accelerate the detection and identification processes. The assay demonstrated a sensitivity of 1 genomic copy per 4-µl sample and is highly specific for Rickettsia 364D. The utility of this assay for ecological and diagnostic samples was evaluated using banked specimens collected in a single-blind manner and yielded a clinical sensitivity and specificity of 100%. In conclusion, we describe the development and evaluation of a novel TaqMan real-time PCR assay for the detection and identification of Rickettsia 364D suitable for ecological and diagnostic applications.


Asunto(s)
Reacción en Cadena en Tiempo Real de la Polimerasa , Infecciones por Rickettsia/diagnóstico , Infecciones por Rickettsia/microbiología , Rickettsia/genética , Enfermedades por Picaduras de Garrapatas/diagnóstico , Enfermedades por Picaduras de Garrapatas/microbiología , Animales , Dermacentor/microbiología , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Infecciones por Rickettsia/transmisión , Sensibilidad y Especificidad , Enfermedades por Picaduras de Garrapatas/transmisión
8.
Cell Rep ; 42(8): 112927, 2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37537841

RESUMEN

Tumor relapse is linked to rapid chemoresistance and represents a bottleneck for cancer therapy success. Engagement of a reduced proliferation state is a non-mutational mechanism exploited by cancer cells to bypass therapy-induced cell death. Through combining functional pulse-chase experiments in engineered cells and transcriptomic analyses, we identify DPPA3 as a master regulator of slow-cycling and chemoresistant phenotype in colorectal cancer (CRC). We find a vicious DPPA3-HIF1α feedback loop that downregulates FOXM1 expression via DNA methylation, thereby delaying cell-cycle progression. Moreover, downregulation of HIF1α partially restores a chemosensitive proliferative phenotype in DPPA3-overexpressing cancer cells. In cohorts of CRC patient samples, DPPA3 overexpression acts as a predictive biomarker of chemotherapeutic resistance that subsequently requires reduction in its expression to allow metastatic outgrowth. Our work demonstrates that slow-cycling cancer cells exploit a DPPA3/HIF1α axis to support tumor persistence under therapeutic stress and provides insights on the molecular regulation of disease progression.

9.
medRxiv ; 2021 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-33758899

RESUMEN

We identified a novel SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. Named B.1.427/B.1.429 to denote its 2 lineages, the variant emerged around May 2020 and increased from 0% to >50% of sequenced cases from September 1, 2020 to January 29, 2021, exhibiting an 18.6-24% increase in transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. Our analyses revealed 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation found in the B.1.1.7, B.1.351, and P.1 variants. Antibody neutralization assays showed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California associated with decreased antibody neutralization warrants further investigation.

10.
Ann Neurol ; 65(3): 257-67, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19334059

RESUMEN

OBJECTIVE: Virus infections are the most common causes of encephalitis, a syndrome characterized by acute inflammation of the brain. More than 150 different viruses have been implicated in the pathogenesis of encephalitis; however, because of limitations with diagnostic testing, causative factors of more than half of the cases remain unknown. METHODS: To investigate whether human herpesvirus-6 (HHV-6) is a causative agent of encephalitis, we examined for evidence of virus infection by determining the presence of viral sequence using polymerase chain reaction and assessed HHV-6 antibody reactivity in the cerebrospinal fluid of encephalitis patients with unknown cause. In a cohort study, we compared virus-specific antibody levels in cerebrospinal fluid samples of patients with encephalitis, relapsing-remitting multiple sclerosis, and other neurological diseases. RESULTS: Our results demonstrated increased levels of HHV-6 IgG, as well as IgM levels, in a subset of encephalitis patients compared with other neurological diseases. Moreover, cell-free viral DNA that is indicative of active infection was detected in 40% (14/35) of encephalitis patients, whereas no amplifiable viral sequence was found in either relapsing-remitting MS or other neurological diseases patients. In addition, a significant correlation between polymerase chain reaction detection and anti-HHV-6 antibody response was also demonstrated. INTERPRETATION: Collectively, these results suggested HHV-6 as a possible pathogen in a subset of encephalitis cases.


Asunto(s)
Encefalitis Viral/líquido cefalorraquídeo , Herpesvirus Humano 6/aislamiento & purificación , Infecciones por Roseolovirus/líquido cefalorraquídeo , Adolescente , Adulto , Anticuerpos Antivirales/líquido cefalorraquídeo , Encéfalo/patología , Encéfalo/virología , Estudios de Casos y Controles , Línea Celular , Niño , Preescolar , Estudios de Cohortes , ADN Viral/líquido cefalorraquídeo , ADN Viral/química , Encefalitis Viral/patología , Femenino , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/inmunología , Humanos , Inmunoensayo , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina M/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Infecciones por Roseolovirus/patología , Análisis de Secuencia de ADN , Adulto Joven
11.
Pharm Biol ; 48(9): 988-93, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20731549

RESUMEN

CONTEXT: This is the first comprehensive study of the acetylcholinesterase (AChE) inhibitory activity of species of the family Amaryllidaceae and 13 related families from Panama. OBJECTIVE: Exploration of the potential sources of AChE inhibitors with radical scavenging activity from Amaryllidaceae and 13 related families from Panama. MATERIALS AND METHODS: The studied plants were screened with anti-acetylcholinesterase bioautographic and DPPH free radical scavenging assays. RESULTS: From the 57 plants studied, eight (14%) showed strong inhibition of AChE, and 29 (51%) plants showed moderate inhibition of AChE. DISCUSSION AND CONCLUSION: Sagittaria lancifolia L. (Alismataceae), Crinum jagus (Thomps.) (Amaryllidaceae), Crinum x amabile Donn (Amaryllidaceae), Crinum zeylanicum (L.) L. (Amaryllidaceae), Crocosmia x crocosmiiflora (Lemoine ex Anonymous) N.E. Br. (Iridaceae), Sisyrinchium tinctorium Kunth (Iridaceae), Agapanthus praecox subsp. orientalis (F.M. Leight.) F.M. Leight. (Liliaceae), and Xyris jupicai Rich. (Xyridaceae) were the most active plants, inhibiting AChE at 100 microg on the TLC bioautographic method for the detection of acetylcholinesterase inhibitors. Out of the eight most active plants, two plants, Crinum zeylanicum (L.) L. and Xyris jupicai Rich., showed antioxidant activity.


Asunto(s)
Inhibidores de la Colinesterasa/química , Descubrimiento de Drogas , Liliaceae/química , Extractos Vegetales/química , Plantas Medicinales/química , Alismataceae/química , Alcaloides/análisis , Evaluación Preclínica de Medicamentos , Depuradores de Radicales Libres/química , Iridaceae/química , Panamá
12.
Pharm Biol ; 48(5): 545-53, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20645798

RESUMEN

In order to explore rationally the medical potential of the plant biodiversity of the Central and South American region as a source of novel antiparasitic molecules, a multinational Organization of American States (OAS) project, which included the participation of multidisciplinary research centers from Argentina, Bolivia, Colombia, Costa Rica, Guatemala, Nicaragua and Panama, was carried out during the period 2001-2004. This project aimed at screening organic plant extracts for antitrypanosomal, antileishmanial and antimalarial activities and subsequently isolating and characterizing bioactive molecules. Plants for antiparasitic screening were selected from a database of ethnomedical uses of Latin American plants (PlanMedia) based on the amount of biological and chemical information available in the literature. We report here the evaluation of 452 extracts from 311 plant species in vitro screens against Plasmodium falciparum, Leishmania mexicana, and Trypanosoma cruzi. Out of 311 species tested, 17 plants (5.4%) showed antiparasitic activities at IC(50) values < or = 10 microg/mL. The most active plants were Acnistus arborescens (L.) Schltdl. (Solanaceae) (leaf, EtOH, IC(50): 4 microg/mL) Monochaetum myrtoideum Naudin (Melastomataceae) (leaf, MeOH, IC(50): 5 microg/mL) and Bourreria huanita (Lex.) Hemsl. (Boraginaceae) (branch, EtOH, IC(50): 6 microg/mL). These were selectively active against P. falciparum, L. mexicana and T. cruzi, respectively.


Asunto(s)
Antimaláricos/uso terapéutico , Antiparasitarios/uso terapéutico , Enfermedad de Chagas , Leishmaniasis , Malaria , Extractos Vegetales/uso terapéutico , Antimaláricos/aislamiento & purificación , Antiparasitarios/aislamiento & purificación , Enfermedad de Chagas/tratamiento farmacológico , Evaluación Preclínica de Medicamentos/métodos , Humanos , América Latina , Leishmaniasis/tratamiento farmacológico , Malaria/tratamiento farmacológico , Extractos Vegetales/aislamiento & purificación , Plantas , Distribución Aleatoria
13.
Virus Res ; 281: 197935, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32194138

RESUMEN

Despite high coverage with measles, mumps, and rubella vaccine in the United States, outbreaks of mumps occur in close contact settings such as schools, colleges, and camps. Starting in late 2015, outbreaks were reported from several universities, and by the end of 2017, greater than 13,800 cases had been reported nation-wide. In 2013, the CDC and the Association of Public Health Laboratories contracted four Vaccine Preventable Diseases Reference Centers (VPD-RCs) to perform real-time reverse transcription PCR (RT-qPCR) to detect mumps RNA in clinical samples and to determine the genotype. Twelve genotypes of mumps virus are currently recognized by the World Health Organization, and the standard protocol for genotyping requires sequencing the entire gene coding for the small hydrophobic (SH) protein. Phylogenetic analysis of the 1862 mumps samples genotyped from 2015 through 2017 showed that the overall diversity of genotypes detected was low. Only 0.8 % of the sequences were identified as genotypes C, H, J, or K, and 0.5 % were identified as vaccine strains in genotypes A or N, while most sequences (98.7 %) were genotype G. The majority of the genotype G sequences could be included into one of two large groups with identical SH sequences. Within genotype G, a small number of phylogenetically significant outlier sequences were associated with epidemiologically distinct chains of transmission. These results demonstrate that molecular and epidemiologic data can be used to track transmission pathways of mumps virus; however, the limited diversity of the SH sequences may be insufficient for resolving transmission in all outbreaks.


Asunto(s)
Brotes de Enfermedades , Virus de la Parotiditis/genética , Paperas/epidemiología , Proteínas Virales/genética , Variación Genética , Genotipo , Humanos , ARN Viral/genética , Estados Unidos/epidemiología
14.
J Med Entomol ; 55(6): 1555-1560, 2018 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-29982649

RESUMEN

The Pacific Coast tick (Dermacentor occidentalis Marx, 1892) is one of the most widely distributed and frequently encountered tick species in California. This tick is the primary vector of an unclassified spotted fever group rickettsial pathogen, designated currently as Rickettsia 364D, the etiologic agent of a recently recognized tick-borne rickettsiosis known as Pacific Coast tick fever. Despite intensified interest in this pathogen, important questions remain regarding its taxonomic status and possible variations in genotype among different strains that could influence its pathogenicity. Only the extensively passaged prototypical isolate (strain 364-D) is widely available to rickettsiologists and public health scientists worldwide. To achieve a larger, more geographically diverse, and contemporary collection of strains, 1,060 questing adult D. occidentalis ticks were collected from 18 sites across six counties in northern and southern California in 2016 and 2017. Fourteen ticks (1.3%) yielded DNA of Rickettsia 364D and from these, 10 unique isolates from Lake and Orange counties were obtained. Additionally, Rickettsia rhipicephali was detected in 108 (10.2%) ticks, from which eight isolates were obtained, and Rickettsia bellii in six (0.6%), from which three isolates were obtained. The panel of recently acquired, low-passage strains of Rickettsia 364D derived from this study could enhance opportunities for investigators to accurately determine the taxonomic standing of this agent and to develop specific diagnostic assays for detecting infections with Rickettsia 364D in ticks and humans.


Asunto(s)
Dermacentor/microbiología , Rickettsia/aislamiento & purificación , Animales , California , Femenino , Masculino , Rickettsia/genética
15.
Genome Announc ; 5(33)2017 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-28818890

RESUMEN

We report here the full coding sequence of nine paramyxovirus genomes, including two full-length mumps virus genomes (genotypes G and H) and seven measles virus genomes (genotypes B3 and D4, D8, and D9), from respiratory samples of patients from California, Virginia, and Alabama obtained between 2010 and 2014.

16.
PLoS Negl Trop Dis ; 10(10): e0005020, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27706171

RESUMEN

Rickettsia philipii (type strain "Rickettsia 364D"), the etiologic agent of Pacific Coast tick fever (PCTF), is transmitted to people by the Pacific Coast tick, Dermacentor occidentalis. Following the first confirmed human case of PCTF in 2008, 13 additional human cases have been reported in California, more than half of which were pediatric cases. The most common features of PCTF are the presence of at least one necrotic lesion known as an eschar (100%), fever (85%), and headache (79%); four case-patients required hospitalization and four had multiple eschars. Findings presented here implicate the nymphal or larval stages of D. occidentalis as the primary vectors of R. philipii to people. Peak transmission risk from ticks to people occurs in late summer. Rickettsia philipii DNA was detected in D. occidentalis ticks from 15 of 37 California counties. Similarly, non-pathogenic Rickettsia rhipicephali DNA was detected in D. occidentalis in 29 of 38 counties with an average prevalence of 12.0% in adult ticks. In total, 5,601 ticks tested from 2009 through 2015 yielded an overall R. philipii infection prevalence of 2.1% in adults, 0.9% in nymphs and a minimum infection prevalence of 0.4% in larval pools. Although most human cases of PCTF have been reported from northern California, acarological surveillance suggests that R. philipii may occur throughout the distribution range of D. occidentalis.


Asunto(s)
Vectores Arácnidos/microbiología , Dermacentor/microbiología , Infecciones por Rickettsia/epidemiología , Infecciones por Rickettsia/transmisión , Rickettsia/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Antibacterianos/sangre , California/epidemiología , Niño , Preescolar , Femenino , Fiebre , Humanos , Inmunoglobulina G/sangre , Larva/microbiología , Masculino , Persona de Mediana Edad , Ninfa/microbiología , Prevalencia , Rickettsia/genética , Rickettsia/inmunología , Rickettsia/patogenicidad , Infecciones por Rickettsia/diagnóstico , Infecciones por Rickettsia/microbiología , Adulto Joven
17.
In Vitro Cell Dev Biol Anim ; 38(7): 378-81, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12534337

RESUMEN

cDNAs representing an endogenous C-type ecotropic murine leukemia virus were isolated from a cDNA library constructed to represent mRNAs present in BC3H1 myogenic cells but not in C2C12 myogenic cells. RNA blot hybridization analysis using the cDNA inserts as probes revealed that BC3H1 cells produce MuLV-related transcirpts of at least three different size classes. A polymerase chain reaction enhanced assay for reverse transcriptase activity revealed the presence of reverse transcriptase in a viral pellet from medium conditioned by BC3H1 cells. A fungizone enhanced assay for syncitium formation provided further evidence of ecotropic retroviral particle production. Exposure of 3T3 cells to medium conditioned by BC3H1 cells, using conditions that facilitate infection, resulted in infection of the 3T3 cells, as confirmed by the syncitium formation assay. We conclude that BC3H1 cells produce an infectious ecotropic murine leukemia virus. Whether or not this feature of BC3H1 cells contributes to their inability to express some muscle-specific genes or to carry out myotube formation is unknown. Investigators will want to take into account that BC3H1 cells are virus producers when planning experiments that involve coculture of BC3H1 with other cell types, BC3H1 conditioned medium, retrovirally mediated transfection into BC3H1 cells, or study of the mCAT-1 amino acid transporter (the viral receptor) in BC3H1 cells. BC3H1 cells and the virus they produce may be of interest to those studying retroviral genomes and products and their effects.


Asunto(s)
Virus de la Leucemia Murina/crecimiento & desarrollo , Replicación Viral , Animales , Línea Celular Tumoral , Medios de Cultivo Condicionados , Virus de la Leucemia Murina/enzimología , Virus de la Leucemia Murina/genética , Virus de la Leucemia Murina/fisiología , Ratones , Células 3T3 NIH , Reacción en Cadena de la Polimerasa , ARN Viral/análisis , ADN Polimerasa Dirigida por ARN/metabolismo
18.
In Vitro Cell Dev Biol Anim ; 38(7): 382-93, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12534338

RESUMEN

To catalog factors that may contribute to the completion of myogenesis, we have been looking for molecular differences between BC3H1 and C2C12 cells. Cells of the BC3H1 tumor line, though myogenic, are nonfusing, and withdraw from the cell cycle only reversibly, whereas cells of the C2C12 line fuse, differentiate terminally, and express several muscle-specific gene products that BC3H1 cells do not. Relative to C2C12 cells, BC3H1 cells underaccumulated cyclin-dependent kinase inhibitor p21 and underaccumulated transcripts for p21, GADD45, CDO, decorin, osteopontin, H19, fibronectin, and thrombospondin-1 (tsp-1). Levels of accumulation of H19, tsp-1, and larger isoforms of fibronectin messenger ribonucleic acid (mRNA) were found to increase in response to expression of myogenic regulatory factors as shown by their accumulation in differentiated myogenically converted 10T1/2 cells but not in 10T1/2 fibroblasts. BC3H1s accumulated a temperature-insensitive, geldanamycin-sensitive, misfolded form of p53 incapable of transactivating a p53 responsive reporter, consistent with underexpression of p21, GADD45, and tsp-1. BC3H1 and C2C12 cells were similar with respect to upregulation of p27 protein, downregulation of mitogen-activated protein kinase phosphatase-1 (MKP-1) protein, upregulation of retinoblastoma (Rb) mRNA, and nuclear localization of hypophosphorylated Rb. Cells of both lines expressed the muscle-specific 1b isoform of MEF2D. Although nonfusing in the short term, after more than 18 d in differentiation medium, some cultures of BC3H1 cells formed viable multinucleated cells in which the nuclei did not reinitiate synthesis of DNA in response to serum. Our findings suggest participation of tsp-1 and specific isoforms of fibronectin in myogenesis and suggest additional avenues of research in myogenesis and oncogenesis.


Asunto(s)
Regulación de la Expresión Génica , Proteína p53 Supresora de Tumor/metabolismo , Animales , Diferenciación Celular , Línea Celular , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Ratones , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculos/citología , Músculos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo
19.
Nat Prod Res ; 27(4-5): 500-5, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22746970

RESUMEN

Acetylcholinesterase (AChE) inhibitors have been used for the symptomatic treatment of Alzheimer's disease. Eleven whole plants from Panama belonging to the Lycopodiaceae family have been screened for their anticholinesterase inhibitory and antioxidant activities by a thin-layer chromatography (TLC) bioautography method. Of these, only Lycopodium clavatum subsp. clavatum showed strong AChE inhibition. Seven plant extracts showed moderate inhibition, two of them, Huperzia cf chamaeleon and Huperzia reflexa, also possessed an antioxidant activity. This is the first report of anticholinesterase and antioxidant activities in these two native plants. Additionally, alkaloid extracts of the Lycopodiaceae plants were also analysed by TLC and LC-MS to identify the well-known AchE inhibitor, huperzine A. Two plants, H. cf chamaeleon and H. reflexa var. minor, showed the presence of huperzine.


Asunto(s)
Inhibidores de la Colinesterasa/química , Lycopodiaceae/química , Alcaloides/química , Antioxidantes/química , Cromatografía en Capa Delgada , Lycopodium/química , Espectrometría de Masas , Panamá , Extractos Vegetales/química , Sesquiterpenos/química
20.
Pediatr Infect Dis J ; 32(9): 1036-9, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23594588

RESUMEN

We describe the clinical course of the first 3 pediatric cases infected with Rickettsia spp. 364D. Although the pathogen was identified in California ticks decades ago, only recently have human cases been documented. Clinical features are generally mild, characterized by eschar, fever, headache, malaise and lymphadenopathy. Antigenic similarity among rickettsiae leads to cross-reactive antibody responses; definitive diagnosis requires molecular methods.


Asunto(s)
Infecciones por Rickettsia/epidemiología , Infecciones por Rickettsia/patología , Rickettsia/clasificación , Rickettsia/aislamiento & purificación , Enfermedades por Picaduras de Garrapatas/epidemiología , Enfermedades por Picaduras de Garrapatas/patología , Adolescente , Niño , Femenino , Humanos , Masculino , Infecciones por Rickettsia/microbiología , Enfermedades por Picaduras de Garrapatas/microbiología
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