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BACKGROUND AND OBJECTIVE: Cartilage-hair hypoplasia (CHH) syndrome is a rare autosomal recessive syndrome associated with skeletal dysplasia, varying degrees of combined immunodeficiency (CID), short stature, hair hypoplasia, macrocytic anemia, increased risk of malignancies, and Hirschsprung disease. To provide clinical and immunological insights obtained from 2 unrelated patients who displayed clinical characteristics of CHH. METHODS: Two patients with suspected CHH syndrome due to skeletal dysplasia and immunodeficiency underwent an immunological and genetic work-up using flow cytometry, next-generation sequencing (NGS) of the immune repertoire, and Sanger sequencing to identify the underlying defects. RESULTS: Patient 1 presented with low birth weight and skeletal dysplasia. Newborn screening was suggestive of T-cell immunodeficiency, as T-cell receptor excision circle levels were undetectable. Both the T-cell receptor (TCR) Vß and TCR-g (TRG) repertoires were restricted, with evidence of clonal expansion. Genetic analysis identified compound heterozygous RMRP variants inherited from both parents. Patient 2 presented with recurrent lung and gastrointestinal infections, skeletal dysplasia, failure to thrive, and hepatomegaly. The polyclonal pattern of the TCRß repertoire was normal, with only slight overexpression of TCR-ßV20 and restricted expression of Vßs. TRG expressed a normal diverse repertoire, similar to that of the healthy control sample. Genetic analysis identified biallelic novel regulatory variants in RMRP. Both parents are carriers of this mutation. CONCLUSION: Our findings demonstrate how the immunological work-up, supported by genetic findings, can dramatically change treatment and future outcome in patients with the same clinical syndrome.
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Enfermedad de Hirschsprung , Síndromes de Inmunodeficiencia , Recién Nacido , Humanos , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/complicaciones , Enfermedad de Hirschsprung/patología , Síndromes de Inmunodeficiencia/genética , Cabello/anomalías , Cabello/patología , Receptores de Antígenos de Linfocitos T/genética , Progresión de la EnfermedadRESUMEN
Introduction: Cartilage-hair hypoplasia (CHH) syndrome is a rare autosomal recessive syndrome associated with skeletal dysplasia, varying degrees of combined immunodeficiency (CID), short stature, hair hypoplasia, macrocytic anemia, increased risk of malignancies, and Hirschsprung disease. Purpose: To provide clinical and immunological insights obtained from 2 unrelated patients who displayed clinical characteristics of CHH. Methods: Two patients with suspected CHH syndrome due to skeletal dysplasia and immunodeficiency underwent an immunological and genetic work-up using flow cytometry, next-generation sequencing (NGS) of the immune repertoire, and Sanger sequencing to identify the underlying defects. Results: Patient 1 presented with low birth weight and skeletal dysplasia. Newborn screening was suggestive of T-cell immunodeficiency, as T-cell receptor excision circle levels were undetectable. Both the T-cell receptor (TCR) Vß and TCR-g (TRG) repertoires were restricted, with evidence of clonal expansion. Genetic analysis identified compound heterozygous RMRP variants inherited from both parents. Patient 2 presented with recurrent lung and gastrointestinal infections, skeletal dysplasia, failure to thrive, and hepatomegaly. The polyclonal pattern of the TCRß repertoire was normal, with only slight overexpression of TCR-ßV20 and restricted expression of Vßs. TRG expressed a normal diverse repertoire, similar to that of the healthy control sample. Genetic analysis identified biallelic novel regulatory variants in RMRP. Both parents are carriers of this mutation. Conclusion: Our findings demonstrate how the immunological work-up, supported by genetic findings, can dramatically change treatment and future outcome in patients with the same clinical syndrome (AU)
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Humanos , Recién Nacido , Lactante , Enfermedad de Hirschsprung , Síndromes de Inmunodeficiencia/genética , Progresión de la Enfermedad , Cabello/anomalías , Cabello/patología , Enfermedad de Hirschsprung/complicaciones , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/patología , Receptores de Antígenos de Linfocitos T/genéticaRESUMEN
Diabetes and cancer are common conditions highly prevalent in the general population. The co-existence of diabetes and cancer in a patient is therefore not unexpected. Diabetes increases the risk of mortality from cancer and morbidity from the treatment of cancer. Furthermore, many cancer chemotherapeutic regimens increase glucose levels, especially those involving glucocorticoids. Many clinical oncologists will deal with patients with diabetes in their clinical work, and some working knowledge of diabetes diagnosis and management is helpful when managing such patients. This overview aims to summarise the clinical diagnosis and management of diabetes, review the potential links between diabetes and cancer, and provide some practical guidance on the management of hyperglycaemia in patients undergoing cancer therapy.
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Antineoplásicos/efectos adversos , Complicaciones de la Diabetes/diagnóstico , Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Oncólogos/normas , Guías de Práctica Clínica como Asunto/normas , Complicaciones de la Diabetes/inducido químicamente , Diabetes Mellitus/inducido químicamente , HumanosRESUMEN
CONTEXT: High-mass stars and star clusters commonly form within hub-filament systems. Monoceros R2 (hereafter Mon R2), at a distance of 830 pc, harbors one of the closest such systems, making it an excellent target for case studies. AIMS: We investigate the morphology, stability and dynamical properties of the Mon R2 hub-filament system. METHODS: We employ observations of the 13CO and C18O 1â0 and 2â1 lines obtained with the IRAM-30m telescope. We also use H2 column density maps derived from Herschel dust emission observations. RESULTS: We identified the filamentary network in Mon R2 with the DisPerSE algorithm and characterized the individual filaments as either main (converging into the hub) or secondary (converging to a main filament) filaments. The main filaments have line masses of 30-100 M â pc-1 and show signs of fragmentation, while the secondary filaments have line masses of 12-60 M â pc-1 and show fragmentation only sporadically. In the context of Ostriker's hydrostatic filament model, the main filaments are thermally supercritical. If non-thermal motions are included, most of them are trans-critical. Most of the secondary filaments are roughly transcritical regardless of whether non-thermal motions are included or not. From the morphology and kinematics of the main filaments, we estimate a mass accretion rate of 10-4-10-3 M â yr-1 into the central hub. The secondary filaments accrete into the main filaments with a rate of 0.1-0.4×10-4 M â yr-1. The main filaments extend into the central hub. Their velocity gradients increase towards the hub, suggesting acceleration of the gas.We estimate that with the observed infall velocity, the mass-doubling time of the hub is ~ 2:5 Myr, ten times larger than the free-fall time, suggesting a dynamically old region. These timescales are comparable with the chemical age of the Hii region. Inside the hub, the main filaments show a ring- or a spiral-like morphology that exhibits rotation and infall motions. One possible explanation for the morphology is that gas is falling into the central cluster following a spiral-like pattern.
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The antigenic specificity of T cells occurs via generation and rearrangement of different gene segments producing a functional T cell receptor (TCR). High-throughput sequencing (HTS) allows in-depth assessment of TCR repertoire patterns. There are limited data concerning whether TCR repertoires are altered in inflammatory bowel disease. We hypothesized that pediatric ulcerative colitis (UC) patients possess unique TCR repertoires, resulting from clonotypical expansions in the gut. Paired blood and rectal samples were collected from nine newly diagnosed treatment-naive pediatric UC patients and four healthy controls. DNA was isolated to determine the TCR-ß repertoire by HTS. Significant clonal expansion was demonstrated in UC patients, with inverse correlation between clinical disease severity and repertoire diversity in the gut. Using different repertoire variables in rectal biopsies, a clear segregation was observed between patients with severe UC, those with mild-moderate disease and healthy controls. Moreover, the overlap between autologous blood-rectal samples in UC patients was significantly higher compared with overlap among controls. Finally, we identified several clonotypes that were shared in either all or the majority of UC patients in the colon. Clonal expansion of TCR-ß-expressing T cells among UC patients correlates with disease severity and highlights their involvement in mediating intestinal inflammation.
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Células Clonales/fisiología , Colitis Ulcerosa/inmunología , Colon/inmunología , Genes Codificadores de la Cadena beta de los Receptores de Linfocito T/genética , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Especificidad del Receptor de Antígeno de Linfocitos T/genética , Linfocitos T/fisiología , Adolescente , Proliferación Celular , Niño , Selección Clonal Mediada por Antígenos , Colitis Ulcerosa/genética , ADN/análisis , Progresión de la Enfermedad , Humanos , Activación de Linfocitos , Receptores de Antígenos de Linfocitos T alfa-beta/genéticaRESUMEN
OBJECTIVE: ThinPrep (TP), one of the Food and Drug Administration-approved liquid-based cytology (LBC) preparations, is widely used for gynaecological and non-gynaecological cytology samples. A unique physical artefact caused by the compression at the periphery in TP slides has not been adequately evaluated to date. METHODS: We processed four established tumour cell lines (MKN28, MKN45, KG-1 and NB4) and mononuclear cells isolated from whole blood over Ficoll-Plaque for TP preparations. For this part of the study, we included five normal cervical LBC preparations. We then auto-counted and auto-measured the area, mean grey value and Feret's diameter in both the inner disc and peripheral rim of the preparations by image morphometry. In addition, we compared the distribution of atypical cell groups in the peripheral rim and inner disc of 132 lung aspirates, 80 thyroid aspirates, 212 cerebrospinal fluids (CSFs) and 50 gynaecological samples. RESULTS: The areas and Feret's diameters of the cytoplasm in the peripheral compressed rim area were statistically larger than those of cells in the inner disc. The mean grey values of cells (cytoplasm and nucleus) in the peripheral compression rim were also smaller than those in the inner disc cells, leading to decreases in nuclear and cytoplasmic chromatism. Except for the mean grey values, the differences were not significant in the cervical samples. CONCLUSIONS: Cellular morphology may be markedly distorted in the peripheral rim, regardless of cell malignancy, which may lead to the misinterpretation of cells during the screening. Accordingly, cytological diagnosis based on the findings within the peripheral rim should take this phenomenon into account. Compressed cells found in the peripheral rim should be interpreted with caution when TP slides are used for cytopathological diagnosis.
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Biopsia con Aguja Fina/métodos , Citodiagnóstico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Línea Celular Tumoral , Cuello del Útero/patología , Femenino , Humanos , Pulmón/patología , Masculino , Embarazo , Glándula Tiroides/patología , Frotis VaginalRESUMEN
To date, all isolated highly pathogenic avian influenza (HPAI) viruses that cause systemic infection with a high mortality rate in poultry species have been known to belong to either the H5 or H7 subtypes. The HPAI viruses may originate because of the insertion of multiple basic amino acids at the cleavage site of the hemagglutinin protein after the low-pathogenic H5 and H7 viruses have been introduced into poultry. In the present study, we investigated the phylogenetic characteristics of the H5 (n = 4) and H7 (n = 3) low-pathogenic avian influenza (LPAI) viruses isolated from wild birds in Korea by using nucleotide sequences of all 8 gene segments of the viral genome. Further, we evaluated the infectivity, transmissibility, and pathogenic potential of these viruses in chickens. Phylogenetic analysis showed that all viruses used in the study clustered in the Eurasian lineage and were similar to the viruses isolated in Asian countries that share the East Asian-Australasian migratory bird flyway. Our H5N2 isolates could not be replicated and transmitted in chickens, but the H7N8 isolates could efficiently be replicated and transmitted to contact-exposure chickens. In addition, because our H7N8 isolates caused watery diarrhea in chickens, these viruses cannot only serve as progenitors of novel HPAI strains but also potentially cause clinical disease in poultry. Although there have been no reports of LPAI mutation to HPAI in these regions, the wild bird surveillance effort should focus on monitoring the introduction and transmission of the HPAI H5N1 and LPAI H5 and H7 viruses.
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Pollos , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H5N2 del Virus de la Influenza A/patogenicidad , Gripe Aviar/virología , Animales , Brotes de Enfermedades/veterinaria , Subtipo H5N2 del Virus de la Influenza A/genética , Gripe Aviar/epidemiología , Filogenia , República de Corea/epidemiologíaAsunto(s)
Enfermedades de los Perros/virología , Subtipo H3N2 del Virus de la Influenza A , Infecciones por Orthomyxoviridae/veterinaria , Animales , Enfermedades de los Perros/epidemiología , Perros , Infecciones por Orthomyxoviridae/epidemiología , Infecciones por Orthomyxoviridae/virología , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
The aim of this study was to determine whether intranasal administration of Lactobacillus sp. could prevent horizontal transmission of H9N2 avian influenza virus (AIV) in specific-pathogen-free chickens. Three-week-old chickens received 500 µL of 1.5 × 10(9) cfu of Lactobacillus fermentum CJL-112 strain (CJL) intranasally for 7 d before and 14 d after a challenge. Challenged chickens, each inoculated with H9N2 AIV, were kept in either direct or indirect contact with naive chickens, and morbidity and viral shedding were monitored. We demonstrated that the intranasal administration of CJL significantly decreased the number of chickens with viral shedding from the gastrointestinal tract in the indirect contact chickens (P < 0.001) and also significantly reduced viral shedding from the respiratory tract in the challenged (P < 0.05) and the direct contact chickens (P < 0.001) than those in the control group. Hence, the use of this lactobacilli strain may constitute a novel and effectively plausible alternative to prevent and control H9N2 AIV infection in chickens.
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Pollos , Gripe Aviar/transmisión , Limosilactobacillus fermentum/fisiología , Probióticos , Animales , Subtipo H9N2 del Virus de la Influenza A , Gripe Aviar/microbiología , Gripe Aviar/virología , Organismos Libres de Patógenos EspecíficosRESUMEN
BACKGROUND AND STUDY AIMS: The incidence of residual stones after mechanical lithotripsy for retained common bile duct (CBD) stones is relatively high. Peroral cholangioscopy using a mother-baby system may be useful for confirming complete extraction of stones, but has several limitations regarding routine use. We evaluated the role of direct peroral cholangioscopy (DPOC) using an ultraslim upper endoscope for the evaluation and removal of residual CBD stones after mechanical lithotripsy. PATIENTS AND METHODS: From August 2006 to November 2010, 48 patients who had undergone mechanical lithotripsy for retained CBD stones with no evidence of filling defects in balloon cholangiography were recruited. The bile duct was inspected by DPOC after balloon cholangiography. Detected residual CBD stones were directly retrieved with a basket or balloon catheter under DPOC. The incidence of residual stones detected by DPOC, and the success rate of residual stone retrieval under DPOC were investigated. RESULTS: DPOC was successfully performed in 46 of the 48 patients (95.8%). Of these, 13 patients (28.3%) had residual CBD stones (mean number 1.4, range 1-3; mean diameter 4.5 mm, range 2.3-9.6). The residual stones were removed directly under DPOC in 11 of these patients (84.6%). There were no complications associated with DPOC or stone removal. CONCLUSION: DPOC using an ultraslim upper endoscope is a useful endoscopic procedure for the evaluation and extraction of residual stones after mechanical lithotripsy for retained CBD stones.
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Endoscopía del Sistema Digestivo/métodos , Cálculos Biliares/terapia , Adulto , Anciano , Anciano de 80 o más Años , Colangiopancreatografia Retrógrada Endoscópica , Endoscopía del Sistema Digestivo/instrumentación , Femenino , Estudios de Seguimiento , Cálculos Biliares/diagnóstico , Humanos , Litotricia , Masculino , Persona de Mediana EdadRESUMEN
Polyphenolic compounds present in green tea, particularly catechins, are known to have strong anti-influenza activity. The goal of this study was to determine whether green tea by-products could function as an alternative to common antivirals in animals compared to original green tea. Inhibition of viral cytopathic effects ascertained by neutral red dye uptake was examined with 50% effective (virus-inhibitory) concentrations (EC50)determined. Against the H1N1 virus A/NWS/33, we found the anti-influenza activity of green tea by-products (EC50 = 6.36 µg/mL) to be equivalent to that of original green tea (EC50= 6.72 µg/mL). The anti-influenza activity of green tea by-products was further examined in mouse and chicken influenza infection models. In mice, oral administration of green tea by-products reduced viral titers in the lungs in the early phase of infection, but they could not protect these animals from disease and death. In contrast, therapeutic administration of green tea by-products via feed or water supplement resulted in a dose-dependent significant antiviral effect in chickens, with a dose of 10 g/kg of feed being the most effective (P < 0.001). We also demonstrated that unidentified hexane-soluble fractions of green tea by-products possessed strong anti-influenza activity, in addition to ethyl acetate-soluble fractions, including catechins. This study revealed green tea by-product extracts to be a promising novel antiviral resource for animals.
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Antivirales/administración & dosificación , Camellia sinensis/química , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H9N2 del Virus de la Influenza A/efectos de los fármacos , Infecciones por Orthomyxoviridae/veterinaria , Extractos Vegetales/administración & dosificación , Administración Intranasal/veterinaria , Administración Oral , Animales , Antivirales/química , Antivirales/farmacología , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Línea Celular , Pollos , Pruebas de Inhibición de Hemaglutinación/veterinaria , Ratones , Ratones Endogámicos BALB C , Neuraminidasa/antagonistas & inhibidores , Rojo Neutro/química , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Organismos Libres de Patógenos EspecíficosRESUMEN
The frequent economic losses incurred with H9N2 low pathogenic avian influenza viruses (LPAI) infection have raised serious concerns for the poultry industry. A 1-dose regimen with inactivated H9N2 LPAI vaccine could not prevent vaccinated poultry from becoming infected and from shedding wild viruses. A study was conducted to determine whether a 2-dose regimen of inactivated H9N2 LPAI vaccine could enhance the immunologic response in chickens. Such gel-primed and mineral oil-boosted regimen has produced encouraging results associated with improved immune responses to an H9N2 LPAI. This strategy could be cost effective and helpful for preventing avian influenza virus in the poultry industry.
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Pollos , Subtipo H9N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Aviar/prevención & control , Adyuvantes Inmunológicos , Animales , Anticuerpos Antivirales/sangre , Geles , Esquemas de Inmunización , Inmunización Secundaria , Aceite Mineral , Organismos Libres de Patógenos Específicos , Vacunas de Productos InactivadosRESUMEN
Measurements in urban Atlanta of transient aerosol events in which PM2.5 mass concentrations rapidly rise and fall over a period of 3-6 hr are reported. The data are based on new measurement techniques demonstrated at the U.S. Environmental Protection Agency (EPA) Atlanta Supersite Experiment in August 1999. These independent instruments for aerosol chemical speciation of NO3-, SO4(2-), NH4+, and organic and elemental carbon (OC and EC), reconstructed the observed hourly dry PM2.5 mass to within 20% or better. Data from the experiment indicated that transient PM2.5 events were ubiquitous in Atlanta and were typically characterized by a sudden increase of EC (soot) and OC in the early morning or SO4(2-) in the late afternoon. The frequent temporal decoupling of these events provides insights into their origins, suggesting mobile sources in metro Atlanta as the main contributor to early morning PM2.5 and more regionally located point SO2 sources for afternoon PM2.5 events. The transient events may also have health implications. New data suggest that short-term PM2.5 exposures may lead to adverse health effects. Standard integrated filter-based techniques used in PM2.5 compliance monitoring networks and in most past PM2.5 epidemiologic studies collect samples over 24-hr periods and thus are unable to capture these transient events. Moreover, health-effects studies that focus on daily PM2.5 mass alone cannot evaluate the health implications of the unique and variable chemical properties of these episodes.
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Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Residuos Peligrosos , Aerosoles/efectos adversos , Contaminantes Atmosféricos/efectos adversos , Ciudades , Monitoreo del Ambiente , Georgia , Humanos , Tamaño de la Partícula , Salud Pública , Factores de TiempoRESUMEN
BACKGROUND: The myocardial sleeve of the superior vena cava (SVC) has been identified as a potential initiating focus in atrial fibrillation, but information on cell-to-cell linkage at this site is lacking. METHODS AND RESULTS: We examined the SVC in 8 dogs by immunoconfocal and electron microscopy. Cardiomyocytes outlined with vinculin and bearing striations positive for alpha-actinin are found in the proximal segment of the SVC. These cells, grouped in bundles of various orientations according to location, extend cephalically as far as 3 cm from the right atrium (RA)-SVC junction. Comparison between the junctional level and the level 2 cm distal shows that the myocardial layer in the latter is thinner and not as compact and is composed of longer cells (87.3+/-15.7 versus 71.6+/-14.4 micrometer, P<0.01). Gap junctions made of connexin43 (Cx43), Cx40, and Cx45 are aggregated mainly at the intercalated disks, and colocalization of connexins is a common feature throughout the myocardial sleeve. Areas of atypical expression exist, however, characterized by a center of abundant Cx43 labels surrounded by a periphery of scattered tiny Cx40-labeled spots. Although in the ventral subluminal compact myocardial layer, individual cells at both levels are surrounded by similar numbers of cells, the number of aggregation of labeled gap junctions at the distal level is less (2.3+/-0.6 versus 3.7+/-0.9, P<0.01). In addition, electron-microscopic examination demonstrates that the gap junctions at the distal level are smaller in size (0.37+/-0.30 versus 0.55+/-0.34 micrometer, P<0.01). CONCLUSIONS: The myocardial sleeve in the canine SVC is a heterogeneous structure, which could potentially form a substrate for heterogeneity of electrical coupling.
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Uniones Comunicantes/metabolismo , Miocardio/metabolismo , Vena Cava Superior/metabolismo , Actinina/análisis , Animales , Conexina 43/análisis , Conexinas/análisis , Perros , Uniones Comunicantes/ultraestructura , Corazón/anatomía & histología , Inmunohistoquímica , Microscopía Confocal , Microscopía Electrónica , Miocardio/ultraestructura , Vena Cava Superior/ultraestructura , Factor de von Willebrand/análisis , Proteína alfa-5 de Unión ComunicanteRESUMEN
Determination and differentiation of skeletal muscle precursors requires cell-cell contact, but the full range of cell surface proteins that mediate this requirement and the mechanisms by which they work are not known. To identify participants in cell contact-mediated regulation of myogenesis, genes that encode secreted proteins specifically upregulated during differentiation of C2C12 myoblasts were identified by the yeast signal sequence trap method (K. A. Jacobs, L. A. Collins-Racie, M. Colbert, M. Duckett, M. Golden-Fleet, K. Kelleher, R. Kriz, E. R. La Vallie, D. Merberg, V. Spaulding, J. Stover, M. J. Williamson, and J. M. McCoy, Gene 198:289-296, 1997), followed by RNA expression analysis. We report here the identification of CD164 as a gene expressed in proliferating C2C12 cells that is upregulated during differentiation. CD164 encodes a widely expressed cell surface sialomucin that has been implicated in regulation of cell proliferation and adhesion during hematopoiesis. Stable overexpression of CD164 in C2C12 and F3 myoblasts enhanced their differentiation, as assessed by both morphological and biochemical criteria. Furthermore, expression of antisense CD164 or soluble extracellular regions of CD164 inhibited myogenic differentiation. Treatment of C2C12 cells with sialidase or O-sialoglycoprotease, two enzymes previously reported to destroy functional epitopes on CD164, also inhibited differentiation. These data indicate that (i) CD164 may play a rate-limiting role in differentiation of cultured myoblasts, (ii) sialomucins represent a class of potential effectors of cell contact-mediated regulation of myogenesis, and (iii) carbohydrate-based cell recognition may play a role in mediating this phenomenon.
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Antígenos CD , Glicoproteínas de Membrana/fisiología , Mucinas/fisiología , Músculos/citología , Moléculas de Adhesión de Célula Nerviosa , Receptores de Superficie Celular/fisiología , Animales , Antígeno CD146 , Diferenciación Celular , Línea Celular , Endolina , Fibroblastos/citología , Glicoproteínas de Membrana/genética , Metaloendopeptidasas/metabolismo , Ratones , Mucinas/genética , Mucolipidosis/metabolismo , Neuraminidasa/metabolismo , Oligonucleótidos Antisentido , Receptores de Superficie Celular/genética , Saccharomyces cerevisiae , Sialomucinas , Solubilidad , Factores de Transcripción , Regulación hacia ArribaRESUMEN
Substituted isoquinolin-1-ones (1) were synthesized to test their in vitro anticancer activity. 3-Biphenyl-N-methylisoquinolin-1-one (7) showed the most potent anticancer activity against five different human cancer cell lines.
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Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Isoquinolinas/síntesis química , Isoquinolinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
A preparation of water soluble components (EA) was made from carpophores of Elfvingia applanata (Pers.) Karst and its in vitro antiviral activity on vesicular stomatitis virus [(Indiana serotype, VSV(IND)] was investigated by plaque reduction assay. EA exhibited potent antiviral activity on VSV(IND) growth and negligible cytotoxicity on Vero cells, 50% effective concentration (EC50) of 104 microg/ml and 50% cytotoxic concentration (CC50) of 3,793 microg/ml, respectively. Selectivity index (SI, CC50/EC50) of EA on Vero cell and VSV(IND) was about 36.5. EA did not display either a direct virucidal effect on VSV(IND) or induction of antiviral substance by Vero cells upon its treatment. Thus, the mode of antiviral activity of EA was studied at steps of viral adsorption onto cell. When both EA and virus were added to cell monolayers, titer of cell-free virus in culture supernatant increased in ca. 30-40% compared with that of control group and titer of cell-associated virus was 60-100% higher than that of control group. These results suggested that antiviral activity of EA on VSV(IND) might be due to the hindrance of viral entry to cells at either endocytosis or loss of envelope.
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Antivirales/farmacología , Endocitosis/efectos de los fármacos , Polyporaceae , Virus de la Estomatitis Vesicular Indiana/efectos de los fármacos , Proteínas del Envoltorio Viral/efectos de los fármacos , Animales , Chlorocebus aethiops , Endocitosis/fisiología , Interferón-alfa/farmacología , Polyporaceae/química , Solubilidad , Células Vero , Virus de la Estomatitis Vesicular Indiana/fisiología , Proteínas del Envoltorio Viral/fisiologíaRESUMEN
Nucleic acid molecules with high affinities for a target transcription factor can be introduced into cells as decoy cis-elements to bind these factors and alter gene expression. This review discusses a synthetic single-stranded palindromic oligonucleotide, which self-hybridizes to form a duplex/hairpin and competes with cAMP response element (CRE) enhancers for binding transcription factors. This oligonucleotide inhibits CRE- and Ap-1-directed gene transcription and promotes growth inhibition in vitro and in vivo in a broad spectrum of cancer cells, without adversely affecting normal cell growth. Evidence presented here suggests that the CRE-decoy oligonucleotide can provide a powerful new means of combating cancers, viral diseases, and other pathological conditions by regulating the expression of cAMP-responsive genes.