RESUMEN
The high versatility of graphene has attracted significant attention in many areas of scientific research from electronics to physics and mechanics. One of the most intriguing utilisation of graphene remains however in nanomedicine and synthetic biology. In particular, the last decade has witnessed an exponential growth in the generation of novel candidate therapeutics of multiple biological activities based on graphene constructs with small molecules, such as anti-cancer drugs. In this Digest, we summarise the different synthetic strategies and routes available to fabricate these promising graphene conjugates and the opportunities for the design of multi-functional tools for synthetic biology that they offer.
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Grafito , Nanomedicina , Biología Sintética , Antineoplásicos/síntesis química , Antineoplásicos/química , Diseño de Fármacos , Grafito/químicaRESUMEN
OBJECTIVES: To examine the potential association of human B19 or V9 erythrovirus infection and onset of ANCA-positive vasculitides. METHODS: We tested the sera of 13 adults with newly diagnosed ANCA-positive vasculitides. Each was age- and sex-matched to three sera obtained from healthy controls. All samples were tested for B19- and V9-specific immunoglobulin (Ig) G and IgM antibodies (Ab) (third-generation ELISA), and B19 or V9 DNA was sought with the polymerase chain reaction. Statistical analysis was performed by conditional logistic regression. RESULTS: Patient diagnoses comprised six cases of Wegener's granulomatosis, six of microscopic polyangiitis and one of Churg-Strauss syndrome. IgG Ab to B19 were detected equally in patient and control sera (77 and 79% respectively) (odds ratio=0.84, P=0.84). All 13 cases and 39 controls were negative for IgM Ab and viral DNA. CONCLUSION: These results suggest that neither acute nor chronic B19 or V9 infection is an aetiological factor in ANCA-associated vasculitides.
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Anticuerpos Anticitoplasma de Neutrófilos/sangre , Erythrovirus/aislamiento & purificación , Infecciones por Parvoviridae/complicaciones , Vasculitis/virología , Enfermedad Aguda , Adulto , Anticuerpos Antivirales/sangre , Estudios de Casos y Controles , Enfermedad Crónica , Síndrome de Churg-Strauss/virología , ADN Viral/sangre , Erythrovirus/inmunología , Femenino , Granulomatosis con Poliangitis/virología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Parvovirus B19 Humano/inmunología , Parvovirus B19 Humano/aislamiento & purificaciónRESUMEN
A human rotavirus (isolate M) with an atypical electropherotype with 14 apparent bands of double-stranded RNA was isolated from a chronically infected immunodeficient child. MA-104 cell culture adaptation showed that the M isolate was a mixture of viruses containing standard genes (M0) or rearranged genes: M1 (containing a rearranged gene 7) and M2 (containing rearranged genes 7 and 11). The rearranged gene 7 of virus M1 (gene 7R) was very unusual because it contained two complete open reading frames (ORF). Moreover, serial propagation of virus M1 in cell culture indicated that gene 7R rapidly evolved, leading to a virus with a deleted gene 7R (gene 7RDelta). Gene 7RDelta coded for a modified NSP3 protein (NSP3m) of 599 amino acids (aa) containing a repetition of aa 8 to 296. The virus M3 (containing gene 7RDelta) was not defective in cell culture and actually produced NSP3m. The rearranged gene 11 (gene 11R) had a more usual pattern, with a partial duplication leading to a normal ORF followed by a long 3' untranslated region. The rearrangement in gene 11R was almost identical to some of those previously described, suggesting that there is a hot spot for gene rearrangements at a specific location on the sequence. It has been suggested that in some cases the existence of short direct repeats could favor the occurrence of rearrangement at a specific site. The computer modeling of gene 7 and 11 mRNAs led us to propose a new mechanism for gene rearrangements in which secondary structures, besides short direct repeats, might facilitate and direct the transfer of the RNA polymerase from the 5' to the 3' end of the plus-strand RNA template during the replication step.
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Rotavirus/genética , Proteínas no Estructurales Virales/genética , Proteínas Virales/genética , Regulación Viral de la Expresión Génica , Reordenamiento Génico , Humanos , Proteínas de Unión al ARN/genéticaRESUMEN
Erythrovirus (formerly parvovirus) B19 causes a wide range of diseases in humans, including anemia due to aplastic crisis. Diagnosis of B19 infection relies on serology and the detection of viral DNA by PCR. These techniques are usually thought to detect all erythrovirus field isolates, since the B19 genome is known to undergo few genetic variations. We have detected an erythrovirus (V9) markedly different from B19 in the serum and bone marrow of a child with transient aplastic anemia. The B19 PCR assay yielded a product that hybridized only very weakly to the B19-specific probe and whose sequence diverged more from those of 24 B19 viruses (11 to 14%) than the divergence found within the B19 group (
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Anemia Aplásica/virología , Erythrovirus/genética , Erythrovirus/aislamiento & purificación , Secuencia de Aminoácidos , Secuencia de Bases , Erythrovirus/clasificación , Genoma Viral , Humanos , Datos de Secuencia Molecular , FilogeniaRESUMEN
BACKGROUND: Vasculitides are diseases of unknown origin in the majority of cases, but sometimes are the consequence of viral infections; for instance, hepatitis B virus (HBV)-related polyarteritis nodosa (PAN) or hepatitis C virus (HCV)-associated cryoglobulinaemia. OBJECTIVE: To investigate the role of hepatitis G or GB virus C (GBV-C) in various forms of medium- and small-vessel vasculitides. DESIGN: Retrospective analyses of sera. SETTING: Tertiary care hospital in Bobigny, France. PATIENTS: Fifty-six vasculitides: 19 HBV-PAN, 10 PAN without HBV infection, 11 microscopic polyangiitis (MPA), seven Churg-Strauss syndrome (CSS) and nine Wegener's granulomatosis (WG). Every sample was collected before treatment. MEASUREMENTS: GBV-C RNA was detected using a reverse transcription-polymerase chain reaction assay with primers derived from the conserved GBV-C helicase and NS5a regions. RESULTS: GBV-C was detected in five of the 56 samples (8.9%): four patients with HBV-related PAN and one with MPA; three of these patients (two with HBV-PAN, one with MPA) had been transfused and two HBV-PAN were i.v. drug addicts. GBV-C was not found in CSS or in WG. CONCLUSION: GBV-C infection was observed only in patients who had been transfused or who were addicts. This virus is unlikely to have a primary role in vasculitides.
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Flaviviridae/inmunología , Hepatitis Viral Humana/diagnóstico , Vasculitis/diagnóstico , Vasculitis/virología , Anticuerpos Antivirales/sangre , Southern Blotting , ADN Viral/análisis , Flaviviridae/genética , Flaviviridae/aislamiento & purificación , Humanos , Inyecciones Intravenosas , Necrosis , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trastornos Relacionados con Sustancias/virología , Vasculitis/patologíaRESUMEN
The authors report 4 personal cases, and analyse 18 cases of anterior pituitary insufficiency in the elderly found in the world literature. The initial symptoms are not specific and are difficult to interpret. They are frequently attributed to physiological ageing. In the absence of early diagnois, the patient may become comatose, this coma is often irreversible in spite of hormone treatment. In 60% of cases, the cause of the pituitary failure was not found. In the onset of the latter, the role of ageing on pituitary function, the responsibility of circulatory failure between the hypothalamus and the pituitary and, finally, the existence of auto-immune mechanisms are then discussed.