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1.
J Oral Rehabil ; 43(4): 286-90, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26440476

RESUMEN

Removable dentures are a non-invasive, cost-effective prosthodontic solution for the reduced dentition. Their intended purpose is the rehabilitation of harmonious oral function and aesthetics on a long-term basis. The prevalence of removable dentures among patients of advanced age is high and the quality of the dentures is often poor. The aim of this study was to find the most important shortcomings of removable dentures and address the main targets for improving the quality of prosthodontic rehabilitation. The records from dental check-ups in Austrian residential homes were analysed retrospectively. Dental anamnesis questionnaires and data from the clinical examinations of 105 denture wearers were analysed. The functional condition and retention of 192 dentures had been assessed, as well as the impact of the dentures on the intra-oral tissues. Insufficient denture retention was very common, particularly in the lower jaw (56·0%). Problems with the masticatory function were reported by 26.7% of the denture wearers, 11·4% were dissatisfied with the denture aesthetics, and 4·8% had difficulties with phonetics. Traumatic ulcers were found in 18·1%. Cracks, broken pieces (6·3%) or missing denture teeth (2·1%) were rare. It may be assumed that the findings of the present study also apply to a great percentage of community-dwelling seniors. The most important issues in prosthodontic rehabilitation with removable dentures are denture retention and masticatory function. Regular dental check-ups, denture adjustment and, when necessary, relining can maintain the primary denture quality and prevent damages of the oral tissues caused by ill-fitting dentures.


Asunto(s)
Dentadura Completa , Dentadura Parcial Removible , Arcada Parcialmente Edéntula/rehabilitación , Masticación/fisiología , Prostodoncia , Anciano , Anciano de 80 o más Años , Austria/epidemiología , Alisadura de la Restauración Dental , Estética Dental/psicología , Femenino , Humanos , Arcada Parcialmente Edéntula/psicología , Arcada Parcialmente Edéntula/terapia , Cuidados a Largo Plazo , Masculino , Persona de Mediana Edad , Salud Bucal , Evaluación del Resultado de la Atención al Paciente , Satisfacción del Paciente/estadística & datos numéricos , Prostodoncia/economía , Calidad de Vida
2.
J Environ Manage ; 183(Pt 3): 794-805, 2016 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-27658655

RESUMEN

Worldwide the renewable energy sector is expanding at sea to address increasing demands. Recently the race for space in heavily used areas such as the North Sea triggered the proposal of co-locating other activities such as aquaculture or fisheries with passive gears in offshore wind farms (OWFs). Our interdisciplinary approach combined a quantification of spatial overlap of activities by using Vessel Monitoring System and logbook data with a stakeholder consultation to conclude and verify on the actual feasibility of co-location. In the German Exclusive Economic Zone (EEZ) of the North Sea up to 90% of Danish and 40% of German annual gillnet fleet landings of plaice overlapped with areas where OWFs are developed. Our results indicated further that the international gillnet fishery could lose up to 50% in landings within the North Sea German EEZ when OWF areas are closed entirely for fisheries. No spatial overlap was found for UK potters targeting brown crab in the German EEZ. We further identified a number of key issues and obstacles that to date hinder an actual implementation of co-location as a measure in the marine spatial planning process: defining the legal base; implementation of safety regulations; delineation of minimum requirements for fishing vessels such as capacities, quotas, technical equipment; implementation of a licensing process; and scoping for financial subsidies to set up business. The stakeholder consultation verified the scientific findings and highlighted that all those points need to be addressed in a planning process. In the German EEZ we have shown that the socio-economic importance of spatial overlap varies within planning boundaries. Therefore we recommend an interdisciplinary bottom-up approach when scoping for suitable areas of co-location. Hence, an informed marine spatial planning process requires comprehensive and spatial explicit socio-economic viability studies factoring in also ecological effects of OWFs on target species.


Asunto(s)
Explotaciones Pesqueras , Energía Renovable , Viento , Animales , Alemania , Mar del Norte , Opinión Pública , Factores Socioeconómicos
3.
Orthopade ; 41(9): 742-8, 2012 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-22825055

RESUMEN

The frequency of infectious diseases of the spine and associated spinal cord injury are constantly increasing. Affected are multimorbid and elderly patients, mostly after prolonged medical treatment. An acute spinal cord injury due to infection is an emergency. A rapid decision for treatment strategy and if at all possible subtle debridement of the infected tissue with decompression of the spinal cord is paramount. Additionally spinal cord injury necessitates specialized treatment and care of the infection. Spinal cord injured patients in general and these patients in particular are prone to complications and need especially trained nursing personnel. It is therefore recommended that patients with vertebral osteomyelitis associated with spinal cord injury should be transferred to dedicated centres of treatment as soon as possible.Just as in cases of spondylodiscitis without spinal cord injury inconsistent surgical or insufficient antibiotic treatment worsens the prognosis significantly. If it is possible to remit the infection, the prognosis for recovery of motor and sensory function is better than in cases with traumatic spinal cord injury. In many cases at least partial recovery can be observed.


Asunto(s)
Osteomielitis/terapia , Paraplejía/terapia , Traumatismos de la Médula Espinal/terapia , Espondilitis/terapia , Humanos , Osteomielitis/complicaciones , Paraplejía/etiología , Traumatismos de la Médula Espinal/complicaciones , Espondilitis/complicaciones
4.
J Virol ; 83(18): 9512-20, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19587054

RESUMEN

The requirement for multiple mutations for protease inhibitor (PI) resistance necessitates a better understanding of the molecular basis of resistance development. The novel bioinformatics resistance determination approach presented here elaborates on genetic profiles observed in clinical human immunodeficiency virus type 1 (HIV-1) isolates. Synthetic protease sequences were cloned in a wild-type HIV-1 background to generate a large number of close variants, covering 69 mutation clusters between multi-PI-resistant viruses and their corresponding genetically closely related, but PI-susceptible, counterparts. The vast number of mutants generated facilitates a profound and broad analysis of the influence of the background on the effect of individual PI resistance-associated mutations (PI-RAMs) on PI susceptibility. Within a set of viruses, all PI-RAMs that differed between susceptible and resistant viruses were varied while maintaining the background sequence from the resistant virus. The PI darunavir was used to evaluate PI susceptibility. Single sets allowed delineation of the impact of individual mutations on PI susceptibility, as well as the influence of PI-RAMs on one another. Comparing across sets, it could be inferred how the background influenced the interaction between two mutations, in some cases even changing antagonistic relationships into synergistic ones or vice versa. The approach elaborates on patient data and demonstrates how the specific mutational background greatly influences the impact of individual mutations on PI susceptibility in clinical patterns.


Asunto(s)
Farmacorresistencia Viral/genética , Proteasa del VIH/genética , VIH-1/fisiología , Mutación/fisiología , Secuencia de Aminoácidos , Clonación Molecular , Biología Computacional , Inhibidores de la Proteasa del VIH/farmacología , VIH-1/enzimología , Humanos , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/genética
5.
J Clin Invest ; 95(1): 328-32, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7814633

RESUMEN

The replication of human immunodeficiency retroviruses involves a complex series of events that is regulated at both transcriptional and posttranscriptional levels. The tat gene product is a potent trans-activator of viral transcription and therefore an attractive target for the development of antiviral drugs. Tat-defective HIV-1 proviral DNA clones have been shown previously to be replication defective. In this study, we report that tat-defective HIV-1 and HIV-2 viral DNA transfected into U937 cells can direct efficient viral replication in the presence of transcriptional stimulators such as TNF-alpha and PMA. In MT-4 cells, tat-defective HIV-1 can replicate without any stimulation. The viruses recovered from MT-4 cells remained tat defective defined by their inability to infect T cell lines (e.g., Molt 4/8) although replication could be rescued with cytokines. Limited replication was observed in primary mononuclear cells. Furthermore, we showed that Ro 24-7429, a potent tat antagonist and antiviral compound, failed to suppress HIV-1 replication in TNF-alpha-stimulated T cells. These results have important implications for targeting tat as a therapeutic strategy for AIDS.


Asunto(s)
Benzodiazepinas/farmacología , Productos del Gen tat/metabolismo , VIH/crecimiento & desarrollo , Monocitos/virología , Pirroles , Factor de Necrosis Tumoral alfa/farmacología , Línea Celular , Virus Defectuosos/crecimiento & desarrollo , Antagonismo de Drogas , Productos del Gen tat/antagonistas & inhibidores , VIH-1/crecimiento & desarrollo , VIH-2/crecimiento & desarrollo , Humanos , Linfocitos T/virología , Acetato de Tetradecanoilforbol/farmacología , Transfección , Replicación Viral , Productos del Gen tat del Virus de la Inmunodeficiencia Humana
6.
Poult Sci ; 85(10): 1795-7, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17012171

RESUMEN

Based on evidence from rodent models, it was hypothesized that furan fatty acids found in corn would inhibit reproduction in the laying hen. An isomeric mixture of furan fatty acids [9, (12)-oxy-10,13-dihydroxystearic acid and 10, (13)-oxy-9,12-dihydroxystearic acid] was administered for a period of 3 wk via the diet (1 and 3 ppm) at levels greater than those in corn to 20-wk-old pullets. There were no overt indications of acute or chronic toxicity (no effects on mortality, feed intake, or average daily gain). Similarly, there was no dose-dependent effect on reproductive parameters [egg production, egg weight, shell thickness, ovarian weight, number or weight of large yolky preovulatory follicles, and number of small yellow follicles (4-8 mm in diameter)]. The present data do not suggest that furan fatty acids are a cause of concern to the poultry industry.


Asunto(s)
Pollos/fisiología , Ácidos Grasos/química , Ácidos Grasos/toxicidad , Reproducción/efectos de los fármacos , Ácidos Esteáricos/química , Ácidos Esteáricos/toxicidad , Zea mays/química , Alimentación Animal , Animales , Peso Corporal , Dieta/veterinaria , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Ácidos Grasos/administración & dosificación , Femenino , Tamaño de los Órganos , Ovario/anatomía & histología , Ovario/efectos de los fármacos , Oviposición/efectos de los fármacos , Reproducción/fisiología , Ácidos Esteáricos/administración & dosificación
7.
Methods Enzymol ; 572: 193-213, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27241755

RESUMEN

Cell communications are essential to the organization, development, and maintenance of multicellular organisms. Much of this communication involves changes in RNA transcription and is dynamic. Most methods for studying transcription require interrupting the continuity of cellular function by sacrificing the communicating cells and capturing gene expression information by periodic sampling of individual cells or the population. The IMAGEtag technology to quantify RNA levels in living cells, demonstrated here in yeast, allows individual cells to be tracked over time as they respond to different environmental cues. IMAGEtags are short RNAs consisting of strings of a variable number of tandem aptamers that bind small-molecule ligands. The aptamer strings can vary in length and in configuration of aptamer constituents, such as to contain multiples of the same aptamer or two or more different aptamers that alternate in their occurrence. A minimum effective length is about five aptamers. The maximum length is undefined. The small-molecule ligands are enabled for imaging as fluorophore conjugates. For each IMAGEtag, two fluorophore conjugates are provided, which are FRET pairs. When a cell expresses an RNA containing an IMAGEtag sequence, the aptamers bind their ligands and bring the fluorophores into sufficiently close proximity to allow FRET. The background fluorescence of both fluorophores is minimal in the FRET channel. These features endow IMAGEtags with the sensitivity to report on mRNA expression levels in living cells.


Asunto(s)
Aptámeros de Nucleótidos/química , Transferencia Resonante de Energía de Fluorescencia/métodos , Colorantes Fluorescentes/análisis , ARN Mensajero/genética , Transcripción Genética , Levaduras/genética , Aptámeros de Nucleótidos/genética , Secuencia de Bases , Clonación Molecular/métodos , Ligandos , Imagen Óptica/métodos , ARN Mensajero/análisis
8.
Photochem Photobiol ; 81(4): 924-33, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15884972

RESUMEN

Hydroxy and methoxy perylene quinones are synthesized in an attempt to isolate the essential spectroscopic and biological features of light-induced antiviral agents such as hypericin and hypocrellin. Unlike their naturally occurring counterparts, these synthetic quinones bear the carbonyl, hydroxyl, and methoxy groups in the "bay region." The hydroxy and methoxy compounds have rich absorption spectra with broad features in the visible (approximately 450-800 nm) and relatively more intense and narrow features at wavelengths < or = 350 nm. High-level ab initio quantum mechanical calculations assign the features in the absorption spectra to electronic transitions from S0 to S2 and to higher-lying electronic states. The calculations indicate that in the ground state the trans dihydroxy isomer is 12.5 kcal/mol lower in energy than the cis dihydroxy isomer and is thus the only species present. The lowest-energy trans methoxy ground state isomer and the lowest-energy cis methoxy ground state isomer are found to be degenerate. An additional cis methoxy isomer 6.3 kcal/mol higher in energy than the global minimum is assumed to contribute to the spectrum and is also considered. Finally, the synthetic compounds exhibit similar light-induced antiviral activity to each other, but significantly less than that of hypericin.


Asunto(s)
Antivirales/farmacología , Perileno/análogos & derivados , Quinonas/síntesis química , Antivirales/química , Perileno/farmacología , Quinonas/farmacología , Espectrometría de Fluorescencia , Espectrofotometría , Relación Estructura-Actividad
9.
Br J Radiol ; 78(928): 355-7, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15774600

RESUMEN

In patients with suspected liver disease, ultrasound is the most commonly performed initial imaging modality. We report a patient who had previously undiagnosed liver cirrhosis with target-shaped lesions interspersed throughout the liver parenchyma on ultrasound seen as multiple uniform round shaped lesions with varying isoechoic to hyperechoic centres surrounded by a hyperechoic rim. We have termed this the "reverse" target sign as there is inversion of the typical echoic pattern that is normally seen in metastatic liver disease. We suggest this ultrasound sign may represent a method for differentiating cirrhotic liver nodules from other nodular liver lesions.


Asunto(s)
Cirrosis Hepática/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler en Color
10.
Hum Gene Ther ; 5(9): 1115-20, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7833371

RESUMEN

We reported previously that human CD4+ T cell lines stably expressing a hairpin ribozyme targeted to the human immunodeficiency virus type 1 (HIV-1) U5 leader sequence were resistant to challenge with diverse HIV-1 viral clones and clinical isolates (Yamada et al., 1994). To simulate more closely the in vivo infection process for investigations of anti-HIV-1 ribozyme gene therapy, we developed a system to transfer this ribozyme gene into freshly isolated human peripheral blood lymphocytes (PBLs) using a murine retrovirus vector. Following transduction and G418 selection, human PBLs from multiple donors expressed the ribozyme and resisted challenge by HIV-1 viral clones and clinical isolates, while control vector-transduced PBLs remained fully permissive for HIV-1 infection. No inhibition of an HIV-2 clone lacking the target was seen in ribozyme-expressing PBLs. Ribozyme expression had no effect on viability or proliferation kinetics of the primary lymphocytes. This study is the first demonstration in primary human T cells of resistance to HIV-1 infection conferred by gene transfer. A human clinical trial is in development to test further the safety and efficacy of this ribozyme in PBLs of HIV-1-infected patients in vivo.


Asunto(s)
Técnicas de Transferencia de Gen , VIH-1/genética , Linfocitos , ARN Catalítico/genética , Replicación Viral , Secuencia de Bases , Células Cultivadas , Resistencia a Medicamentos/genética , Vectores Genéticos , Gentamicinas/farmacología , VIH-1/fisiología , VIH-2/fisiología , Humanos , Inmunidad Innata , Linfocitos/virología , Datos de Secuencia Molecular , ARN Polimerasa III/metabolismo , ARN Catalítico/biosíntesis , Proteínas Recombinantes de Fusión/biosíntesis , Selección Genética
11.
Int J Radiat Oncol Biol Phys ; 49(3): 665-71, 2001 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-11172947

RESUMEN

BACKGROUND: In locally advanced pancreatic cancer, the combination of chemotherapy with radiotherapy is gaining increasing importance; although, in view of the reported long-term results of several contemporary trials, further improvements are certainly warranted. The aim of the present study was to evaluate the effectiveness and safety of a combined-treatment modality consisting of systemic chemotherapy with 24-h continuous infusional gemcitabine and mitomycin C, plus external beam radiotherapy in patients with localized unresectable adenocarcinoma of the pancreas. METHODS AND MATERIALS: Systemic chemotherapy consisted of mitomycin C 8 mg/m2 given as i.v. bolus injection on day 1 and gemcitabine administered as a 24-h continous infusion once weekly for 3 of 4 weeks. The starting dose of gemcitabine was 100 mg/m2 and dose levels were escalated in consecutive cohorts of 3-6 patients to 130 and 160 mg/m2, utilizing an escalating-dose Phase I trial design. Radiation therapy using megavolt irradiation (total dose, 45 Gy, 1.8 Gy/day) of 6 MV photons or greater with a 3- or 4-field technique was delivered concurrently for 5-6 weeks. RESULTS: Between January 1997 and August 1998, a total of 15 patients were enrolled in this trial, all of whom were assessable for toxicity, response, and survival. The dose-limiting toxicities at the 160 mg/m2 gemcitabine level were myelosuppression, specifically neutropenia +/- thrombocytopenia, and gastrointestinal symptoms, including stomatitis, vomiting, and diarrhea. Only 1 partial response was observed (7%), and disease was stabilized in 10 additional patients (67%). The median time to progression was 5.5 months (range, 2-12 months). Whereas all patients developed distant metastases, locoregional failure occurred in only 3. The median survival time was 8.3 months (range, 2.5 to 22.0+ months), and the 1-year survival rate was 13.3%. CONCLUSION: The MTD of gemcitabine when given as prolonged infusion in combination with mitomycin C and radiation therapy was 130 mg/m2/week. Therapeutic results suggest that combined chemoradiation with this regimen is feasible and effective for local control of pancreatic cancer, but essentially ineffective in counteracting metastatic tumor growth.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Adenocarcinoma/patología , Anciano , Terapia Combinada , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Humanos , Inyecciones Intravenosas , Leucopenia/etiología , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Estadificación de Neoplasias , Neutropenia/etiología , Neoplasias Pancreáticas/patología , Análisis de Supervivencia , Trombocitopenia/etiología , Gemcitabina
12.
Transplantation ; 69(12): 2525-30, 2000 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-10910272

RESUMEN

BACKGROUND: Graft vessel disease (GVD) is an important problem often responsible for late graft loss. The effects of FTY720, an immunomodulator with a novel mechanism of action were investigated in combination with cyclosporine A (CsA) in a carotid artery allograft model. METHODS: A segment of the carotid artery of Lewis rats was replaced by a DA allograft. Seven groups of eight rats were treated for 8 weeks with vehicle (P), CsA 0.3 (C0.3), 1 (C1) or 3 (C3) mg x kg(-1).day(-1) or a combination of CsA 1 with FTY 0.01 (C1F0.01), 0.03 (C1F0.03), and 0.1 (C1F0.1) mg x kg(-1).day(-1). Lumen area was estimated by magnetic resonance imaging, peripheral lymphocyte count and drug concentrations were determined at 1 and 8 weeks. Neointima, media, and lumen area were measured morphometrically. Intimal and adventitial infiltration of mononuclear cells, and medial smooth muscle cells number was assessed using a score. RESULTS: FTY720 did not influence CsA blood concentrations. FTY720 but not CsA decreased the PLC dose dependently. Magnetic resonance imaging revealed that treatment groups have larger lumen size than group P. Histological and morphometric evaluation showed that all aspects of GVD were dose dependently suppressed by treatment and lumen narrowing was prevented. CONCLUSIONS: CsA, at clinically relevant blood levels, suppressed GVD only partly. The addition of FTY720 was well tolerated and completely suppressed GVD development. In vivo lumen size did not correlate with the histologically estimated neointimal thickness.


Asunto(s)
Arterias Carótidas/trasplante , Enfermedades de las Arterias Carótidas/prevención & control , Ciclosporina/administración & dosificación , Inmunosupresores/administración & dosificación , Glicoles de Propileno/administración & dosificación , Animales , Arterias Carótidas/patología , Ciclosporina/sangre , Clorhidrato de Fingolimod , Recuento de Linfocitos , Imagen por Resonancia Magnética , Masculino , Músculo Liso Vascular/patología , Glicoles de Propileno/sangre , Ratas , Ratas Endogámicas Lew , Esfingosina/análogos & derivados
13.
Clin Pharmacokinet ; 18(1): 77-81, 1990 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-2311331

RESUMEN

The pharmacokinetic and pharmacodynamic properties of the H2-receptor antagonist famotidine have been well described in adult subjects. However, similar data for children are not available. Therefore, this study looked at the disposition of the drug (given to prevent aspiration following cardiac surgery) in 10 paediatric patients with normal kidney function (age range 2 to 7 years, bodyweight 14 to 25 kg) after a single intravenous dose of famotidine 0.3 mg/kg. Plasma concentrations of the drug and gastric pH values were both monitored for 20 hours by high performance liquid chromatography and aspiration of gastric juice, respectively. Plasma famotidine concentrations declined with an elimination half-life of 3.3 +/- 1.8 h (mean +/- SD) and the drug was effective in elevating the gastric pH above 3.5 for about 9 hours in 6 patients. The variable volume of distribution and total plasma clearance of famotidine averaged 1.4 +/- 1.0 L/kg and 0.3 +/- 0.17 L/h/kg, respectively. In 4 patients unchanged famotidine could also be measured in a 12-hour urine fraction. The amount excreted (21 to 79%) correlated with clearance (r = 0.97). All these data are comparable to those obtained in healthy adults, indicating that paediatric patients receiving intensive medical treatment after cardiac surgery can handle famotidine in a way very similar to healthy adult subjects. A dosage of 0.3 mg/kg every 8 hours appears to be advisable.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Famotidina/farmacocinética , Ácido Gástrico/metabolismo , Cuidados Posoperatorios , Niño , Preescolar , Famotidina/uso terapéutico , Humanos
14.
AIDS Res Hum Retroviruses ; 11(6): 663-9, 1995 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7576925

RESUMEN

The TAt protein of the human immunodeficiency virus type 1 (HIV-1) activates the expression of viral mRNA through a cis-acting element in the LTR termed TAR. TAR RNA forms a stable stem-loop structure. Mutagenesis studies indicate that the stem structure, the primary sequence of the loop, and three unpaired bases in the stem (bulge) are important for Tat activation. Using the in vitro-transcribed TAR RNA as a probe, we have cloned a gene (TARBP-b) that encodes a TAR-binding protein from a cDNA expression library derived from Hut-78 cells. Expression of the 1.4-kb TARBP-b mRNA was observed in all mammalian cell lines tested. TARBP-b binds specifically to the bulge region of TAR RNA and trans-activates the HIV-1 long terminal repeat in the presence of ptat and prev expression plasmids. These results suggest that TARBP-b contributes to tat-mediated trans-activation.


Asunto(s)
VIH-1/genética , ARN Viral/metabolismo , Proteínas de Unión al ARN/genética , Linfocitos T/virología , Activación Transcripcional/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Línea Celular , Regulación Viral de la Expresión Génica/genética , Productos del Gen rev/fisiología , Productos del Gen tat/fisiología , Genes Virales/genética , Duplicado del Terminal Largo de VIH/genética , Humanos , Linfocitos/virología , Ratones , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Sondas ARN , ARN Mensajero/biosíntesis , ARN Viral/química , Proteínas de Unión al ARN/química , Análisis de Secuencia de ADN , Productos del Gen rev del Virus de la Inmunodeficiencia Humana , Productos del Gen tat del Virus de la Inmunodeficiencia Humana
15.
AIDS Res Hum Retroviruses ; 11(7): 795-804, 1995 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-7546906

RESUMEN

The rev gene product of human immunodeficiency virus (HIV) is obligatory for viral replication. Rev interacts specifically with a structured RNA sequence within the viral genome termed the REV response element (RRE). Although the importance of Rev for the expression of viral proteins is well documented, its functional mechanism remains unresolved. Previous studies identified Rev in the absence of RRE to be a nuclear protein localized primarily within the nucleoli. To extend our understanding of the role of Rev in viral replication, immunolocalization studies of Rev and other nuclear components were carried out in transfected cells expressing both the Rev protein and RRE-containing mRNA and in cells infected with HIV. In both types of cells, Rev-like immunoreactivity was distributed both in the nucleoplasm and cytoplasm. Within the nucleus, Rev immunoreactivity was not evenly distributed but was present within focal concentrations. In transfected cells that were double labeled for Rev and SC-35, which labels a known component of spliceosomes, the foci of Rev labeling were distinct from the "speckles" labeled by SC-35, although Rev foci and speckles were often juxtaposed. In addition, morphological changes in the three-dimensional network of speckles were observed in both transfected cells expressing both the Rev protein and RRE-containing mRNA and in cells infected with HIV-1 and HIV-2. Our observations are consistent with the proposed dual role of Rev in mRNA transport and splicing.


Asunto(s)
Productos del Gen rev/análisis , VIH-2/fisiología , Replicación Viral , Secuencia de Bases , Nucléolo Celular/virología , Cartilla de ADN , Expresión Génica , Productos del Gen rev/biosíntesis , Genes rev , Genoma Viral , VIH-2/genética , Células HeLa , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Proteínas Recombinantes/análisis , Proteínas Recombinantes/biosíntesis , Mapeo Restrictivo , Transfección , Proteínas Virales/biosíntesis , Productos del Gen rev del Virus de la Inmunodeficiencia Humana
16.
AIDS Res Hum Retroviruses ; 14(1): 65-77, 1998 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-9453253

RESUMEN

A lambda phage clone containing a full-length HIV-2 provirus, designated HIV-2KR, was obtained from the genomic DNA of Molt4 clone 8 (Molt4/8) lymphoblastic cells infected with the HIV-2PEI2 strain. HIV-2KR is genetically distinct from known HIV-2 isolates, possessing both a unique deletion in the LTR promoter region, and a long rev reading frame. It is replication competent in vitro after transfection into Molt4/8 cells, replicates in a variety of established human T lymphoblastic (Molt-3, Molt4/8, SupT1, H9, C8166) and myelomonocytic (U937) cell lines, and displays prominent cytopathic effects on infection of Molt4/8 cells, reflecting usage of both CCR5 and CXCR4 coreceptors. In addition, HIV-2KR was found to be infectious for human and Macaca nemestrina peripheral blood lymphocytes, and primary human monocyte-macrophage cultures. Intravenous inoculation of cell-free virus into M. nemestrina resulted in infection characterized by transient, low-level viremia and modest temporary decline in CD4 lymphocyte numbers, making HIV-2KR the first HIV-2 molecular clone reported to be infectious for this primate species.


Asunto(s)
Infecciones por VIH/virología , VIH-2/genética , Macaca nemestrina , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Modelos Animales de Enfermedad , VIH-2/clasificación , VIH-2/patogenicidad , Humanos , Datos de Secuencia Molecular , Fenotipo , Filogenia , Alineación de Secuencia , Homología de Secuencia de Aminoácido
17.
Org Lett ; 2(16): 2409-10, 2000 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-10956508

RESUMEN

The hindered nonionic phosphazene base P(4)-t-Bu efficiently deprotonates o-arylmethoxy benzaldehydes, leading to a direct synthesis of benzofurans. Strong ionic bases such as LDA, LiTMP, and KH failed.


Asunto(s)
Benzaldehídos , Benzofuranos/síntesis química , Benzofuranos/química , Indicadores y Reactivos , Conformación Molecular , Estructura Molecular , Compuestos Organofosforados
18.
Transpl Immunol ; 8(3): 177-87, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11147698

RESUMEN

OBJECTIVE: FTY720 is a new immunosuppressant active in transplantation models, which modulates lymphocyte recirculation, leading to transient peripheral lymphopenia and increased lymphocytes in lymph nodes and Peyer's patches. Here, we investigated the susceptibility of cynomolgus monkeys to FTY720 given orally either alone or in combination with two other immunosuppressants, Cyclosporin Neoral or RAD, as an introductory study to transplantation protocols. METHODS: Each of the three phases of the study comprised a 3-week treatment period with FTY720 administered daily orally at 0.3, 0.1 or 0.03 mg/kg/day, respectively, followed by a 3-week recovery. FTY720 was given as single compound during the first week and in combination with Neoral at 20 mg/kg/day p.o. or RAD at 0.5 mg/kg/day p.o. during the subsequent 2 weeks. MAIN FINDINGS: These treatment regimen were well tolerated, except for some body weight loss at high FTY720 dose (0.3 mg/kg/day). FTY720 treatment resulted in a rapid decrease of white blood cell counts which reached a plateau after 3 days. A decrease in both T- and B-lymphocyte counts by up to 80-90% was seen with FTY720 doses of 0.1 and 0.3 mg/kg/day. FTY720 blood levels, both trough levels and AUC(0-24 h), showed a linear relationship with FTY720 dose. The reduction in lymphocyte counts was not directly proportional to FTY720 blood levels. The exposure to FTY720 significantly increased upon coadministration of Neoral. This pharmacokinetic interaction was not observed for coadministration of RAD. However, the peripheral lymphodepletion was slightly increased after coadministration of RAD but not of Neoral. This may be related to the intrinsic effects of RAD on hematopoietic cells. CONCLUSIONS: FTY720 given orally was effective in terms of peripheral T- and B-lymphodepletion and was well tolerated in cynomolgus monkeys even in combination with Cyclosporine Neoral or RAD, indicating that such combination protocols could be used in allo- and xenotransplantation in this species. However, the data indicate a potentiation of FTY720 exposure by CsA coadministration and additional lymphodepletion by coadministration of FTY720 and RAD which should be carefully monitored.


Asunto(s)
Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Inmunosupresores/farmacología , Depleción Linfocítica/métodos , Glicoles de Propileno/farmacología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Administración Oral , Animales , Ciclosporina/administración & dosificación , Relación Dosis-Respuesta a Droga , Tolerancia a Medicamentos , Everolimus , Clorhidrato de Fingolimod , Inmunosupresores/administración & dosificación , Inmunosupresores/sangre , Recuento de Linfocitos , Macaca fascicularis , Glicoles de Propileno/administración & dosificación , Glicoles de Propileno/sangre , Sirolimus/administración & dosificación , Sirolimus/análogos & derivados , Esfingosina/análogos & derivados , Inmunología del Trasplante
19.
Transpl Immunol ; 7(3): 149-57, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10608298

RESUMEN

OBJECTIVE: FTY720, a new immunosuppressant active in transplantation models, modulates lymphocyte re-circulation, leading to peripheral lymphopenia and increased lymphocytes in lymph nodes and Peyer's patches. Here, we investigated the susceptibility of baboons to FTY720 as an introductory study to transplantation protocols. METHODS: FTY720 was administered orally to Chacma baboons at 0.3 or 0.1 mg/kg/day for 3 days or at 0.03 mg/kg/day for 10 days. Haematological parameters, lymphocyte phenotype (CD3, CD4, CD8, CD20), cell apoptosis, ex vivo blood cell proliferation in response to mitogens and drug blood levels were monitored during treatment and up to 4 weeks thereafter. MAIN FINDINGS: FTY720 administered p.o. in baboons at 0.3 mg/kg/day caused a marked decrease in circulating lymphocytes within 4 h of treatment, reaching 60-80% decrease within 24-48 h. The effect of FTY720 was seen both on T- and B cells, although it was slightly more rapid/pronounced on T cells. CD4+ cells were slightly more affected than CD8+ cells. The response onset was faster and the duration longer at higher dose, but the maximal peripheral lymphodepletion achieved was similar within the dose range 0.03-0.3 mg/kg tested. Ex vivo mitogen-induced lymphoproliferation was drastically decreased after FTY720 treatment, corresponding to the reduced blood lymphocyte counts. The blood drug levels measured after FTY720 administration correlated well with the dose applied but there was a poor correlation between FTY720 blood levels and the extent of peripheral lymphodepletion, suggestive of a high tissue distribution of the drug. When compared with cynomolgus monkeys treated in the same way, baboons had a lower initial exposure and a slightly lower response 24 h after one or two doses of FTY720 0.03-0.3 mg/kg. However, the stabilized drug blood levels and peripheral lymphodepletion achieved after 7 days of FTY720 0.03 mg/kg/day were similar in both nonhuman primate species. CONCLUSIONS: FTY720 was well tolerated and was effective in terms of peripheral T- and B lymphodepletion in baboons, indicating that it could be used in protocols of allo- and xenotransplantation. The pharmacokinetic and pharmacodynamic profiles of FTY720 in baboons suggest the use of high induction doses to optimize immediate response followed by a reduced dose regimen for drug maintenance.


Asunto(s)
Linfocitos B/efectos de los fármacos , Inmunosupresores/farmacología , Depleción Linfocítica/métodos , Glicoles de Propileno/farmacología , Linfocitos T/efectos de los fármacos , Animales , Linfocitos B/citología , Linfocitos B/inmunología , Relación Dosis-Respuesta a Droga , Clorhidrato de Fingolimod , Inmunosupresores/administración & dosificación , Inmunosupresores/sangre , Técnicas In Vitro , Activación de Linfocitos/efectos de los fármacos , Recuento de Linfocitos , Macaca fascicularis , Papio , Glicoles de Propileno/administración & dosificación , Glicoles de Propileno/sangre , Especificidad de la Especie , Esfingosina/análogos & derivados , Linfocitos T/citología , Linfocitos T/inmunología , Inmunología del Trasplante , Trasplante Heterólogo , Trasplante Homólogo
20.
Clin Psychol Rev ; 21(3): 345-73, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11288605

RESUMEN

This article is a summary of some of the more recent research on the diagnosis, etiology, and treatment of Cluster B personality disorders (antisocial, histrionic, borderline, and narcissistic). Research on psychological, psychosocial, and biological perspectives of these disorders is presented. Individual psychotherapy, group psychotherapy, and other forms of multi-person therapies are also discussed. Finally, perspectives on issues of countertransference when treating these personality-disordered patients are addressed.


Asunto(s)
Trastornos de la Personalidad , Psicoterapia , Contratransferencia , Diagnóstico Diferencial , Humanos , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/etiología , Trastornos de la Personalidad/terapia , Psicoterapia de Grupo
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