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1.
Mult Scler Relat Disord ; 45: 102360, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32688302

RESUMEN

BACKGROUND: Multiple sclerosis (MS) is the most common cause of non-traumatic neurological disability affecting young adults during their best working years. Previous studies have shown that approximately two-thirds of patients with MS (PwMS) are unable to retain employment in the long term, and many retire soon after the diagnosis. However, it is not known, how the rate of retirement has changed over the decades, especially after the introduction of disease modifying therapies (DMTs). The year 1995 was selected as a division point because DMTs have been increasingly available ever since. OBJECTIVE: To evaluate the change in retirement rate due to MS and to present risk factors for early retirement. METHODS: A retrospective survey of all PwMS treated at the Department of Neurology, Kanta-Häme Central Hospital, Finland between 1978 and 2015, was conducted. The population was divided into two groups: those diagnosed before year 1995 and those diagnosed thereafter. A Kaplan-Meier analysis was performed to evaluate the time from diagnosis to beginning of a pension in both groups. Crude incidence rates, incidence rate differences as well as age and multivariable adjusted Cox proportional hazard regression analysis were calculated for all pension predictors collected. RESULTS: A total of 484 PwMS were identified, 140 of whom were diagnosed before the year 1995 and 344 after. Actual retirement rates were 88 (63%) before the year the year 1995 and 111 (32%) after, respectively. The hazard for disability pension diminished in PwMS diagnosed after the year 1995 compared to those diagnosed before, HR 0.41 (95% confidence interval 0.31-0.55). The median time from diagnosis to retirement was 8.3 years in the group diagnosed before year 1995 and 11.1 years in the group diagnosed later. Male sex and age were statistically significant risk factors in relapsing-remitting MS, HR for male sex 1.8 (95% confidence interval 1.18-2.75) and for age 1.1 (95% confidence interval 1.07-1.12). Only age was a risk factor in progressive MS with HR 1.09 (95% confidence interval 1.07-1.11). In subgroup of relapsing-remitting MS, not using disease modifying therapies was a statistically significant risk factor, HR 1.89 (95% confidence interval 1.19-3.01). CONCLUSION: The rate of retirement due to MS in Finland has decreased significantly since 1995 and the median time from diagnosis to retirement has become longer. Not using disease modifying therapies for relapsing remitting MS was identified as one risk factor for losing ability to work prematurely.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Finlandia/epidemiología , Hospitales , Humanos , Lactante , Masculino , Esclerosis Múltiple/epidemiología , Jubilación , Estudios Retrospectivos , Adulto Joven
2.
Allergol. immunopatol ; 44(1): 9-17, ene.-feb. 2016. graf, ilus
Artículo en Inglés | IBECS | ID: ibc-147478

RESUMEN

BACKGROUND: Allergen-specific immunotherapy balances the Th2-biased immunity towards Th1 and Treg responses. Adjuvants are used in allergen preparations to intensify the immune responses. The increased prevalence of allergies in developed societies has been associated with decreased microbial load during childhood. This has initiated a search for microbial structures to be used as adjuvants. Our study has shown that a synthetic triacedimannose (TADM) may suppress the Th2-type allergic inflammatory response. The aim of this study was to compare the properties of TADM with capacities of other adjuvants, CpG ODN and MPL, to modulate cytokine production in PBMC and regulate sensitisation in an OVA-sensitised mouse asthma model. METHODS: The effects of TADM were studied in vitro on birch stimulated PBMC cultures of birch allergic rhinitis patients with other known adjuvants. Cytokines in supernatants were measured by Luminex. Effects of TADM were analysed in vivo in a mouse model of OVA-induced allergic asthma by analysing BAL, cytokine mRNA and serum antibodies. RESULTS: TADM was the only adjuvant that significantly suppressed the production of all birch induced Th2-type cytokines. In a murine model, TADM significantly suppressed the specific IgE production and enhanced IFN-γ production. CONCLUSIONS: TADM suppresses the birch allergen induced Th2-type cytokine responses in allergic subjects more efficiently than the two other adjuvants, MPL and CpG ODN. TADM is immunomodulatory also in vivo and decreases the IgE levels and increases the IFN-γ responses in a murine model. These results suggest that TADM may be a promising candidate for novel adjuvants in immunotherapy


No disponible


Asunto(s)
Animales , Masculino , Femenino , Ratones , Adyuvantes Inmunológicos , Adyuvantes Inmunológicos/uso terapéutico , Inmunoterapia/instrumentación , Inmunoterapia/métodos , Inmunoterapia/veterinaria , Modelos Animales de Enfermedad , Modelos Animales , Inmunoterapia/normas , Inmunoterapia , Asma/inmunología , Asma/veterinaria , Técnicas In Vitro/instrumentación , Técnicas In Vitro/veterinaria
3.
Allergol Immunopathol (Madr) ; 44(1): 9-17, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26395525

RESUMEN

BACKGROUND: Allergen-specific immunotherapy balances the Th2-biased immunity towards Th1 and Treg responses. Adjuvants are used in allergen preparations to intensify the immune responses. The increased prevalence of allergies in developed societies has been associated with decreased microbial load during childhood. This has initiated a search for microbial structures to be used as adjuvants. Our study has shown that a synthetic triacedimannose (TADM) may suppress the Th2-type allergic inflammatory response. The aim of this study was to compare the properties of TADM with capacities of other adjuvants, CpG ODN and MPL, to modulate cytokine production in PBMC and regulate sensitisation in an OVA-sensitised mouse asthma model. METHODS: The effects of TADM were studied in vitro on birch stimulated PBMC cultures of birch allergic rhinitis patients with other known adjuvants. Cytokines in supernatants were measured by Luminex. Effects of TADM were analysed in vivo in a mouse model of OVA-induced allergic asthma by analysing BAL, cytokine mRNA and serum antibodies. RESULTS: TADM was the only adjuvant that significantly suppressed the production of all birch induced Th2-type cytokines. In a murine model, TADM significantly suppressed the specific IgE production and enhanced IFN-γ production. CONCLUSIONS: TADM suppresses the birch allergen induced Th2-type cytokine responses in allergic subjects more efficiently than the two other adjuvants, MPL and CpG ODN. TADM is immunomodulatory also in vivo and decreases the IgE levels and increases the IFN-γ responses in a murine model. These results suggest that TADM may be a promising candidate for novel adjuvants in immunotherapy.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Asma/terapia , Conjuntivitis/terapia , Desensibilización Inmunológica , Manósidos/administración & dosificación , Rinitis Alérgica/terapia , Células Th2/inmunología , Adulto , Alérgenos/administración & dosificación , Alérgenos/inmunología , Animales , Asma/inmunología , Betula/inmunología , Células Cultivadas , Conjuntivitis/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Lípido A/administración & dosificación , Lípido A/análogos & derivados , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Oligodesoxirribonucleótidos/administración & dosificación , Ovalbúmina/inmunología , Rinitis Alérgica/inmunología
4.
J Gen Virol ; 95(Pt 7): 1415-1429, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24722679

RESUMEN

Potyviruses represent one of the most economically important and widely distributed groups of plant viruses. Despite considerable progress towards understanding the cellular and molecular basis of their pathogenicity, many questions remain about the mechanisms by which potyviruses suppress host defences and create an optimal intracellular environment for viral translation, replication, assembly and spread. The review focuses on the multifunctional roles of potyviral proteins and their interplay with various host factors in different compartments of the infected cell. We place special emphasis on the recently discovered and currently putative mechanisms by which potyviruses subvert the normal functions of different cellular organelles in order to establish an efficient and productive infection.


Asunto(s)
Interacciones Huésped-Patógeno , Enfermedades de las Plantas/virología , Potyvirus/fisiología , Proteínas Virales/metabolismo
5.
J Biotechnol ; 162(4): 356-65, 2012 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-22828164

RESUMEN

Probiotics, defined as live microorganisms which when consumed in adequate amounts confer a health benefit on the host, are a common part of our daily diet. Since their conception in the early 20th century, the health benefit applications of probiotics have been expanding, culminating in the recent challenge of health claim substantiation in Europe. This paper highlights the different application areas of probiotics, introduces the use of non-viable microorganisms to confer health benefits, and explains the recent regulatory challenges surrounding probiotics. It then describes in detail the different stages in the development of food products containing probiotic bacteria starting from the selection of suitable strains for industrial production. The description of production of probiotic powders with specific focus on strategies to maintain high viability during drying and storage then follows. The paper finishes with a discussion of probiotic stability in liquid products, followed by a description of the use of probiotics to improve nutrient bioavailability and digestibility of the food products, which they ferment or biotransform.


Asunto(s)
Biotecnología , Microbiología de Alimentos , Probióticos , Humanos
6.
Virology ; 422(2): 254-64, 2012 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-22099968

RESUMEN

Regulation of NIa-Pro is crucial for polyprotein processing and hence, for successful infection of potyviruses. We have examined two novel mechanisms that could regulate NIa-Pro activity. Firstly, the influence of VPg domain on the proteolytic activity of NIa-Pro was investigated. It was shown that the turnover number of the protease increases when these two domains interact (cis: two-fold; trans: seven-fold) with each other. Secondly, the protease activity of NIa-Pro could also be modulated by phosphorylation at Ser129. A mutation of this residue either to aspartate (phosphorylation-mimic) or alanine (phosphorylation-deficient) drastically reduces the protease activity. Based on these observations and molecular modeling studies, we propose that interaction with VPg as well as phosphorylation of Ser129 could relay a signal through Trp143 present at the protein surface to the active site pocket by subtle conformational changes, thus modulating protease activity of NIa-Pro.


Asunto(s)
Endopeptidasas/metabolismo , Regulación Viral de la Expresión Génica/fisiología , Genoma Viral , Potyvirus/metabolismo , Proteínas Virales/metabolismo , Secuencia de Bases , Cromatografía en Capa Delgada , Dicroismo Circular , Endopeptidasas/genética , Mutación , Fosforilación , ARN Viral/química , ARN Viral/genética , ARN Viral/metabolismo , Espectrometría de Fluorescencia , Proteínas Virales/genética
7.
Gene Ther ; 19(4): 392-5, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21776026

RESUMEN

Vascular endothelial growth factor (VEGF)-mediated gene therapy (GT) has shown promising results as a novel method in the treatment of severe cardiovascular diseases. VEGF GT has proved to be safe and well tolerated in short-term studies, but there is only very limited data available on long-term effects. In this study we examined the effects of VEGF GT on patients having received VEGF-A gene transfer for the treatment of symptomatic (that is, claudication or critical lower limb ischemia) peripheral arterial occlusive disease. Out of 54 patients, 25 (46%) were interviewed for this study and 26 (48%) had died during the follow-up. Interviewed patients were treated with adenoviral (n=8, mean age 76 (62.7-90.6) years) or plasmid/liposome (n=8, mean age 84.2 (71.9-94.7) years) vectors compared with a randomized control group (n=10, mean age 80.5 (70.7-88.1) years) using a local balloon catheter device. The follow-up time was 10 years. Causes of death were clarified from hospital records. There were no statistically significant differences between the study groups in the causes of death or in the incidence of cancer (VEGF-Adv 0/10 vs VEGF-p/l 1/8 vs Control 1/7, P=0.5), diabetes (3/10 vs 3/8 vs 2/7, P=1.00) or diabetic retinopathy (0/10 vs 1/8 vs 0/7, P=0.45). In addition, we found no differences in the number of amputations of the treated leg (0/10 vs 3/8 vs 1/7, P=0.17). We conclude that transient VEGF-A-mediated GT did not increase the incidence of cancer, diabetes, retinopathy or any other diseases during the 10-year follow-up time. No significant differences were detected in the number of amputations or causes of death. This study supports our previous findings that local adenovirus and plasmid/liposome-mediated VEGF-A GT is safe and well-tolerated treatment in elderly patients with cardiovascular diseases.


Asunto(s)
Terapia Genética/efectos adversos , Enfermedades Vasculares Periféricas/terapia , Factor A de Crecimiento Endotelial Vascular/genética , Adenoviridae/genética , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica , Catéteres , Causas de Muerte , Ensayos Clínicos Fase III como Asunto , Femenino , Estudios de Seguimiento , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Humanos , Isquemia/terapia , Pierna/irrigación sanguínea , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/mortalidad
8.
Virology ; 411(2): 374-82, 2011 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-21295323

RESUMEN

Many plus-strand (+)RNA viruses co-opt protein chaperones from the host cell to assist the synthesis, localization and folding of abundant viral proteins, to regulate viral replication via activation of replication proteins and to interfere with host antiviral responses. The most frequently subverted host chaperones are heat shock protein 70 (Hsp70), Hsp90 and the J-domain co-chaperones. The various roles of these host chaperones in RNA virus replication are presented to illustrate the astonishing repertoire of host chaperone functions that are subverted by RNA viruses. This review also discusses the emerging roles of cyclophilins, which are peptidyl-prolyl isomerases with chaperone functions, in replication of selected (+)RNA viruses.


Asunto(s)
Ciclofilinas/metabolismo , Interacciones Huésped-Patógeno , Chaperonas Moleculares/metabolismo , Virus ARN/fisiología , Replicación Viral
9.
Scand J Surg ; 99(3): 167-72, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21044935

RESUMEN

BACKGROUND AND AIMS: this multicenter prospective observational study defined the incidence and risk factors of surgical wound infections (SWI) after infrarenal aortic and lower limb vascular surgery procedures and evaluated the severity and costs of these infections. METHODS: the study cohort comprised of 184 consecutive patients. Postoperative complications were recorded. The additional costs attributable to SWI were calculated. RESULTS: Eighty-four (46%) patients had critical ischaemia, 81 (45%) patients underwent infrainguinal bypass surgery and 64 (35%) received vascular prosthesis or prosthetic patch. Forty-nine (27%) patients developed SWI. Staphylococcus aureus was the leading pathogen cultured from the wound. Forty-seven of the 49 infected wounds responded to and healed with the treatment. SWI was the cause of one major amputation. Independent predictors for SWI were infrainguinal surgery (OR 7.2, 95% Cl 2.92-17.65, p < 0.001), obesity (OR 6.1, 95% Cl 2.44-15.16, p < 0.001) and arteriography injection site within the operative area (OR 2.5, 95% Cl 1.13-5.48, p = 0.02). The average cost attributable to SWI was 3320 Ä. CONCLUSION: the incidence of SWI after vascular surgery is high. The risk factors for SWI are infrainguinal surgery, obesity and arteriography injection site within the operative area. SWI increases morbidity and costs of operative treatment.


Asunto(s)
Isquemia/cirugía , Pierna/irrigación sanguínea , Infección de la Herida Quirúrgica/economía , Infección de la Herida Quirúrgica/epidemiología , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/economía , Anciano , Anciano de 80 o más Años , Profilaxis Antibiótica , Aorta Abdominal/cirugía , Enfermedades de la Aorta/economía , Enfermedades de la Aorta/cirugía , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/economía , Comorbilidad , Costo de Enfermedad , Femenino , Finlandia , Oclusión de Injerto Vascular/cirugía , Costos de Hospital , Hospitalización/economía , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Estudios Prospectivos , Factores de Riesgo , Infección de la Herida Quirúrgica/prevención & control
10.
J Virol Methods ; 164(1-2): 101-10, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20026122

RESUMEN

A quantitation method based on the sensitive detection of Renilla luciferase (Rluc) activity was developed and optimized for Potato virus A (PVA; genus Potyviridae) gene expression. This system is based on infections initiated by Agrobacterium infiltration and subsequent detection of the translation of PVA::Rluc RNA, which is enhanced by viral replication, first within the cells infected initially and later by translation and replication within new cells after spread of the virus. Firefly luciferase (Fluc) was used as an internal control to normalize the Rluc activity. An approximately 10-fold difference in the Rluc/Fluc activity ratio between a movement-deficient and a replication-deficient mutant was observed starting from 48h post Agrobacterium infiltration (h.p.i.). The Rluc activity derived from wild type (wt) PVA increased significantly between 48 and 72h.p.i. and the Rluc/Fluc activity deviated clearly from that of the mutant viruses. Quantitation of the Rluc and Fluc mRNAs by semi-quantitative RT-PCR indicated that increases and decreases in the Renillareniformis luciferase (rluc) mRNA levels coincided with changes in Rluc activity. However, a subtle increase in the mRNA level led to pronounced changes in Rluc activity. PVA CP accumulation was quantitated by enzyme-linked immunosorbent assay. The increase in Rluc activity correlated closely with virus accumulation.


Asunto(s)
Luciferasas de Renilla/metabolismo , Nicotiana/virología , Enfermedades de las Plantas/virología , Potyvirus/aislamiento & purificación , Carga Viral/métodos , Genes Reporteros , Vectores Genéticos , Luciferasas de Renilla/genética , Hojas de la Planta/virología , Rhizobium/genética , Coloración y Etiquetado/métodos , Transfección
11.
Eur J Clin Invest ; 39(12): 1048-54, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19807785

RESUMEN

OBJECTIVES: Occlusion in a limb artery leads to impaired blood supply and ischaemia. Collateral artery growth (arteriogenesis) is one of the most effective natural response mechanisms to compensate this pathologic situation. However, it is unknown if clinically important features, like poor run-off, have an impact on compensatory vessel growth. METHODS: Study population of this retrospective study consisted of 70 patients who suffered from lower limb ischaemia and underwent bypass surgery because of an occlusion of the superficial femoral artery. Clinical data were collected and pre- and postoperative angiograms were reviewed. Number of collateral vessels bypassing the occluded segment was counted. Features of inflow and outflow vessels were recorded. RESULTS: The mean number of collaterals was 13 + or - 0.5 per patient. In univariate analysis, short daily walking distance, chronic critical leg ischaemia, low ankle brachial index, low number of patent calf arteries and stenosed inflow arteries predicted low number of collateral arteries. In the multivariate analysis, only the quality of inflow and the number of patent calf vessels demonstrated an independent association (P < 0.05) with the number of collaterals. CONCLUSIONS: Ankle-brachial index, grade of symptoms and daily walking capacity could be used to predict collateral density. Importantly, a good antegrade flow and peripheral runoff seem to have a significant effect on collateral density, implying an impact on the activation of arteriogenesis.


Asunto(s)
Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/fisiopatología , Circulación Colateral/fisiología , Neovascularización Fisiológica/fisiología , Enfermedades Vasculares Periféricas/diagnóstico por imagen , Enfermedades Vasculares Periféricas/fisiopatología , Resistencia Vascular/fisiología , Anciano , Angiografía , Índice Tobillo Braquial , Arterias/crecimiento & desarrollo , Arteriosclerosis/diagnóstico por imagen , Arteriosclerosis/fisiopatología , Femenino , Arteria Femoral/diagnóstico por imagen , Humanos , Isquemia/diagnóstico por imagen , Isquemia/etiología , Masculino , Análisis Multivariante , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional/fisiología , Estudios Retrospectivos , Caminata
12.
Caries Res ; 43(5): 331-3, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19648742

RESUMEN

Clinical trials and laboratory studies involving the administration of oral health treatments and foods have benefited from the observance of the so-called crossover study design. Field experience and a growing number of laboratory experiments have shown, however, that 'blind' reliance on crossover designs may in some instances lead to unexpected results and erroneous conclusions. Some dietary substances, antibiotic agents, and even fluoride applications may have long-term effects that call into question the appropriateness of the washout periods between treatments. Studies have also been conducted on compounds that have turned out to display synergistic effects. When long-term and synergistic effects are simultaneously present in trials involving a crossover design, difficulties may arise in the interpretation of results. This communication uses as an example the long-term clinical and microbiological effects of xylitol and suggests that inclusion of the crossover practice in clinical trials should be separately and carefully contemplated in each instance.


Asunto(s)
Cariostáticos/uso terapéutico , Estudios Cruzados , Caries Dental/prevención & control , Investigación Dental/métodos , Xilitol/uso terapéutico , Humanos , Reproducibilidad de los Resultados , Proyectos de Investigación/normas , Edulcorantes/uso terapéutico
13.
Eur J Vasc Endovasc Surg ; 37(5): 578-84, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19231250

RESUMEN

UNLABELLED: Early results of a thrupass endograft in the treatment of femoral lesions are promising. Less morbidity and better cost-effectiveness are suggested to be achieved in the treatment of chronic lower limb ischaemia with endovascular treatment compared to surgical treatment. PATIENTS AND METHODS: This randomised multicentre trial aimed to enroll a group of 60+60 patients for the treatment of 5-25-cm occlusions of superficial femoral artery (SFA) to be followed up for 3 years. Patients were treated either with endoluminal PTFE thrupass (WL Gore & Ass) or with surgical polytetrafluoroethylene (PTFE) bypass to proximal popliteal artery. Primary patency at 3 years was scheduled to be the primary end-point and secondary patency, functional success, costs and quality of life the secondary end-points. RESULTS: A sample of 100 consecutive SFA occlusions in one of the centres revealed that only 4% of the lesions were amenable for the study. The trial was prematurely terminated due to the results of an interim analysis at the time when 44 patients were recruited: the 1-year primary patency (excluding technical failures) was 48% for thrupass and 95% for bypass (p=0.02). The patency difference in favour of surgical bypass over endovascular thrupass was also sustained after completion of 1-year follow-up, the primary patencies being 46% and 84% at 1 year with grossly equilinear life-table curves thereafter (p=0.18), respectively. The corresponding secondary patencies were 63% and 100% (p=0.05) when excluding technical failures and 58% and 100% (p=0.02) according to intention-to-treat analysis. Secondary outcomes were thus not analysed. CONCLUSION: Treatment of SFA occlusions (TASC IIB and C or Imelda Ia and II) should be done by PTFE bypass rather than by PTFE thrupass, as thrupass is connected with worse early outcome. These results represent only a small category of femoral disease.


Asunto(s)
Arteriopatías Oclusivas/cirugía , Prótesis Vascular , Materiales Biocompatibles Revestidos , Arteria Femoral , Politetrafluoroetileno , Arteria Poplítea/cirugía , Stents , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/métodos , Angiografía , Angioscopía , Arteriopatías Oclusivas/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diseño de Prótesis , Países Escandinavos y Nórdicos , Resultado del Tratamiento
14.
Protein Expr Purif ; 59(2): 274-81, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18406168

RESUMEN

The use of recombinant DNA-based protein production using genetically modified plants could provide a reproducible, consistent quality, safe, animal-component free, origin-traceable, and cost-effective source for industrial proteins required in large amounts (1000s of metric tons) and at low cost (below US$100/Kg). The aim of this work was to demonstrate the feasibility of using barley suspension cell culture to support timely testing of the genetic constructs and early product characterization to detect for example post-translational modifications within the industrial protein caused by the selected recombinant system. For this study the human Collagen I alpha 1 (CIa1) chain gene encoding the complete helical region of CIa1 optimized for monocot expression was fused to its N- and C-terminal telopeptide and to a bacteriophage T4 fibritin foldon peptide encoding sequences. The CIa1 accumulation was targeted to the endoplasmic reticulum (ER) by fusing the CIa1 gene to an ER-directing signal peptide sequence and an ER retention signal HDEL. The construct containing the CIa1 gene was then introduced into immature barley half embryos or barley cells by particle bombardment. Transgenic barley cells resulting from these transformations were grown as suspension cultures in flasks and in a Wave bioreactor producing CIa1 similar to CIa1 purified from the yeast Pichia pastoris based on Western blotting, pepsin resistance, and mass spectroscopy analysis. The barley cell culture derived-CIa1 intracellular accumulation levels ranged from 2 to 9 microg/l illustrating the need for further process improvement in order to use this technology to supply material for product development activities.


Asunto(s)
Biotecnología/métodos , Colágeno Tipo I/biosíntesis , Hordeum/genética , Plantas Modificadas Genéticamente , Proteínas Recombinantes/biosíntesis , Técnicas de Cultivo de Célula , Colágeno Tipo I/química , Colágeno Tipo I/genética , Hordeum/citología , Humanos , Pepsina A/química , Pichia/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética
15.
Eur J Vasc Endovasc Surg ; 31(3): 258-61, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16293426

RESUMEN

OBJECTIVES: The purpose of this study was to assess limb salvage and functional outcome in patients who underwent distal reconstructions. DESIGN: Retrospective study. MATERIALS AND METHODS: Fifty-nine consecutive patients underwent 63 femorodistal bypass operations during 1998-2002 at a university hospital. Late functional outcome was assessed using a questionnaire (mean 27 months after the primary operation). RESULTS: At the end of the study, 81% (30/37) of the surviving patients were alive with a viable limb. In all, 90% (27/30) of patients were living in their own homes and 3% (1/30) in a nursing home. Sixty percent (18/30) were able to walk independently. The walking distance was unlimited in 42% (13/31) and limited in 42% (13/31) of the operated limbs. In 16% (5/31) of cases, the treated limbs served only as a support. CONCLUSIONS: According to our results, the functional outcome of distal bypasses seems to be favourable. It is recommended that these operations should be performed even in elderly patients to avoid major amputations and to maintain the independence of the patient.


Asunto(s)
Isquemia/cirugía , Pierna/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Recuperación del Miembro , Masculino , Persona de Mediana Edad , Recuperación de la Función , Factores de Riesgo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares
16.
Caries Res ; 39(3): 207-15, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15914983

RESUMEN

Several sugar alcohols (polyols) have been promoted as potential sugar substitutes in caries limitation. However, differences in the effects of simple alditol-type sugar alcohol homologues on dental plaque have not been compared in clinical tests. The effects of 6-month use of erythritol (a sugar alcohol of the tetritol type), xylitol (a pentitol) and D-glucitol (sorbitol, a hexitol) were investigated in a cohort of 136 teenage subjects assigned to the respective polyol groups or to an untreated control group (n = 30-36 per group). The daily use of the polyols was 7.0 g in the form of chewable tablets, supplemented by twice-a-day use of a dentifrice containing those polyols. The use of erythritol and xylitol was associated with a statistically significant reduction (p < 0.001 in most cases) in the plaque and saliva levels of mutans streptococci. The amount of dental plaque was also significantly reduced in subjects receiving erythritol and xylitol. Such effects were not observed in other experimental groups. Chemical analyses showed D-glucitol to be a normal finding in dental plaque while xylitol was less consistently detected. Erythritol was detected in measurable amounts only in the plaque of subjects receiving this polyol. Erythritol and xylitol may exert similar effects on some risk factors of dental caries, although the biochemical mechanism of the effects may differ. These in vivo studies were supported by cultivation experiments in which xylitol, and especially erythritol, inhibited the growth of several strains of mutans streptococci.


Asunto(s)
Cariostáticos/uso terapéutico , Caries Dental , Eritritol/uso terapéutico , Ácidos Nicotínicos/uso terapéutico , Sorbitol/análogos & derivados , Streptococcus mutans/efectos de los fármacos , Edulcorantes/uso terapéutico , Xilitol/uso terapéutico , Adolescente , Análisis de Varianza , Cariostáticos/administración & dosificación , Caries Dental/tratamiento farmacológico , Caries Dental/microbiología , Caries Dental/prevención & control , Placa Dental/microbiología , Placa Dental/prevención & control , Índice de Placa Dental , Eritritol/administración & dosificación , Femenino , Humanos , Masculino , Masticación , Ácidos Nicotínicos/administración & dosificación , Saliva/efectos de los fármacos , Saliva/microbiología , Sorbitol/administración & dosificación , Sorbitol/uso terapéutico , Estadísticas no Paramétricas , Edulcorantes/administración & dosificación , Comprimidos/administración & dosificación , Xilitol/administración & dosificación
17.
Acta Chir Belg ; 103(5): 470-4, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14653030

RESUMEN

The vasculature is mostly quiescent in the normal adult, with the exception of the growth of new blood vessels during the female reproductive cycle. Recent advances in the knowledge concerning the molecular changes and the identification of genetic events in this vascular quiescence, as well as in vascular growth, has led to an increasing number of studies in which these phenomena are manipulated. Angiogenesis is the growth of new vessels from existing ones. Although new vessel formation is involved in many pathologic situations, like tumour growth, therapeutic angiogenesis has been presented as a novel method for the treatment of ischemic diseases, like peripheral arterial occlusive disease (PAOD). In experimental studies therapeutic angiogenesis has been produced by recombinant growth-factor protein application as well as by growth factor gene therapy. Most widely studied factors belong to vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF) families. Studies have also shown that, angiogenic growth factors stimulate endothelial cell migration and accelerate endothelial repair by enhancing post-injury re-endothelization. In clinical studies angiogenic therapy has been evaluated in patients with severe vascular diseases. The results have revealed that therapy is well tolerated as well as safe and that angiogenic therapy has a clear biologic effect. However, controlled studies are still needed to answer the question whether therapeutic angiogenesis offers a real clinical benefit to patients with PAOD.


Asunto(s)
Moduladores de la Angiogénesis/farmacología , Arteriopatías Oclusivas/tratamiento farmacológico , Neovascularización Fisiológica/genética , Neovascularización Fisiológica/fisiología , Enfermedades Vasculares Periféricas/tratamiento farmacológico , Adulto , Estudios de Evaluación como Asunto , Factores de Crecimiento de Fibroblastos/farmacología , Terapia Genética/métodos , Humanos , Neovascularización Fisiológica/efectos de los fármacos , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/farmacología
18.
J Gen Virol ; 84(Pt 3): 727-732, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12604825

RESUMEN

Replication of tobacco mosaic virus (TMV) is connected with endoplasmic reticulum (ER)-associated membranes at early stages of infection. This study reports that TMV movement protein (MP)-specific protein kinases (PKs) associated with the ER of tobacco were capable of phosphorylating Thr(104) in TMV MP. The MP-specific PKs with apparent molecular masses of about 45-50 kDa and 38 kDa were revealed by gel PK assays. Two types of mutations were introduced in TMV MP gene of wild-type TMV U1 genome to substitute Thr(104) by neutral Ala or by negatively charged Asp. Mutation of Thr(104) to Ala did not affect the size of necrotic lesions induced by the mutant virus in Nicotiana tabacum Xanthi nc. plants. Conversely, mutation of Thr to Asp mimicking Thr(104) phosphorylation strongly inhibited cell-to-cell movement. The possible role of Thr(104) phosphorylation in TMV MP function is discussed.


Asunto(s)
Treonina/metabolismo , Virus del Mosaico del Tabaco/metabolismo , Proteínas Virales/metabolismo , Sustitución de Aminoácidos , Transporte Biológico , Retículo Endoplásmico/enzimología , Peso Molecular , Mutación , Fosforilación , Proteínas de Movimiento Viral en Plantas , Proteínas Quinasas/química , Proteínas Quinasas/metabolismo , Nicotiana/virología
19.
Caries Res ; 35(2): 129-35, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11275673

RESUMEN

The effect of 2-month usage of saliva-stimulating pastils containing either erythritol or xylitol was studied in a cohort of 30 subjects assigned to the respective polyol groups (n = 15). The daily consumption level of both polyols was 5.2 g, used in 5 daily chewing episodes. The mean weight of total plaque mass (collectable during a standard period of 3 min from all available tooth surfaces) was reduced significantly in the xylitol-group, while no such effect was observed in the erythritol-group. This reduction in plaque mass was accompanied by a significant reduction in the turbidity readings (A(660)) of aqueous plaque suspensions; no such effect was observed in the erythritol-group. However, plaque protein levels did not differ between baseline and endpoint in either polyol group. The plaque and salivary levels of Streptococcus mutans and plaque levels of total streptococci were reduced significantly in the xylitol-group, while no such effect was detected in the erythritol-group. However, either polyol regimen had no effect on plaque levels of S. sobrinus. The results suggest that systematic use of xylitol-containing saliva stimulants may be more effective in controlling some oral-hygiene-related and caries-associated parameters than similar use of erythritol-containing products. The results also speak for a special relationship between xylitol and S. mutans. However, owing to the great potential of erythritol as a caries-reducing agent -- based on the tetritol nature of erythritol -- the present laboratory results should be considered preliminary and subject to verifying clinical studies.


Asunto(s)
Cariostáticos/uso terapéutico , Placa Dental/prevención & control , Eritritol/uso terapéutico , Saliva/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos , Xilitol/uso terapéutico , Administración Oral , Adulto , Cariostáticos/administración & dosificación , Estudios de Cohortes , Recuento de Colonia Microbiana , Placa Dental/química , Placa Dental/microbiología , Método Doble Ciego , Eritritol/administración & dosificación , Estudios de Seguimiento , Humanos , Masticación , Proteínas/análisis , Saliva/metabolismo , Saliva/microbiología , Tasa de Secreción/efectos de los fármacos , Estadísticas no Paramétricas , Streptococcus mutans/crecimiento & desarrollo , Streptococcus sobrinus/efectos de los fármacos , Streptococcus sobrinus/crecimiento & desarrollo , Comprimidos , Xilitol/administración & dosificación
20.
J Gen Virol ; 82(Pt 2): 449-458, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11161285

RESUMEN

Complementation of movement-deficient potato virus X (PVX) coat protein (CP) mutants, namely PVX.CP-Xho lacking the 18 C-terminal amino acid residues and PVX.DeltaCP lacking the entire CP gene, was studied by transient co-expression with heterologous proteins. These data demonstrated that the potyvirus CPs and both the major and minor CPs of beet yellows closterovirus could complement cell-to-cell movement of PVX.CP-Xho but not PVX.DeltaCP. These data also indicated that the C-terminally truncated PVX CP lacked a movement function which could be provided in trans by the CPs of other filamentous viruses, whereas another movement determinant specified by some region outside the most C-terminal part of the PVX CP could not be complemented either by potyvirus or closterovirus CPs. Surprisingly, the CP of spherical cocksfoot mottle sobemovirus rescued all of the PVX CP movement functions, complementing the spread of PVX.CP-Xho and, to a lesser extent, PVX.DeltaCP. Both these mutants were also rescued by the tobacco mosaic virus (TMV) movement protein (MP). To shed light on the movement function of PVX CP, attempts were made to complement PVX.CP-Xho by a series of TMV MP mutants. An internal deletion abolished complementation, suggesting that the internal region of TMV MP, which includes a number of overlapping functional domains important for cell-to-cell transport, provides an activity complementing movement determinant(s) specified by the C-terminal region of PVX CP.


Asunto(s)
Cápside/metabolismo , Movimiento , Nicotiana/citología , Nicotiana/virología , Plantas Tóxicas , Potexvirus/fisiología , Transporte Biológico , Cápside/química , Cápside/genética , Closterovirus/química , Closterovirus/genética , Prueba de Complementación Genética , Mutación/genética , Hojas de la Planta/citología , Hojas de la Planta/virología , Plásmidos/genética , Potexvirus/química , Potexvirus/genética , Homología de Secuencia , Virus del Mosaico del Tabaco/química , Virus del Mosaico del Tabaco/genética
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