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2.
Biochemistry (Mosc) ; 83(3): 281-293, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29625547

RESUMEN

We have purified the MutL protein from Rhodobacter sphaeroides mismatch repair system (rsMutL) for the first time. rsMutL demonstrated endonuclease activity in vitro, as predicted by bioinformatics analysis. Based on the alignment of 1483 sequences of bacterial MutL homologs with presumed endonuclease activity, conserved functional motifs and amino acid residues in the rsMutL sequence were identified: five motifs comprising the catalytic site responsible for DNA cleavage were found in the C-terminal domain; seven conserved motifs involved in ATP binding and hydrolysis and specific to the GHKL family of ATPases were found in the N-terminal domain. rsMutL demonstrated the highest activity in the presence of Mn2+. The extent of plasmid DNA hydrolysis declined in the row Mn2+ > Co2+ > Mg2+ > Cd2+; Ni2+ and Ca2+ did not activate rsMutL. Divalent zinc ions inhibited rsMutL endonuclease activity in the presence of Mn2+ excess. ATP also suppressed plasmid DNA hydrolysis by rsMutL. Analysis of amino acid sequences and biochemical properties of five studied bacterial MutL homologs with endonuclease activity revealed that rsMutL resembles the MutL proteins from Neisseria gonorrhoeae and Pseudomonas aeruginosa.


Asunto(s)
Reparación de la Incompatibilidad de ADN , Endonucleasas/metabolismo , Proteínas MutL/metabolismo , Rhodobacter sphaeroides/enzimología , Biología Computacional , ADN Bacteriano/genética , ADN Bacteriano/metabolismo
3.
Methods Mol Biol ; 1658: 347-354, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28861800

RESUMEN

Across the spectrum of sporadic human prion diseases (also known as transmissible spongiform encephalopathies: TSE), there is considerable phenotypic diversity. Cumulative scientific evidence supports that prions, the infectious agents of prion diseases, are constituted predominantly, if not exclusively, by misfolded, typically protease-resistant, disease-associated isoforms of the prion protein (PrPres). Consequently, tissue deposition of PrPres is considered a hallmark of prion disease pathology, and this can be visualized by Western blotting after tissue homogenization and treatment with proteinases, particularly proteinase K (PK). Indeed, Western blot profiles of PrPres are utilized as one marker of different prion strains, with such strains thought to contribute to at least part of the phenotypic variation observed in sporadic human prion disease. Typically, Western blotting of PrPres demonstrates three bands of different electrophoretic mobility, depicting the di-glycosylated, mono-glycosylated and unglycosylated species although further subclassification and the delineation of novel sporadic disease subtypes, such as variably protease-sensitive prionopathy, has contributed greater complexity. Nevertheless, it is the mobility of the unglycosylated PrPres band, the relative abundance of the two glycosylated bands or overall profile of the banding post-PK, in combination with the prion protein gene (PRNP) codon 129 genotype that allows the categorisation of molecular subtypes of sporadic human prion disease. These subtypes appear to correlate with distinct clinico-pathological profiles of sporadic Creutzfeldt-Jakob disease.


Asunto(s)
Western Blotting/métodos , Síndrome de Creutzfeldt-Jakob/diagnóstico , Electroforesis en Gel de Poliacrilamida/métodos , Proteínas PrPC/química , Proteínas Priónicas/clasificación , Encéfalo/metabolismo , Encéfalo/patología , Química Encefálica , Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/metabolismo , Síndrome de Creutzfeldt-Jakob/patología , Endopeptidasa K/química , Expresión Génica , Glicosilación , Humanos , Fenotipo , Proteínas PrPC/genética , Proteínas PrPC/metabolismo , Proteínas Priónicas/química , Proteínas Priónicas/genética , Proteínas Priónicas/metabolismo , Pliegue de Proteína
4.
Int J Cardiovasc Imaging ; 33(11): 1789-1794, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28528429

RESUMEN

To quantify myocardial edema by using a T2 relaxometry approach with a dual-contrast turbo spin-echo (dcTSE) sequence in patients with acute myocarditis regarding focal late gadolinium enhancement (LGE) burden. CMR T2 relaxometry was performed in 39 patients (age 41 ± 19 years; 36% women) with LGE in a typical myocarditis pattern and in ten healthy volunteers (age 46 ± 12; 60% woman). dcTSE sequence (echo time 29 and 75 ms, respectively) was used for T2 mapping, analysis were performed on the basis of region of interest (ROI). Myocardial T2 relaxation times (T2 RT) in patients-ROI with focal LGE were significantly (p < 0.001) higher than T2 RT in patients-ROI without apparent LGE pattern (65 ms (IQR 36-95) vs. 60 ms (IQR 26-88), respectively). T2 RT in healthy volunteers [55 ms (IQR 35-71)] were significantly lower than in patients ROI with or without focal LGE-pattern (p < 0.001, respectively). T2 RT assessed by dcTSE are significantly higher in patients segments with and without focal LGE compared to normal controls, supporting a global myocardial inflammatory process in acute myocarditis. Furthermore, this quantitative T2-mapping approach highlights the potential to identify patients with diffuse myocarditis.


Asunto(s)
Medios de Contraste/administración & dosificación , Edema Cardíaco/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Cinemagnética/métodos , Meglumina/análogos & derivados , Miocarditis/diagnóstico por imagen , Compuestos Organometálicos/administración & dosificación , Enfermedad Aguda , Adolescente , Adulto , Anciano , Edema Cardíaco/patología , Edema Cardíaco/fisiopatología , Femenino , Humanos , Masculino , Meglumina/administración & dosificación , Persona de Mediana Edad , Miocarditis/patología , Miocarditis/fisiopatología , Miocardio/patología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Función Ventricular Izquierda , Adulto Joven
5.
J Bacteriol ; 199(14)2017 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-28507242

RESUMEN

Under unfavorable growth conditions, bacteria enter stationary phase and can maintain cell viability over prolonged periods with no increase in cell number. To obtain insights into the regulatory mechanisms that allow bacteria to resume growth when conditions become favorable again (outgrowth), we performed global transcriptome analyses at different stages of growth for the alphaproteobacterium Rhodobacter sphaeroides The majority of genes were not differentially expressed across growth phases. After a short stationary phase (about 20 h after growth starts to slow down), only 7% of the genes showed altered expression (fold change of >1.6 or less than -1.6, corresponding to a log2 fold change of >0.65 or less than -0.65, respectively) compared to expression at exponential phase. Outgrowth induced a distinct response in gene expression which was strongly influenced by the length of the preceding stationary phase. After a long stationary phase (about 64 h after growth starts to slow down), a much larger number of genes (15.1%) was induced in outgrowth than after a short stationary phase (1.7%). Many of those genes are known members of the RpoHI/RpoHII regulons and have established functions in stress responses. A main effect of RpoHI on the transcriptome in outgrowth after a long stationary phase was confirmed. Growth experiments with mutant strains further support an important function in outgrowth after prolonged stationary phase for the RpoHI and RpoHII sigma factors.IMPORTANCE In natural environments, the growth of bacteria is limited mostly by lack of nutrients or other unfavorable conditions. It is important for bacterial populations to efficiently resume growth after being in stationary phase, which may last for long periods. Most previous studies on growth-phase-dependent gene expression did not address outgrowth after stationary phase. This study on growth-phase-dependent gene regulation in a model alphaproteobacterium reveals, for the first time, that the length of the stationary phase strongly impacts the transcriptome during outgrowth. The alternative sigma factors RpoHI and RpoHII, which are important regulators of stress responses in alphaproteobacteria, play a major role during outgrowth following prolonged stationary phase. These findings provide the first insight into the regulatory mechanisms enabling efficient outgrowth.


Asunto(s)
Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica/fisiología , Rhodobacter sphaeroides/metabolismo , Proteínas Bacterianas/genética , Secuencia de Bases , División Celular , Supervivencia Celular , ADN Bacteriano , Regiones Promotoras Genéticas , Rhodobacter sphaeroides/citología , Rhodobacter sphaeroides/genética , Activación Transcripcional , Transcriptoma
6.
HNO ; 62(12): 873-8, 2014 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-25270838

RESUMEN

BACKGROUND: Results of empirical research on the effectiveness of psychotherapeutic treatment of chronic complex tinnitus are still unclear and require further studies for clarification. OBJECTIVE: The objective of this study is to investigate the effectiveness of multimodal treatment of patients with chronic complex tinnitus in a day care unit setting. PATIENTS AND METHODS: In this prospective study, the effectiveness of an intense 5-day multimodal treatment delivered to 93 patients was assessed using a pre-post design. Tinnitus-specific effects were captured by the Mini-TQ-12 measurement instrument and psychiatric comorbidity assessed using the Brief Symptom Inventory (BSI). In statistical analyses, t-tests, χ(2) tests and Wilcoxon signed ranks tests were performed to determine statistical significance; effect sizes (ES) were calculated according to Cohen's d. RESULTS: The pre-post difference in Mini-TQ-12 was highly significant in t-test (p < 0.001); the ES was small (ES = 0.45). In BSI, the pre-post difference in the Global Severity Index (GSI) as a global measure was also highly significant in t-test (p < 0.001); ES was small (ES = 0.40). Nonparametric tests (Wilcoxon test) confirmed these results. CONCLUSION: This study demonstrates the statistically significant effectiveness of a multimodal therapeutic approach. Moreover, the results indicate that patients could benefit from more intensive therapeutic interventions.


Asunto(s)
Centros de Día/métodos , Psicoterapia/métodos , Calidad de Vida/psicología , Acúfeno/diagnóstico , Acúfeno/terapia , Adulto , Terapia Combinada/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Acúfeno/psicología , Resultado del Tratamiento
7.
Int J Cardiol ; 173(2): 253-8, 2014 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-24650659

RESUMEN

BACKGROUND: Aortic pulse wave velocity (PWV) was linked to LV-geometry and -function in patients with kidney disease and non-ischemic cardiomyopathy. The role of aortic compliance after acute STEMI is so far unknown. In the present study, we prospectively investigated the relationship of increased aortic stiffness with biomarkers of myocardial wall stress 4 months after STEMI. METHODS: 48 STEMI patients who were reperfused by primary coronary angioplasty underwent cardiovascular magnetic resonance (CMR) at baseline and at 4-month follow-up. The CMR protocol comprised cine-CMR as well as gadolinium contrast-enhanced CMR. Aortic PWV was determined by velocity-encoded, phase-contrast CMR. Blood samples were routinely drawn at baseline and follow-up to determine N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a subgroup of patients, mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-A-type natriuretic peptide (MR-proANP) levels were determined. RESULTS: Patients with a PWV above median (>7.0m/s) had significantly higher NT-proBNP, MR-proADM and MR-proANP concentrations at 4-month follow-up than patients with a PWV below median (all p<0.02). PWV showed moderate to good correlation with NT-proBNP, MR-proAMD and MR-proANP levels 4 months after STEMI (all p<0.05). Multivariate analysis revealed PWV, beside myocardial infarct size, as an independent predictor of 4-month NT-proBNP levels after correction for age, creatinine and LV ejection fraction (model r: 0.781, p<0.001). CONCLUSION: Aortic stiffness is directly associated with biomarkers of myocardial wall stress 4 months after reperfused STEMI, suggesting a role for aortic stiffness in chronic LV-remodelling.


Asunto(s)
Angioplastia Coronaria con Balón , Enfermedades de la Aorta/epidemiología , Enfermedades de la Aorta/metabolismo , Infarto del Miocardio , Miocardio/metabolismo , Rigidez Vascular , Adulto , Anciano , Factor Natriurético Atrial/metabolismo , Biomarcadores/metabolismo , Creatinina/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/epidemiología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/terapia , Péptido Natriurético Encefálico/metabolismo , Fragmentos de Péptidos/metabolismo , Flujo Pulsátil , Factores de Riesgo , Estrés Mecánico , Volumen Sistólico
8.
Eur Heart J Acute Cardiovasc Care ; 3(1): 10-7, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24337918

RESUMEN

BACKGROUND: Pulse wave velocity is a measure of aortic stiffness and an independent predictor of cardiovascular morbidity and mortality. Adiponectin is involved in atherosclerosis and inflammation. In the present study we aimed to explore the association between plasma adiponectin concentrations and pulse wave velocity in the acute phase after ST-segment elevation myocardial infarction (STEMI). METHODS: Forty-six consecutive STEMI patients (mean age 57 ± 11 years) treated with primary percutaneous coronary intervention (PCI) were enrolled in this cross-sectional study. Plasma adiponectin was measured 2 days after index event by enzyme-linked immunosorbent assay. Aortic pulse wave velocity (PWV) was calculated by the transit-time method with the use of a velocity-encoded, phase-contrast cardiac magnetic resonance protocol. RESULTS: Median plasma adiponectin concentration was 2385 ng/ml (interquartile range 1735-5403). Males had lower plasma adiponectin values than females and current smokers had lower values than non-smokers (all p<0.02). Adiponectin was significantly associated with PWV (r=0.505, p<0.001), age (r=0.437, p=0.002), and total cholesterol (r=0.468, p=0.001). Multiple linear regression analysis revealed adiponectin as a predictor of PWV independently of age, sex, smoking status, total cholesterol, and N-terminal pro-B-type natriuretic peptide (p=0.027). CONCLUSIONS: Plasma adiponectin concentrations are strongly associated with aortic stiffness in patients after acute STEMI treated with primary PCI. Our data support a possible role for adiponectin as an independent risk marker for increased aortic stiffness in STEMI patients.


Asunto(s)
Adiponectina/sangre , Aorta Torácica/fisiopatología , Electrocardiografía , Infarto del Miocardio/sangre , Intervención Coronaria Percutánea/métodos , Rigidez Vascular/fisiología , Aorta Torácica/patología , Biomarcadores/sangre , Velocidad del Flujo Sanguíneo , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/cirugía , Pronóstico , Estudios Prospectivos
10.
Clin Res Cardiol ; 100(8): 669-74, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21311895

RESUMEN

BACKGROUND: Every year millions of tourists spend their vacation in Tyrol, Austria during the winter season. They often perform sports at high altitudes and at low temperatures, factors that might cause acute myocardial infarction (AMI). This study aimed to evaluate the relationship of first physical activity and the onset of AMI in winter tourists. METHODS: We carried out a retrospective analysis of consecutive patients admitted to the Department of Internal Medicine III at the Medical University of Innsbruck with the diagnosis of an AMI between 2006 and 2010. We identified 172 patients as potential candidates for the questionnaire. We successfully contacted 110 patients (mean age: 60 ± 10 years). The location of visit, duration of stay, time of arrival, first sportive activity and onset of symptoms were assessed. RESULTS: During the first 2 days of physical activity , 56% of AMIs occurred. In tourists who suffered AMI during, or within 1 h after cessation of activity (52%), the mean time from the start of the activity to the onset of symptoms was 2.0 ± 1.7 h. 56% of patients performed less than 2.5 h of sport per week before their vacation and 70% had ≥2 cardiovascular risk factors. Although the mean planned vacation time was 8.3 ± 3.7 days, 39% of the patients suffered from AMI on the day of arrival or the day after. CONCLUSION: The majority of AMIs in winter tourists happens within the first 2 days after arrival and within the first 2 days of physical activity.


Asunto(s)
Frío , Infarto del Miocardio/etiología , Estaciones del Año , Viaje , Anciano , Altitud , Enfermedad de la Arteria Coronaria/complicaciones , Ejercicio Físico , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios
11.
Z Gerontol Geriatr ; 44 Suppl 2: 41-54, 2011 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-22270973

RESUMEN

BACKGROUND: The objective of the KORA-Age research consortium is to assess the determinants and consequences of multimorbidity in the elderly and to look into reasons for successful aging in the general public. PATIENTS AND METHODS: In the KORA-Age cohort study 9,197 persons were included who where born in the year 1943 or before and participants of previous KORA cohort studies conducted between 1984 and 2001 (KORA: Cooperative Health Research in the Region of Augsburg). The randomized intervention study KORINNA (Coronary infarct follow-up treatment in the elderly) tested a nurse-based case management program with 338 patients with myocardial infarct and included an evaluation in health economics. RESULTS: A total of 2,734 deaths were registered, 4,565 participants submitted a postal health status questionnaire and 4,127 participants were interviewed by telephone (response 76.2% and 68.9% respectively). A gender and age-stratified random sample of the cohort consisting of 1,079 persons took part in a physical examination (response 53.8%). CONCLUSION: The KORA-Age consortium was able to collect data in a large population-based sample and is contributing to the understanding of multimorbidity and successful aging.


Asunto(s)
Enfermedad Crónica/epidemiología , Ensayos Clínicos como Asunto , Comorbilidad , Medicina Basada en la Evidencia , Investigación sobre Servicios de Salud/organización & administración , Servicios de Salud para Ancianos , Anciano , Anciano de 80 o más Años , Alemania , Humanos
12.
J Neurol Neurosurg Psychiatry ; 80(9): 998-1001, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19332421

RESUMEN

OBJECTIVE: Brain amyloid imaging using positron emission tomography (PET) is of increasing importance in the premortem evaluation of dementias, particularly in relation to Alzheimer disease (AD). The purpose of this study was to explore the premortem diagnostic utility of (11)C-PiB PET in sporadic Creutzfeldt-Jakob disease (CJD). METHODS: Two patients, 72 and 59 years old, underwent evaluation for rapidly progressive cognitive decline, dying after illness durations of 5 and 7 months, respectively. As part of their comprehensive assessment, (18)F-FDG PET and (11)C-PiB PET studies were performed approximately 2-4 weeks prior to death, and the brain regional distributions compared with those from cohorts of healthy controls (HC) and AD patients. RESULTS: Routine investigations, including brain MRI scans, revealed changes typical of sporadic CJD, with the diagnosis confirmed at autopsy in both patients. The (18)F-FDG PET showed global hypometabolism in one patient and thalamic and frontal hypometabolism with unexpected hypermetabolism in the dentate nuclei of the cerebellum in the other. Neither patient displayed cerebral cortical (11)C-PiB PET retention above the levels observed in HC. CONCLUSIONS: No grey-matter (11)C-PiB retention was observed in two pathologically confirmed cases of typical sporadic CJD. We speculate that low PrP plaque density and small plaque size, as well as a relatively low affinity of the radioligand, explain the absence of (11)C-PiB retention. More studies to validate this hypothesis are warranted.


Asunto(s)
Benzotiazoles , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagen , Anciano , Compuestos de Anilina , Encéfalo/patología , Química Encefálica/fisiología , Codón/genética , Síndrome de Creutzfeldt-Jakob/metabolismo , Síndrome de Creutzfeldt-Jakob/patología , Resultado Fatal , Femenino , Fluorodesoxiglucosa F18 , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos , Tiazoles
14.
Int J Sports Med ; 28(8): 667-72, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17455117

RESUMEN

31-Phosphorous magnetic resonance spectroscopy (31P MRS) is a unique tool to investigate IN VIVO high-energy phosphates (HEP) in the human heart. We hypothesized that physical capacity may be associated with myocardial HEP status. Healthy, male volunteers (n = 105, mean age 51 +/- 7 years) underwent bicycle ergometry with a stepwise increasing workload to determine maximal working capacity (MWC). Heart rate (HR) and blood pressure (BP) were measured continuously during exercise and 4 minutes of recovery. Further 31-Phosphorous 2-dimensional chemical shift imaging (31P 2D CSI) MRS was performed to assess myocardial HEP metabolism by determining phosphocreatinine to beta-ATP ratios (PCr/b-ATP) using a 1.5 tesla scanner. Volunteers with MWC > 230 Watt had significantly higher PCr/b-ATP ratios than those with MWC < 200 Watt (1.93 +/- 0.36 vs. 1.59 +/- 0.35; p < 0.001). Additionally, those with a recovery systolic (S)BP < 195 mmHg had significantly higher ratios than those with a recovery SBP > 195 mmHg (1.74 +/- 0.3 vs. 1.51 +/- 0.2; p < 0.05). We observed a linear correlation between the PCr/b-ATP ratio and MWC (r = 0.411; p < 0.001) and recovery SBP (r = - 0.290; p < 0.01). After statistical correction for age, these correlations remained significant. In this study, we observed a correlation of parameters of physical fitness determined by bicycle exercise testing and cardiac PCr/b-ATP ratios.


Asunto(s)
Ejercicio Físico/fisiología , Espectroscopía de Resonancia Magnética , Miocardio/metabolismo , Fosfocreatina/metabolismo , Adulto , Austria , Prueba de Esfuerzo , Humanos , Masculino , Persona de Mediana Edad
15.
Int J Cardiol ; 118(2): 249-52, 2007 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-17049390

RESUMEN

Apical ballooning is an increasingly reported transient cardiomyopathy with yet unknown origin. In this study 2 cases of apical ballooning are described in whom we used a combined approach of cardiac magnetic resonance imaging (CMR) and 31-Phosphorous magnetic resonance spectroscopy (31P MRS). Electrocardiogram showed ST abnormalities and cardiac serum markers were mildly elevated, but CAG demonstrated smooth coronary arteries. Cine-CMR revealed severe apical akinesia and significantly decreased ejection fraction. Furthermore we detected reduced myocardial phosphocreatine to beta-ATP (PCr/b-ATP) ratios during the first week of acute disease. After 1 week we observed an improvement of PCr/b-ATP ratios by 68% and 34%, which was associated with an increase in left ventricular function. Our data suggest that 31P MRS might be a valuable tool in the evaluation of apical ballooning, but larger cohorts are needed to improve the understanding of metabolic changes during transient apical ballooning.


Asunto(s)
Cardiomiopatías/diagnóstico , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Disfunción Ventricular Izquierda/diagnóstico , Anciano , Femenino , Humanos , Espectroscopía de Resonancia Magnética/instrumentación , Isótopos de Fósforo , Sensibilidad y Especificidad
16.
Brain ; 129(Pt 9): 2278-87, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16816392

RESUMEN

To validate the provisional findings of a number of smaller studies and explore additional determinants of characteristic diagnostic investigation results across the entire clinical spectrum of sporadic Creutzfeldt-Jakob disease (CJD), an international collaborative study was undertaken comprising 2451 pathologically confirmed (definite) patients. We assessed the influence of age at disease onset, illness duration, prion protein gene (PRNP) codon 129 polymorphism (either methionine or valine) and molecular sub-type on the diagnostic sensitivity of EEG, cerebral MRI and the CSF 14-3-3 immunoassay. For EEG and CSF 14-3-3 protein detection, we also assessed the influence of the time point in a patient's illness at which the investigation was performed on the likelihood of a typical or positive result. Analysis included a large subset of patients (n = 743) in whom molecular sub-typing had been performed using a combination of the PRNP codon 129 polymorphism and the form of protease resistant prion protein [type 1 or 2 according to Parchi et al. (Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999; 46: 224-233.)] present in the brain. Findings for the whole group paralleled the subset with molecular sub-typing data available, showing that age at disease onset and disease duration were independent determinants of typical changes on EEG, while illness duration significantly influenced positive CSF 14-3-3 protein detection; changes on brain MRI were not influenced by either of these clinical parameters, but overall, imaging data were less complete and consequently conclusions are more tentative. In addition to age at disease onset and illness duration, molecular sub-type was re-affirmed as an important independent determinant of investigation results. In multivariate analyses that included molecular sub-type, time point of the investigation during a patient's illness was found not to influence the occurrence of a typical or positive EEG or CSF 14-3-3 protein result. A typical EEG was most often seen in MM1 patients and was significantly less likely in the MV1, MV2 and VV2 sub-types, whereas VV2 patients had an increased likelihood of a typical brain MRI. Overall, the CSF 14-3-3 immunoassay was the most frequently positive investigation (88.1%) but performed significantly less well in the very uncommon MV2 and MM2 sub-types. Our findings confirm a number of determinants of principal investigation results in sporadic CJD and underscore the importance of recognizing these pre-test limitations before accepting the diagnosis excluded or confirmed. Combinations of investigations offer the best chance of detection, especially for the less common molecular sub-types such as MV2 and MM2.


Asunto(s)
Síndrome de Creutzfeldt-Jakob/diagnóstico , Proteínas 14-3-3/líquido cefalorraquídeo , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Encéfalo/patología , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquídeo , Síndrome de Creutzfeldt-Jakob/genética , Electroencefalografía/métodos , Femenino , Genotipo , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Proteínas Priónicas , Priones/genética , Precursores de Proteínas/genética , Sensibilidad y Especificidad , Factores de Tiempo
17.
Fortschr Neurol Psychiatr ; 73 Suppl 1: S66-73, 2005 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-16270247

RESUMEN

The paper presents the network concept and filters research results according to practical relevance. By way of introduction, the concept of the social network SNW is briefly outlined in terms of its origins and significance. The "socially intact" network of 25 - 40 individuals, of which 15 - 20 % are very close and familiar, is compared with that of people suffering from schizophrenia, averaging 13 individuals. The changes are compiled according to the individuals involved, the type of relationship, and the type of perception. Outcome-relevant results of the network research are summarised on a general basis and according to the parameters social support, social and family contacts, distribution by sex, symptoms, and relatives. The changes in the network in the course of the disease and their importance are described separately according to the phases premorbid phase, prodromal phase, early psychosis, untreated psychosis, first phase of treatment, and long-term phase, illustrating their importance in the context of the overall pathological process. Possibilities of intervention in the SNW are outlined for the phases premorbid, prodromal, onset of the first episode, chronicity development, and existing chronicity. The conclusion rounds off with a brief enumeration of the often lacking intervention options in the German-speaking world.


Asunto(s)
Trastornos Psicóticos/epidemiología , Esquizofrenia/epidemiología , Psicología del Esquizofrénico , Apoyo Social , Relaciones Familiares , Humanos , Trastornos Psicóticos/psicología
18.
Neurology ; 65(1): 113-8, 2005 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-16009895

RESUMEN

OBJECTIVE: To define the protease-resistant prion protein (PrPres) types and associated clinical profiles in Australian patients with sporadic Creutzfeldt-Jakob disease (CJD) to allow comparison with those reported from other continents and concomitantly reaffirm absence of variant CJD (vCJD). METHODS: Reassessment of available clinical and neuropathologic data on patients referred to the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR) who died between January 1, 1992, and June 30, 2003, was conducted. Molecular classification of PrPres was determined by immunoblot analysis of available frozen brain tissue. Brain homogenate pH and codon 129 genotype on the prion protein gene (PRNP) were established. RESULTS: PrPres patterns in 35 of 37 patients with sporadic CJD conformed to one of three common reported types. Of a range of clinical features assessed, illness duration was the only clinical feature significantly associated with PrPres type. Two patients displayed coexistence of more than one PrP type, with one displaying a novel pattern of three PrPres types in a single brain region. The absence of vCJD was reconfirmed, supported by the lack of the typical PrPres glycoform pattern. CONCLUSIONS: Given Australia's geographic isolation and environmental uniqueness, the general congruity of these results with those reported from other continents suggests that endogenous factors predominantly determine sporadic Creutzfeldt-Jakob disease (CJD) phenotypic subtypes or "strains." These results support a clinicopathologic classification system whereby both PrPres type and codon 129 genotype are utilized to most accurately depict phenotypic subtypes or strains of sporadic CJD.


Asunto(s)
Síndrome de Creutzfeldt-Jakob/clasificación , Síndrome de Creutzfeldt-Jakob/genética , Variación Genética/genética , Proteínas PrPSc/genética , Adulto , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Western Blotting , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Codón/genética , Síndrome de Creutzfeldt-Jakob/epidemiología , Femenino , Genotipo , Geografía , Humanos , Masculino , Persona de Mediana Edad , Neuronas/metabolismo , Neuronas/patología , Fenotipo , Proteínas PrPSc/química , Sistema de Registros/estadística & datos numéricos
19.
Neurology ; 64(9): 1586-91, 2005 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-15883321

RESUMEN

BACKGROUND: An international study of the epidemiologic characteristics of Creutzfeldt-Jakob disease (CJD) was established in 1993 and included national registries in France, Germany, Italy, the Netherlands, Slovakia, and the United Kingdom. In 1997, the study was extended to Australia, Austria, Canada, Spain, and Switzerland. METHODS: Data were pooled from all participating countries for the years 1993 to 2002 and included deaths from definite or probable CJD of all etiologic subtypes. RESULTS: Four thousand four hundred forty-one cases were available for analysis and included 3,720 cases of sporadic CJD, 455 genetic cases, 138 iatrogenic cases, and 128 variant cases. The overall annual mortality rate between 1999 and 2002 was 1.67 per million for all cases and 1.39 per million for sporadic CJD. Mortality rates were similar in all countries. There was heterogeneity in the distribution of cases by etiologic subtype with an excess of genetic cases in Italy and Slovakia, of iatrogenic cases in France and the UK, and of variant CJD in the UK. CONCLUSIONS: This study has established overall epidemiologic characteristics for Creutzfeldt-Jakob disease (CJD) of all types in a multinational population-based study. Intercountry comparisons did not suggest any relative change in the characteristics of sporadic CJD in the United Kingdom, and the evidence in this study does not suggest the occurrence of a novel form of human bovine spongiform encephalopathy infection other than variant CJD. However, this remains a possibility, and countries currently unaffected by variant CJD may yet have cases.


Asunto(s)
Síndrome de Creutzfeldt-Jakob/mortalidad , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Canadá/epidemiología , Causalidad , Niño , Síndrome de Creutzfeldt-Jakob/clasificación , Europa (Continente)/epidemiología , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Geografía , Salud Global , Humanos , Enfermedad Iatrogénica/epidemiología , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Vigilancia de la Población/métodos , Enfermedades por Prión/etiología , Enfermedades por Prión/mortalidad , Factores Sexuales , Zoonosis/epidemiología , Zoonosis/transmisión
20.
Mol Genet Genomics ; 267(2): 202-9, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11976963

RESUMEN

Expression of the puf and puc operons, which encode proteins of the photosynthetic apparatus of Rhodobacter capsulatus, is regulated by oxygen. A drop in the oxygen tension in the environment leads to an increase in the levels of puf and puc mRNAs. In strains lacking bacteriochlorophyll (Bchl) due to mutations in bch genes, the rise in puf and puc mRNA levels observed on reduction of oxygen tension is much less pronounced than in wild-type cells, indicating co-regulation of the syntheses of pigments and pigment-binding proteins. Here we show that Bchl synthesis also affects the expression of the bchC gene, which codes for a subunit of bacteriochlorophyll synthase, suggesting an autoregulatory mechanism for the Bchl biosynthetic pathway. Furthermore, our data provide evidence that the RegB/RegA two-component system, which is known to play a central role in oxygen-controlled expression of photosynthesis genes, is also involved in the Bchl-dependent regulation. Mutant strains which do not synthesize RegB or RegA show similar oxygen-dependent puf and puc expression in the presence and absence of Bchl. Our results support the view that the RegB/RegA system can directly or indirectly sense whether Bchl synthesis takes place or not.


Asunto(s)
Bacterioclorofilas/genética , Genes Bacterianos , Proteínas del Complejo del Centro de Reacción Fotosintética/genética , Proteínas Quinasas , Rhodobacter capsulatus/genética , Transactivadores/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Bacterioclorofilas/metabolismo , Secuencia de Bases , Ligasas de Carbono-Oxígeno/genética , Ligasas de Carbono-Oxígeno/metabolismo , ADN Bacteriano/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación Bacteriana de la Expresión Génica , Complejos de Proteína Captadores de Luz , Mutación , Oxígeno/metabolismo , Proteínas del Complejo del Centro de Reacción Fotosintética/química , Proteínas del Complejo del Centro de Reacción Fotosintética/metabolismo , Plásmidos/genética , Estructura Terciaria de Proteína , ARN Bacteriano/genética , ARN Bacteriano/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Rhodobacter capsulatus/metabolismo , Transactivadores/química , Transactivadores/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
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