RESUMEN
BACKGROUND: We assessed the development in the number of new base of tongue squamous-cell carcinoma (BSCC) cases per year in eastern Denmark from 2000 to 2010 and whether HPV may explain any observable increased incidence. METHODS: We performed HPV DNA PCR and p16 immunohistochemistry analysis for all (n=210) BSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and the Danish Pathology Data Bank, and genotyped all HPV-positive specimens with amplicon-based next-generation sequencing. RESULTS: The overall crude incidence of BSCCs increased significantly (5.4% per year) during the study period. This was explained by a significant increase in the number of HPV-positive BSCCs (8.1% per year), whereas the number of HPV-negative BSCCs did not increase significantly. The overall HPV prevalence was 51%, with HPV16 as the predominant HPV type. CONCLUSIONS: The increased number of HPV-positive BSCCs may explain the increasing incidence of BSCCs in eastern Denmark, 2000-2010.
Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Neoplasias de la Lengua/epidemiología , Alphapapillomavirus/genética , Dinamarca/epidemiología , Humanos , Incidencia , Neoplasias de la Lengua/virologíaRESUMEN
Systematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA-A, -B, and -DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central-European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA-A accurately depicts the effects of genetic drift, HLA-B, and -DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection.
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Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadenas HLA-DRB1/genética , Polimorfismo Genético , Romaní , Población Blanca , Adolescente , Adulto , Alelos , Trasplante de Médula Ósea , Femenino , Efecto Fundador , Flujo Genético , Haplotipos , Humanos , Hungría , Masculino , Persona de Mediana Edad , Filogeografía , Donantes de TejidosRESUMEN
BACKGROUND: A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based on diagnostic measures and definition of p16 overexpression. We evaluated means of p16 and HPV diagnostics, and quantified overexpression of p16 in HPV-positive and -negative OP-SCCs by mode of immunohistochemical staining of carcinoma cells. METHODS: PubMed, Embase, and the Cochrane Library were searched from 1980 until October 2012. We applied the following inclusion criteria: a minimum of 20 cases of site-specific OP-SCCs, and HPV and p16 results present. Studies were categorised into three groups based on their definition of p16 overexpression: verbal definition, nuclear and cytoplasmatic staining between 5 and 69%, and ≥70% staining. RESULTS: We identified 39 studies with available outcome data (n=3926): 22 studies (n=1980) used PCR, 6 studies (n=688) used ISH, and 11 studies (n=1258) used both PCR and ISH for HPV diagnostics. The methods showed similar HPV-positive results. Overall, 52.5% of the cases (n=2062) were HPV positive. As to p16 overexpression, 17 studies (n=1684) used a minimum of 5-69% staining, and 7 studies (n=764) used ≥70% staining. Fifteen studies (n=1478) referred to a verbal definition. Studies showed high heterogeneity in diagnostics of HPV and definition of p16. The correlation between HPV positivity and p16 overexpression proved best numerically in the group applying ≥70% staining for p16 overexpression. The group with verbal definitions had a significantly lower false-positive rate, but along with the group applying 5-69% staining showed a worse sensitivity compared with ≥70% staining. CONCLUSIONS: There are substantial differences in how studies diagnose HPV and define p16 overexpression. Numerically, p16 staining is better to predict the presence of HPV (i.e. larger sensitivity), when the cutoff is set at ≥70% of cytoplasmatic and nuclear staining.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virología , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/virología , Proteínas de Neoplasias/biosíntesis , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/virología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Femenino , Genes p16 , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patología , Papillomaviridae/genética , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Pronóstico , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello , Adulto JovenRESUMEN
Phosphatase enzymes are capable of releasing phosphate through cleavage of phosphoester bonds. The seasonal importance of this process was examined by using a model substrate paranitrophenylphosphate and the Michaelis-Menten equation to estimate the release rate of PO 4 -P from phosphomonoesters. The seasonal occurrence of phosphomonoesters and acid phosphatase activity was used to estimate the velocity of phosphate release from these compounds. Filter fractionation of phosphatase activity demonstrated that most activity (>60%) was in size fractions less than 0.45 microm. The release rates were highest in May and June (15 to 25 nmol L -1 min -1 ) during the Gonyostomum semen (Raphidophyta) bloom and decreased to less than 2 nmol L -1 min -1 in two weeks and remained low throughout the summer and the fall. Fractionation of 32 P-H 3 PO 4 labelled dissolved organic phosphorus showed this fraction to vary considerably through the year. Potential phosphate release declined through the summer and into the fall. Significance of the co-occurrence of phosphomonoesters and acid phosphatase activity maxima and Gonyostomum semen (Raphidophyta) bloom is discussed.
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Fosfatasa Ácida/metabolismo , Eucariontes/enzimología , Clorofila/metabolismo , Clorofila A , Ambiente , Concentración de Iones de Hidrógeno , Estaciones del Año , Suelo , Agua/químicaRESUMEN
OBJECTIVE: To report the use of a human fixation device, the Mennen clamp-on plate (MCOP), for fracture repair in dogs as the sole method of fixation, or in combination with another fixation method such as an intramedullary pin. METHODS: The study, which was performed to evaluate the use of the MCOP in fracture repair in dogs, included 36 cases that were selected between 2004 and 2008. The selected cases were all closed diaphyseal fractures, in which sufficient plate prongs could engage the bone on either side of the fracture. RESULTS: Of the 36 cases, 32 had excellent outcomes, and four had complications; these were two cases of fixation failure, one case of osteomyelitis, and one with mild sciatic nerve deficits. DISCUSSION: The MCOP is a promising method for fracture repair on its own for young puppies (six months or less), and in conjunction with other fixation methods in older dogs. It is quick to apply, as no screw holes are created and it achieved a successful outcome in 95% of the cases, provided the cases were appropriately selected for this method. CONCLUSIONS: Using the MCOP has produced promising preliminary results in this study and warrants further evaluation.
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Enfermedades de los Perros/cirugía , Fijación de Fractura/veterinaria , Fracturas Óseas/veterinaria , Fijadores Internos/veterinaria , Animales , Perros , Miembro Anterior , Fijación de Fractura/instrumentación , Fracturas Óseas/cirugía , Miembro Posterior , Resultado del TratamientoRESUMEN
BACKGROUND: Early repolarization in the anterior ECG leads (ERV2-4) is considered to be a sign of right ventricular (RV) remodeling, but its etiology and importance are unclear. METHODS: A total of 243 top-level endurance-trained athletes (ETA; 183 men and 60 women, weekly training hours: 15-20) and 120 leisure-time athletes (LTA; 71 men and 49 women, weekly training hours: 5-6) were investigated. The ERV2-4 sign was evaluated concerning type of sport, gender, transthoracic echocardiographic parameters, and ECG changes, which can indicate elevated RV systolic pressure [left atrium enlargement (LAE), right atrium enlargement (RAE), RV conduction defect (RVcd)]. RESULTS: Stroke volume and left ventricular mass were higher in ETAs vs. LTAs in both genders (p < 0.01). Prevalence of the ERV2-4 sign was significantly higher in men than in women [p = 0.000, odds ratio (OR) = 36.4] and in ETAs than in LTAs (p = 0.000). The highest ERV2-4 prevalence appeared in the most highly trained triathlonists and canoe and kayak paddlers (OR = 13.8 and 5.2, respectively). Within the ETA group, the post-exercise LAE, RAE, and RVcd changes developed more frequently in cases with than without ERV2-4 (LAE: men: p < 0.05, females: p < 0.005; RAE: men: p < 0.05, females: p < 0.005; RVcd: N.S.). These post-exercise appearing LAE, RAE, and RVcd are associated with the ERV2-4 sign (OR = 4.0, 3.7, and 3.8, respectively). CONCLUSIONS: According to these results, ERV2-4 develops mainly in male ETAs due to long-lasting and repeated endurance training. The ERV2-4 sign indicates RV's adaptation to maintain higher compensatory pulmonary pressure and flow during exercise but its danger regarding malignant arrhythmias is unclear.
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Infarto del Miocardio con Elevación del ST/fisiopatología , Deportes/fisiología , Adaptación Fisiológica/fisiología , Adolescente , Adulto , Arritmias Cardíacas/fisiopatología , Atletas , Ecocardiografía/métodos , Electrocardiografía/métodos , Femenino , Humanos , Masculino , Resistencia Física/fisiología , Volumen Sistólico/fisiología , Función Ventricular Izquierda/fisiología , Remodelación Ventricular/fisiología , Adulto JovenRESUMEN
Correlating the Raman and infrared spectra of shocked minerals in Csátalja ordinary chondrite (H4, S2, W2) with controlling the composition by EPMA measurements, we identified and improved various shock indicators, as infrared spectro-microscopic analysis has been poorly used for shock impact alteration studies of meteorites to date. We also provide reference spectra as SOM for the community with local mineralogical and shock alteration related context to support further standardization of the IR ATR based measurements. Raman band positions shifted in conjunction with the increase in full width half maximum (FWHM) with shock stage in olivine minerals while in the infrared spectra when comparing the IR band positions and IR maximal absorbance, increasing correlation was found as a function of increasing shock effects. This is the first observational confirmation with the ATR method of the already expected shock related disordering. In the case of shocked pyroxenes the well-known peak broadening and peak shift was confirmed by Raman method, beyond the level that could have been produced by only chemical changes. With increasing shock level the 852-864cm-1 and 1055-1071cm-1 FTIR bands finally disappeared. From the shock effect occasionally mixed mineral structures formed, especially feldspars together with pyroxene. Feldspars were only present in the shock melted volumes, thus produced by the shock effect itself. Based on the above mentioned observations in Csátalja meteorite the less shocked (only fractured) part witnessed 2-6GPa shock pressure with temperature below 100°C. The moderately shocked parts (minerals with mosaicism and mechanical twins) witnessed 5-10GPa pressure and 900°C temperature. The strongly shocked area (many olivine and pyroxene grains) was subject to 10-15GPa and 1000°C. The existence of broad peak near 510cm-1 and disappearance of other peaks of feldspar at 480 and 570cm-1 indicate the presence of maskelynite, which proposes that the peak shock pressure could reach 20GPa at certain locations. We identified higher shock levels than earlier works in this meteorite and provided examples how heterogeneous the shock effect and level could be at small spatial scale. The provided reference spectra support the future improvement for the standardization of infrared ATR based methods and the understanding of shock-related mineral alterations beyond the optical appearance.
RESUMEN
The PC12 phaeochromocytoma cell line provides a useful model to study nerve growth factor-induced neuronal differentiation. The central signaling route of this process is mediated by the Ras-dependent extracellular signal-regulated kinase cascade. However, Ras-independent pathways are also stimulated by nerve growth factor and may contribute to differentiation signaling. One mediator for Ras-independent signal transduction in PC12 cells is phospholipase C-gamma that generates the second messengers diacylglycerol and inositol-trisphosphate. To probe the possible involvement of this enzyme in nerve growth factor-promoted differentiation, we used the phospholipase C inhibitor U73122 and the inositol-trisphosphate-receptor inhibitor Xestospongin C. Our results show that both chemicals block nerve growth factor-promoted neurite outgrowth, but the blockage of phospholipase C does not inhibit nerve growth factor-induced expression of c-fos, zif268 and transin genes. In addition, induction of these genes by nerve growth factor plus dibutyryl-cAMP is comparable in wild-type PC12 cells as well as in cells in which both Ras- and phospholipase C-gamma-mediated pathways are inhibited. The phospholipase C-gamma pathway thus belongs to those nerve growth factor receptor-originated signaling routes that contribute to the biological response of PC12 cells to nerve growth factor, but its gene activating potential does not have a major role in its neuritogenic effect.
Asunto(s)
Diferenciación Celular/fisiología , Regulación de la Expresión Génica , Factor de Crecimiento Nervioso/metabolismo , Fosfolipasa C gamma/metabolismo , Animales , Estrenos/metabolismo , Inositol 1,4,5-Trifosfato/antagonistas & inhibidores , Compuestos Macrocíclicos/metabolismo , Neuronas/citología , Neuronas/metabolismo , Oxazoles/metabolismo , Células PC12 , Inhibidores de Fosfodiesterasa/metabolismo , Fosfolipasa C gamma/antagonistas & inhibidores , Pirrolidinonas/metabolismo , Ratas , Transducción de Señal/fisiología , Activación TranscripcionalRESUMEN
NUT carcinoma (NC) is a recently described, rare and extremely aggressive cancer primarily located to supradiaphragmatic structures and affecting young individuals. NC is characterized by translocations involving the NUT gene on 15q14 with the most common translocation partner gene being BRD4 on 19p13, resulting in the t(15;19)(q14;p13) karyotype. NC is poorly differentiated and is likely to be overlooked and misdiagnosed as poorly differentiated squamous cell carcinoma (SCC) when immunohistochemical evaluation of NUT protein expression is omitted. Previously, NC has been found in the parotid and submandibular glands and we present the first case in the sublingual gland arising in a 40-year-old woman. We discuss the diagnostic considerations for poorly differentiated carcinomas of the salivary glands and advocate the inclusion of NUT immunohistochemistry in this setting. Not only does the NC diagnosis confer a grave prognosis when treated as SCC as illustrated by the present case, but is important for the inclusion of patients in ongoing clinical trials.
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Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Neoplasias de la Glándula Sublingual/genética , Neoplasias de la Glándula Sublingual/patología , Adulto , Biomarcadores de Tumor/análisis , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Proteínas de Neoplasias , Proteínas Oncogénicas/genéticaRESUMEN
OBJECTIVES: The goal of this study was to investigate the association between the atherosclerotic arterial remodeling and the incidence of cardiac events after coronary interventions in patients with stable angina. BACKGROUND: The local mode of de novo atherosclerotic remodeling is associated with plaque vulnerability and clinical symptoms. It may, therefore, reflect plaque morphology influencing the long-term outcome after coronary interventions. METHODS: Quantitative angiography and intravascular ultrasound were obtained in 244 patients with stable angina before and after single-vessel revascularization. On the basis of the lesion and the reference segment vessel size, patients were categorized into three groups (adaptive [AR], constrictive [CR] and intermediate [IR] remodeling). The lesion was analyzed for lumen, total vessel and plaque areas. Clinical follow-up was obtained at a mean period of 7.7+/-3.7 months. RESULTS: Patients with CR had a higher rate of in-hospital complications (10.9% vs. 2.9% and 2.7% in group CR vs. AR and IR, p = 0.035). In contrast, patients with AR had the highest rate of major adverse cardiac events (MACE) (44.3% vs. 25.5% in IR and 28.1% in CR, p = 0.024) with a predominance of revascularization at follow-up. Both target lesion restenosis (p = 0.036) and nontarget lesion de novo stenosis (p = 0.007) occurred more frequently in this group. Adaptive remodeling was a significant predictor of MACE in multivariate analysis. CONCLUSIONS: Adaptive remodeling is associated with a higher rate of MACE, target lesion restenosis and nontarget de novo stenosis. This finding may be due to differential responses of the adaptively remodeled vessel to revascularization and a generally accelerated course of systemic atherosclerosis.
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Angina de Pecho/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/patología , Ultrasonografía Intervencional , Anciano , Angina de Pecho/diagnóstico por imagen , Angina de Pecho/patología , Angina de Pecho/cirugía , Angioplastia Coronaria con Balón , Angiografía Coronaria , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios ProspectivosRESUMEN
Effective carrier function of selected representatives of new branched polypeptides covalently coupled with the synthetic monovalent hapten, oxazolone was studied. The effectiveness of oxazolone-synthetic polypeptide conjugates in inducing oxazolone-as well as carrier-specific antibody responses in inbred mice was compared to that of bovine serum albumin (BSA)- and KLH-oxazolone conjugates. The synthetic polypeptides, poly[Lys-(D-Leui-DL-Alam)] (D-LAK), LAK and FAK, as well as the common poly[Lys-(DL-Alam)](AK) core covalently coupled to oxazolone (Ox) induced a T cell-dependent antibody response when repeatedly administered with or without Freund's adjuvant in mice. This was evidenced by: the increasing titer of oxazolone-specific IgG during the course of the memory response; the appearance of all IgG subclasses; the effective oxazolone-specific priming by the conjugates; and the induction of an intense oxazolone- and carrier-specific DTH reaction. Although the oxazolone-specific antibody response was 10-100 times lower than that induced by KLH- or BSA-oxazolone conjugates, it was accompanied by a lower level or no detectable carrier-specific antibody response despite an effective carrier-specific T cell-mediated response. Significant differences were observed between the effectiveness of synthetic polypeptides used as carrier: highest oxazolone-specific antibody titers were observed using the AK, LAK and FAK conjugates. The intensity and specificity of the DTH reaction and antibody response induced by the carrier-oxazolone conjugates suggested that the distinct effectiveness of L- and D-amino acid-containing conjugates (LAK vs D-LAK and FAK vs D-FAK) was dependent on altered B cell recognition of the haptenic group. Circular dichroism (CD) spectra indicating different local orientation of oxazolone, when coupled to L or D side chain-terminating amino acids, support this suggestion.
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Proteínas Portadoras/inmunología , Péptidos/inmunología , Aminoácidos/inmunología , Animales , Citotoxicidad Inmunológica , Hipersensibilidad Tardía/inmunología , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/clasificación , Cinética , Masculino , Ratones , Ratones Endogámicos , Oxazolona/inmunología , Péptidos/síntesis química , Relación Estructura-ActividadRESUMEN
BACKGROUND: Superficial temporal artery biopsy is a frequent procedure performed in the diagnosis of giant cell arteritis. METHODS AND RESULTS: An otherwise healthy 69-year-old man presented with 2months complaint of right temporal region pain. Giant cell arteritis was suspected and a temporal artery biopsy was performed. The histopathology revealed perineural invasion of squamous cell carcinoma (SCC). A thorough investigation revealed no other primary site for the SCC and the patient was treated with surgical excision. CONCLUSION: Malignancy is rarely found in superficial temporal artery biopsies and lymphoma is the most common malignancy reported. In this rare case, the patient had right temporal pain explained by perineural invasion of a primary SCC in the right temporal region, which was treated with surgical excision guided by perioperative fresh frozen histology.
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Carcinoma de Células Escamosas/diagnóstico , Neoplasias Faciales/diagnóstico , Neoplasias Cutáneas/diagnóstico , Arterias Temporales/patología , Anciano , Biopsia , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/cirugía , Diagnóstico Diferencial , Neoplasias Faciales/complicaciones , Neoplasias Faciales/cirugía , Arteritis de Células Gigantes/diagnóstico , Humanos , Masculino , Dolor/etiología , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/cirugía , Resultado del TratamientoRESUMEN
Transplantation-associated thrombotic microangiopathy (TA-TMA) is a serious complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT) with high mortality rate. We retrospectively studied the frequency, clinical and genetic associations and prognostic effect of TA-TMA, in a total of 425 consecutive adult patients, who underwent allo-HSCT for a malignant haematological condition between 2007 and 2013 at our single centre. TA-TMA developed in 19% of the patients. Unrelated donor type (P<0.001), acute GvHD grades II-IV (P<0.001), myeloablative conditioning regimens (P=0.003), tacrolimus-based GvHD prophylaxis (P=0.003), CMV infection (P=0.003) and carriership for HLA-DRB1*11 (P=0.034) were associated with the development of TA-TMA. Survival was adversely affected by the presence of TA-TMA (P<0.001). Among patients with TA-TMA, the outcome of HLA-DRB1*11 carriers was significantly better compared with non-carriers (P=0.003). As a new finding, our observations suggest that the presence of HLA-DRB1*11 antigen contributes to the development of TA-TMA and affects the outcome.
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Cadenas HLA-DRB1/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Microangiopatías Trombóticas/terapia , Acondicionamiento Pretrasplante/efectos adversos , Femenino , Cadenas HLA-DRB1/inmunología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/mortalidad , Acondicionamiento Pretrasplante/métodos , Resultado del TratamientoRESUMEN
Since a B-cell growth-inhibitory natural IgM antibody was identified in the culture supernatants of LPS-stimulated murine splenic B lymphocytes [11], attempts have been made to define other possible functional role(s) of this antibody. Here we show that this regulatory IgM is able to inhibit not only the proliferation of splenic B cells, but also their IgM secretion during LPS-induced polyclonal, as well as antigen (FITC-KLH)-specific antibody responses. In contrast, IgG1 production of hapten (FITC)-specific B cells neither during restimulation with LPS nor in the presence of carrier-specific T lymphocytes in vitro was affected by regulatory IgM. Therefore, whereas newly emerging naive B cells are highly susceptible, IgG-secreting B cells appear to be completely resistant to inactivation by the regulatory IgM autoantibody.
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Especificidad de Anticuerpos/inmunología , Linfocitos B/inmunología , Inmunoglobulina G/biosíntesis , Inmunoglobulina M/fisiología , Animales , Ensayo de Inmunoadsorción Enzimática , Epítopos , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Haptenos/inmunología , Hemocianinas/análogos & derivados , Hemocianinas/metabolismo , Inmunoglobulina M/biosíntesis , Lipopolisacáridos/inmunología , Ratones , Ratones Endogámicos DBA , Autotolerancia , Albúmina Sérica Bovina , Bazo/citologíaRESUMEN
Pyridinol carbamate was nitrosated to the N,N1-dinitroso derivative and the structure was proved by spectroscopic methods, including chemical ionization mass spectroscopy. By the Ames test, the dinitroso derivative showed a significant dose-dependent mutagenic response with Salmonella typhimurium strains TA 1535 and TA 100; the response became more pronounced in the presence of microsomes. As the dosage of N-nitroso pyridinol carbamate increased, the number of revertant colonies also increased. Pyridinol carbamate was not mutagenic.
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Carbamatos , Mutágenos , Nitrosaminas/farmacología , Piridinolcarbamato , Animales , Carbamatos/análogos & derivados , Evaluación Preclínica de Medicamentos , Técnicas In Vitro , Hígado/efectos de los fármacos , Hígado/metabolismo , Piridinolcarbamato/análogos & derivados , Piridinolcarbamato/metabolismo , Piridinolcarbamato/farmacología , RatasRESUMEN
The agent of acute and chronic Q fever, Coxiella burnetii, occupies a unique niche among intracellular pathogens. The mechanisms the organism employs to cause disease are unclear but involve persistence in a parasitophorous vacuole and the subsequent host response. Studies designed to model molecular mechanisms of pathogenesis have relied upon indirect evidence for testing the role of virulence factors since methods for generation of defined mutations have not been developed. Evidence suggests replication involving a developmental lifecycle is critical for intra- and extracellular survival but this cycle is incompletely defined. It has been proposed that survival in the phagolysosomal-like parasitophorous vacuole requires specific iron uptake systems, secretion of enzymes to detoxify the compartment (catalase and SOD), and down-regulation of an oxidative burst (acid phosphatase). Studies to test these potential virulence mechanisms can be accelerated with the recent development of the complete genome sequence for the prototype acute disease isolate, Nine Mile. Proteins differentially expressed during the developmental cycle can more readily be identified with MALDI-TOF description of proteomic profiles. Genes encoding secreted Cu/Zn SOD, catalase, and acid phosphatase are predicted and can be tested for function and expression. An iron regulon is predicted based upon Fur-regulated open reading frames. The specific role the iron-regulated genes play in iron acquisition can be tested. Confirmation of the iron regulon and others can be tested using microarrays based upon the genomic ORF predictions. These are examples of how we are rapidly changing the experimental approaches used to investigate C. burnetii to improve our understanding of the biology of this unusual and highly adapted organism.
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Coxiella burnetii/genética , Coxiella burnetii/patogenicidad , Genómica , Coxiella burnetii/ultraestructura , Enzimas/genética , Genes Bacterianos/genética , Variación Genética , Humanos , Fiebre Q/microbiologíaRESUMEN
BACKGROUND: The aim of this study was to analyze the lifetime comorbidity between DSM-III-R anxiety disorders in separate subgroups of patients with major depression, bipolar II and bipolar I disorder in a community sample of a Hungarian population. METHODS: Randomly selected subjects (aged between 18 and 64 years, N=2953) were interviewed by the Diagnostic Interview Schedule (DIS) which generated DSM-III-R diagnoses. RESULTS: The prevalence of generalized anxiety disorder, agoraphobia and simple phobia was the highest among bipolar II patients (20.8, 37.5 and 16.7%, respectively), social phobia was most prevalent in (nonbipolar) major depression (17.6%), while the rate of panic disorder was the same in the (nonbipolar) major depressive and bipolar II subgroups (12.4 and 12.5%, respectively). Bipolar I patients showed a relatively low rate of comorbidity. CONCLUSIONS: The findings support previous results on the particularly high rate of lifetime comorbidity between anxiety disorders and unipolar major depression and particularly bipolar II illness. LIMITATIONS: Underestimation of the prevalence of bipolar II disorder by the diagnostic methodology used, resulting in a small number of bipolar II cases, lack of analysis of data by gender, no data on obsessive-compulsive disorder.
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Trastornos de Ansiedad/psicología , Trastorno Bipolar/psicología , Trastorno Depresivo/psicología , Adolescente , Adulto , Trastornos de Ansiedad/epidemiología , Trastorno Bipolar/epidemiología , Comorbilidad , Trastorno Depresivo/epidemiología , Femenino , Humanos , Hungría/epidemiología , Masculino , PrevalenciaRESUMEN
The attenuated Newcastle Disease Virus (NDV) vaccine MTH-68/H has been found to cause regression of various tumors including certain types of human neoplasms (See Table 1 and References 86-88). The mechanism of its oncolytic action is poorly understood, but it appears to affect specific signaling pathways in the target cell. We studied the cellular effects of NDV employing PC12 rat phaeochromocytoma cells, a widely used model system to analyze differentiation, proliferation and apoptosis. The MTH-68/H vaccine was found to be cytotoxic on PC12 cells. It caused internucleosomal DNA fragmentation, the most characteristic feature of programmed cell death (PCD). A brief exposure (30 min) of P12 cells to the virus was sufficient to produce a full-blown apoptotic response. Major mitogen-activated protein kinase pathways (including the stress inducible c-Jun N-terminal kinase pathway and p38 pathway) or mechanisms regulated by reactive oxygen species appear to have no role in virus-induced cell death. The PCD-inducing effect of MTH-68/H could not be prevented by simultaneous treatment of the P12 cells with growth factors or second messenger analogs stimulating protein kinase C or Ca(++)-mediated pathways. In contrast, treatment with a cyclic AMP analog partially protected the them from virus-induced apoptosis. These experimental results suggests that MTH-68/H might disrupt a growth factor-stimulated survival pathway and that direct stimulation of protein kinase A-catalyzed phosphorylation events bypass this NDV-induced block.
Asunto(s)
Apoptosis/efectos de los fármacos , Virus de la Enfermedad de Newcastle/inmunología , Vacunas Virales/farmacología , Adolescente , Adulto , Anciano , Animales , Bucladesina/farmacología , Vacunas contra el Cáncer/farmacología , División Celular/efectos de los fármacos , Núcleo Celular/ultraestructura , Preescolar , Fragmentación del ADN/efectos de los fármacos , Sustancias de Crecimiento/farmacología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismo , Vacunas Virales/toxicidadRESUMEN
BACKGROUND: Recurrent ischemic events occur during the hospital stay of 7-32% of patients after successful thrombolytic treatment of acute myocardial infarction (AMI). OBJECTIVE: To define the association between postinfarction angina pectoris and the clinical, angiographic, and intravascular ultrasound (IVUS) parameters of the infarct-related artery for consecutive prospectively included patients. METHODS: Clinical, qualitative, and quantitative angiographic and IVUS data for 64 patients (56 men, aged 53+/-12 years) with thrombolysis of AMI were analyzed. All patients underwent coronary angiography and pre-interventional IVUS measurement electively within 1 month of AMI or at the time of the occurrence of postinfarction angina pectoris. Classification as adaptive or constrictive remodeling was according to whether the cross-sectional area of a vessel was larger or smaller than that of the proximal or distal reference segment. RESULTS: Nineteen of the 64 patients (29.7%) suffered from recurrence of ischemic events (group 1), whereas 45 patients (60.3%, group 2) remained free from symptoms. In univariate analyses, multivessel disease (42 versus 24%, P= 0.0236) and adaptive remodeling (63 versus 24%, P= 0.0032) were found to occur more commonly among patients in group 1. The patients in group 1 exhibited larger total vessel cross-sectional areas than did the patients in group 2 (17.5+/-4.2 versus 14.9+/-6.1 mm2, P = 0.0556). In multivariate regression analysis, adaptive remodeling proved to be a significant predictor (P = 0.0145) of the recurrence of ischemic events after thrombolysis of AMI. CONCLUSIONS: Adaptive remodeling of the infarct-related artery is associated with early postinfarction angina pectoris after thrombolysis of AMI.