RESUMEN
Background: Certain variants of NHL repeat (named after NCL-1, HT2A and LIN-41)-containing protein 2 (NHLRC2) gene have been linked to severe fibrotic interstitial lung disease in children. The aim of the current study was to evaluate the expression of NHLRC2 in lung cell and tissue samples from patients with lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Methods: The expression of NHLRC2 in lung tissue samples was studied by immunohistochemistry (102 ADC, 111 SCC), mRNA in situ hybridization (4 ADC, 3 SCC), and Western blot analysis (3 ADC, 2 SCC). The immunohistochemical NHLRC2 expression was measured by image analysis software and the percentage of NHLRC2-positive cancer cells was evaluated by semiquantitative analysis. The immunohistochemical results of NHLRC2 were compared with the clinical and histological characteristics of the patients. NHLRC2 protein levels in primary stromal and epithelial lung cancer cell lines were measured by Western blot analysis. Results: NHLRC2 was mainly expressed in cancer cells and inflammatory cells within the tumor. The NHLRC2 expression evaluated by image analysis method was significantly higher in ADC compared with that in SCC (P<0.001). High NHLRC2 expression was associated with reduced disease specific survival (P=0.002), overall survival (P=0.001), and high mitotic activity (P=0.042) in ADC. Additionally, the proportion of NHLRC2-positive cancer cells analyzed by the semiquantitative method was significantly higher in ADC than in SCC (P<0.001). Conclusions: NHLRC2 expression was higher in lung ADC than in SCC and its expression was associated with poor survival in ADC patients. Further studies are required to clarify the pathogenetic role of NHLRC2 in lung cancer.
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AIMS: Until the launch of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society adenocarcinoma classification in 2011, there were no uniform histological grading criteria for pulmonary adenocarcinomas. The current classification highlights the prognostic importance of the various histological growth patterns observed in these morphologically heterogeneous neoplasias. In this study, we aimed to evaluate the classic histological parameters of malignancy in correlation with the growth patterns and patient outcomes in a series of 112 surgically operated stage I-IV lung adenocarcinomas. METHODS AND RESULTS: Architectural growth pattern analysis was performed according to the current adenocarcinoma classification. Histological features including, for example, nuclear atypia, mitotic activity, tumour necrosis, and different patterns of invasion were assessed and correlated statistically with the architecture and the clinical data. A solid predominant histology was associated with increased levels of atypia (P = 0.027), mitotic activity (P < 0.001), necrosis (P < 0.001), and lymphovascular invasion (P = 0.001), and a non-predominant solid pattern was associated with intra-alveolar tumour spread (P = 0.004). The presence of a non-predominant lepidic tumour component showed inverse correlations with atypia (P = 0.002), mitotic rate (P = 0.009), and tumour necrosis (P < 0.001). Tumour size (P < 0.001), mitotic activity (P = 0.019), tumour necrosis (P = 0.002), lymphovascular invasion (P = 0.001) and visceral pleural involvement (P = 0.001) were all associated with reduced disease-specific survival. CONCLUSIONS: The classic histological features of malignancy correlate with tumour architecture and patient outcome, confirming the prognostic value of the growth pattern analysis and questioning the need for a parallel grading system in pulmonary adenocarcinoma.
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Adenocarcinoma/patología , Neoplasias Pulmonares/patología , Adenocarcinoma/clasificación , Adenocarcinoma/mortalidad , Adenocarcinoma del Pulmón , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Interferon-gamma (IFN-γ) is a key cytokine in defense against mycobacteria, including Bacillus Calmette-Guérin (BCG). Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are pattern-recognizing molecules of innate immunity. The aim of the present study was to investigate the relationship between polymorphisms in MBL, TLR1, TLR2 and TLR6 encoding genes and stimulated IFN-γ and interleukin-12 (IL-12) ex vivo production in BCG osteitis survivors. METHODS: Data on single nucleotide polymorphisms in the MBL2 gene and TLR1, TLR2 and TLR6 genes were available from 132 former BCG osteitis patients, and data on ex vivo IFN-γ and IL-12 production were available from 115 and 118 patients, respectively. The present study is a secondary analysis of these available data. In an earlier study, we were able to characterize low IFN-γ and low IL-12 producers after BCG+IL-12 or BCG+IFN-γ stimulations, respectively. RESULTS: Three patients had the homozygous variant MBL2 genotype, and one of them was a low IFN-γ producer (both concentration and response <5th percentile). The heterozygous variant MBL2 genotype showed no association with IFN-γ or IL-12 production. The TLR2 variant genotype was present in 14 subjects; 28.6% of them were low IFN-γ producers versus 7.8% of those 103 with the TLR2 wild genotype (P = 0.037). TLR1 or TLR6 polymorphisms had no significant associations with stimulated ex vivo IFN-γ or IL-12 production. CONCLUSIONS: Preliminary evidence was found that variant genotypes of the MBL2 gene (if homozygous) and variant genotypes of the TLR2 gene (only heterozygotes present) are associated with low IFN-γ production.
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Vacuna BCG/efectos adversos , Enfermedades Óseas Infecciosas/genética , Interferón gamma/sangre , Interleucina-12/sangre , Lectina de Unión a Manosa/genética , Osteítis/genética , Receptores Toll-Like/genética , Adulto , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium bovis , Polimorfismo de Nucleótido Simple/genética , Tuberculosis/genética , Adulto JovenRESUMEN
Mucin-1 (MUC1) affects cancer progression in lung adenocarcinoma, and its aberrant expression pattern has been correlated with poor tumor differentiation and impaired prognosis. In this study, the immunohistochemical expression of MUC1 and Mucin-4 (MUC4) was analyzed in a series of 106 surgically operated stage I-IV pulmonary adenocarcinomas. MUC1 immunohistochemistry was evaluated according to the Nagai classification, and the immunohistochemical profile of the tumors was correlated with detailed clinical and histological data. The effect of cigarette smoke on MUC1 expression in lung cancer cell lines was examined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunoelectron microscopy (IEM). In contrast to the normal apical localization of MUC1, a basolateral and cytoplasmic (depolarized) MUC1 expression pattern was frequently encountered in the high-grade subtypes, i.e., solid predominant adenocarcinoma and the cribriform variant of acinar predominant adenocarcinoma (p < 0.001), and was rarely observed in tumors containing a non-predominant lepidic component (p < 0.001). Furthermore, the altered staining pattern of MUC1 correlated with stage (p = 0.002), reduced overall survival (p = 0.031), and was associated with smoking (p < 0.001). When H1650 adenocarcinoma cells were exposed to cigarette smoke and analyzed by RT-qPCR and IEM, the levels of the MUC1 transcript and protein were elevated (p = 0.042). In conclusion, MUC1 participates in the pathogenesis of lung adenocarcinoma and associates with smoking both in vitro and in vivo. In lung adenocarcinoma, depolarized MUC1 protein expression correlated with histological growth patterns, stage, and patient outcome.
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Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Mucina-1/metabolismo , Fumar/efectos adversos , Adenocarcinoma/etiología , Adenocarcinoma/metabolismo , Anciano , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/metabolismo , Masculino , Microscopía Inmunoelectrónica , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
BACKGROUND: Inborn errors of interferon-gamma (IFN-γ)-mediated immunity underlie disseminated disease caused by Mycobacterium bovis Bacillus Calmette-Guérin (BCG) live vaccines. We hypothesized that some patients with osteitis after BCG vaccination may have an impaired IFN-γ immunity. Our aim was to investigate interleukin (IL)-12 and IFN-γ ex vivo production stimulated with BCG and BCG + IFN-γ or BCG + IL-12, respectively, in BCG osteitis survivors. METHODS: Fresh blood samples were collected from 132 former BCG osteitis Finnish patients now aged 21-49 years, and IL-12 and IFN-γ were measured in cell cultures with and without stimulation with BCG and with BCG + IFN-γ or BCG + IL-12, respectively. As a pilot study, known disease-causing genes controlling IFN-γ immunity (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, IRF8, NEMO and CYBB) were investigated in 20 selected patients by whole exome sequencing. RESULTS: By the limit of <5th percentile, ex vivo IL-12 concentration and increase in concentration was low in 5 and ex vivo IFN-γ concentration and increase in concentration was low in 6 patients (including 2 samples with both IL-12 and IFN-γ findings). By the limit of <10th percentile, an additional 6 and 4 patients were, respectively, detected (including 2 samples with both findings). With 2 exceptions, low concentrations and low increases in concentrations picked-up the same cases. Mutations in known disease-causing IFN-γ-related genes were not found in any of these patients. CONCLUSION: These findings call for searching of mutations in new genes governing IFN-γ-dependent immunity to live BCG vaccine.
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Vacuna BCG/efectos adversos , Interferón gamma/metabolismo , Interleucina-12/metabolismo , Leucocitos Mononucleares/inmunología , Mycobacterium bovis/inmunología , Osteítis/inducido químicamente , Osteítis/inmunología , Adulto , Vacuna BCG/administración & dosificación , Femenino , Finlandia , Humanos , Factores Inmunológicos/genética , Masculino , Persona de Mediana Edad , Sobrevivientes , Adulto JovenRESUMEN
OBJECTIVES: Histologic heterogeneity is a typical feature of pulmonary adenocarcinoma. This study aimed to deconstruct the intratumoral growth pattern composition and to examine the prognostic relevance of the current lung adenocarcinoma classification in a series of Finnish lung cancer patients. MATERIALS AND METHODS: A cohort of 112 patients with surgically operated stage I-IV lung adenocarcinoma was retrospectively reviewed. Histologic subtyping was performed according to the classification system established by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS). Systematically collected clinical information including survival data was correlated with the subtype status. In addition, emphasis was placed on the nonpredominant histologic patterns, gender and smoking history. RESULTS: The most common subtype was acinar predominant adenocarcinoma with 56 cases (50%). Most tumors were composed of a mixture of two or more growth patterns, and single pattern tumors were rare (9.8%). Micropapillary predominant adenocarcinoma and solid predominant adenocarcinoma were the subtypes with the lowest disease-specific survival rates (5-year DSS 21.4% and 30.4%; shared mean DSS 46.3 months, p=0.040). A nonpredominant lepidic component was observed in 24 (21.4%) tumors, and its presence predicted a better outcome (mean DSS 127.4 months vs. 55.7 months, p=0.001). This association was confirmed by multivariate analysis (p=0.004). Solid pattern and solid, papillary, micropapillary and cribriform predominant histology associated with smoking (p<0.001), while mucinous pattern was more common in nonsmokers (p<0.001) and in women (p=0.050). CONCLUSIONS: Micropapillary and solid predominant adenocarcinomas showed significantly lower survival rate than other major subtypes, yet the prognostic value of the current lung adenocarcinoma classification is not limited only to the predominant growth patterns. The more favorable outcome associated with the nonpredominant lepidic pattern further emphasizes the importance of histologic subtyping and assessment of tumor heterogeneity in the diagnostics of lung adenocarcinoma.
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Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma del Pulmón , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Toll-like receptor 4 is a part of the innate immune system and recognizes Helicobacter pylori lipopolysaccharide. The goal of this study was to analyze the role of Toll-like receptor 4 polymorphisms +896 (rs4986790) and +1196 (rs4986791) in the pathogenesis of Helicobacter pylori related gastroduodenal diseases in relation to gastric secretion and inflammation. Toll-like receptor 4 polymorphisms, serum gastrin-17 and pepsinogen I and II concentrations were determined, and gastroscopies with histopathological analyses were performed to 216 dyspeptic patients. As genotype controls, 179 controls and 61 gastric cancer patients were studied. In our study, the Toll-like receptor 4 +896 and +1196 polymorphisms were in total linkage disequilibrium. The homozygous wild types displayed higher gastrin-17 serum concentrations than the mutants (p = 0.001) and this effect was independent of Helicobacter pylori. The homozygous wild types also displayed an increased risk for peptic ulcers (OR: 4.390). Toll-like receptor 4 genotypes did not show any association with Helicobacter pylori positivity or the features of gastric inflammation. Toll-like receptor 4 expression was seen in gastrin and somatostatin expressing cells of antral mucosa by immunohistochemistry. Our results suggest a role for Toll-like receptor 4 in gastric acid regulation and that the Toll-like receptor 4 +896 and +1196 wild type homozygozity increases peptic ulcer risk via gastrin secretion.
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Gastrinas/sangre , Úlcera Péptica/genética , Polimorfismo de Nucleótido Simple , Receptor Toll-Like 4/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Gastritis/sangre , Gastritis/genética , Gastritis/microbiología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/microbiología , Helicobacter pylori/fisiología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pepsinógeno A/sangre , Pepsinógeno C/sangre , Úlcera Péptica/sangre , Úlcera Péptica/microbiología , Factores de Riesgo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Receptor Toll-Like 4/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by structural changes in alveoli and airways. Our aim was to analyse the numbers of alpha-smooth muscle actin (α-SMA) positive cells, as a marker of myofibroblasts, in different lung compartments in non-smokers and smokers with normal lung function or COPD. METHODS: α-SMA, tenascin-C (Tn-C) and EDA-fibronectin in alveolar level and airways were assayed by immunohistochemistry and quantified by image analysis. Immunohistochemical findings were correlated with clinical data. α-SMA protein was also analysed by Western blotting from fibroblastic cells cultured from peripheral lung of non-smokers, smokers without COPD and smokers with COPD. RESULTS: In many cases, the endings of the detached alveolar walls were widened, the structures of which were named as widened alveolar tips. Widened alveolar tips contained α-SMA positive cells, which were obviously myofibroblasts. There were less alveolar tips containing positive cells for α-SMA in alveoli and α-SMA positive cells in bronchioles in smokers and in COPD compared to non-smokers. The quantity of α-SMA positive cells was increased in bronchi in COPD. Tn-C was elevated in bronchi in COPD and smokers' lung. The α-SMA protein level was 1.43-fold higher in stromal cells cultured from non-smokers than in those of smokers. CONCLUSIONS: Myofibroblasts are localized variably in normal and diseased lung. This indicates that they have roles in both regeneration of lung and pathogenesis of COPD. The widened alveolar tips, these newly characterized histological structures, seemed to be the source of myofibroblasts at the alveolar level.
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Pulmón/patología , Miofibroblastos/patología , Enfermedad Pulmonar Obstructiva Crónica/patología , Fumar/patología , Anciano , Células Cultivadas , Citocinas/inmunología , Femenino , Humanos , Pulmón/inmunología , Masculino , Persona de Mediana Edad , Miofibroblastos/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Fumar/inmunologíaRESUMEN
The aim of this study was to assess the significance of the interleukin 6 gene polymorphism -174 in gastric cancer risk. The interleukin 6 -174 G/C (rs1800795) gene polymorphisms was analyzed in gastric cancer, peptic ulcer, and nonulcer dyspepsia patients and in healthy control subjects and the data were correlated with the histopathological features of the patients' biopsies. The interleukin 6 -174 GG and GC genotypes have been previously associated with high interleukin 6 serum levels. We discovered that the interleukin 6 -174 GG and GC genotypes are associated with an increased risk of the diffuse histologic subtype of gastric carcinomas (OR: 6.809, P = 0.034), but absent in the intestinal type carcinomas (OR: 1.109, P = 0.908). No significant associations with peptic ulcer, gastric atrophy, or intestinal metaplasia were seen. Our results demonstrate that the interleukin 6 -174 GG and GC genotypes increase the risk of the diffuse type gastric carcinoma, but not the intestinal type gastric carcinoma or its precursor conditions, including atrophy or intestinal metaplasia. Thus, interleukin 6 seems to be an important carcinogenetic factor in the diffuse type gastric adenocarcinoma and its carcinogenetic effect could be noninflammatory.
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Interleucina-6/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Adulto , Anciano , Distribución de Chi-Cuadrado , Femenino , Gastritis/genética , Gastritis/patología , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Estudios RetrospectivosRESUMEN
Nearly half of all lung cancers are adenocarcinomas falling into various subtypes. Other common types of lung cancer include squamous cell carcinoma and small cell carcinoma. The pathogenesis and molecular biology of lung cancer has been the subject of considerable research over the last few years, and new pharmacologic therapies have been developed. The histological classification of lung adenocarcinomas has been revised in 2011, and is already becoming established in replacing the WHO classification. The aim of the new classification is to make the diagnostics of lung cancer and assessment of treatment options more precise.
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Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/clasificación , Adenocarcinoma/diagnóstico , Carcinoma de Células Pequeñas/clasificación , Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Escamosas/clasificación , Carcinoma de Células Escamosas/diagnóstico , Humanos , Neoplasias Pulmonares/clasificación , Organización Mundial de la SaludRESUMEN
BACKGROUND: Animal mycobacterioses are regarded as a potential zoonotic risk and cause economical losses world wide. M. avium subsp. hominissuis is a slow-growing subspecies found in mycobacterial infected humans and pigs and therefore rapid and discriminatory typing methods are needed for epidemiological studies. The genetic similarity of M. avium subsp. hominissuis from human and porcine origins using two different typing methods have not been studied earlier. The objective of this study was to compare the IS1245 RFLP pattern and MIRU-VNTR typing to study the genetic relatedness of M. avium strains isolated from slaughter pigs and humans in Finland with regard to public health aspects. METHODS: A novel PCR-based genotyping method, variable number tandem repeat (VNTR) typing of eight mycobacterial interspersed repetitive units (MIRUs), was evaluated for its ability to characterize Finnish Mycobacterium avium subsp. hominissuis strains isolated from pigs (n = 16) and humans (n = 13) and the results were compared with those obtained by the conventional IS1245 RFLP method. RESULTS: The MIRU-VNTR results showed a discriminatory index (DI) of 0,92 and the IS1245 RFLP resulted in DI 0,98. The combined DI for both methods was 0,98. The MIRU-VNTR test has the advantages of being simple, reproducible, non-subjective, which makes it suitable for large-scale screening of M. avium strains. CONCLUSIONS: Both typing methods demonstrated a high degree of similarity between the strains of human and porcine origin. The parallel application of the methods adds epidemiological value to the comparison of the strains and their origins. The present approach and results support the hypothesis that there is a common source of M. avium subsp. hominissuis infection for pigs and humans or alternatively one species may be the infective source to the other.
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Mycobacterium avium/genética , Polimorfismo de Longitud del Fragmento de Restricción , Enfermedades de los Porcinos/microbiología , Secuencias Repetidas en Tándem/genética , Tuberculosis/microbiología , Animales , Finlandia , Humanos , Mycobacterium avium/clasificación , Filogenia , ARN Ribosómico 16S/genética , PorcinosRESUMEN
BACKGROUND: We conducted a 5-year follow-up study on the persistence of pertussis-specific antibody and cell-mediated immunity after booster immunization of adolescents aged 11-13 years with a tricomponent acellular pertussis vaccine (Boostrix; trials diphtheria-tetanus-acellular pertussis [Tdap]-004/030). METHODS: Cellular and humoral immunity to pertussis toxin (PT), filamentous hemagglutinin, and pertactin were measured in adolescents (age, 16 years) 5 years after booster immunization. Similar investigations were performed for control adolescents who had received only diphtheria and tetanus booster vaccination. RESULTS: Five years after pertussis booster vaccination, the geometric mean concentrations of immunoglobulin G (IgG) elicited by each of the 3 pertussis vaccine antigens decreased from 1-month and 3-year postvaccination levels, but with the exception of PT IgG, were still higher than the prevaccination levels. PT IgG levels were undetectable in 28% of the subjects, but 44% of those subjects still tested positive for cell-mediated immunity to PT. Filamentous hemagglutinin IgG and pertactin IgG levels were significantly higher in Tdap-boosted adolescents than in the control subjects. Antibody concentrations at 1 month after vaccination strongly predicted antibody persistence. Cell-mediated immunity levels to PT, filamentous hemagglutinin, and pertactin persisted above the prebooster levels measured 5 years earlier. CONCLUSIONS: The results of the present study of adolescents indicate that the interval between acellular pertussis booster immunizations might be extended beyond 5 years.
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Vacuna contra Difteria, Tétanos y Tos Ferina/uso terapéutico , Inmunización Secundaria/métodos , Tos Ferina/inmunología , Adolescente , Formación de Anticuerpos/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Femenino , Estudios de Seguimiento , Humanos , Inmunidad Celular/inmunología , Masculino , Tos Ferina/prevención & controlRESUMEN
Bordetella holmesii is a Gram-negative bacterium first identified in 1995. It can cause pertussis-like symptoms in humans. B. holmesii contains insertion sequences IS481 and IS1001, two frequently used targets in the PCR diagnosis of Bordetella pertussis and Bordetella parapertussis infections. To investigate the prevalence of B. holmesii in Finnish and Dutch patients with pertussis-like symptoms and whether B. holmesii has caused any false-positive results in diagnostic PCRs, B. holmesii-specific real-time PCRs were developed. The Finnish methods were conventional IS481 PCR and B. holmesii-specific real-time PCR (LightCycler, Roche) targeting the B. holmesii recA gene. The Dutch methods were IS481 and IS1001 PCRs with conventional or real-time formats and B. holmesii-specific real-time PCR targeting the homologue of IS1001. Of 11,319 nasopharyngeal swabs, 2804 were collected from Finnish patients from 2000 to 2003, and 8515 from Dutch patients from 1992 to 2003. B. holmesii DNA was not found in the samples analysed. The results suggest that B. holmesii is not among the causative agents of pertussis-like symptoms in Finnish and Dutch patients and thus does not in practice confound IS481 and IS1001 PCRs.
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Bordetella/aislamiento & purificación , ADN Bacteriano/genética , Nasofaringe/microbiología , Tos Ferina/epidemiología , Proteínas Bacterianas/genética , Secuencia de Bases , Bordetella/genética , Elementos Transponibles de ADN/genética , Finlandia/epidemiología , Humanos , Datos de Secuencia Molecular , Países Bajos/epidemiología , Reacción en Cadena de la Polimerasa/métodos , Rec A Recombinasas/genética , Sensibilidad y Especificidad , Alineación de Secuencia , Tos Ferina/diagnósticoRESUMEN
Cancer cell budding at the invasive margin has been associated with poor prognosis in rectal cancer. beta-Catenin is an adhesion protein involved in the nuclear Wnt/beta-catenin pathway, and mesenchymal transition of colorectal cancer cells. Hence, we investigated the relationship between cancer cell budding at the invasive margin, beta-catenin expression, and 5-year-survival in colorectal cancer. Four hundred and sixty six colorectal cancer specimens were analysed for budding margin, and 108 specimens from the same set for beta-catenin by immunohistochemistry. A budding margin was present in 24.0% of the cases and predicted a poor 5-year-survival (15.4%, P < 0.00001). Nuclear beta-catenin expression increased from the central area towards the invasive margin (P < 0.001), but did not predict budding. Budding margin is an independent factor associated with poor prognosis in colorectal cancer, and could be utilised in diagnostic pathology. Nuclear beta-catenin was often found at the invasive margin, but is unlikely to be the sole cause of budding.
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Neoplasias Colorrectales/metabolismo , Proteínas de Neoplasias/metabolismo , beta Catenina/metabolismo , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Humanos , Inmunohistoquímica , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Variaciones Dependientes del Observador , Pronóstico , Análisis de Regresión , Análisis de SupervivenciaRESUMEN
Two commercially available DNA line probe assays, Genotype MTBDR and INNO-LiPA Rif. TB, were evaluated for their abilities to detect resistance to isoniazid (INH) and rifampin (RIF) in 52 Mycobacterium tuberculosis isolates. The test results were compared to those obtained by phenotypic drug susceptibility testing and sequencing. Compared to the results of phenotypic drug susceptibility testing, the Genotype MTBDR test results were concordant for INH for 47 of the 52 (90.4%) isolates, and both the Genotype MTBDR and the INNO-LiPA Rif. TB test results were concordant for RIF for 51 of the 52 (98.1%) isolates. The Genotype MTBDR test results correlated with the sequencing results for 48 of the 52 (92.3%) isolates and the INNO-LiPA Rif. TB results for 50 of the 52 (96.2%) isolates. Both assays are useful for the rapid screening of M. tuberculosis isolates obtained from patients suspected of having multidrug-resistant tuberculosis, but the GenoType MTBDR assay has the advantage of being able to detect resistance to both INH and RIF simultaneously.
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Antibióticos Antituberculosos/farmacología , Isoniazida/farmacología , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Hibridación de Ácido Nucleico/métodos , Rifampin/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Proteínas Bacterianas/genética , Catalasa/genética , Farmacorresistencia Bacteriana , Humanos , Mycobacterium tuberculosis/genética , Fenotipo , Juego de Reactivos para Diagnóstico , Análisis de Secuencia de ADNRESUMEN
AIM OF THE STUDY: Previous work has indicated that quantification of inflammatory cell reaction is of prognostic value in colorectal cancer. We evaluated the prognostic significance of inflammatory cell reaction patterns in colorectal cancer and developed a grading method which could be used in the routine assessment of tumours. METHODS: The intensity of overall inflammatory cell reaction, numbers of neutrophilic and eosinophilic granulocytes, lymphoid cells and macrophages in both the central region and the invasive margin were estimated in 386 colorectal cancer patients. Prognostic significance was analysed by uni- and multivariate analysis. RESULTS: Our method for classification of inflammatory reaction was reliable. High-grade inflammation at the invasive margin in Dukes' stage A and B cancers (pT1-2N0 and pT3N0, respectively) was associated with better 5-year-survival (87.6%) than low-grade inflammation (47.0%). CONCLUSIONS: Inflammatory cell response at the invasive border is a relevant prognostic indicator and could be easily incorporated into the routine evaluation of histopathological specimens.
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Colitis/patología , Neoplasias Colorrectales/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Niño , Enfermedad de Crohn/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Macrófagos/patología , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , PronósticoRESUMEN
Colorectal serrated adenocarcinoma originates from serrated adenoma, but definite histological criteria have not yet been established. It presents with frequent DNA microsatellite instability (MSI), but the frequency of low-level (MSI-L) and high-level MSI (MSI-H) and the expression of mismatch-repair (MMR) enzymes in serrated adenocarcinoma are not known. To address these questions, morphological criteria for serrated cancers were established, their validity was tested, and MSI analysis was performed with NIH consensus markers and MMR enzyme immunohistochemistry for hMLH1, hMSH2, and hMSH6 in 35 serrated and 75 non-serrated colorectal carcinomas. Serrated carcinomas frequently showed a serrated, mucinous or trabecular growth pattern; abundant eosinophilic cytoplasm; chromatin condensation; preserved polarity; and the absence of necrosis. With these features, it was possible to distinguish them from non-serrated cancers, with the mean kappa score for five observers being 0.509. MSI analysis was successful in 31 serrated and 73 non-serrated carcinomas. 54.8% of serrated carcinomas were microsatellite-stable (MSS), 29.0% presented with MSI-L, and 16.1% presented with MSI-H, whereas 78.1% of non-serrated carcinomas were MSS, 13.7% were MSI-L, and 8.2% were MSI-H. MSI-L was more common in serrated cancers (p=0.035) and it was associated with patchy immunohistochemical staining (33.3%) of MLH1. MSI-H did not differ between serrated and non-serrated cancers (p=0.14). These results suggest that the biological background of serrated carcinomas differs from sporadic non-serrated colorectal cancer, but is not directly related to MSI.
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Adenocarcinoma/patología , Neoplasias Colorrectales/patología , Repeticiones de Microsatélite/genética , Proteínas Adaptadoras Transductoras de Señales , Adenocarcinoma/genética , Adenoma/genética , Adenoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Disparidad de Par Base/genética , Biomarcadores de Tumor/genética , Proteínas Portadoras/genética , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Colon/patología , Neoplasias Colorrectales/genética , ADN de Neoplasias/genética , Eosinófilos/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Proteínas MutL , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Variaciones Dependientes del Observador , Recto/patologíaAsunto(s)
Bordetella pertussis/clasificación , Bordetella pertussis/aislamiento & purificación , Brotes de Enfermedades , Tos Ferina/epidemiología , Adulto , Bordetella pertussis/genética , Niño , Dermatoglifia del ADN/métodos , Electroforesis en Gel de Campo Pulsado , Finlandia/epidemiología , Humanos , Instituciones Académicas , Población Urbana , Tos Ferina/microbiología , Tos Ferina/transmisiónRESUMEN
We evaluated pertussis-specific cell-mediated immunity (CMI) and humoral immunity in adolescents 3 years after they received an acellular pertussis booster immunization. Two hundred sixty-four adolescents were examined for immunoglobulin G antibodies, and 49 were examined for CMI against Bordetella pertussis antigens 40 months after receiving the booster. A control group of similarly aged adolescents who had received diphtheria and tetanus vaccination 3 years earlier was included for comparison. Pertussis-specific CMI persisted at greater than prebooster immunization levels. Although they had decreased by the 3-year follow-up, antibody levels remained significantly higher than prebooster immunization levels. Antibodies against pertussis antigens and CMI against filamentous hemagglutinin and pertactin were significantly higher in vaccinated adolescents than in control subjects. The acellular pertussis booster immunization provides long-term CMI and humoral immunity lasting for >or=3 years. The significantly higher immunity observed in the diphtheria, tetanus, and acellular pertussis vaccine recipients, compared with that in control subjects, indicates that these responses are more likely to have resulted from the booster immunization than from the boosting effects of natural B. pertussis infection.
Asunto(s)
Bordetella pertussis/inmunología , Vacuna contra la Tos Ferina/inmunología , Adolescente , Anticuerpos Antibacterianos/sangre , Niño , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Femenino , Estudios de Seguimiento , Humanos , Inmunidad Celular , Inmunización Secundaria , Inmunoglobulina G/sangre , Masculino , Vacunas Acelulares/inmunologíaRESUMEN
Fas (CD95, APO-1) is widely expressed on lymphatic cells, and by interacting with its natural ligand (Fas-L), Fas induces apoptosis through a complex caspase cascade. In this study we sought to survey Fas-L expression in vascular and sinusoidal structures of human reactive lymph nodes. Immunohistochemical Fas-L expression was present in all paracortical high endothelial venules (HEVs), in cells lining the marginal sinus wall, and in a few lymphocytes, but only occasionally in non-HEV vascular endothelium. In the paracortical zone over 60% of all vessels and all paracortical HEVs showed Fas-L expression, whereas in the medullary zone less than 10% of the blood vessels were stained with Fas-L. Normal vessels outside lymph nodes mostly showed no Fas-L expression. We show that in human reactive lymph nodes Fas-L expression is predominantly present in HEVs. Because the circulating lymphocytes gain entry to nodal parenchyma by transendothelial migration through HEVs, the suggested physiological importance of Fas-L expression in these vessels lies in the regulation of lymphocyte access to lymph node parenchyma by possibly inducing Fas/Fas-L mediated apoptosis of activated Fas-expressing lymphoid cells. The Fas-L expressing cells in the marginal sinus might have a similar function for cells accessing the node in afferent lymph.