RESUMEN
BACKGROUND AND AIMS: Several studies have demonstrated that breast cancer survival rates differ with ethnicity. Most of these studies analyzed discrepancies between African-American and Caucasian-American women and were performed in the United States. There are increasing concerns about differences in breast cancer survival among immigrants from Asia and Africa living in Europe, including those living in Scandinavian countries. There are few data on breast cancer survival in relation to race or ethnicity in Scandinavian countries, even though immigrants from Asia and Africa have lived in Scandinavian countries for decades. The aim of this study was to identify variations in breast cancer incidence, treatment modalities, relapse, and survival among women from Pakistan, Sri Lanka, and Somalia compared to ethnic Norwegian women. MATERIAL AND METHODS: The incidence, treatment modalities, relapse, and survival of breast cancer were analyzed in women from Pakistan, Sri Lanka, and Somalia in a nation-based study over a period of 7 ears. Results for women from Pakistan, Sri Lanka, and Somalia were compared with those from a group of ethnic Norwegian women during the same period. In our study, 63 patients from Pakistan, Sri Lanka, and Somalia were diagnosed with breast cancer during the period 2002-2009 in Norway. RESULTS AND CONCLUSION: Comparison between women from Pakistan, Sri Lanka, and Somalia and ethnic women from Norway revealed significant differences in cancer stage at the time of diagnosis, age at diagnosis, type of surgical treatment, and relapse and breast cancer mortality rates. The findings of this study demonstrate that the outcome after a breast cancer diagnosis is significantly worse for women from Pakistan, Sri Lanka, and Somalia than for ethnic Norwegian women. In addition, the mean age at the breast cancer diagnosis was lower for women from Pakistan, Sri Lanka, and Somalia, especially those from Sri Lanka and Somalia, than for ethnic Norwegian women.
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Neoplasias de la Mama/etnología , Etnicidad , Mamografía/métodos , Estadificación de Neoplasias/métodos , Sistema de Registros , Medición de Riesgo/métodos , Adulto , Distribución por Edad , Anciano , Biopsia , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Terapia Combinada , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Morbilidad/tendencias , Recurrencia Local de Neoplasia/etnología , Noruega/epidemiología , Pakistán/etnología , Factores de Riesgo , Somalia/etnología , Sri Lanka/etnología , Tasa de Supervivencia/tendenciasRESUMEN
BACKGROUND: Infection is the most common reason for early revision after hip and knee arthroplasty, and the revision rate is increasing. Surgical site infection (SSI) surveillance data are important to assess the true infection rate. There is little information regarding the potential time trend in SSI incidence following orthopaedic surgery. AIM: To evaluate whether a time trend exists in SSI incidence due to surveillance following orthopaedic surgery. METHODS: The SSI rates after hip and knee replacements and osteosynthesis of trochanteric femoral fractures and ankle fractures were recorded prospectively from May 1998 to October 2008 according to the criteria of the US Centers for Disease Control and Prevention. In total, 4177 procedures were analysed, 65.8% of which were performed on female patients. Linear regression was used to analyse trends in SSI rates. FINDINGS: SSI incidence decreased significantly from 7% in the first year to 3% in the last year; a 57% relative reduction. The duration of surgery was the only significant predictor for infection (P < 0.001) in a logistic regression model that also included age, American Society of Anesthesiologists' score and level of emergency. CONCLUSION: Surveillance following orthopaedic procedures showed a significant decrease in SSI incidence over the 11-year surveillance period. The causality between surveillance and SSI incidence is difficult to prove, but surveillance with feedback probably influences several procedures that affect the quality of health care, even if duration of surgery is the only significant predictor of this effect.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Infecciones Relacionadas con Prótesis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Monitoreo Epidemiológico , Femenino , Fracturas Óseas/cirugía , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Adulto JovenRESUMEN
INTRODUCTION: Adherence to infection control guidelines is low, and several efforts have been made to improve healthcare workers' performance of infection control measures. In this study, the performance and evaluation of a hospital-wide infection control programme is described. The most important measure was distribution of an infection control newsletter. METHODS: In evaluation of the programme, a randomised selection of healthcare workers received a questionnaire to investigate in what degree the healthcare workers was aware of the programme and whether they reported behavioural change and refreshed knowledge as result of the programme. RESULTS: The intervention made it possible to reach >80% of the personnel in a Norwegian university hospital. Among those who actually read Infection Control Newsletter, 92.9% reported that their knowledge was refreshed and 60.6% reported behavioural change. DISCUSSION: The intervention had a significant impact on nurses and nurse assistants' reports on knowledge and behaviour related to infection control. Our study supports the importance of a long-term and multimodal approach to healthcare workers in infection control work. The time and resources spent to produce and distribute the Infection Control Newsletter was an effective way to reach out to a large number of healthcare workers.
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Conocimientos, Actitudes y Práctica en Salud , Control de Infecciones/métodos , Personal de Hospital/psicología , Femenino , Adhesión a Directriz , Humanos , Masculino , Noruega , Evaluación de Programas y Proyectos de Salud , Encuestas y CuestionariosRESUMEN
Reports of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) causing hospital infections are increasing, and it is questionable whether the existing molecular definition of CA-MRSA is suitable for the characterization of all strains involved. The 821 methicillin-resistant S. aureus (MRSA) isolates recovered from patients in Health Region East, Norway during the period 1991-2006 were characterized by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) gene typing, and their content of exotoxin-encoding genes. Cluster analysis based on exotoxin-encoding gene content was performed to separate the MRSA isolates into valid clusters with respect to microbiological characteristics. The analysis gave a four-cluster structure, and the four toxin clusters differed in the genetic lineages they included and in the diversity of the genetic lineages. A few genetic lineages were present in several toxin clusters. These results support the theory that mobile genetic elements encoding virulence genes do not move randomly among genetic lineages, but are restricted by the clonal lineages' genetic background. Using the molecular criteria, MLST type, SCCmec type and the presence of the lucS/F-Panton-Valentine leukocidin (PVL) gene to define a CA-MRSA isolate, it was found that the CA-MRSA isolates mainly grouped together in two toxin clusters with a low prevalence of exotoxin-encoding genes. Statistical analyses supported the conclusion that toxin clusters with CA-MRSA genetic lineages were characterized by a low prevalence of exotoxin-encoding genes, whereas toxin clusters with hospital-acquired MRSA genetic lineages were characterized by a higher prevalence of exotoxin-encoding genes.
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Toxinas Bacterianas/genética , Infecciones Comunitarias Adquiridas/epidemiología , Infección Hospitalaria/epidemiología , Exotoxinas/genética , Staphylococcus aureus Resistente a Meticilina/genética , Infecciones Estafilocócicas/epidemiología , Proteínas Bacterianas/genética , Técnicas de Tipificación Bacteriana , Infecciones Comunitarias Adquiridas/microbiología , Infección Hospitalaria/microbiología , Enterotoxinas/genética , Humanos , Leucocidinas/genética , Noruega/epidemiología , Análisis de Secuencia de ADN , Infecciones Estafilocócicas/microbiología , Proteína Estafilocócica A/genéticaRESUMEN
The aim of this study was to investigate the patterns and dynamics of the microbiota in the airways of ventilated patients. Seventy-four mechanically-ventilated patients were recruited consecutively, and oropharyngeal, tracheal and bronchoalveolar (BAL) fluid specimens were collected 48 h after intubation, and every 72 h thereafter until the patient was extubated or a total of five sample sets had been collected. Ventilator-associated pneumonia (VAP) pathogens were identified, quantified and genotyped. Microbial findings were highly correlated both between airway locations and over time when samples were taken no more than 72 h apart. If no VAP pathogen was present in the oral flora, it was unlikely to be found in a lower airway sample; i.e., the positive predictive value of the oropharyngeal sample was 0.73 (95% CI 0.67-0.80), and the negative predictive value was 0.95 (95% CI 0.92-0.99). Colonisation with Enterobacteriacae, non-fermentative bacteria and Staphylococcus aureus was monoclonal in the airways and over time, whereas colonisation with microbes normally found in the oropharynx, i.e., Haemophilus influenzae, Haemophilus parainfluenzae and Streptococcus pneumoniae, was polyclonal. When antibiotics were used, the chance of recovering VAP pathogens from all sampling sites was reduced three-fold. No correlation was observed between a bacterial count of > or =10(4) CFU/mL in BAL fluid and chest X-rays compatible with VAP.
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Bacterias/crecimiento & desarrollo , Líquido del Lavado Bronquioalveolar/microbiología , Orofaringe/microbiología , Neumonía Asociada al Ventilador/microbiología , Respiración Artificial/efectos adversos , Tráquea/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Colonia Microbiana , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Neumonía Asociada al Ventilador/fisiopatología , Vigilancia de GuardiaRESUMEN
BACKGROUND: Contaminated oral swabs caused a nationwide monoclonal Pseudomonas aeruginosa outbreak involving 27 Norwegian hospitals. The aim of the study was to study the consequences on mortality and morbidity of the introduction of this P. aeruginosa strain to intensive care unit (ICU) patients. METHODS: Forty-four out of 96 patients admitted to the general ICU of Akershus University Hospital during the outbreak, ventilated for more than 24 h and with at least one microbiological sample, were included and followed until death or hospital discharge. All isolated P. aeruginosa strains were genotyped. Demographic data, admission diagnosis, Simplified Acute Physiology Score II (SAPS II), Sequential Organ Failure Assessment (SOFA) score, comorbidities, and antibiotics used in the first week were recorded. RESULTS: The outbreak strain was found in 18 patients (41%) of whom seven became infected. Median time to the first positive culture was 4 days. These 18 patients spent a significantly longer time on mechanical ventilation (P =0.03) and had a significantly higher hospital mortality, 55.5% vs. 19.2% (P =0.03), than non-colonized patients. The number of patients with severe underlying disease was significantly higher (P =0.01) and the decline in SOFA score was significantly slower in the pseudomonas group (P =0.02). Irrespective of colonization status, patients with severe underlying disease had a significantly higher mortality (58%) than those without (16%) (P =0.009). CONCLUSION: Use of contaminated oral swabs led to a high rate of early airways colonization. Patients with severe underlying disease were more likely to become colonized, but whether colonization has any influence on hospital mortality requires further study.
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Infección Hospitalaria/epidemiología , Contaminación de Equipos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Infecciones por Pseudomonas/epidemiología , APACHE , Anciano , Antibacterianos/uso terapéutico , Líquido del Lavado Bronquioalveolar/microbiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/mortalidad , Brotes de Enfermedades , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/mortalidad , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crecimiento & desarrolloRESUMEN
UNLABELLED: Deregulation of cell cycle control is a hallmark of cancer. The primary cyclins (A, B1, D1, D3 and E) are crucial for cell cycle progression. Secondary cyclins (C and H) have putative indirect effects on cell cycle propulsion and are not previously evaluated in breast cancer. We have examined protein expression and gene amplification of cyclins in breast carcinomas and correlated the findings with clinical follow-up data. We have previously demonstrated that over-expression of cyclin A is associated with poor prognosis in breast cancer patients. In this study we wanted to evaluate the mechanisms behind overexpression of cyclin A, as well as the impact of other cyclins, both at the gene level and at the protein level, on prognosis of breast cancer patients. The impact of TP53 gene mutations on gene amplification of cyclins was also evaluated. METHODS: Real-Time Quantitative PCR was used to detect gene amplification of cyclins in tumour tissue from 86 patients operated for invasive breast carcinomas, while immunohistochemistry was applied to detect protein expression of the same cyclins. RESULT: Of the 80-breast tumour samples available for cyclin A gene amplification analyses, 26.7% (23/80) was defined to have cyclin A gene amplification. 37.2% (32/79) had cyclin B1 gene amplification, 82.6% (71/82) of the samples harboured amplification of cyclin C gene, 74.4% (64/82) had cyclin D1 gene amplification, 41.9% (36/86) had cyclin D3 gene amplification, 29.1% (25/81) of the patients had cyclin E gene amplification and 9.3% (8/86) of the samples showed amplification of the cyclin H gene. When correlation between gene amplification and protein expression was evaluated, we observed a statistical significant correlation between gene amplification and protein expression of cyclin A (p=0.009) and cyclin D3 (p<0.001). However, the correlation between gene amplification and protein expression of cyclin A, as well as the prognostic value of cyclin A overexpression, was affected by gene amplification of cyclin E. Gene amplification of none of the other cyclins was associated with patient prognosis. There was a statistical significant correlation between TP53 gene mutations and gene amplification of cyclins A, D3 and B1. No correlation was observed between gene amplification of secondary cyclins (H and C) and TP53 gene mutations. CONCLUSIONS: The overexpression of cyclin A is correlated to gene amplification of both cyclin A and cyclin E. Over-expression of cyclin A is associated with poor prognosis in breast cancer patients. When analysed in a multivariate analyses model, gene amplification as well as protein expression of none of the other cyclins than cyclin A are associated with patient prognosis in breast carcinomas. TP53 gene mutation seems to correlate with gene amplification of primary, but not secondary cyclins.
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Neoplasias de la Mama/genética , Ciclina A/genética , Ciclina E/genética , Amplificación de Genes/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Ciclina A/análisis , Ciclina E/análisis , Análisis Mutacional de ADN , ADN de Neoplasias/química , ADN de Neoplasias/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Genes p53/genética , Humanos , Inmunohistoquímica/métodos , Persona de Mediana Edad , Análisis Multivariante , Mutación/genética , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , PronósticoRESUMEN
A retrospective population-based study of genotypes of methicillin-resistant Staphylococcus aureus (MRSA) was performed during the period 1991-2003 in two counties in the south-eastern part of Norway. Isolates of MRSA from all individuals in the two counties in whom MRSA was detected were genotyped by means of multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A gene (spa) typing and amplified fragment length polymorphism (AFLP) analysis. Until 1999, only sporadic cases of MRSA infection were reported in these counties, but the incidence increased during the following years. Nine new MLST types were identified in this study. The predominant strains were ST239-MRSA-III, the novel ST125-MRSA-IV, and the central European community-acquired strain ST80-MRSA-IV reported previously. ST80-MRSA-IV was introduced into the two counties in 1997, and the incidence of infections has increased since 2000, so that ST80-MRSA-IV is now the commonest MRSA strain in the region. An increase in MRSA clones carrying SCCmecIV has occurred during recent years, which could indicate a shift in the MRSA population in Norway from hospital-acquired MRSA to community-acquired-MRSA.
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Proteínas Bacterianas/genética , Resistencia a la Meticilina/genética , Staphylococcus aureus/genética , Técnicas de Tipificación Bacteriana , Infecciones Comunitarias Adquiridas/genética , Infecciones Comunitarias Adquiridas/microbiología , Infección Hospitalaria/genética , Infección Hospitalaria/microbiología , Genotipo , Humanos , Noruega , Proteínas de Unión a las Penicilinas , Estudios Retrospectivos , Análisis de Secuencia de ADN , Staphylococcus aureus/clasificaciónRESUMEN
BACKGROUND/AIMS: Deregulation of cell cycle control is a hallmark of cancer. The primary cyclins (A, B1, D1, D3, and E) are crucial for cell cycle progression. Secondary cyclins (C and H) have putative indirect effects on cell cycle progression and have not previously been evaluated in colon cancer. This study examined cyclin protein expression and gene amplification in colon adenocarcinoma and the correlation with patient outcome. METHODS: Immunohistochemistry and real time quantitative polymerase chain reaction were used to determine cyclin expression and gene amplification in 219 tumours. The results were compared with clinical variables and patient outcomes. RESULTS: Cyclin H was overexpressed in all tumours, cyclin C in 88%, cyclin B1 in 58%, cyclin A in 83%, cyclin D3 in 36%, cyclin E in 25%, and cyclin D1 in 11% of the tumours. Extra gene copies of cyclin A were seen in 6.2% of the tumours, cyclin B1 in 9%, cyclin C in 26.9%, cyclin D1 in 55%, cyclin D3 in 20.5%, cyclin E in 19.1%, and cyclin H in 5.1%. A significant correlation between protein overexpression and gene amplification was seen for cyclin C only. High expression of cyclin A was independently associated with improved survival. Amplification of cyclin C was independently associated with an unfavourable prognosis. CONCLUSIONS: Amplification of the cyclin C gene was related to an unfavourable prognosis and high protein expression of cyclin A was associated with a better outcome in colon adenocarcinoma.
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Adenocarcinoma/genética , Neoplasias del Colon/genética , Ciclinas/genética , Regulación Neoplásica de la Expresión Génica/genética , Adulto , Anciano , Anciano de 80 o más Años , Ciclo Celular/genética , Femenino , Amplificación de Genes/genética , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , PronósticoRESUMEN
This study involved observation of hand-hygiene behaviour and evaluation of the effect of alcohol-based hand disinfection and handwashing with plain liquid soap on microbial flora. The study was performed in a combined medical and surgical intensive care unit. We demonstrated a crude compliance of hand hygiene of 50.4%, which was only performed adequately in 20.8% of cases. Of this group, handwashing and hand-disinfection procedures were performed properly 34.0% and 71.6% of the time, respectively. Hand samples for bacteriological examinations with the glove juice method demonstrated that whilst handwashing was sensitive to the way in which hand hygiene was performed, alcohol-based hand disinfection was less sensitive to such performance. Our study demonstrated that alcohol-based hand disinfection is a robust hand-hygiene method with many advantages in a practical setting. It is very feasible for use in hospital wards.
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Alcoholes/administración & dosificación , Infección Hospitalaria/prevención & control , Adhesión a Directriz , Desinfección de las Manos/métodos , Unidades de Cuidados Intensivos/normas , Guías de Práctica Clínica como Asunto , Jabones/administración & dosificación , Tensoactivos/administración & dosificación , Adulto , Alcoholes/normas , Infección Hospitalaria/microbiología , Desinfección de las Manos/normas , Hospitales Universitarios , Humanos , Control de Infecciones/métodos , Noruega , Personal de Hospital , Jabones/normas , Tensoactivos/normasRESUMEN
AIM: Most patients with stage I and stage II colon adenocarcinomas do not have disseminated disease, and the group is not offered adjuvant therapy. However, more than 30% of stage II colon adenocarcinoma patients get metastases to remote organs. Thus, it is important to identify patients in this group at risk of disease relapse. PATIENTS AND METHODS: We have examined the prognostic value of isolated tumour cells (ITC) in mesenteric lymph nodes in a consecutive series of 156 colon carcinoma patients with stage II disease. Immunohistochemistry, using antibodies to cytokeratins, and morphology were used to identify presence of ITC. RESULTS: ITC were detected in 59 (37.8%) patients. Presence of ITC in mesenteric lymph nodes was independently associated with reduced relative survival both in univariate (p=0.0199) and in a multivariate analysis (p=0.041). CONCLUSION: The results strongly suggest that presence of ITC in mesenteric lymph nodes is associated with reduced relative survival in colon carcinoma patients stage II, and that detection of ITC may be important in treatment of these patients.
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Adenocarcinoma/patología , Neoplasias del Colon/patología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica/métodos , Metástasis Linfática , Masculino , Mesenterio/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de RiesgoRESUMEN
AIM: Increased proliferation of tumour cells has prognostic value in human invasive breast carcinomas (IBCs), and high histology grade and cyclin A expression, which may reflect high proliferation rate, are associated with poor prognosis. Expression of HsMCM2 is related to cell proliferation. This study evaluates the correlation between the expression of cyclins A, D1, D3, and E, Ki-67, proliferating cell nuclear antigen (PCNA), histology grade, and HsMCM2 expression, in addition to the independent prognostic value of HsMCM2 expression in human IBCs. METHODS: Immunohistochemistry to evaluate HsMCM2, Ki-67, and PCNA expression in tumours from 147 patients with IBC. RESULTS: Nuclear staining for HsMCM2 was seen in 10-30% of the tumour cells in 30 samples, in 30-70% in 40 samples, in > 70% in 44 samples, and in < 10% in 33 samples. One way ANOVA showed a significant association between expression of HsMCM2 and cyclin A, D3, E, histology grade, and Ki-67. A borderline correlation was seen between HsMCM2 and PCNA. In multivariate analysis, the only association was with cyclin A, in addition to a borderline association with histology grade. In a Cox regression hazards model, expression of HsMCM2 was associated with poor patient survival, although it lost its independent prognostic value when cyclin A expression was included. Ki-67 and PCNA expression were not associated with patient survival. CONCLUSION: Cyclin A expression is independently associated with HsMCM2 expression, histology grade, and Ki-67. HsMCM2 expression is associated with poor patient survival, although it loses prognostic value when adjusted for cyclin A.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Ciclina A/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , División Celular , Femenino , Humanos , Técnicas para Inmunoenzimas , Antígeno Ki-67/metabolismo , Componente 2 del Complejo de Mantenimiento de Minicromosoma , Invasividad Neoplásica , Proteínas de Neoplasias/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de SupervivenciaRESUMEN
Previously, we have shown that Helicobacter pylori can spontaneously and reversibly change its membrane lipid composition, producing variants with low or high content of lysophospholipids. The "lyso" variant contains a high percentage of lysophospholipids, adheres better to epithelial cells, and releases more proteins such as urease and VacA, compared to the "normal" variant, which has a low content of lysophospholipids. Prolonged growth of the normal variant at pH 3.5, but not under neutral conditions, leads to enrichment of lyso variant colonies, suggesting that the colony switch is relevant to acid adaptation. In this study we show that the change in membrane lipid composition is due to phase variation in the pldA gene. A change in the (C) tract length of this gene results in reversible frameshifts, translation of a full-length or truncated pldA, and the production of active or inactive outer membrane phospholipase A (OMPLA). The role of OMPLA in determining the colony morphology was confirmed by the construction of an OMPLA-negative mutant. Furthermore, variants with an active OMPLA were able to survive acidic conditions better than variants with the inactive form. This explains why the lyso variant is selected at low pH. Our studies demonstrate that phase variation in the pldA gene, resulting in an active form of OMPLA, is important for survival under acidic conditions. We also demonstrated the active OMPLA genotype in fresh isolates of H. pylori from patients referred to gastroscopy for dyspepsia.
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Ácidos/farmacología , Adaptación Biológica/genética , Proteínas de la Membrana Bacteriana Externa/genética , Variación Genética , Helicobacter pylori/genética , Fosfolipasas A/genética , Sistema de Lectura Ribosómico , Helicobacter pylori/enzimología , Lipopolisacáridos/química , Lisofosfolípidos/análisis , Fosfolipasas A1 , Selección Genética , Ureasa/biosíntesisRESUMEN
Progression through the mammalian cell cycle is facilitated by cyclin-cyclin-dependent kinase (cdk) complexes, which are activated at specific points during the cell cycle. Alteration in cyclin-cdk complexess may lead to altered cell cycle and tumorigenesis. In this study, we analyzed expression of cyclins A, D1, D3 and E in tumor tissue from 170 patients with primary invasive breast carcinomas. Immunohistochemical methods were used to detect protein expression of these cyclins. We detected positive immunoreactivity in 55 (32%), 22 (13%), 38 (22%) and 37 (21.8%) of the samples for cyclins A, D1, D3 and E, respectively. A highly statistically significant association was observed between expression of cyclin A and early relapse (p = 0.001 univariate analysis, p = 0.006 multivariate analysis) as well as cancer-specific death (p < 0.0001) during the follow-up time. No association was observed between cyclin D1 or cyclin E, respectively, and relapse of disease or survival, while cyclin D3 over-expression was associated with development of metastases during follow-up (p = 0.005 univariate analysis, p = 0.01 multivariate analysis). However, cyclin D3 did not show any statistically significant association when cancer-specific death was examined in a multivariate analysis (Cox regression for survival function).
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Ciclina A/análisis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Pronóstico , Recurrencia , Tasa de SupervivenciaRESUMEN
BACKGROUND AND AIMS: Helicobacter pylori is a frequent gram-negative colonizer of the human stomach. Its interaction with complement may be involved in the pathogenesis of chronic gastritis, and was mechanistically studied in vitro. METHODS: Four H. pylori strains, 2 cytotoxin-associated genes (cag)A+ and 2 cagA-, were isolated from infected patients. Bacteria or purified H. pylori lipopolysaccharides (LPSs) were incubated with nonimmune serum at 37 degrees C; the activation products C3b/iC3b/C3c (C3bc) and terminal complement complex (TCC) were then quantified by immunoassays. The serum sensitivity of 1 strain (L01, cagA+) was tested by counting the numbers of colony-forming units. RESULTS: All strains and LPSs generated large amounts of C3bc and TCC. Blocking of the classic complement pathway by the calcium chelator ethylene glycol tetraacetic acid (EGTA) markedly reduced the complement products, suggesting that H. pylori and its LPSs directly engage the classic activation pathway. H. pylori was shown to be serum sensitive, but 30% or more nonimmune serum was necessary to induce marked killing. After 5 minutes, swelled bacteria coated with C3bc and TCC were shown. CONCLUSIONS: H. pylori is complement sensitive and activates the classic pathway even in the absence of specific antibodies. Released cell wall constituents such as LPSs can activate complement and may explain why this bacterium induces gastric pathology without invading the mucosa.
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Antígenos Bacterianos , Activación de Complemento/inmunología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Anticuerpos Antibacterianos/inmunología , Proteínas Bacterianas/genética , Proteínas Sanguíneas/farmacología , Activación de Complemento/efectos de los fármacos , Complemento C3b/inmunología , Complemento C3c/inmunología , ADN Bacteriano/análisis , Técnica del Anticuerpo Fluorescente , Helicobacter pylori/genética , Humanos , Técnicas In Vitro , Lipopolisacáridos/farmacologíaRESUMEN
A phase variation in Helicobacter pylori has been previously described. In one phase the bacterium had a cell wall lipid content typical for gram-negative bacteria (HpL), whereas in the other phase the bacterium was found to have a cell wall with increased amounts of lysophospholipids (HpS). The conversion is spontaneous, but could also be induced by acid (HpS(ind)) and was associated with in vitro release of Vac A and urease. The purpose of the present study was to determine the full phospholipid content of the cell wall to indicate a molecular mechanism of the colony variation. There were no appreciable differences between the lipid profiles of HpS and HpS(ind), while there were major differences between HpL and the S-variant. In the S-variant, lysophospholipids constituted about 50% of the total phospholipids, as compared to less than 2% in the L-variant. The proportion of total and individual cholesteryl glucosides also showed considerable changes. HpL was dominated by the phosphate-linked cholesteryl glucoside (72%) while the acylated cholesteryl glucoside was the main cholesteryl glucoside of the S-variant (65%). Our results demonstrate a dramatic change in cell wall properties after acid induction and spontaneously in vitro, and suggest some molecular mechanisms for this variation from an in vitro non-virulent to a virulent variant.
Asunto(s)
Helicobacter pylori/química , Lípidos/análisis , Cardiolipinas/análisis , Pared Celular/química , Colesterol/análisis , Ácidos Grasos/análisis , Fosfolípidos/análisisRESUMEN
BACKGROUND: Differences in expression of disease after infection with Helicobacter pylori have so far been connected with host factors and bacterial interstrain variation. In this study, spontaneous and ecology-mediated intrastrain variation was examined. METHODS: Four clinical isolates of H. pylori were shown to give rise to two colony forms. Bacterial morphology was examined by electron microscopy. Bacterial fractions were examined for proteins using ion exchange chromatography and SDS-PAGE; for lipids using thin-layer chromatography, lipid anion-exchange chromatography, column chromatography on silica gel, 31P-NMR, gas chromatography and mass spectrometry. Bacterial in vitro invasiveness and adhesiveness were examined in two different systems, and urease and VacA toxin were assayed by Western blot analysis. RESULTS: H. pylori was shown to give rise to two colony forms: at normal pH the population was dominated by L colonies. One strain was chosen for further studies. Bacteria from L colonies retained VacA toxin and urease, did not invade or adhere to epithelial cells, and contained normal quantities of phosphatidylethanolamine. In a small frequency, spontaneous S colonies were formed. Bacteria from these colonies released VacA and urease, adhered to and invaded epithelial cells and contained increased amounts of lysophosphatidyl ethanolamine and phosphatidyl serine. After addition of HCl to the culture medium (pH6), almost only S colonies were formed. The results demonstrate that environmental factors, such as HCl, can change the bacterial cell wall, and thereby enhance expression of virulence factors of H. pylori in vitro. A similar in vivo variation would have implications for our understanding of the interaction between HCl secretion in the gastric mucosa and H. pylori in the development of peptic ulcer disease.
Asunto(s)
Esqueleto de la Pared Celular/metabolismo , Mucosa Gástrica/microbiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Fosfolípidos/metabolismo , Adhesión Bacteriana , Proteínas Bacterianas/metabolismo , Cromatografía de Gases , Recuento de Colonia Microbiana , Técnicas de Cultivo , Citotoxinas/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/patología , Helicobacter pylori/metabolismo , Helicobacter pylori/ultraestructura , Humanos , Lisofosfolípidos/metabolismo , Espectrometría de Masas , Microscopía Electrónica de Rastreo , Ureasa/metabolismoRESUMEN
The effect of interferon (IFN) on herpes simplex virus type 1 (HSV-1)-induced glycoproteins gC and gE was investigated in a heterologous IFN/cell model. In this model, the effect on surface expression of the glycoproteins could be studied separately from the effect on virus multiplication. Pretreatment of baby hamster kidney cells (BHK) with heterologous human leukocyte IFN suppressed surface expression of HSV-1-encoded gC and gE but had no influence on total production of the glycoproteins. This was in contrast to the effect on human embryonic fibroblast cells (HE) (homologous IFN and cells), where surface expression as well as total production of glycoproteins were reduced. The surface expression was demonstrated by antibody-sensitized monodisperse polystyrene beads, and immunoblotting and two-dimensional electrophoretic analysis of radioisotope-labeled proteins were used to study the total production.
Asunto(s)
Antivirales/farmacología , Interferones/farmacología , Proteínas de la Membrana/biosíntesis , Simplexvirus , Proteínas del Envoltorio Viral/biosíntesis , Animales , Células Cultivadas , Cricetinae , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Interferón Tipo I/farmacología , Riñón/citología , Riñón/efectos de los fármacos , Riñón/metabolismo , Biosíntesis de Proteínas , Proteínas RecombinantesRESUMEN
Introducing molecular biological technology into medical microbiology promotes deeper insight into the epidemiology, pathogenesis, diagnostics and treatment of infectious diseases. New technology has helped to highlight the complicated biological interaction between host and microbes and has created a need for more advanced technology both in microbiological diagnostics and in microbiological science. Extra-professional factors like the high prestige of new techniques have also been of considerable significance. Medical microbiologists will become an important link between the inventors of new technology and the physicians who diagnose and treat the patients. Through these contacts and their diagnostic laboratory work, they will become important generators and communicators of knowledge. In this connection it will be important to represent reason in introducing technology in medical microbiological diagnostics. Since patients are expected to play a more active part in health care, communicating knowledge to patients and the population in general will become an obligation.