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1.
Clin Radiol ; 74(4): 327.e1-327.e5, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30745157

RESUMEN

AIM: To evaluate whether digital breast tomosynthesis (DBT) can predict if circumscribed masses are benign or malignant by assessing margin sharpness. MATERIALS AND METHODS: Circumscribed masses were evaluated on co-registered two-dimensional digital mammography (2DDM) and DBT. Lesions were categorised as follows: category 1=visible sharp border 0-25% of the total margin; category 2 = 26-50% category 3= 51-75%, and category 4=76-100%. Changes in category between 2DDM and DBT were analysed; if the category was lower on DBT the change was negative, if higher the change was positive. RESULTS: Of 759 lesions, 121 masses classified as circumscribed on DBT were included; 25 were malignant and 96 benign. Of the benign lesions, 8/96 were within category 3 or 4 on 2DDM compared with 48/96 benign lesions within category 3 or 4 on DBT (Fisher's exact test p<0.000527). Forty-eight of 51 (94.1%) lesions categorised as 3 or 4 on DBT were benign and 65/67 (97.01%) of the positive category change group were benign. Lesions in category 1 on DBT had 45.4% chance of being malignant (20/44) compared with 22.72% (20/88) on 2DDM (chi-squared test p<0.001). Sixty-five of 67 (97.01%) lesions in the positive category change group were benign and 23/54 (42.6%) lesions with either no or negative category change were malignant. CONCLUSION: The present study demonstrates 97% accuracy in predicting circumscribed lesions as benign when using positive category change and 94% accuracy when >50% of the margin is sharply defined on DBT.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Mamografía/métodos , Mama/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados
2.
Clin Radiol ; 74(8): 653.e19-653.e25, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31078275

RESUMEN

AIM: To review all cases of B3 lesion diagnosed at initial image-guided needle biopsy over two 5-year cohorts to identify upgrade rates to malignancy and the effect of changing guidance on the management of such lesions. MATERIALS AND METHODS: Data was collected retrospectively. Mammographic features, biopsy type and management were recorded for each lesion. Upgrade rates for each B3 histological category were quantified. Statistical analysis was performed using SPSS. RESULTS: There were 224 cases in 2005-2010 and 240 cases in 2010-2015. Mammographically 211 lesions were microcalcifications, 182 masses, 65 distortions and six asymmetric densities with no difference in the mammographic features in the two cohorts. Two hundred and eight 14 G core biopsies and 256 initial vacuum-assisted biopsies were performed. There was a statistically significant reduction in benign surgical biopsies and an increase in second-line vacuum biopsy/excision in the latter cohort, with no significant change in the upgrade rate. There was an overall 6% upgrade to invasive malignancy and 13% upgrade to ductal carcinoma in situ (DCIS). The upgrade rates for the following histological categories were atypical intraductal epithelial proliferation (AIDEP) 33.2% (21/63); classical (not pleomorphic) in situ lobular neoplasia (ISLN) 18.2% (6/33); flat epithelial hyperplasia (FEA) 21.7% (20/92); papilloma with atypia 53.8% (7/13), without atypia 12.1% (8/66); and radial scar/complex sclerosing lesion with atypia 16.7% (2/12), and without atypia 7.9% (6/76). CONCLUSION: Upgrade rates remain high for some histological categories even with first-line use of vacuum biopsy. Management of borderline lesions should be considered carefully in a multidisciplinary meeting. In many cases, the need for diagnostic surgical excision has been replaced by image-guided vacuum sampling.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Mamografía/métodos , Auditoría Médica/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Mama/diagnóstico por imagen , Mama/patología , Femenino , Humanos , Biopsia Guiada por Imagen , Auditoría Médica/métodos , Estudios Retrospectivos
3.
J Viral Hepat ; 25(5): 442-456, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29397014

RESUMEN

Hepatitis C virus (HCV)-infected patients are at risk of developing hepatocellular carcinoma (HCC). Individuals at heightened risk could be targeted by intensive follow-up surveillance. We have conducted a systematic review of the literature to identify host genetic predisposition to HCC in HCV-infected patients. A comprehensive search of Medline and Embase databases was performed, and the strength of evidence of associations for each gene on development of HCC was evaluated. We identified 166 relevant studies, relating to 137 different genes, or combinations thereof. Seventeen genes were classified as having "good" evidence of an association, a significant association was observed for 37 genes but this finding had not yet been replicated, 56 genes had mixed or limited evidence of an association, and 27 genes showed no association. IFNL3/4, TNF-α and PNPLA3 genes had the most evidence of an association. There was, however, considerable heterogeneity in study design and data quality. In conclusion, we identified a number of genes with evidence of association with HCC, but also a need for more standardized approaches to address this clinically critical question. It is important to consider the underlying mechanism of these relationships and which are confounded by the presence of other HCC risk factors and response to therapy. We also identified many genes where the evidence of association is contradictory or requires replication, as well as a number where associations have been studied but no evidence found. These findings should help to direct future studies on host genetic predisposition to HCC in HCV-infected patients.


Asunto(s)
Carcinoma Hepatocelular/genética , Predisposición Genética a la Enfermedad , Hepatitis C Crónica/complicaciones , Neoplasias Hepáticas/genética , Estudios de Asociación Genética , Humanos
4.
Clin Radiol ; 69(11): 1112-6, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25100302

RESUMEN

AIM: To compare the diagnostic accuracy of the digital breast tomosynthesis (DBT) with coned compression magnification mammography (CCMM). MATERIALS AND METHODS: The study design included two reading sessions completed by seven experienced radiologists. In the first session, all readers read bilateral standard two-view mammograms and a CCMM view of the lesion before giving a combined score for assessment. In the second session, readers read bilateral standard two-view mammograms plus one-view DBT. The two reading sessions of the experiment were separated by at least 2 weeks to reduce the chance of reader memory of the images read in the previous session from influencing the performance in the subsequent session. RESULTS: Three hundred and fifty-four lesions were assessed and receiver-operative characteristic (ROC) analysis was used to evaluate the difference between the two modes. For standard two-view mammography plus CCMM, the area under the curve (AUC) was 0.87 [95% confidence interval (CI): 0.83-0.91] and for standard two-view mammography plus DBT the AUC was 0.93 (95% CI: 0.91-0.95). The difference between the AUCs was 0.06 with p-value of 0.0014. CONCLUSION: Two-view mammography with one-view DBT showed significantly improved accuracy compared to two-view mammography and CCMM in the assessment of mammographic abnormalities. These results show that DBT can be used effectively in the further evaluation of mammographic abnormalities found at screening and in symptomatic diagnostic practice.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Mamografía/métodos , Intensificación de Imagen Radiográfica/métodos , Anciano , Compresión de Datos , Femenino , Humanos , Persona de Mediana Edad , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Estudios Retrospectivos , Sensibilidad y Especificidad
5.
Clin Radiol ; 67(10): 976-81, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22625656

RESUMEN

AIM: To measure the change in diagnostic accuracy of conventional film-screen mammography and full-field digital mammography (FFDM) with the addition of digital breast tomosynthesis (DBT) in women recalled for assessment following routine screening. MATERIALS AND METHODS: Ethics approval for the study was granted. Women recalled for assessment following routine screening with screen-film mammography were invited to participate. Participants underwent bilateral, two-view FFDM and two-view DBT. Readers scored each lesion separately for probability of malignancy on screen-film mammography, FFDM, and then DBT. The scores were compared with the presence or absence of malignancy based on the final histopathology outcome. RESULTS: Seven hundred and thirty-eight women participated (93.2% recruitment rate). Following assessment 204 (26.8%) were diagnosed as malignant (147 invasive and 57 in-situ tumours), 286 (37.68%) as benign, and 269 (35.4%) as normal. The diagnostic accuracy was evaluated by using receiving operating characteristic (ROC) and measurement of area under the curve (AUC). The AUC values demonstrated a significant (p = 0.0001) improvement in the diagnostic accuracy with the addition of DBT combined with FFDM and film-screen mammography (AUC = 0.9671) when compared to FFDM plus film-screen mammography (AUC = 0.8949) and film-screen mammography alone (AUC = 0.7882). The effect was significantly greater for soft-tissue lesions [AUC was 0.9905 with the addition of DBT and AUC was 0.9201 for FFDM with film-screen mammography combined (p = 0.0001)] compared to microcalcification [with the addition of DBT (AUC = 0.7920) and for FFDM with film-screen mammography combined (AUC = 0.7843; p = 0.3182)]. CONCLUSION: The addition of DBT increases the accuracy of mammography compared to FFDM and film-screen mammography combined and film-screen mammography alone in the assessment of screen-detected soft-tissue mammographic abnormalities.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Mamografía/estadística & datos numéricos , Intensificación de Imagen Radiográfica/métodos , Película para Rayos X/estadística & datos numéricos , Adulto , Neoplasias de la Mama/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Variaciones Dependientes del Observador , Prevalencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Reino Unido/epidemiología , Adulto Joven
6.
Arthroplasty ; 4(1): 40, 2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36050799

RESUMEN

BACKGROUND: To assess the Nickel sensitizing potential of total knee arthroplasty (TKA), explore the relationship between hypersensitivity and clinical outcomes, and evaluate the utility of skin patch testing pre- and/or postoperatively. MATERIALS AND METHODS: A literature search was performed through EMBASE, Medline and PubMed databases. Articles were screened independently by two investigators. The level of evidence of studies was assessed using the Oxford Centre for Evidence-Based Medicine Criteria and the quality evaluated using the Methodological Index for Non-randomized Studies and Cochrane risk-of-bias tools. RESULTS: Twenty studies met the eligibility criteria, reporting on 1354 knee arthroplasties. Studies included patients undergoing primary or revision TKA, pre- and/or postoperatively, and used patch testing to identify Nickel hypersensitivity. Prevalence of Nickel hypersensitivity ranged from 0% to 87.5%. One study compared the prevalence of Nickel hypersensitivity in the same patient group before and after surgery and noted newly positive patch test reactions in three patients (4.2%). Three studies reported lower prevalence of Nickel hypersensitivity in postoperative patients compared to preoperative ones. Seven studies suggested that hypersensitivity might cause adverse clinical outcomes, but six did not support any relationship. Seven studies recommended preoperative patch testing in patients with history of metal allergy, and nine concluded that testing may be valuable postoperatively. CONCLUSIONS: Patients undergoing TKA with no prior history of metal hypersensitivity do not seem to be at an increased risk of developing Nickel hypersensitivity, and there is conflicting evidence that patients with pre-existing hypersensitivity are more likely to experience adverse outcomes. Patch testing remains the most commonly used method for diagnosing hypersensitivity, and evidence suggests preoperative testing in patients with history of metal allergy to aid prosthesis selection, and postoperatively in patients with suspected hypersensitivity once common causes of implant failure have been excluded, since revision with hypoallergenic implants may alleviate symptoms.

7.
Parasite Immunol ; 32(8): 599-606, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20626815

RESUMEN

The last decade has seen rapid advances in the genetic technology that is allowing researchers to examine host-pathogen interactions at a whole organism level. The advent of 'affordable' post-genomic technology has opened up a world of proteomic, transcriptomic and metabolomic methodologies that have been utilized by research groups in the Australasian region to examine the hosts' response to parasitic infections. Significant contributions have been made to many areas of parasitic infections with particular strengths being in malaria vaccine development, genetic susceptibility to leishmaniasis, genomic and proteomic analysis of schistosomiasis and genetic determination of resistance to helminthes in domestic animals. This review highlights some of these studies that have made significant contributions to our knowledge of the pathogenesis of parasitic diseases with a particular emphasis placed on studies reported in the last couple of years.


Asunto(s)
Genómica/tendencias , Interacciones Huésped-Patógeno , Enfermedades Parasitarias en Animales/inmunología , Enfermedades Parasitarias en Animales/parasitología , Enfermedades Parasitarias/inmunología , Enfermedades Parasitarias/parasitología , Animales , Australasia , Investigación Biomédica/tendencias , Humanos , Leishmaniasis/genética , Vacunas contra la Malaria/inmunología , Enfermedades Parasitarias/genética , Enfermedades Parasitarias en Animales/genética , Esquistosomiasis/genética
8.
Parasite Immunol ; 31(5): 254-66, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19388946

RESUMEN

Ninety per cent of the 500,000 annual new cases of visceral leishmaniasis (VL) occur in India/Bangladesh/Nepal, Sudan and Brazil. Importantly, 80-90% of human infections are sub-clinical or asymptomatic, usually associated with strong cell-mediated immunity. Understanding the environmental and genetic risk factors that determine why two people with the same exposure to infection differ in susceptibility could provide important leads for improved therapies. Recent research using candidate gene association analysis and genome-wide linkage studies (GWLS) in collections of families from Sudan, Brazil and India have identified a number of genes/regions related both to environmental risk factors (e.g. iron), as well as genes that determine type 1 vs. type 2 cellular immune responses. However, until now all of the allelic association studies carried out have been underpowered to find genes of small effect sizes (odds ratios or OR < 2), and GWLS using multicase pedigrees have only been powered to find single major genes, or at best oligogenic control. The accumulation of large DNA banks from India and Brazil now makes it possible to undertake genome-wide association studies (GWAS), which are ongoing as part of phase 2 of the Wellcome Trust Case Control Consortium. Data from this analysis should seed research into novel genes and mechanisms that influence susceptibility to VL.


Asunto(s)
Predisposición Genética a la Enfermedad , Genoma Humano , Estudio de Asociación del Genoma Completo , Leishmania donovani/patogenicidad , Leishmaniasis Visceral/genética , Animales , Asia Occidental/epidemiología , Brasil/epidemiología , Estudio de Asociación del Genoma Completo/métodos , Humanos , Hipersensibilidad Tardía/genética , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/inmunología , Leishmaniasis Visceral/parasitología , Ratones , Ratones Endogámicos BALB C , Sudán/epidemiología
9.
Adv Parasitol ; 97: 47-109, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28325373

RESUMEN

Trypanosomes constitute a group of flagellate protozoan parasites responsible for a number of important, yet neglected, diseases in both humans and livestock. The most significantly studied include the causative agents of African sleeping sickness (Trypanosoma brucei) and Chagas disease (Trypanosoma cruzi) in humans. Much of our knowledge about trypanosome host-parasite relationships and life histories has come from these two human pathogens. Recent investigations into the diversity and life histories of wildlife trypanosomes in Australia highlight that there exists a great degree of biological and behavioural variation within and between trypanosomes. In addition, the genetic relationships between some Australian trypanosomes show that they are unexpectedly more closely related to species outside Australia than within it. These findings have led to a growing focus on the importance of understanding parasites occurring naturally in wildlife to (1) better document parasite biodiversity, (2) determine evolutionary relationships and degree of host specificity, (3) understand host-parasite interactions and the role of parasites in the natural ecosystem and (4) identify biosecurity issues of emerging disease in both wildlife and human populations. Here we review what is known about the diversity, life histories, host-parasite interactions and evolutionary relationships of trypanosomes in Australian wildlife. In this context, we focus upon the genetic proximity of key Australian species to the pathogenic T. cruzi and discuss similarities in their biology and behaviour that present a potential risk of human disease transmission by Australian vectors and wildlife.


Asunto(s)
Enfermedad de Chagas/parasitología , Interacciones Huésped-Parásitos , Trypanosoma brucei brucei/fisiología , Trypanosoma cruzi/fisiología , Tripanosomiasis Africana/parasitología , Animales , Australia , Biodiversidad , Evolución Biológica , Humanos , Ganado , Filogenia
10.
Oncogene ; 36(39): 5544-5550, 2017 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-28581526

RESUMEN

Hedgehog (Hh) signaling regulates cell fate and self-renewal in development and cancer. Canonical Hh signaling is mediated by Hh ligand binding to the receptor Patched (Ptch), which in turn activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway inhibitors used as cancer therapeutics. Small cell lung cancer (SCLC) is a common, aggressive malignancy with universally poor prognosis. Although preclinical studies have shown that Hh inhibitors block the self-renewal capacity of SCLC cells, the lack of activating pathway mutations have cast doubt over the significance of these observations. In particular, the existence of autocrine, ligand-dependent Hh signaling in SCLC has been disputed. In a conditional Tp53;Rb1 mutant mouse model of SCLC, we now demonstrate a requirement for the Hh ligand Sonic Hedgehog (Shh) for the progression of SCLC. Conversely, we show that conditional Shh overexpression activates canonical Hh signaling in SCLC cells, and markedly accelerates tumor progression. When compared to mouse SCLC tumors expressing an activating, ligand-independent Smo mutant, tumors overexpressing Shh exhibited marked chromosomal instability and Smoothened-independent upregulation of Cyclin B1, a putative non-canonical arm of the Hh pathway. In turn, we show that overexpression of Cyclin B1 induces chromosomal instability in mouse embryonic fibroblasts lacking both Tp53 and Rb1. These results provide strong support for an autocrine, ligand-dependent model of Hh signaling in SCLC pathogenesis, and reveal a novel role for non-canonical Hh signaling through the induction of chromosomal instability.


Asunto(s)
Proteínas Hedgehog/metabolismo , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Proteínas Hedgehog/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología
11.
J Leukoc Biol ; 60(1): 44-50, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8699122

RESUMEN

We have shown that normal C57BL/6J mice are moderately resistant to infection with murine cytomegalovirus (MCMV) and that this resistance is impaired by prior infection with LP-BM5 MuLV, which causes a disease (MAIDS) similar to early HIV-induced disease. This study investigates macrophage function in MAIDS+ mice challenged with MCMV. MAIDS reduces the influx of cells into the peritoneal cavity seen in normal C57BL/6J mice 6 days after MCMV infection. The infiltrates contained cells that resembled activated macrophages, as they took up colloidal gold, expressed the macrophage marker Mac-1, had high levels of acid phosphatase activity, and were lymphocytostatic when co-cultured with activated T cells. MAIDS+ mice had a higher percentage of cells able to take up colloidal gold and higher acid phosphatase activity per cell. The cells were also more lymphocytostatic and produced higher levels of interleukin-1 and tumor necrosis factor-alpha on days 4 and 6 after MCMV infection. Hence, MAIDS enhances baseline and induced macrophage activity, but depresses infiltration into the site of inflammation.


Asunto(s)
Infecciones por Citomegalovirus/complicaciones , Macrófagos Peritoneales/inmunología , Síndrome de Inmunodeficiencia Adquirida del Murino/complicaciones , Síndrome de Inmunodeficiencia Adquirida del Murino/inmunología , Fosfatasa Ácida/análisis , Animales , Células Cultivadas , Técnicas de Cocultivo , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/inmunología , Femenino , Citometría de Flujo , Inflamación , Interleucina-1/biosíntesis , Activación de Linfocitos , Activación de Macrófagos , Antígeno de Macrófago-1/análisis , Ratones , Ratones Endogámicos C57BL , Linfocitos T/inmunología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/biosíntesis
12.
AIDS ; 7(12): 1569-79, 1993 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7904450

RESUMEN

BACKGROUND: HIV disease is epidemic in Africa, but associated mortality, underlying pathology and CD4+ T-lymphocyte counts have not previously been evaluated in a representative study. Such data help to determine the management of HIV-positive people. Both HIV-1 and HIV-2 infections are prevalent in Côte d'Ivoire, and the pathology of HIV-2 infection in Africa is unclear. METHODS: Consecutive adult medical admissions to a large city hospital in Côte d'Ivoire were studied in 1991, and a sample of HIV-positive deaths autopsied. RESULTS: Of 5401 patients evaluated, 50% were HIV-positive; 38% of these died, with a median survival of 1 week. At autopsy (n = 294, including 24% of HIV-positive deaths in hospital), tuberculosis (TB), bacteraemia (predominantly Gram-negative rods) and cerebral toxoplasmosis caused 53% of deaths. TB was seen in 54% of cadavers with AIDS-defining pathology and Pneumocystis pneumonia in 4%. The median CD4+ T-lymphocyte counts in those who died was < 90 x 10(6)/l. Compared with HIV-1-positives, patients with HIV-2-positivity had a greater frequency of severe cytomegalovirus infection, HIV encephalitis and cholangitis. CONCLUSIONS: In this population, HIV-positive adults present to hospital with advanced disease associated with high mortality. The three major underlying pathologies (TB, toxoplasmosis and bacteraemia) are either preventable or treatable. TB is an underestimated cause of the 'slim' syndrome in Africa. The patterns of pathology in HIV-2-positive patients suggest a more prolonged terminal course compared with HIV-1. There is an urgent need for attention towards the issues of therapy and care for HIV disease in developing countries.


Asunto(s)
Infecciones por VIH/mortalidad , Infecciones por VIH/patología , VIH-1 , VIH-2 , Infecciones Oportunistas Relacionadas con el SIDA/etiología , Infecciones Oportunistas Relacionadas con el SIDA/patología , Adolescente , Adulto , África Occidental , Infecciones Bacterianas/complicaciones , Encéfalo/patología , Linfocitos T CD4-Positivos , Enfermedades del Sistema Nervioso Central/etiología , Enfermedades del Sistema Nervioso Central/patología , Encefalitis/etiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Humanos , Recuento de Leucocitos , Masculino , Toxoplasmosis Cerebral/etiología , Tuberculosis/complicaciones , Tuberculosis/patología
13.
Free Radic Biol Med ; 28(6): 934-43, 2000 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-10802225

RESUMEN

Neutrophil apoptosis is important for the resolution of airway inflammation in a number of lung diseases. Inflammatory mediators, endogenous reactive oxygen and nitrogen species, and intracellular and extracellular antioxidants may all influence neutrophil apoptosis. This study investigated the involvement of these factors during apoptosis of neutrophils cultured in vitro. Neutrophils undergoing spontaneous apoptosis in culture as assessed by annexin V binding generated significant amounts of nitrite. Incubation with agonistic anti-Fas monoclonal antibody or tumor necrosis factor-alpha (TNF-alpha) enhanced neutrophil apoptosis at 6 h, although it decreased nitrite accumulation. Although granulocyte-macrophage colony-stimulating factor significantly reduced neutrophil apoptosis, this was also associated with decreased nitrite accumulation. In contrast, inhibition of apoptosis at 16 h by dibutyryl cyclic adenosine monophosphate was associated with increased nitrite accumulation. Exogenous glutathione (GSH) or N-acetylcysteine significantly enhanced neutrophil apoptosis at 6 h and stimulated the production of H(2)O(2), which may mediate apoptosis through intracellular hydroxyl radical production. Intracellular GSH concentrations decreased in neutrophils undergoing apoptosis, and this was more marked in neutrophils treated with anti-Fas or TNF-alpha. These results suggest a causal association between reduced endogenous nitric oxide production, reduced intracellular GSH, and Fas- and TNF-alpha-mediated neutrophil apoptosis, whereas enhanced neutrophil survival mediated by dibutyryl cyclic adenosine monophosphate is associated with increased nitrite generation and maintenance of intracellular GSH. The interaction of endogenous reactive oxygen species with extracellular antioxidants such as GSH could also contribute to the complex processes regulating neutrophil apoptosis and hence the resolution of inflammation in the lung.


Asunto(s)
Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Nitritos/metabolismo , Acetilcisteína/farmacología , Adulto , Anticuerpos Monoclonales/farmacología , Bucladesina/farmacología , Fragmentación del ADN , Femenino , Glutatión/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Humanos , Peróxido de Hidrógeno/metabolismo , Pulmón/patología , Masculino , Unión Proteica , Factor de Necrosis Tumoral alfa/farmacología , Receptor fas/inmunología
14.
Cancer Epidemiol Biomarkers Prev ; 9(10): 1067-70, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11045789

RESUMEN

HLA genes have been shown to be associated with cervical intraepithelial neoplasia (CIN), a precursor of cervical cancer. The human papillomaviruses (HPV) types 16 and 18 are the major environmental cause of this disease. Because the immune system plays an important role in the control of HPV infection, the association of polymorphic HLA could lead to a different immune response to control the development of cervical cancer. The aim of this study was to analyze the association between CIN and a microsatellite polymorphism of tumor necrosis factor (TNFa) taking HPV exposure and CIN-associated HLA haplotypes into account. In a nested case-control study in northern Sweden, 64 patients and 147 controls matched for age and sex and derived from the same population-based cohort were typed for TNFA, HLA-DR, and DQ and assayed for antibodies to HPV types 16 and 18. TNFa polymorphism was not associated with CIN per se. However, there was a significant increase in the frequency of TNFa-11 among HPV16-positive and HLA DR15-DQ6 (B*0602) patients compared with HPV16- and HLA-DQ6-negative patients (odds ratios, 5.4 and 9.3, respectively). The relative risk for CIN conferred by the combination of TNFa-11, HLA-DQ6, and HPV 16 positivity was 15. Our study suggests that the TNFa-11 allele is associated with HPV16 infection and associated with CIN in combination with HLA-DQ6 but not by itself.


Asunto(s)
Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/complicaciones , Polimorfismo Genético , Factor de Necrosis Tumoral alfa/genética , Infecciones Tumorales por Virus/complicaciones , Displasia del Cuello del Útero/genética , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/genética , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Humanos , Repeticiones de Microsatélite/genética , Medición de Riesgo , Suecia/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/epidemiología
15.
J Neuroimmunol ; 88(1-2): 137-43, 1998 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-9688335

RESUMEN

The aim of this study was to analyze associations between myasthenia gravis (MG) and polymorphisms in the tumor necrosis factor (TNF) region in 79 Swedish patients and 155 unrelated controls. The frequency of the TNFa2 allele of a microsatellite located 3.5 kb upstream of the lymphotoxin alpha (LT-alpha) gene in the TNF region was found to be increased in overall MG patients compared to controls. The frequency of the short 5.5 kb fragment (TNFB * 1) of a bi-allelic NcoI RFLP polymorphism located at the first intron of the LT-alpha gene was increased in patients with an early onset of disease compared to patients with a later onset.


Asunto(s)
Miastenia Gravis/genética , Polimorfismo Genético/genética , Factor de Necrosis Tumoral alfa/genética , Edad de Inicio , Alelos , Humanos , Intrones/genética , Linfotoxina-alfa/genética , Repeticiones de Microsatélite/genética , Miastenia Gravis/epidemiología , Fragmentos de Péptidos/genética , Polimorfismo de Longitud del Fragmento de Restricción , Valores de Referencia
16.
Biochem Pharmacol ; 68(6): 1055-60, 2004 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-15313401

RESUMEN

Hedgehog (Hh) signalling mediates axial patterning and stem cell fate in development. This is mediated by Sonic, Desert and Indian Hedgehogs whose morphogen gradients determine the level of signalling in recipient tissues. Aberrant, cell autonomous, ligand-dependent Hh signalling has recently been demonstrated in small cell lung cancer (SCLC), as well as in upper gastrointestinal malignancies arising from pancreas, esophagus and stomach. These tumors lack mutations in the Hh receptor PATCHED, identifying a mechanism of pathway activation distinct from Gorlin's syndrome associated neural and skin tumors. We believe that this phenomenon represents a conserved mechanism for establishing niche-independent stem cell fates in cancer which is essential for malignant transformation and metastasis. Specific inhibition of Hh signalling by the naturally occurring plant alkaloid cyclopamine provides the opportunity for pharmacologic assessment of the role of Hh signalling in these tumors. Cyclopamine inhibits growth of SCLC and a wide range of foregut derived malignancies both in vitro and in vivo. This demonstrates an ongoing requirement for Hh signalling in these highly lethal and aggressive tumors. A novel therapeutic strategy is proposed using pharmacologic targeting of Hh dependent tumors with high potency pathway antagonists.


Asunto(s)
Proteínas de Drosophila/fisiología , Neoplasias/metabolismo , Transducción de Señal/fisiología , Transactivadores/fisiología , Animales , Drosophila , Proteínas Hedgehog , Mamíferos , Trasplante de Células Madre
17.
J Clin Pathol ; 44(9): 756-8, 1991 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1918404

RESUMEN

Unambiguous identification of lymphocytes is sometimes difficult because of weak immunostaining of the cell membrane immunoglobulins. A simple method of intensifying the diaminobenzidine (DAB) peroxidase reaction was therefore devised. Paraffin wax sections of formalin fixed tonsils and lymphomas were digested with trypsin and immunostained for kappa and lambda light immunoglobulin chains and CD3 antigen by various peroxidase linked detection systems. After reaction with hydrogen peroxide and DAB the sections were immersed in methenamine silver solution at 60 degrees C for three to seven minutes. The light brown stain on the cell membranes of the mantle zone lymphocytes became dark brown and the stronger stain of the plasma cells became black. Mantle zone B lymphocytes and CD3 positive T lymphocytes were precisely outlined even at low magnification and the lymphomas were easily classified as monoclonal or polyclonal. At high magnification, staining was clearer than with the immunogold-silver stain. Cryostat and paraffin wax sections of other tissues immunostained for various antigens showed similar intensification. Silver methenamine provides an easy means of increasing the sensitivity and visual impact of an immunoperoxidase/DAB reaction in any preparation.


Asunto(s)
Técnicas para Inmunoenzimas , Peroxidasas , Plata , Antígenos CD/análisis , Linfocitos B/inmunología , Cadenas kappa de Inmunoglobulina/análisis , Cadenas lambda de Inmunoglobulina/análisis , Adhesión en Parafina , Polímeros , Linfocitos T/inmunología
18.
J Clin Pathol ; 44(7): 558-63, 1991 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-1856287

RESUMEN

Fifty nine patients seropositive for human immunodeficiency virus (HIV) and diarrhoea and 20 with weight loss were investigated for microsporidiosis using light and electron microscopical examination of duodenal and jejunal biopsy specimens. Eight cases of microsporidiosis were found, in five of whom it was the sole pathogen. In all eight cases the organism was identified at light microscopy without prior knowledge of the electron microscopical findings. All stages of the life cycle are best seen in resin sections cut at 1 micron and stained with Giemsa, but spores could easily be identified in paraffin sections cut at 5 microns and stained with haematoxylin and eosin. In all cases the parasite was identified both in duodenal pinch and jejunal "Crosby" capsule biopsy specimens. All cases of microsporidiosis occurred in patients with diarrhoea. Both electron and light microscopical examination suggested that the pathogenic mechanism involves the shedding of infected enterocytes containing large numbers of spores. It is suggested that the optimal way to diagnose microsporidiosis is by light microscopical examination of duodenal pinch biopsy specimens.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Parasitosis Intestinales/diagnóstico , Intestino Delgado/patología , Infecciones por Protozoos/diagnóstico , Animales , Biopsia , Diarrea/complicaciones , Duodeno/parasitología , Duodeno/patología , Eucariontes/ultraestructura , Humanos , Parasitosis Intestinales/complicaciones , Parasitosis Intestinales/parasitología , Parasitosis Intestinales/patología , Yeyuno/parasitología , Yeyuno/patología , Microscopía , Microscopía Electrónica , Prevalencia , Infecciones por Protozoos/complicaciones , Infecciones por Protozoos/parasitología , Infecciones por Protozoos/patología
19.
Clin Oncol (R Coll Radiol) ; 7(2): 136-7, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7619766

RESUMEN

Lymphangioma circumscriptum is a rare disorder of lymphatic channels, the cause of which is poorly understood. It is an unpleasant, but benign, condition conventionally managed by wide local excision, which provides symptom control and often prevents recurrence. No long term complications and no association with squamous cell carcinoma have been previously documented. We present a 20-year-old patient with lymphangioma circumscriptum involving the vulval and perianal areas, which recurred after surgery and seems to have predisposed to squamous cell carcinoma 11 years after presentation.


Asunto(s)
Neoplasias del Ano , Carcinoma de Células Escamosas , Linfangioma , Neoplasias Primarias Múltiples , Neoplasias de la Vulva , Adulto , Femenino , Humanos
20.
East Afr Med J ; 73(5 Suppl): S29-30, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8756025

RESUMEN

PIP: During a 9-month period in 1991, an autopsy was conducted on 247 cadavers of HIV-positive adult patients who died in a hospital in Abidjan, Ivory Coast. The most common cause of death among adults in Abidjan is AIDS. During 8 months in 1991-92, an autopsy was also conducted on 78 HIV-positive cadavers of children 2 months to 8 years old and on 78 HIV-negative cadavers of children 2 months to 12 years old located in a morgue in Abidjan. The pathologists aimed to determine the incidence of lymphoma among HIV-infected adults and children. Seven (2.8%) adult cadavers had B-cell lymphoma, each having been diagnosed with it in the postmortem. The types were visceral (4) and primary cerebral (3) lymphomas. The researchers estimated the non-Hodgkin's lymphoma crude incidence rate among adults in Abidjan to be 84/100,000 per year. This incidence is 10 times greater than expected among HIV-negative people. With 11% HIV prevalence, the incidence of non-Hodgkin's lymphoma is expected to double. None of the HIV-positive cadavers of children had B-cell lymphoma. Two HIV-negative children (ages 5 and 9) had B-cell lymphoma of Burkitt and lymphoblastic type lymphoma, respectively. In both child cases, the viscera was involved.^ieng


Asunto(s)
VIH-1 , VIH-2 , Linfoma Relacionado con SIDA/virología , Adolescente , Adulto , Biopsia , Causas de Muerte , Niño , Preescolar , Côte d'Ivoire/epidemiología , Femenino , Humanos , Incidencia , Lactante , Linfoma Relacionado con SIDA/epidemiología , Linfoma Relacionado con SIDA/patología , Masculino , Persona de Mediana Edad
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