RESUMO
Heterosis, also known as hybrid vigor, is the superior performance of a heterozygous hybrid relative to its homozygous parents. Despite the scientific curiosity of this phenotypic phenomenon and its significance for food production in agriculture, its genetic basis is insufficiently understood. Studying heterosis in yeast can potentially yield insights into its genetic basis, can allow one to test the different hypotheses that have been proposed to explain the phenomenon and allows better understanding of how to take advantage of this phenomenon to enhance food production. We therefore crossed 16 parental yeast strains to form 120 yeast hybrids, and measured their growth rates under five environmental conditions. A considerable amount of dominant genetic variation was found in growth performance, and heterosis was measured in 35% of the hybrid-condition combinations. Despite previous reports of correlations between heterosis and measures of sequence divergence between parents, we detected no such relationship. We used several analyses to examine which genetic model might explain heterosis. We found that dominance complementation of recessive alleles, overdominant interactions within loci and epistatic interactions among loci each contribute to heterosis. We concluded that in yeast heterosis is a complex phenotype created by the combined contribution of different genetic interactions.
Assuntos
Vigor Híbrido , Leveduras/crescimento & desenvolvimento , Leveduras/genética , Variação Genética , Modelos Genéticos , FilogeniaRESUMO
BACKGROUND: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC. METHODS: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis. RESULTS: The OS was 49% for patients with LNDîº0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LNDîº0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures. CONCLUSION: This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.
Assuntos
Carcinoma de Células Escamosas/patologia , Linfonodos/patologia , Neoplasias Bucais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
Phenotypic variation in natural populations is the outcome of the joint effects of environmentally induced adaptations and neutral processes on the genetic architecture of quantitative traits. In this study, we examined the role of adaptation in shaping wild barley phenotypic variation along different environmental gradients. Detailed phenotyping of 164 wild barley (Hordeum spontaneum) accessions from Israel (of the Barley1K collection) and 18 cultivated barley (H. vulgare) varieties was conducted in common garden field trials. Cluster analysis based on phenotypic data indicated that wild barley in this region can be differentiated into three ecotypes in accordance with their ecogeographical distribution: north, coast and desert. Population differentiation (Q(ST) ) for each trait was estimated using a hierarchical Bayesian model and compared to neutral differentiation (F(ST) ) based on 42 microsatellite markers. This analysis indicated that the three clusters diverged in morphological but not in reproductive characteristics. To address the issue of phenotypic variation along environmental gradients, climatic and soil gradients were compared with each of the measured traits given the geographical distance between sampling sites using a partial Mantel test. Flowering time and plant growth were found to be differentially correlated with climatic and soil characteristic gradients, respectively. The H. vulgare varieties were superior to the H. spontaneum accessions in yield components, yet resembled the Mediterranean types in vegetative characteristics and flowering time, which may indicate the geographical origin of domesticated barley.
Assuntos
Variação Genética , Hordeum/genética , Teorema de Bayes , Análise por Conglomerados , Produtos Agrícolas/genética , Flores , Genética Populacional , Hordeum/crescimento & desenvolvimento , Israel , Repetições de Microssatélites , Modelos Genéticos , Fenótipo , SoloRESUMO
BACKGROUND: PSA blood test and other present screening tools fail to provide the required sensitivity and specificity and, at early stages, lack correlation with tumor grade, volume, and location. Thus alternative approaches are highly desired. We present and assess a novel method for PCa detection, grading, volume evaluation and tumor location, based on non-invasive zinc concentration mapping in the gland by means of a dedicated rectal probe. METHODS: Zinc-concentration values measured in histologically examined tissue fragments from needle biopsy of 598 patients were analyzed. They were used to generate computer simulated zinc-concentration maps, further analyzed with image-processing tools. The tumor detection performances versus Gleason grade were assessed. RESULTS: A significant increase of zinc depletion with increasing Gleason pattern (grade) classification was established. Tumor detection performance in zinc-concentration maps progressively improves with the cancer's first component score. Reliable information on the location, size and Gleason-grade combination of the lesion can be extracted for clinically relevant volumes. CONCLUSIONS: Zinc depletion in the prostate peripheral zone is the basis for a novel, non-invasive PCa detection, localization, volume evaluation and grading method. Its realization and application as a pre-biopsy and pre-treatment examination, or a follow-up tool, relies on the development of a dedicated transrectal probe. It should have significant impact on biopsy effectiveness, point at a possible extraprostatic extension and provide critical data for focal treatment. The information on tumor grade and distribution may have an important impact on disease management.
Assuntos
Adenocarcinoma/química , Adenocarcinoma/patologia , Neoplasias da Próstata/química , Neoplasias da Próstata/patologia , Zinco/análise , Adenocarcinoma/diagnóstico , Simulação por Computador , Histocitoquímica , Humanos , Estudos Longitudinais , Masculino , Estadiamento de Neoplasias/métodos , Neoplasias da Próstata/diagnósticoRESUMO
Ideomotor apraxia is a disorder mainly of praxis planning, and the deficit is typically more evident in pantomiming transitive (tool related) than intransitive (communicative) gestures. The goal of the present study was to assess differential hemispheric lateralization of praxis production using event-related functional magnetic resonance imaging. Voxel-based analysis demonstrated significant activations in posterior parietal cortex (PPC) and premotor cortex (PMC) association areas, which were predominantly left hemispheric, regardless of whether planning occurred for right or left hand transitive or intransitive pantomimes. Furthermore, region of interest-based calculation of mean laterality index (LI) revealed a significantly stronger left lateralization in PPC/PMC clusters for planning intransitive (LI = -0.49 + 0.10, mean + standard deviation [SD]) than transitive gestures (-0.37 + 0.08, P = 0.02, paired t-tests) irrespective of the hand involved. This differential left lateralization for planning remained significant in PMC (LI = -0.47 + 0.14 and -0.36 + 0.13, mean + SD, P = 0.04), but not in PPC (-0.56 + 0.11 and -0.45 + 0.12, P = 0.11), when both regions were analyzed separately. In conclusion, the findings point to a left-hemispheric specialization for praxis planning, being more pronounced for intransitive gestures in PMC, possibly due to their communicative nature.
Assuntos
Lateralidade Funcional/fisiologia , Gestos , Imageamento por Ressonância Magnética/métodos , Destreza Motora/fisiologia , Movimento/fisiologia , Adulto , Idoso , Mapeamento Encefálico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In this study, we present the genetic analysis of a new collection of wild barley (Hordeum spontaneum) using 42 simple sequence repeat (SSR) markers that represent the seven chromosomes. The Barley1K (B1K) infrastructure consists of 1020 accessions collected in a hierarchical sampling mode (HSM) from 51 sites across Israel and represents the wide adaptive niche of the modern barley's ancestor. According to the genetic structure analysis, the sampled sites can be divided into seven groups, and sampled microsites located on opposing slopes or in different soil types did not show significant genetic differentiation. Although the genetic analysis indicates a simple isolation-by-distance model among the populations, examination of the genetic populations' structure with abiotic parameters in an ordination analysis revealed that the combination of elevation, mid-day temperature and rainfall explains a high proportion of the variance in the principal components analysis. Our findings demonstrate that the current populations have therefore been shaped and distinguished by non-selective forces such as migration; however, we suggest that aridity and temperature gradients played major roles as selective forces in the adaptation of wild barley in this part of the Fertile Crescent. This unique collection is a prelude for the investigation of the molecular basis underlying plant adaptation and responsiveness to harsh environments.
Assuntos
Genética Populacional , Hordeum/genética , Chuva , Temperatura , Adaptação Fisiológica/genética , Altitude , DNA de Plantas/genética , Genes de Plantas , Marcadores Genéticos , Variação Genética , Israel , Repetições de Microssatélites , Modelos Genéticos , Análise de Componente PrincipalRESUMO
The present work deals with the analysis of prostatic-zinc-concentration images. The goal is to evaluate potential clinically relevant information that can be extracted from such images. In the absence of experimental images, synthetic ones are produced from clinically measured zinc-concentration distributions in certified benign and cancerous tissue samples, classified by the lesion grade. We describe the method for producing the images and model the effect of counting statistics noise. We present in detail the image analysis, which is based on a combination of standard image processing and segmentation tools, optimized for this particular application. The information on lowest zinc value obtained from the image analysis is translated to clinical data such as tumour presence, location, size and grade. Their confidence is evaluated with the help of standard statistical tools such as receiver operating characteristic analysis. The present work predicts a potential for detecting small prostate-cancer lesions, of grade (4+3) and above, with very good specificity and sensitivity. The present analysis further provides data on the pixel size and image counting statistics requested from the trans-rectal probe that will record in vivo prostatic-zinc maps in patients.
Assuntos
Algoritmos , Biomarcadores Tumorais/análise , Interpretação de Imagem Assistida por Computador/métodos , Modelos Biológicos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Zinco/análise , Simulação por Computador , Humanos , Aumento da Imagem/métodos , Masculino , Modelos Estatísticos , Neoplasias da Próstata/classificação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição TecidualRESUMO
Neurofibromatosis type 1 (NF1) is characterized by a high incidence of benign and malignant tumors attributed to loss of function of Nf1, which encodes neurofibromin, a tumor suppressor with Ras-GAP activity. Neurofibromin deficiency typically causes chronic activation of Ras, considered the major contributor to manifestation of NF1. Resistance to radio- and chemotherapy are typical of NF1-associated tumors, but the underlying mechanism is unknown. Here, we investigated interrelationships between neurofibromin expression, Ras activity, and sensitivity to apoptosis. Neurofibromin-deficient mouse embryonic fibroblasts (MEFs) and human NF1 tumor cells were more resistant than neurofibromin-expressing cells to apoptosis. Moreover, Nf1(-/-), Nf1(+/-), and Nf1(+/+) MEFs exhibited gene-dosage-related resistance to apoptosis. Resistance of the Nf1-deficient cells was mediated by two survival pathways: a Ras-dependent pathway, and a Ras-independent pathway promoted by the lack of an NF1-GRD-independent proapoptotic action of neurofibromin. Therefore, besides its Ras-dependent growth inhibition, neurofibromin can exert tumor suppression via a proapoptotic effect.
Assuntos
Apoptose , Neurofibromina 1/metabolismo , Proteínas ras/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Transformada , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , AMP Cíclico/metabolismo , Embrião de Mamíferos/citologia , Embrião de Mamíferos/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Farneseno Álcool/análogos & derivados , Farneseno Álcool/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Dosagem de Genes/efeitos dos fármacos , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Camundongos , Neurofibromina 1/deficiência , Fosforilação/efeitos dos fármacos , Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Salicilatos/farmacologia , Vírus 40 dos Símios , Serina-Treonina Quinases TOR , Proteínas ras/antagonistas & inibidoresRESUMO
Our aim was to investigate whether patients with epileptiform foci in the frontal lobe, as revealed by video EEG (VEEG) analysis, exhibit non-forced grasping behaviour and manipulatory movements during seizures. We retrospectively reviewed ictal videotapes of 30 consecutive patients with frontal and 30 with temporal lobe epilepsy undergoing VEEG for the presence and type of grasping and manipulatory movements. Four of the 30 patients with frontal lobe epilepsy (13%) showed unilateral grasping behaviour, three of whom had whole hand prehension (one with manipulation movements as well) and one pinching movements. In all patients, arm abduction and elevation resembling reaching invariably preceded grasping hand movements. The epileptogenic focus was located in the contralateral and ipsilateral frontocentral region in two and one patient, respectively, and in the ipsilateral orbitofrontal region in another. However, none of the patients with temporal lobe epilepsy showed grasping behaviour. Patients with frontal lobe epilepsy may show non-forced grasping with or without manipulatory finger movements as part of ictal phenomena.
Assuntos
Epilepsia do Lobo Frontal/fisiopatologia , Força da Mão , Mãos/fisiopatologia , Atividade Motora , Adolescente , Adulto , Eletroencefalografia , Epilepsia do Lobo Frontal/diagnóstico , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Masculino , Tempo de Reação , Estudos Retrospectivos , Gravação de VideoteipeRESUMO
Ultrasound examination of a woman in early pregnancy with right lower quadrant abdominal pain demonstrated an edematous appendix with amorphous fluid surrounding the appendix. At laparotomy, these findings were confirmed. On pathological evaluation following surgical removal of the appendix a rare case of carcinoid tumor of the appendix was diagnosed. This is the first description of the transvaginal ultrasound features of a carcinoid tumor of the appendix.
Assuntos
Neoplasias do Apêndice/diagnóstico por imagem , Tumor Carcinoide/diagnóstico por imagem , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Dor Abdominal/etiologia , Aborto Espontâneo/tratamento farmacológico , Adulto , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Tumor Carcinoide/patologia , Tumor Carcinoide/cirurgia , Feminino , Humanos , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/cirurgia , Resultado do Tratamento , UltrassonografiaRESUMO
Tumor spread along nerves, a phenomenon known as perineurial invasion, is common in various cancers including pancreatic ductal adenocarcinoma (PDAC). Neural invasion is associated with poor outcome, yet its mechanism remains unclear. Using the transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we investigated the mechanism of neural invasion in PDAC. To detect tissue-specific factors that influence neural invasion by cancer cells, we characterized the perineurial microenvironment using a series of bone marrow transplantation (BMT) experiments in transgenic mice expressing single mutations in the Cx3cr1, GDNF and CCR2 genes. Immunolabeling of tumors in KPC mice of different ages and analysis of human cancer specimens revealed that RET expression is upregulated during PDAC tumorigenesis. BMT experiments revealed that BM-derived macrophages expressing the RET ligand GDNF are highly abundant around nerves invaded by cancer. Inhibition of perineurial macrophage recruitment, using the CSF-1R antagonist GW2580 or BMT from CCR2-deficient donors, reduced perineurial invasion. Deletion of GDNF expression by perineurial macrophages, or inhibition of RET with shRNA or a small-molecule inhibitor, reduced perineurial invasion in KPC mice with PDAC. Taken together, our findings show that RET is upregulated during pancreas tumorigenesis and its activation induces cancer perineurial invasion. Trafficking of BM-derived macrophages to the perineurial microenvironment and secretion of GDNF are essential for pancreatic cancer neural spread.
Assuntos
Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/patologia , Macrófagos/patologia , Sistema Nervoso/patologia , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas c-ret/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Animais , Apoptose , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Proliferação de Células , Feminino , Humanos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Sistema Nervoso/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas c-ret/genética , Células Tumorais CultivadasRESUMO
Cardiac steroids (CS) are specific inhibitors of Na+, K+-ATPase activity. Although the presence of CS-like compounds in animal tissues has been established, their physiological role is not clear. In a previous study we showed that in pulse-chase membrane-labeling experiments, long term (hours) interaction of CS at physiological concentrations (nM) with Na+, K+-ATPase, caused changes in endocytosed membrane traffic in human NT2 cells. This was associated with the accumulation of large vesicles adjacent to the nucleus. For this sequence of events to function in the physiological setting, however, CS would be expected to modify membrane traffic upon short term (min) exposure and membrane labeling. We now demonstrate that CS affects membrane traffic also following a short exposure. This was reflected by the CS-induced accumulation of FM1-43 and transferrin in the cells, as well as by changes in their colocalization with Na+, K+-ATPase. We also show that the CS-induced changes in membrane traffic following up to 2 hrs exposure are reversible, whereas longer treatment induces irreversible effects. Based on these observations, we propose that endogenous CS-like compounds are physiological regulators of the recycling of endocytosed membrane proteins and cargo in neuronal cells, and may affect basic mechanisms such as neurotransmitter release and reuptake.
Assuntos
Apoptose/fisiologia , Bufanolídeos/metabolismo , Glicosídeos Cardíacos/metabolismo , Digoxina/metabolismo , Ouabaína/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Apoptose/efeitos dos fármacos , Transporte Biológico Ativo , Bufanolídeos/farmacologia , Glicosídeos Cardíacos/farmacologia , Linhagem Celular , Membrana Celular , Células Cultivadas , Digoxina/farmacologia , Ativação Enzimática , Humanos , Neurônios , Ouabaína/farmacologia , Transdução de Sinais , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidoresRESUMO
AIMS: Platinum-based neoadjuvant chemotherapy (NAC) improves overall survival in muscle-invasive bladder cancer (MIBC). A pathological complete response (pCR) at radical cystectomy after NAC is associated with better overall survival, but there are no established predictive biomarkers of response to NAC in MIBC. The aim of this study was to find laboratory variables associated with pCR following NAC. MATERIALS AND METHODS: We carried out a retrospective review of MIBC patients treated with NAC followed by radical cystectomy at the Sheba Medical Center between 2005 and 2015. Overall survival was calculated using the Kaplan-Meier product-limit method and compared between patients who achieved or did not achieve pCR using the Log-rank test. Baseline and pre-surgery laboratory values were collected and compared between patients who subsequently achieved pCR and those who did not using logistic regression. RESULTS: Fifty-eight patients underwent radical cystectomy after NAC, with a median follow-up of 32 (range 4.8-111.4) months from diagnosis. Of 55 patients with documented pathological outcome on radical cystectomy, 17 (31%) achieved pCR (complete responders). Of the 15 complete responders with follow-up data, 13 (87%) were still alive at time of last follow-up for this study (July 2015). Patients who did not achieve pCR had a significantly worse overall survival than complete responders (P = 0.0007). The baseline lymphocyte count, neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were significantly associated with response (P = 0.037, P = 0.045, P = 0.042, respectively) on univariate analysis, whereas baseline albumin, haemoglobin, neutrophils, platelets and the total white blood count were not significantly associated with response. Lymphocyte counts were significantly higher in responders than non-responders throughout three time points (P = 0.003 using a generalised linear mixed model). CONCLUSIONS: A high baseline level of lymphocytes is associated with the achievement of pCR at radical cystectomy after NAC, which, in turn, is associated with a significantly longer overall survival. Our results suggest that chemosensitivity in MIBC is associated with lymphocyte count.
Assuntos
Antineoplásicos/uso terapêutico , Linfócitos , Compostos de Platina/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologia , Adulto , Idoso , Cistectomia , Feminino , Humanos , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVE: To assess the association between gestational age at delivery and adverse neonatal outcome among term low-risk singleton neonates. METHODS: A retrospective cohort study design was used. The study group included all low-risk singleton term (37 + 0 to 41 + 6 weeks) newborns delivered in a single tertiary university-affiliated medical center over a 5-year period. Outcome of neonates delivered at 37 + 0 to 37 + 6 weeks of gestation (early term) and 41 + 0 to 41 + 6 weeks of gestation (late term) was compared to that of neonates delivered at 39 + 0-39 + 6 weeks of gestation (control). RESULTS: Overall, the outcome of 30 229 neonates was analyzed. The incidence of neonatal mortality was 1.0 per 1000 live-born neonates, with no significant difference between the various gestational age groups. Early term newborns were at higher risk for respiratory morbidity, hypoglycemia, hypocalcemia, thrombocytopenia and unexplained jaundice, and had higher rates of prolonged hospital stay, NICU admission, sepsis workup and antibiotic treatment. On multivariate analysis, early term delivery was an independent predictor for composite respiratory morbidity (OR=2.4, 95% CI 1.6-3.8, p < 0.001), unexplained jaundice (OR=2.1, 95% CI 1.7-2.5, p < 0.001), hypoglycemia (OR=2.5, 95% CI 1.5-4.3, p < 0.001) and NICU admission (OR=1.9, 95% CI 1.5-2.5, p < 0.001). Late term neonates had a significantly higher rate of large for gestational date, but did not differ from controls with respect to the rate of composite neurologic or respiratory complications, NICU admission, birth trauma or infectious morbidity. CONCLUSION: Even in low-risk singleton deliveries, early term is associated with an increased risk of neonatal morbidity.
Assuntos
Idade Gestacional , Doenças do Recém-Nascido/epidemiologia , Nascimento a Termo , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Masculino , Paridade , Gravidez , Resultado da Gravidez , Estudos RetrospectivosRESUMO
BACKGROUND AND PURPOSE: Several lines of evidence point toward a relationship between infection and atherosclerotic vascular disease. Thus, infection and inflammation often precede ischemic neurological events. Transient alterations in coagulation and direct arterial invasion by certain microorganisms have been reported. Helicobacter pylori infection is the major cause of peptic ulcer disease and appears to be a risk factor for ischemic cerebrovascular disease. However, in contrast to other chronic infectious agents, H pylori has not been consistently isolated from atherosclerotic lesions. METHODS: We investigated the presence of H pylori in 38 atherosclerotic plaques obtained at carotid endarterectomy by using morphological and immunohistochemical techniques and a highly sensitive polymerase chain reaction method. We performed immunohistochemical detection of intercellular adhesion molecule-1, a marker related to inflammatory cell response. We also examined 7 carotid arteries obtained at autopsy from subjects without carotid atherosclerosis. RESULTS: H pylori DNA was found in 20 of 38 atherosclerotic plaques. Ten of the H pylori DNA-positive plaques also showed morphological and immunohistochemical evidence of H pylori infection. None of 7 normal carotid arteries was positive for H pylori. Intercellular adhesion molecule-1 was expressed in 75% of H pylori-positive plaques and in 22% of H pylori-negative plaques. The presence of the microorganism was associated with male sex but was independent of age, vascular risk factor profile, and prior neurological symptoms. CONCLUSIONS: H pylori is present in a substantial number of carotid atherosclerotic lesions and is associated with features of inflammatory cell response. This study provides additional evidence of the relationship between H pylori infection and atherosclerotic disease.
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Artérias Carótidas/microbiologia , Artérias Carótidas/patologia , Estenose das Carótidas/microbiologia , Estenose das Carótidas/patologia , Helicobacter pylori/isolamento & purificação , Fatores Etários , Idoso , Artérias Carótidas/metabolismo , Estenose das Carótidas/complicações , Estenose das Carótidas/metabolismo , DNA Bacteriano/isolamento & purificação , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/metabolismo , Modelos Logísticos , Masculino , Razão de Chances , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: Hirschsprung's disease (HD) is a congenital disorder characterised by the absence of ganglion cells in the large bowel, leading to functional obstruction and colonic dilatation proximal to the affected segment. A subclass of nerve cell bodies in both submucosa and myenteric ganglia of the human gastrointestinal tract were found to show immunopositivity for calretinin, a calcium binding protein, which plays an important role in the organisation and functioning of the central nervous system. AIM: To investigate calretinin immunostaining in ganglionic and aganglionic HD colon specimens, and compare it with staining for S100, neurone specific enolase, and c-kit. METHODS: Ten large bowel, full thickness specimens from patients with classic rectosigmoid HD were selected from the pathology repository. In total, 54 paraffin wax blocks-24 from the ganglionic zone, 17 from the aganglionic zone, and 13 from the transitional zone-were processed. RESULTS: Calretinin was not expressed in aganglionic segments of HD and associated nerve fibres, whereas in ganglionic HD segments and in normal colon both ganglion cells and nerve fibres were immunopositive. In addition, c-kit showed an altered distribution in the interstitial cells of Cajal. The transitional zone showed a broad spectrum of histomorphological and immunohistochemical patterns of both calretinin and c-kit expression. CONCLUSION: The absence of calretinin expression may serve as a diagnostic aid in identifying aganglionic segments in HD.
Assuntos
Doença de Hirschsprung/diagnóstico , Proteína G de Ligação ao Cálcio S100/metabolismo , Adulto , Biomarcadores/análise , Calbindina 2 , Pré-Escolar , Colo/inervação , Colo/metabolismo , Colo/patologia , Gânglios/metabolismo , Doença de Hirschsprung/metabolismo , Doença de Hirschsprung/patologia , Humanos , Lactente , Recém-Nascido , Fibras Nervosas/metabolismo , Fibras Nervosas/patologia , Fosfopiruvato Hidratase/análise , Proteínas Proto-Oncogênicas c-kit/análise , Proteínas S100/análiseRESUMO
OBJECTIVE: This study evaluates the effectiveness and safety of fiberoptic carbon dioxide (CO2) laser welding for graft closure of tympanic membrane perforations in an animal model. STUDY DESIGN AND SETTING: Tympanic membrane perforation was surgically induced in 11 eardrums of 7 given pigs. A lumbar facial graft was placed over the wound, and albumin drops served as a biologic solder. CO2 laser energy, transmitted through silver halide infrared transmitting fibers, was used for "spot-welding" along the circumference of the graft. The welded sites were evaluated by using a surgical microscope as well as by evaluating the sites histologically. RESULTS: Healing started 3 to 4 days after surgery and was completed within 3 weeks with the formation of a neotympanum. Some inflammation with granulation tissue was noted in 5 eardrums. CONCLUSIONS AND SIGNIFICANCE: These preliminary results indicate that CO2 laser tympanoplasty with a fiberoptic delivery system may be a promising new technique for the clinical setting.
Assuntos
Terapia a Laser , Modelos Animais , Miringoplastia/métodos , Perfuração da Membrana Timpânica/cirurgia , Animais , Dióxido de Carbono , Estudos de Viabilidade , Tecnologia de Fibra Óptica , Cobaias , Terapia a Laser/métodos , CicatrizaçãoRESUMO
INTRODUCTION: Fibrinolytic agents are effective in the treatment of acute ischemic stroke. However, logistic and clinical factors limit their use. Neuroprotective drugs pose less risks and can be used even before performance of computed tomography of the brain as they are not detrimental in hemorrhagic stroke. These aspects, in theory, will allow the use of neuroprotective drugs in larger number of patients. OBJECTIVE: To evaluate the feasibility of a neuroprotection protocol and the potential usefulness of citicoline in acute ischemic stroke. PATIENTS AND METHODS: Thirty seven patients admitted with a clinical diagnosis of acute ischemic stroke (later confirmed with computed tomography) received, within 12 hours of onset of symptoms, citicoline 500 mg intravenously in a single bolus daily for 7 days. Neurological outcome in this group was compared with a group of 37 patients admitted during the 6 month period before the initiation of the trial and not treated with citicoline. Groups were matched by National Institute of Health Stroke Scale (NIHSS) on admission. RESULTS: Patients treated with citicoline (aged 69+/-14 years) improved on their NIHSS from admission (5.7+/-4.2) to discharge (4.7+/-4.5), p= 0.015. The control group (aged 60+/-17 years) did not change between admission (5.7+/-4.3) and discharge (5.2+/-3.5), ns. Patients treated within 6 hours of admission (n= 12) had more substantial improvement, from 5.4+/-2.3 on admission to 3.9+/-2.9 at discharge, p= 0.008. There were no differences in vascular risk factor profile between the groups. Citicoline was well tolerated in every subject. CONCLUSIONS: A protocol of acute stroke management using neuroprotective agents presents clear logistic advantages allowing the inclusion of larger number of patients. Citicoline appears as a safe and potentially effective option.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Citidina Difosfato Colina/uso terapêutico , Guias como Assunto , Fármacos Neuroprotetores/uso terapêutico , Nootrópicos/uso terapêutico , Doença Aguda , Idoso , Isquemia Encefálica/diagnóstico , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
A modification of the method of cross protection of mice was developed for the study of influenza virus antigenic drift. This modification does not require a pre-adaptation of the virus to mouse lungs. The experiments of cross protection of immune animals carried out by the modified method demonstrated antigenic variability of the influenza A virus strains (H3N2) isolated in 1968-1983. Immunologically significant differences between influenza A/Hong Kong/68/ and A/Victoria/36/72 virus strains were detected. Subsequently, with isolation of more influenza virus strains immunologically significant differences were found between A/Victoria/36/72 and A/Leningrad/42/75 (an analogue of A/Scotland/840/74) strains, A/Leningrad/42/75 and A/Leningrad/399/76 (an analogue of A/Victoria/3/75) strains. The differences between influenza A/Texas/1/77 and A/Leningrad/527/80 (an analogue of A/Bangkok/1/79), A/Leningrad/385/80 (an analogue of A/Bangkok/1/79), and A/Leningrad/50/83, (an analogue of A/Philippines/2/82) strains were not immunologically significant.
Assuntos
Antígenos Virais/imunologia , Variação Genética , Vírus da Influenza A/imunologia , Infecções por Orthomyxoviridae/imunologia , Animais , Embrião de Galinha , Reações Cruzadas , Imunidade , Imunização/métodos , Vacinas contra Influenza/imunologia , Camundongos , Vacinas Atenuadas/imunologiaRESUMO
A comparative study of the antigenic characteristics of influenza A (H1N1) and A (H3N2) virus strains isolated during the same epidemic season, 1989-1990, in St. Petersburg and CzSFR was carried out by routine serological methods and by cross-challenge of immunized mice. Antigenic differences were found only among serosubtype A (H1N1) strains isolated in different areas. The study was carried out in connection with potential occurrence of influenza epidemic outbreaks from local sources.