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David A Hunstad - One of the best experts on this subject based on the ideXlab platform.

  • virulence gene expression in Human Community acquired staphylococcus aureus infection
    The Journal of Infectious Diseases, 2009
    Co-Authors: Jennifer A Loughman, Stephanie A Fritz, Gregory A Storch, David A Hunstad
    Abstract:

    Staphylococcus aureus is a persistent Human pathogen that is responsible for a range of diseases that vary widely in clinical presentation and severity. The capacity of S. aureus to cause a spectrum of Human diseases reflects an ability to adapt to distinct microenvironments in the Human body and suggests that the pathogenesis of S. aureus infections is a complex process involving a diverse array of secreted and surface-associated virulence determinants that are coordinately expressed at different stages of infection [1]. Distinct networks of virulence genes are likely activated in response to host signals, including those found in target tissues and those related to innate defenses activated during the infectious process. This expectation manifests in vitro as a growth phase-dependent pattern of virulence determinant expression that is established by global regulatory elements (reviewed in [2]). During exponential growth, the organism synthesizes cell-wall proteins with adhesive functions, including protein A, fibrinogen-binding, fibronectin-binding, and collagen-binding proteins; such expression might augment the initial establishment of colonization in the host. In the transition from exponential to stationary phase, the expression of cell-wall proteins is repressed, while the synthesis of extracellular toxins and enzymes predominates. Through their proteolytic activities and toxic effects on host cells, these exotoxins might facilitate local invasion and dissemination during infection. The transition from exponential to stationary-phase protein expression is coordinately controlled by global regulators and the Agr quorum-sensing system [3]. During this transition, secretion of a modified peptide pheromone signals cell density-dependent gene expression via RNAIII, the regulatory effector molecule of the Agr system [4–6], resulting in up-regulation of exoprotein gene expression (e.g., hla, hlb) and down-regulation of cell surface adhesins such as protein A (spa) [7]. While this mechanism establishes temporal regulation in vitro, it also likely contributes to spatial regulation by limiting the expression of target genes to compartments where the signal molecule reaches a high concentration. Evidence of an in vivo role for this regulatory pathway is restricted to animal models of S. aureus infection. For example, agr inactivation resulted in reduced virulence in experimental staphylococcal musculoskeletal infection models [8, 9]. Recently, Agr-mediated expression of cytolytic peptides by CA-MRSA was shown to be important for Human neutrophil lysis and pathogenesis in a murine model of soft-tissue infection [10]. Animal studies have yielded conflicting conclusions regarding the pathogenic importance of PVL [11, 12] but indicate that PVL expression may alter agr expression patterns [12]. Though animal models of staphylococcal infection are valuable tools for relating the contribution of putative virulence factors identified in vitro to pathogenesis, their relevance to clinical disease is inherently limited and may not reflect Human-specific adaptive behavior. To address this, we identified patients with active Community-acquired S. aureus infections and defined bacterial gene expression profiles directly in tissue from multiple forms of Human infection.

  • virulence gene expression in Human Community acquired staphylococcus aureus infection
    The Journal of Infectious Diseases, 2009
    Co-Authors: Jennifer A Loughman, Stephanie A Fritz, Gregory A Storch, David A Hunstad
    Abstract:

    Isolates of methicillin-resistant Staphylococcus aureus (MRSA) were once linked uniformly with hospital-associated infections; however, Community-acquired MRSA (CA-MRSA) now represents an emerging threat worldwide. To examine the association of differential virulence gene expression with outcomes of Human infection, we measured transcript levels of target staphylococcal genes directly in clinical samples from children with active known or suspected CA-MRSA infections. Virulence genes encoding secreted toxins, including Panton-Valentine leukocidin, were highly expressed during superficial and invasive CA-MRSA infections. In contrast, increased expression of surface-associated protein A was linked only with invasive disease. Comparisons with laboratory-grown corresponding clinical isolates revealed that tissue-specific expression profiles reflect the activity of the staphylococcal accessory gene regulator during Human infection. These results represent the first demonstration of staphylococcal gene expression and regulation directly in Human tissue. Such analysis will help to unravel the complex interactions between CA-MRSA and its host environmental niches during disease development.

Gregory A Storch - One of the best experts on this subject based on the ideXlab platform.

  • virulence gene expression in Human Community acquired staphylococcus aureus infection
    The Journal of Infectious Diseases, 2009
    Co-Authors: Jennifer A Loughman, Stephanie A Fritz, Gregory A Storch, David A Hunstad
    Abstract:

    Staphylococcus aureus is a persistent Human pathogen that is responsible for a range of diseases that vary widely in clinical presentation and severity. The capacity of S. aureus to cause a spectrum of Human diseases reflects an ability to adapt to distinct microenvironments in the Human body and suggests that the pathogenesis of S. aureus infections is a complex process involving a diverse array of secreted and surface-associated virulence determinants that are coordinately expressed at different stages of infection [1]. Distinct networks of virulence genes are likely activated in response to host signals, including those found in target tissues and those related to innate defenses activated during the infectious process. This expectation manifests in vitro as a growth phase-dependent pattern of virulence determinant expression that is established by global regulatory elements (reviewed in [2]). During exponential growth, the organism synthesizes cell-wall proteins with adhesive functions, including protein A, fibrinogen-binding, fibronectin-binding, and collagen-binding proteins; such expression might augment the initial establishment of colonization in the host. In the transition from exponential to stationary phase, the expression of cell-wall proteins is repressed, while the synthesis of extracellular toxins and enzymes predominates. Through their proteolytic activities and toxic effects on host cells, these exotoxins might facilitate local invasion and dissemination during infection. The transition from exponential to stationary-phase protein expression is coordinately controlled by global regulators and the Agr quorum-sensing system [3]. During this transition, secretion of a modified peptide pheromone signals cell density-dependent gene expression via RNAIII, the regulatory effector molecule of the Agr system [4–6], resulting in up-regulation of exoprotein gene expression (e.g., hla, hlb) and down-regulation of cell surface adhesins such as protein A (spa) [7]. While this mechanism establishes temporal regulation in vitro, it also likely contributes to spatial regulation by limiting the expression of target genes to compartments where the signal molecule reaches a high concentration. Evidence of an in vivo role for this regulatory pathway is restricted to animal models of S. aureus infection. For example, agr inactivation resulted in reduced virulence in experimental staphylococcal musculoskeletal infection models [8, 9]. Recently, Agr-mediated expression of cytolytic peptides by CA-MRSA was shown to be important for Human neutrophil lysis and pathogenesis in a murine model of soft-tissue infection [10]. Animal studies have yielded conflicting conclusions regarding the pathogenic importance of PVL [11, 12] but indicate that PVL expression may alter agr expression patterns [12]. Though animal models of staphylococcal infection are valuable tools for relating the contribution of putative virulence factors identified in vitro to pathogenesis, their relevance to clinical disease is inherently limited and may not reflect Human-specific adaptive behavior. To address this, we identified patients with active Community-acquired S. aureus infections and defined bacterial gene expression profiles directly in tissue from multiple forms of Human infection.

  • virulence gene expression in Human Community acquired staphylococcus aureus infection
    The Journal of Infectious Diseases, 2009
    Co-Authors: Jennifer A Loughman, Stephanie A Fritz, Gregory A Storch, David A Hunstad
    Abstract:

    Isolates of methicillin-resistant Staphylococcus aureus (MRSA) were once linked uniformly with hospital-associated infections; however, Community-acquired MRSA (CA-MRSA) now represents an emerging threat worldwide. To examine the association of differential virulence gene expression with outcomes of Human infection, we measured transcript levels of target staphylococcal genes directly in clinical samples from children with active known or suspected CA-MRSA infections. Virulence genes encoding secreted toxins, including Panton-Valentine leukocidin, were highly expressed during superficial and invasive CA-MRSA infections. In contrast, increased expression of surface-associated protein A was linked only with invasive disease. Comparisons with laboratory-grown corresponding clinical isolates revealed that tissue-specific expression profiles reflect the activity of the staphylococcal accessory gene regulator during Human infection. These results represent the first demonstration of staphylococcal gene expression and regulation directly in Human tissue. Such analysis will help to unravel the complex interactions between CA-MRSA and its host environmental niches during disease development.

Jennifer A Loughman - One of the best experts on this subject based on the ideXlab platform.

  • virulence gene expression in Human Community acquired staphylococcus aureus infection
    The Journal of Infectious Diseases, 2009
    Co-Authors: Jennifer A Loughman, Stephanie A Fritz, Gregory A Storch, David A Hunstad
    Abstract:

    Staphylococcus aureus is a persistent Human pathogen that is responsible for a range of diseases that vary widely in clinical presentation and severity. The capacity of S. aureus to cause a spectrum of Human diseases reflects an ability to adapt to distinct microenvironments in the Human body and suggests that the pathogenesis of S. aureus infections is a complex process involving a diverse array of secreted and surface-associated virulence determinants that are coordinately expressed at different stages of infection [1]. Distinct networks of virulence genes are likely activated in response to host signals, including those found in target tissues and those related to innate defenses activated during the infectious process. This expectation manifests in vitro as a growth phase-dependent pattern of virulence determinant expression that is established by global regulatory elements (reviewed in [2]). During exponential growth, the organism synthesizes cell-wall proteins with adhesive functions, including protein A, fibrinogen-binding, fibronectin-binding, and collagen-binding proteins; such expression might augment the initial establishment of colonization in the host. In the transition from exponential to stationary phase, the expression of cell-wall proteins is repressed, while the synthesis of extracellular toxins and enzymes predominates. Through their proteolytic activities and toxic effects on host cells, these exotoxins might facilitate local invasion and dissemination during infection. The transition from exponential to stationary-phase protein expression is coordinately controlled by global regulators and the Agr quorum-sensing system [3]. During this transition, secretion of a modified peptide pheromone signals cell density-dependent gene expression via RNAIII, the regulatory effector molecule of the Agr system [4–6], resulting in up-regulation of exoprotein gene expression (e.g., hla, hlb) and down-regulation of cell surface adhesins such as protein A (spa) [7]. While this mechanism establishes temporal regulation in vitro, it also likely contributes to spatial regulation by limiting the expression of target genes to compartments where the signal molecule reaches a high concentration. Evidence of an in vivo role for this regulatory pathway is restricted to animal models of S. aureus infection. For example, agr inactivation resulted in reduced virulence in experimental staphylococcal musculoskeletal infection models [8, 9]. Recently, Agr-mediated expression of cytolytic peptides by CA-MRSA was shown to be important for Human neutrophil lysis and pathogenesis in a murine model of soft-tissue infection [10]. Animal studies have yielded conflicting conclusions regarding the pathogenic importance of PVL [11, 12] but indicate that PVL expression may alter agr expression patterns [12]. Though animal models of staphylococcal infection are valuable tools for relating the contribution of putative virulence factors identified in vitro to pathogenesis, their relevance to clinical disease is inherently limited and may not reflect Human-specific adaptive behavior. To address this, we identified patients with active Community-acquired S. aureus infections and defined bacterial gene expression profiles directly in tissue from multiple forms of Human infection.

  • virulence gene expression in Human Community acquired staphylococcus aureus infection
    The Journal of Infectious Diseases, 2009
    Co-Authors: Jennifer A Loughman, Stephanie A Fritz, Gregory A Storch, David A Hunstad
    Abstract:

    Isolates of methicillin-resistant Staphylococcus aureus (MRSA) were once linked uniformly with hospital-associated infections; however, Community-acquired MRSA (CA-MRSA) now represents an emerging threat worldwide. To examine the association of differential virulence gene expression with outcomes of Human infection, we measured transcript levels of target staphylococcal genes directly in clinical samples from children with active known or suspected CA-MRSA infections. Virulence genes encoding secreted toxins, including Panton-Valentine leukocidin, were highly expressed during superficial and invasive CA-MRSA infections. In contrast, increased expression of surface-associated protein A was linked only with invasive disease. Comparisons with laboratory-grown corresponding clinical isolates revealed that tissue-specific expression profiles reflect the activity of the staphylococcal accessory gene regulator during Human infection. These results represent the first demonstration of staphylococcal gene expression and regulation directly in Human tissue. Such analysis will help to unravel the complex interactions between CA-MRSA and its host environmental niches during disease development.

Stephanie A Fritz - One of the best experts on this subject based on the ideXlab platform.

  • virulence gene expression in Human Community acquired staphylococcus aureus infection
    The Journal of Infectious Diseases, 2009
    Co-Authors: Jennifer A Loughman, Stephanie A Fritz, Gregory A Storch, David A Hunstad
    Abstract:

    Staphylococcus aureus is a persistent Human pathogen that is responsible for a range of diseases that vary widely in clinical presentation and severity. The capacity of S. aureus to cause a spectrum of Human diseases reflects an ability to adapt to distinct microenvironments in the Human body and suggests that the pathogenesis of S. aureus infections is a complex process involving a diverse array of secreted and surface-associated virulence determinants that are coordinately expressed at different stages of infection [1]. Distinct networks of virulence genes are likely activated in response to host signals, including those found in target tissues and those related to innate defenses activated during the infectious process. This expectation manifests in vitro as a growth phase-dependent pattern of virulence determinant expression that is established by global regulatory elements (reviewed in [2]). During exponential growth, the organism synthesizes cell-wall proteins with adhesive functions, including protein A, fibrinogen-binding, fibronectin-binding, and collagen-binding proteins; such expression might augment the initial establishment of colonization in the host. In the transition from exponential to stationary phase, the expression of cell-wall proteins is repressed, while the synthesis of extracellular toxins and enzymes predominates. Through their proteolytic activities and toxic effects on host cells, these exotoxins might facilitate local invasion and dissemination during infection. The transition from exponential to stationary-phase protein expression is coordinately controlled by global regulators and the Agr quorum-sensing system [3]. During this transition, secretion of a modified peptide pheromone signals cell density-dependent gene expression via RNAIII, the regulatory effector molecule of the Agr system [4–6], resulting in up-regulation of exoprotein gene expression (e.g., hla, hlb) and down-regulation of cell surface adhesins such as protein A (spa) [7]. While this mechanism establishes temporal regulation in vitro, it also likely contributes to spatial regulation by limiting the expression of target genes to compartments where the signal molecule reaches a high concentration. Evidence of an in vivo role for this regulatory pathway is restricted to animal models of S. aureus infection. For example, agr inactivation resulted in reduced virulence in experimental staphylococcal musculoskeletal infection models [8, 9]. Recently, Agr-mediated expression of cytolytic peptides by CA-MRSA was shown to be important for Human neutrophil lysis and pathogenesis in a murine model of soft-tissue infection [10]. Animal studies have yielded conflicting conclusions regarding the pathogenic importance of PVL [11, 12] but indicate that PVL expression may alter agr expression patterns [12]. Though animal models of staphylococcal infection are valuable tools for relating the contribution of putative virulence factors identified in vitro to pathogenesis, their relevance to clinical disease is inherently limited and may not reflect Human-specific adaptive behavior. To address this, we identified patients with active Community-acquired S. aureus infections and defined bacterial gene expression profiles directly in tissue from multiple forms of Human infection.

  • virulence gene expression in Human Community acquired staphylococcus aureus infection
    The Journal of Infectious Diseases, 2009
    Co-Authors: Jennifer A Loughman, Stephanie A Fritz, Gregory A Storch, David A Hunstad
    Abstract:

    Isolates of methicillin-resistant Staphylococcus aureus (MRSA) were once linked uniformly with hospital-associated infections; however, Community-acquired MRSA (CA-MRSA) now represents an emerging threat worldwide. To examine the association of differential virulence gene expression with outcomes of Human infection, we measured transcript levels of target staphylococcal genes directly in clinical samples from children with active known or suspected CA-MRSA infections. Virulence genes encoding secreted toxins, including Panton-Valentine leukocidin, were highly expressed during superficial and invasive CA-MRSA infections. In contrast, increased expression of surface-associated protein A was linked only with invasive disease. Comparisons with laboratory-grown corresponding clinical isolates revealed that tissue-specific expression profiles reflect the activity of the staphylococcal accessory gene regulator during Human infection. These results represent the first demonstration of staphylococcal gene expression and regulation directly in Human tissue. Such analysis will help to unravel the complex interactions between CA-MRSA and its host environmental niches during disease development.

V Rajinikanth - One of the best experts on this subject based on the ideXlab platform.

  • social group optimization based tumor evaluation tool for clinical brain mri of flair diffusion weighted modality
    Biocybernetics and Biomedical Engineering, 2019
    Co-Authors: Nilanjan Dey, V Rajinikanth, Joao Manuel R S Tavares, Fuqian Shi, Luminita Moraru, Arvind K Karthik, Hong Lin, K Kamalanand, C Emmanuel
    Abstract:

    Abstract Brain tumor is one of the harsh diseases among Human Community and is usually diagnosed with medical imaging procedures. Computed-Tomography (CT) and Magnetic-Resonance-Image (MRI) are the regularly used non-invasive methods to acquire brain abnormalities for medical study. Due to its importance, a significant quantity of image assessment and decision-making procedures exist in literature. This article proposes a two-stage image assessment tool to examine brain MR images acquired using the Flair and DW modalities. The combination of the Social-Group-Optimization (SGO) and Shannon’s-Entropy (SE) supported multi-thresholding is implemented to pre-processing the input images. The image post-processing includes several procedures, such as Active Contour (AC), Watershed and region-growing segmentation, to extract the tumor section. Finally, a classifier system is implemented using ANFIS to categorize the tumor under analysis into benign and malignant. Experimental investigation was executed using benchmark datasets, like ISLES and BRATS, and also clinical MR images obtained with Flair/DW modality. The outcome of this study confirms that AC offers enhanced results compared with other segmentation procedures considered in this article. The ANFIS classifier obtained an accuracy of 94.51% on the used ISLES and real clinical images.

  • Social-Group-Optimization based tumor evaluation tool for clinical brain MRI of Flair/diffusion-weighted modality
    'Elsevier BV', 2019
    Co-Authors: Nilanjan Dey, V Rajinikanth, Joao Manuel R S Tavares, Fuqian Shi, Luminita Moraru, Arvind K Karthik, Hong Lin, K Kamalanand, C Emmanuel
    Abstract:

    Brain tumor is one of the harsh diseases among Human Community and is usually diagnosed with medical imaging procedures. Computed-Tomography (CT) and Magnetic-Resonance-Image (MRI) are the regularly used non-invasive methods to acquire brain abnormalities for medical study. Due to its importance, a significant quantity of image assessment and decision-making procedures exist in literature. This article proposes a two-stage image assessment tool to examine brain MR images acquired using the Flair and DW modalities. The combination of the Social-Group-Optimization (SGO) and Shannon's-Entropy (SE) supported multi-thresholding is implemented to pre-processing the input images. The image post-processing includes several procedures, such as Active Contour (AC), Watershed and region-growing segmentation, to extract the tumor section. Finally, a classifier system is implemented using ANFIS to categorize the tumor under analysis into benign and malignant. Experimental investigation was executed using benchmark datasets, like ISLES and BRATS, and also clinical MR images obtained with Flair/DW modality. The outcome of this study confirms that AC offers enhanced results compared with other segmentation procedures considered in this article. The ANFIS classifier obtained an accuracy of 94.51% on the used ISLES and real clinical images. (C) 2019 Nalecz Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of Sciences

  • social group optimization supported segmentation and evaluation of skin melanoma images
    Symmetry, 2018
    Co-Authors: Nilanjan Dey, V Rajinikanth, Amira S Ashour, Joao Manuel R S Tavares
    Abstract:

    The segmentation of medical images by computational methods has been claimed by the medical Community, which has promoted the development of several algorithms regarding different tissues, organs and imaging modalities. Nowadays, skin melanoma is one of the most common serious malignancies in the Human Community. Consequently, automated and robust approaches have become an emerging need for accurate and fast clinical detection and diagnosis of skin cancer. Digital dermatoscopy is a clinically accepted device to register and to investigate suspicious regions in the skin. During the skin melanoma examination, mining the suspicious regions from dermoscopy images is generally demanded in order to make a clear diagnosis about skin diseases, mainly based on features of the region under analysis like border symmetry and regularity. Predominantly, the successful estimation of the skin cancer depends on the used computational techniques of image segmentation and analysis. In the current work, a social group optimization (SGO) supported automated tool was developed to examine skin melanoma in dermoscopy images. The proposed tool has two main steps, mainly the image pre-processing step using the Otsu/Kapur based thresholding technique and the image post-processing step using the level set/active contour based segmentation technique. The experimental work was conducted using three well-known dermoscopy image datasets. Similarity metrics were used to evaluate the clinical significance of the proposed tool such as Jaccard’s coefficient, Dice’s coefficient, false positive/negative rate, accuracy, sensitivity and specificity. The experimental findings suggest that the proposed tool achieved superior performance relatively to the ground truth images provided by a skin cancer physician. Generally, the proposed SGO based Kapur’s thresholding technique combined with the level set based segmentation technique is very effective for identifying melanoma dermoscopy digital images with high sensitivity, specificity and accuracy.

  • segmentation of ischemic stroke lesion in brain mri based on social group optimization and fuzzy tsallis entropy
    Arabian Journal for Science and Engineering, 2018
    Co-Authors: V Rajinikanth, Suresh Chandra Satapathy
    Abstract:

    Stroke is one of the widespread causes of morbidity worldwide and is also the foremost reason for attained disability in Human Community. Ischemic stroke can be confirmed by investigating the interior brain regions. Magnetic resonance image (MRI) is one of the noninvasive imaging techniques widely adopted in medical discipline to record brain malformations. In this paper, a hybrid semi-automated image processing methodology is proposed to inspect the ischemic stroke lesion using the MRI recorded with flair and diffusion-weighted modality. The proposed approach consists of two sections, namely the preprocessing based on the social group optimization monitored Fuzzy-Tsallis entropy and post-processing technique, which consists of a segmentation algorithm to extract the ISL from preprocessed image in order to estimate the stroke severity and also to plan for further treatment process. The proposed hybrid approach is experimentally investigated using the ischemic stroke lesion segmentation challenge database. This work also presents a detailed investigation among well-known segmentation approaches, like watershed algorithm, region growing technique, principal component analysis, Chan–Vese active contour, and level set approaches, existing in the literature. The results of the experimental work executed using ISLES 2015 challenge dataset confirm that proposed methodology offers superior average values for image similarity indices like Jaccard (78.60%), Dice (88.54%), false positive rate (3.69%), and false negative rate (11.78%). This work also helps to achieve improved value of sensitivity (99.65%), specificity (78.05%), accuracy (91.17%), precision (98.11%), BCR (90.19%), and BER (6.09%).

  • segmentation and analysis of brain tumor using tsallis entropy and regularised level set
    2018
    Co-Authors: V Rajinikanth, Steven Lawrence Fernandes, Bharath Bhushan, Nayak Ramesh Sunder
    Abstract:

    Image processing is extensively considered in medical field for computer-supported disease assessment. Brain tumor is one of the deadliest cancers for the Human Community and requires image/signal processing approaches to record and analyze the disease-affected regions. In this work, Cuckoo Search Algorithm (CA) assisted approach is proposed to segment tumor from a two-dimensional Magnetic Resonance Image (MRI). Primarily, Tsallis entropy-monitored multilevel thresholding is implemented for the brain MRI dataset based on CA. Afterward, the skull section is detached by means of an image filtering approach. The skull stripped image is then treated using the image morphological function in order to obtain a smooth image exterior. Lastly, the tumor section is mined using the regularized level set technique. The efficiency and the clinical importance of presented method are confirmed based on the image similarity measures and the statistical measures. Experimental results of the proposed approach offer better values of Jaccard, Dice, precision, sensitivity, and accuracy values. Hence the proposed approach is clinically significant and in future, it can be used to diagnose the brain tumor images.