Multi-platform 'Omics Analysis of Human Ebola Virus Disease Pathogenesis.

PubMed

Eisfeld, Amie J; Halfmann, Peter J; Wendler, Jason P; Kyle, Jennifer E; Burnum-Johnson, Kristin E; Peralta, Zuleyma; Maemura, Tadashi; Walters, Kevin B; Watanabe, Tokiko; Fukuyama, Satoshi; Yamashita, Makoto; Jacobs, Jon M; Kim, Young-Mo; Casey, Cameron P; Stratton, Kelly G; Webb-Robertson, Bobbie-Jo M; Gritsenko, Marina A; Monroe, Matthew E; Weitz, Karl K; Shukla, Anil K; Tian, Mingyuan; Neumann, Gabriele; Reed, Jennifer L; van Bakel, Harm; Metz, Thomas O; Smith, Richard D; Waters, Katrina M; N'jai, Alhaji; Sahr, Foday; Kawaoka, Yoshihiro

2017-12-13

The pathogenesis of human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform 'omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that Ebola virus infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integrated biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. This work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity. Copyright © 2017 Elsevier Inc. All rights reserved.

Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths

PubMed Central

Gause, William C.; Wynn, Thomas A.; Allen, Judith E.

2013-01-01

Helminth-induced type 2 immune responses, which are characterized by the T helper 2 cell-associated cytokines interleukin-4 (IL-4) and IL-13, mediate host protection through enhanced tissue repair, the control of inflammation and worm expulsion. In this Opinion article, we consider type 2 immunity in the context of helminth-mediated tissue damage. We examine the relationship between the control of helminth infection and the mechanisms of wound repair, and we provide a new understanding of the adaptive type 2 immune response and its contribution to both host tolerance and resistance. PMID:23827958

Multispecies Biofilms and Host Responses: “Discriminating the Trees from the Forest”

PubMed Central

Peyyala, R.; Ebersole, J.L.

2014-01-01

Periodontal diseases reflect a tissue destructive process of the hard and soft tissues of the periodontium that are initiated by the accumulation of multispecies bacterial biofilms in the subgingival sulcus. This accumulation, in both quantity and quality of bacteria, results in a chronic immunoinflammatory response of the host to control this noxious challenge, leading to collateral damage of the tissues. As knowledge of the characteristics of the host-bacterial interactions in the oral cavity has expanded, new knowledge has become available on the complexity of the microbial challenge and the repertoire of host responses to this challenge. Recent results from the Human Microbiome Project continue to extend the array of taxa, genera, and species of bacteria that inhabit the multiple niches in the oral cavity; however, there is rather sparse information regarding variations in how host cells discriminate commensal from pathogenic species, as well as how the host response is affected by the 3-dimensional architecture and interbacterial interactions that occur in the oral biofilms. This review provides some insights into thes- processes by including existing literature on the biology of nonoral bacterial biofilms, and the more recent literature just beginning to document how the oral cavity responds to multispecies biofilms. PMID:23141757

Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

PubMed Central

Gaihre, Bipin; Uswatta, Suren; Jayasuriya, Ambalangodage C.

2017-01-01

Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies. PMID:29156629

Overview on the effects of parasites on fish health

USGS Publications Warehouse

Iwanowicz, D.D.; Cipriano, R.C.; Bruckner, A.W.; Shchelkunov, I.S.

2011-01-01

It is believed by many that parasites are only as important as the fish they infect. Parasites are ubiquitous, primarily surviving in a dynamic equilibrium with their host(s) and they are often overlooked in fish health assessments. Changes in the environment, both anthropogenic and environmental, can alter the parasite/host equilibrium and cause disease or mortality in fish. Therefore it is imperative that we have knowledge of both parasites and parasitic communities within a given population. When fish kills occur, it can often be associated with changes in parasite density and community composition. Often the damage associated with these fish is relative to the rate of infestation with the parasite; a fish that is lightly infected will show few signs of the parasite, while a heavily infected fish may become physiologically impaired and even die. Parasites can cause mechanical damage (fusion of gill lamellae, tissue replacement), physiological damage (cell proliferation, immunomodulation, detrimental behavioral responses, altered growth) and reproductive damage. As parasitism is the most common lifestyle on the planet, understanding its role in the environment may help researchers understand changes in a given fish population or stream ecosystem.

At the Bench: Helicobacter pylori, dysregulated host responses, DNA damage, and gastric cancer

PubMed Central

Hardbower, Dana M.; Peek, Richard M.; Wilson, Keith T.

2014-01-01

Helicobacter pylori infection is the strongest known risk factor for the development of gastric cancer. Given that ∼50% of the global population is infected with this pathogen, there is great impetus to elucidate underlying causes that mediate progression from infection to cancer. Recent evidence suggests that H. pylori-induced chronic inflammation and oxidative stress create an environment conducive to DNA damage and tissue injury. DNA damage leads to genetic instability and eventually, neoplastic transformation. Pathogen-encoded virulence factors induce a robust but futile immune response and alter host pathways that lower the threshold for carcinogenesis, including DNA damage repair, polyamine synthesis and catabolism, antioxidant responses, and cytokine production. Collectively, such dysregulation creates a protumorigenic microenvironment within the stomach. This review seeks to address each of these aspects of H. pylori infection and to call attention to areas of particular interest within this field of research. This review also seeks to prioritize areas of translational research related to H. pylori-induced gastric cancer based on insights garnered from basic research in this field. See related review by Dalal and Moss, At the Bedside: H. pylori, dysregulated host responses, DNA damage, and gastric cancer. PMID:24868089

Intravaginal Chlamydia trachomatis Challenge Infection Elicits TH1 and TH17 Immune Responses in Mice That Promote Pathogen Clearance and Genital Tract Damage

PubMed Central

Quispe Calla, Nirk E.; Pavelko, Stephen D.; Cherpes, Thomas L.

2016-01-01

While ascension of Chlamydia trachomatis into the upper genital tract of women can cause pelvic inflammatory disease and Fallopian tube damage, most infections elicit no symptoms or overt upper genital tract pathology. Consistent with this asymptomatic clinical presentation, genital C. trachomatis infection of women generates robust TH2 immunity. As an animal model that modeled this response would be invaluable for delineating bacterial pathogenesis and human host defenses, herein we explored if pathogen-specific TH2 immunity is similarly elicited by intravaginal (ivag) infection of mice with oculogenital C. trachomatis serovars. Analogous to clinical infection, ascension of primary C. trachomatis infection into the mouse upper genital tract produced no obvious tissue damage. Clearance of ivag challenge infection was mediated by interferon (IFN)-γ-producing CD4+ T cells, while IFN-γ signaling blockade concomitant with a single ivag challenge promoted tissue damage by enhancing Chlamydia-specific TH17 immunity. Likewise, IFN-γ and IL-17 signaling blockade or CD4+ T cell depletion eliminated the genital pathology produced in untreated controls by multiple ivag challenge infections. Conversely, we were unable to detect formation of pathogen-specific TH2 immunity in C. trachomatis-infected mice. Together, our work revealed C. trachomatis infection of mice generates TH1 and TH17 immune responses that promote pathogen clearance and immunopathological tissue damage. Absence of Chlamydia-specific TH2 immunity in these mice newly highlights the need to identify experimental models of C. trachomatis genital infection that more closely recapitulate the human host response. PMID:27606424

Analysis of Cryptic, Systemic Botrytis Infections in Symptomless Hosts

PubMed Central

Shaw, Michael W.; Emmanuel, Christy J.; Emilda, Deni; Terhem, Razak B.; Shafia, Aminath; Tsamaidi, Dimitra; Emblow, Mark; van Kan, Jan A. L.

2016-01-01

Botrytis species are generally considered to be aggressive, necrotrophic plant pathogens. By contrast to this general perception, however, Botrytis species could frequently be isolated from the interior of multiple tissues in apparently healthy hosts of many species. Infection frequencies reached 50% of samples or more, but were commonly less, and cryptic infections were rare or absent in some plant species. Prevalence varied substantially from year to year and from tissue to tissue, but some host species routinely had high prevalence. The same genotype was found to occur throughout a host, representing mycelial spread. Botrytis cinerea and Botrytis pseudocinerea are the species that most commonly occur as cryptic infections, but phylogenetically distant isolates of Botrytis were also detected, one of which does not correspond to previously described species. Sporulation and visible damage occurred only when infected tissues were stressed, or became mature or senescent. There was no evidence of cryptic infection having a deleterious effect on growth of the host, and prevalence was probably greater in plants grown in high light conditions. Isolates from cryptic infections were often capable of causing disease (to varying extents) when spore suspensions were inoculated onto their own host as well as on distinct host species, arguing against co-adaptation between cryptic isolates and their hosts. These data collectively suggest that several Botrytis species, including the most notorious pathogenic species, exist frequently in cryptic form to an extent that has thus far largely been neglected, and do not need to cause disease on healthy hosts in order to complete their life-cycles. PMID:27242829

Pulmonary cestodiasis in a cynomolgus monkey (Macaca fascicularis).

PubMed

Guillot, L M; Green, L C

1992-04-01

Cestodiasis in primates has been noted historically to occur quite frequently, although tissue damage and clinical signs may or may not be apparent. Larval cestodes, such as hydatid cysts or cysticercus cysts, are known to cause extensive tissue damage, while other larval cestodes, such as tetrathyridia, cause minimal damage to the host. This case history concerns an apparently healthy cynomolgus monkey that was part of a surgical study. During the study, all parameters were normal. The monkey died 3 hours postsurgery. The apparent cause of death was respiratory arrest. At necropsy, it was discovered there were 1- to 3-mm-diameter cysts, which on transection extruded 2- to 5-mm-long larvae. The larvae could not be positively identified; however, they resembled tetrathyridia of Mesocestoides sp.

Acute exposure to space flight results in evidence of reduced lymph Transport, tissue fluid Shifts, and immune alterations in the rat gastrointestinal system

NASA Astrophysics Data System (ADS)

Cromer, W. E.; Zawieja, D. C.

2018-05-01

Space flight causes a number of alterations in physiological systems, changes in the immunological status of subjects, and altered interactions of the host to environmental stimuli. We studied the effect of space flight on the lymphatic system of the gastrointestinal tract which is responsible for lipid transport and immune surveillance which includes the host interaction with the gut microbiome. We found that there were signs of tissue damage present in the space flown animals that was lacking in ground controls (epithelial damage, crypt morphological changes, etc.). Additionally, morphology of the lymphatic vessels in the tissue suggested a collapsed state at time of harvest and there was a profound change in the retention of lipid in the villi of the ileum. Contrary to our assumptions there was a reduction in tissue fluid volume likely associated with other fluid shifts described. The reduction of tissue fluid volume in the colon and ileum is a likely contributing factor to the state of the lymphatic vessels and lipid transport issues observed. There were also associated changes in the number of MHC-II+ immune cells in the colon tissue, which along with reduced lymphatic competence would favor immune dysfunction in the tissue. These findings help expand our understanding of the effects of space flight on various organ systems. It also points out potential issues that have not been closely examined and have to potential for the need of countermeasure development.

Methods for assessing infestations of sunflower stem weevil (Coleoptera: Curculionidae) in sunflower stems

USDA-ARS?s Scientific Manuscript database

The sunflower stem weevil, Cylindrocopturus adspersus LeConte (Coleoptera: Curculionidae), reduces sunflower, Helianthus annuus L. (Asteraceae), yields by spreading pathogens, damaging vascular tissues, and promoting lodging of sunflower plants. To assess weevil populations for host plant resistanc...

Biomaterials for tissue engineering applications.

PubMed

Keane, Timothy J; Badylak, Stephen F

2014-06-01

With advancements in biological and engineering sciences, the definition of an ideal biomaterial has evolved over the past 50 years from a substance that is inert to one that has select bioinductive properties and integrates well with adjacent host tissue. Biomaterials are a fundamental component of tissue engineering, which aims to replace diseased, damaged, or missing tissue with reconstructed functional tissue. Most biomaterials are less than satisfactory for pediatric patients because the scaffold must adapt to the growth and development of the surrounding tissues and organs over time. The pediatric community, therefore, provides a distinct challenge for the tissue engineering community. Copyright © 2014. Published by Elsevier Inc.

Disentangling Detoxification: Gene Expression Analysis of Feeding Mountain Pine Beetle Illuminates Molecular-Level Host Chemical Defense Detoxification Mechanisms

PubMed Central

Robert, Jeanne A.; Pitt, Caitlin; Bonnett, Tiffany R.; Yuen, Macaire M. S.; Keeling, Christopher I.; Bohlmann, Jörg; Huber, Dezene P. W.

2013-01-01

The mountain pine beetle, Dendroctonus ponderosae, is a native species of bark beetle (Coleoptera: Curculionidae) that caused unprecedented damage to the pine forests of British Columbia and other parts of western North America and is currently expanding its range into the boreal forests of central and eastern Canada and the USA. We conducted a large-scale gene expression analysis (RNA-seq) of mountain pine beetle male and female adults either starved or fed in male-female pairs for 24 hours on lodgepole pine host tree tissues. Our aim was to uncover transcripts involved in coniferophagous mountain pine beetle detoxification systems during early host colonization. Transcripts of members from several gene families significantly increased in insects fed on host tissue including: cytochromes P450, glucosyl transferases and glutathione S-transferases, esterases, and one ABC transporter. Other significantly increasing transcripts with potential roles in detoxification of host defenses included alcohol dehydrogenases and a group of unexpected transcripts whose products may play an, as yet, undiscovered role in host colonization by mountain pine beetle. PMID:24223726

Disentangling detoxification: gene expression analysis of feeding mountain pine beetle illuminates molecular-level host chemical defense detoxification mechanisms.

PubMed

Robert, Jeanne A; Pitt, Caitlin; Bonnett, Tiffany R; Yuen, Macaire M S; Keeling, Christopher I; Bohlmann, Jörg; Huber, Dezene P W

2013-01-01

The mountain pine beetle, Dendroctonus ponderosae, is a native species of bark beetle (Coleoptera: Curculionidae) that caused unprecedented damage to the pine forests of British Columbia and other parts of western North America and is currently expanding its range into the boreal forests of central and eastern Canada and the USA. We conducted a large-scale gene expression analysis (RNA-seq) of mountain pine beetle male and female adults either starved or fed in male-female pairs for 24 hours on lodgepole pine host tree tissues. Our aim was to uncover transcripts involved in coniferophagous mountain pine beetle detoxification systems during early host colonization. Transcripts of members from several gene families significantly increased in insects fed on host tissue including: cytochromes P450, glucosyl transferases and glutathione S-transferases, esterases, and one ABC transporter. Other significantly increasing transcripts with potential roles in detoxification of host defenses included alcohol dehydrogenases and a group of unexpected transcripts whose products may play an, as yet, undiscovered role in host colonization by mountain pine beetle.

Beta-lactamase targeted enzyme activatable photosensitizers for antimicrobial PDT

NASA Astrophysics Data System (ADS)

Zheng, Xiang; Verma, Sarika; Sallum, Ulysses W.; Hasan, Tayyaba

2009-06-01

Photodynamic therapy (PDT) as a treatment modality for infectious disease has shown promise. However, most of the antimicrobial photosensitizers (PS) non-preferentially accumulate in both bacteria and host tissues, causing host tissue phototoxicity during treatment. We have developed a new antimicrobial PDT strategy which exploits beta-lactam resistance mechanism, one of the major drug-resistance bacteria evolved, to achieve enhanced target specificity with limited host damage. Our strategy comprises a prodrug construct with a PS and a quencher linked by beta-lactam ring, resulting in a diminished phototoxicity. This construct, beta-lactamase enzyme-activated-photosensitizer (beta-LEAP), can only be activated in the presence of both light and bacteria, and remains inactive elsewhere such as mammalian tissue. Beta-LEAP construct had shown specific cleavage by purified beta-lactamase and by beta-lactamase over-expressing methicillin resistant Staphylococcus aureus (MRSA). Specific photodynamic toxicity was observed towards MRSA, while dark and light toxicity were equivalent to reference strains. The prodrug design, synthesis and photophysical properties will be discussed.

Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin

PubMed Central

Allen, Judith E.; Sutherland, Tara E.

2014-01-01

Metazoan parasites typically induce a type 2 immune response, characterized by T helper 2 (Th2) cells that produce the cytokines IL-4, IL-5 and IL-13 among others. The type 2 response is host protective, reducing the number of parasites either through direct killing in the tissues, or expulsion from the intestine. Type 2 immunity also protects the host against damage mediated by these large extracellular parasites as they migrate through the body. At the center of both the innate and adaptive type 2 immune response, is the IL-4Rα that mediates many of the key effector functions. Here we highlight the striking overlap between the molecules, cells and pathways that mediate both parasite control and tissue repair. We have proposed that adaptive Th2 immunity evolved out of our innate repair pathways to mediate both accelerated repair and parasite control in the face of continual assault from multicellular pathogens. Type 2 cytokines are involved in many aspects of mammalian physiology independent of helminth infection. Therefore understanding the evolutionary relationship between helminth killing and tissue repair should provide new insight into immune mechanisms of tissue protection in the face of physical injury. PMID:25028340

Ambient ozone and pulmonary innate immunity

PubMed Central

Al-Hegelan, Mashael; Tighe, Robert M.; Castillo, Christian; Hollingsworth, John W.

2013-01-01

Ambient ozone is a criteria air pollutant that impacts both human morbidity and mortality. The effect of ozone inhalation includes both toxicity to lung tissue and alteration of the host immunologic response. The innate immune system facilitates immediate recognition of both foreign pathogens and tissue damage. Emerging evidence supports that ozone can modify the host innate immune response and that this response to inhaled ozone is dependent on genes of innate immunity. Improved understanding of the complex interaction between environmental ozone and host innate immunity will provide fundamental insight into the pathogenesis of inflammatory airways disease. We review the current evidence supporting that environmental ozone inhalation: (1) modifies cell types required for intact innate immunity, (2) is partially dependent on genes of innate immunity, (3) primes pulmonary innate immune responses to LPS, and (4) contributes to innate-adaptive immune system cross-talk. PMID:21132467

Philometra floridensis (Nematoda: Philometridae) damages ovarian tissue without reducing host (Sciaenops ocellatus) fecundity.

PubMed

Bakenhaster, Micah D; Lowerre-Barbieri, Susan; Kiryu, Yasunari; Walters, Sarah; Fajer-Avila, Emma J

2014-04-03

The parasitic nematode Philometra floridensis infects the ovary of its only host, the economically important fish species Sciaenops ocellatus, but the factors influencing host susceptibility and potential pathogenic effects are unknown. Here we report new information on these topics from evaluations of infected and uninfected hosts collected from the northeastern Gulf of Mexico. Fish length and age were evaluated vis-à-vis nematode prevalence to check for ontogenetic differences in host susceptibility. To evaluate health and reproductive consequences of infection, we looked for effects in Fulton's condition factor (K) and batch fecundity estimates (BF), and we evaluated ovarian tissue histologically to check for oocyte atresia and other host responses. We observed localized pathological changes in fish ovarian tissue associated with female nematodes, including leucocytic exudates, granulomatous inflammation, and Langhans-type multinucleated giant cells; the hosts, however, appeared to maintain high fecundity and actually exhibited, on average, better health index scores and higher relative fecundity than did uninfected fish. These differences are likely explained by the parasite's tendency to disproportionately infect the largest, actively spawning fish and by the localization of pathogenic changes, which could have masked effects that otherwise would have been reflected in mass-based health indicators. Although we did not detect negative effects on measures of overall health or reproductive output, further research is needed to better elucidate the relationship between these parasites and other factors affecting host reproductive potential, such as egg quality.

Intra- and inter-dairy heifer variation of cellular neutrophil functions

USDA-ARS?s Scientific Manuscript database

Immune competence of dairy cattle is difficult to determine as a healthy immune system requires the resolution of pathogen invasion without excessive host-tissue damage. Neutrophil phagocytosis (PG) is important for eliminating pathogens, but PG induces an oxidative burst (OB), which helps destroy t...

Herpesviruses and Their Host Cells: A Successful Liaison.

PubMed

Adler, Barbara; Sattler, Christine; Adler, Heiko

2017-03-01

During a long history of coevolution, herpesviruses have reached a fine-tuned balance with their hosts, allowing them to successfully persist and spread to new hosts without causing too much damage. Only under certain circumstances, as in neonates or immunocompromised individuals, they may cause serious diseases. The delicate balance between herpesviruses and their hosts results from interactions of a great variety of viral and cellular factors which together shape the tropism for a particular host, tissue, or cell. Understanding these interactions will provide insight into the viral life cycle and cell biology in general. Moreover, it will also facilitate comprehension of herpesvirus pathogenesis, enabling the development of new strategies to combat herpesviruses in cases where they cause disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute exposure to space flight results in evidence of reduced lymph Transport, tissue fluid Shifts, and immune alterations in the rat gastrointestinal system.

PubMed

Cromer, W E; Zawieja, D C

2018-05-01

Space flight causes a number of alterations in physiological systems, changes in the immunological status of subjects, and altered interactions of the host to environmental stimuli. We studied the effect of space flight on the lymphatic system of the gastrointestinal tract which is responsible for lipid transport and immune surveillance which includes the host interaction with the gut microbiome. We found that there were signs of tissue damage present in the space flown animals that was lacking in ground controls (epithelial damage, crypt morphological changes, etc.). Additionally, morphology of the lymphatic vessels in the tissue suggested a collapsed state at time of harvest and there was a profound change in the retention of lipid in the villi of the ileum. Contrary to our assumptions there was a reduction in tissue fluid volume likely associated with other fluid shifts described. The reduction of tissue fluid volume in the colon and ileum is a likely contributing factor to the state of the lymphatic vessels and lipid transport issues observed. There were also associated changes in the number of MHC-II + immune cells in the colon tissue, which along with reduced lymphatic competence would favor immune dysfunction in the tissue. These findings help expand our understanding of the effects of space flight on various organ systems. It also points out potential issues that have not been closely examined and have to potential for the need of countermeasure development. Copyright © 2018 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Study of the circadian rhythm in radiation response

USDA-ARS?s Scientific Manuscript database

Gamma-Radiation is often used for the treatment of solid tumors. It induces DNA double-stranded breaks that lead to cell cycle arrest or apoptosis of tumor cells. However, such treatment could also damage normal host tissues that need cell proliferation for function. We have reported previously that...

Field response of Dendroctonus frontalis (Coleoptera: Scolytinae) to Synthetic Semiochemicals in Chiapas, Mexico.

Treesearch

Benjamin Moreno; Jorge Macias; Brian T. Sullivan; Stephen R. Clarke

2008-01-01

Dendroctonus frontalis Zimmermann (Coleoptera: Scolytinae) is the most serious pest of pines (Pinus spp.) in Mexico. Con specifics are attracted to trees undergoing colonization by the aggregation pheromone frontalin, which is synergized by odors of pine oleoresin released from beetle-damaged host tissue. Synthetic racemic frontalin...

Manipulation of Neutrophils by Porphyromonas gingivalis in the Development of Periodontitis

PubMed Central

Sochalska, Maja; Potempa, Jan

2017-01-01

The pathogenesis of the chronic periodontal disease is associated with a skewed host inflammatory response to periodontal pathogens, such as Porphyromonas gingivalis, that accounts for the majority of periodontal tissue damage. Neutrophils are the most abundant leukocytes in periodontal pockets and depending on the stage of the disease, also plentiful PMNs are present in the inflamed gingival tissue and the gingival crevice. They are the most efficient phagocytes and eliminate pathogens by a variety of means, which are either oxygen-dependent or -independent. However, these secretory lethal weapons do not strictly discriminate between pathogens and host tissue. Current studies describe conflicting findings about neutrophil involvement in periodontal disease. On one hand literature indicate that hyper-reactive neutrophils are the main immune cell type responsible for this observed tissue damage and disease progression. Deregulation of neutrophil survival and functions, such as chemotaxis, migration, secretion of antimicrobial peptides or enzymes, and production of reactive oxygen species, contribute to observed tissue injury and the clinical signs of periodontal disease. On the other hand neutrophils deficiencies in patients and mice also result in periodontal phenotype. Therefore, P. gingivalis represents a periodontal pathogen that manipulates the immune responses of PMNs, employing several virulence factors, such as gingipains, serine proteases, lipid phosphatases, or fimbriae. This review will sum up studies devoted to understanding different strategies utilized by P. gingivalis to manipulate PMNs survival and functions in order to inhibit killing by a granular content, prolong inflammation, and gain access to nutrient resources. PMID:28589098

Brains and Brawn: Toxoplasma Infections of the Central Nervous System and Skeletal Muscle.

PubMed

Wohlfert, Elizabeth A; Blader, Ira J; Wilson, Emma H

2017-07-01

Toxoplasma gondii is a widespread parasitic pathogen that infects over a third of the world's population. Following an acute infection, the parasite can persist within its mammalian host as intraneuronal or intramuscular cysts. Cysts will occasionally reactivate, and - depending on the host's immune status and site of reactivation - encephalitis or myositis can develop. Because these diseases have high levels of morbidity and can be lethal, it is important to understand how Toxoplasma traffics to these tissues, how the immune response controls parasite burden and contributes to tissue damage, and what mechanisms underlie neurological and muscular pathologies that toxoplasmosis patients present with. This review aims to summarize recent important developments addressing these critical topics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation of inflammation and disease tolerance by DNA damage response pathways.

PubMed

Neves-Costa, Ana; Moita, Luis F

2017-03-01

The accurate replication and repair of DNA is central to organismal survival. This process is challenged by the many factors that can change genetic information such as replication errors and direct damage to the DNA molecule by chemical and physical agents. DNA damage can also result from microorganism invasion as an integral step of their life cycle or as collateral damage from host defense mechanisms against pathogens. Here we review the complex crosstalk of DNA damage response and immune response pathways that might be evolutionarily connected and argue that DNA damage response pathways can be explored therapeutically to induce disease tolerance through the activation of tissue damage control processes. Such approach may constitute the missing pillar in the treatment of critical illnesses caused by multiple organ failure, such as sepsis and septic shock. © 2016 Federation of European Biochemical Societies.

Molecular responses of calreticulin genes to iron overload and bacterial challenge in channel catfish Ictalurus punctatus

USDA-ARS?s Scientific Manuscript database

Infection and inflammation are often accompanied by oxidative stress caused by the accumulation of reactive oxygen species which can be deleterious to the health of the host. Antioxidant defense mechanisms and components are crucial in limiting cellular and tissue-level damage and restoring homeosta...

Molecular responses of calreticulin genes to iron overload and bacterial challenge in channel catfish (Ictalurus punctatus)

USDA-ARS?s Scientific Manuscript database

Infection and inflammation are often accompanied by oxidative stress caused by the accumulation of reactive oxygen species which can be deleterious to the health of the host. Antioxidant defense mechanisms and components are crucial in limiting cellular and tissue-level damage and restoring homeosta...

Fasciola hepatica vaccine: we may not be there yet but we're on the right road.

PubMed

Molina-Hernández, Verónica; Mulcahy, Grace; Pérez, Jose; Martínez-Moreno, Álvaro; Donnelly, Sheila; O'Neill, Sandra M; Dalton, John P; Cwiklinski, Krystyna

2015-02-28

Major advances have been made in identifying potential vaccine molecules for the control of fasciolosis in livestock but we have yet to reach the level of efficacy required for commercialisation. The pathogenesis of fasciolosis is associated with liver damage that is inflicted by migrating and feeding immature flukes as well as host inflammatory immune responses to parasite-secreted molecules and tissue damage alarm signals. Immune suppression/modulation by the parasites prevents the development of protective immune responses as evidenced by the lack of immunity observed in naturally and experimentally infected animals. In our opinion, future efforts need to focus on understanding how parasites invade and penetrate the tissues of their hosts and how they potentiate and control the ensuing immune responses, particularly in the first days of infection. Emerging 'omics' data employed in an unbiased approach are helping us understand liver fluke biology and, in parallel with new immunological data, to identify molecules that are essential to parasite development and accessible to vaccine-induced immune responses. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Neutrophil cell surface receptors and their intracellular signal transduction pathways☆

PubMed Central

Futosi, Krisztina; Fodor, Szabina; Mócsai, Attila

2013-01-01

Neutrophils play a critical role in the host defense against bacterial and fungal infections, but their inappropriate activation also contributes to tissue damage during autoimmune and inflammatory diseases. Neutrophils express a large number of cell surface receptors for the recognition of pathogen invasion and the inflammatory environment. Those include G-protein-coupled chemokine and chemoattractant receptors, Fc-receptors, adhesion receptors such as selectins/selectin ligands and integrins, various cytokine receptors, as well as innate immune receptors such as Toll-like receptors and C-type lectins. The various cell surface receptors trigger very diverse signal transduction pathways including activation of heterotrimeric and monomeric G-proteins, receptor-induced and store-operated Ca2 + signals, protein and lipid kinases, adapter proteins and cytoskeletal rearrangement. Here we provide an overview of the receptors involved in neutrophil activation and the intracellular signal transduction processes they trigger. This knowledge is crucial for understanding how neutrophils participate in antimicrobial host defense and inflammatory tissue damage and may also point to possible future targets of the pharmacological therapy of neutrophil-mediated autoimmune or inflammatory diseases. PMID:23994464

Histopathology and the inflammatory response of European perch, Perca fluviatilis muscle infected with Eustrongylides sp. (Nematoda).

PubMed

Dezfuli, Bahram S; Manera, Maurizio; Lorenzoni, Massimo; Pironi, Flavio; Shinn, Andrew P; Giari, Luisa

2015-04-15

The European perch, Perca fluviatilis L. is a common paratenic host of dioctophymatid nematodes belonging to the genus Eustrongylides. In this host, once infected oligochaetes, which serve as the first intermediate host, are ingested, Eustrongylides migrates through the intestine and is frequently encountered within the musculature, free within the body cavity, or encapsulated on the viscera. The current study details the first Italian record of Eustrongylides sp. with larvae reported in the muscle of P. fluviatilis. Uninfected and nematode-infected muscle tissues of perch were fixed and prepared for histological evaluation and electron microscopy. Some sections were subjected to an indirect immunohistochemical method using anti-PCNA, anti-piscidin 3 and anti-piscidin 4 antibodies. A total of 510 P. fluviatilis (TL range 15-25 cm) from Lake Trasimeno, Perugia were post-mortemed; 31 individuals had encysted nematode larvae within their musculature (1-2 worms fish(-1)). Histologically, larvae were surrounded by a capsule with an evident acute inflammatory reaction. Muscle degeneration and necrosis extending throughout the sarcoplasm, sarcolemmal basal lamina, endomysial connective tissue cells and capillaries was frequently observed. Within the encapsulating reaction, macrophage aggregates (MAs) were seen. Immunohistochemical staining with the proliferating cell nuclear antigen (PCNA) revealed numerous PCNA-positive cells within the thickness of the capsule and in the immediate vicinity surrounding Eustrongylides sp. larvae (i.e. fibroblasts and satellite cells), suggesting a host response had been initiated to repair the nematode-damaged muscle. Mast cells (MCs) staining positively for piscidin 3, were demonstrated for the first time in response to a muscle-infecting nematode. The piscidin 3 positive MC's were seen principally in the periphery of the capsule surrounding the Eustrongylides sp. larva. A host tissue response to Eustrongylides sp. larvae infecting the musculature of P. fluviatilis was observed. Numerous fibroblasts, MAs and MCs were seen throughout the thick fibroconnectival layer of the capsule enclosing larvae. PCNA positive cells within the capsule suggest that host repair of nematode damaged muscle does occur, while the presence of the antimicrobial peptide piscidin 3 is shown for the first time. This is first report of Eustrongylides sp. in an Italian population of P. fluviatilis.

"Host tissue damage" signal ATP promotes non-directional migration and negatively regulates toll-like receptor signaling in human monocytes.

PubMed

Kaufmann, Andreas; Musset, Boris; Limberg, Sven H; Renigunta, Vijay; Sus, Rainer; Dalpke, Alexander H; Heeg, Klaus M; Robaye, Bernard; Hanley, Peter J

2005-09-16

The activation of Toll-like receptors (TLRs) by lipopolysaccharide or other ligands evokes a proinflammatory immune response, which is not only capable of clearing invading pathogens but can also inflict damage to host tissues. It is therefore important to prevent an overshoot of the TLR-induced response where necessary, and here we show that extracellular ATP is capable of doing this in human monocytes. Using reverse transcription-PCR, we showed that monocytes express P2Y(1), P2Y(2), P2Y(4), P2Y(11), and P2Y(13) receptors, as well as several P2X receptors. To elucidate the function of these receptors, we first studied Ca(2+) signaling in single cells. ATP or UTP induced a biphasic increase in cytosolic Ca(2+), which corresponded to internal Ca(2+) release followed by activation of store-operated Ca(2+) entry. The evoked Ca(2+) signals stimulated Ca(2+)-activated K(+) channels, producing transient membrane hyperpolarization. In addition, ATP promoted cytoskeleton reorganization and cell migration; however, unlike chemoattractants, the migration was non-directional and further analysis showed that ATP did not activate Akt, essential for sensing gradients. When TLR2, TLR4, or TLR2/6 were stimulated with their respective ligands, ATPgammaS profoundly inhibited secretion of proinflammatory cytokines (tumor necrosis factor-alpha and monocyte chemoattractant protein-1) but increased the production of interleukin-10, an anti-inflammatory cytokine. In radioimmune assays, we found that ATP (or ATPgammaS) strongly increased cAMP levels, and, moreover, the TLR-response was inhibited by forskolin, whereas UTP neither increased cAMP nor inhibited the TLR-response. Thus, our data suggest that ATP promotes non-directional migration and, importantly, acts as a "host tissue damage" signal via the G(s) protein-coupled P2Y(11) receptor and increased cAMP to negatively regulate TLR signaling.

Cavisoma magnum (Cavisomidae), a unique Pacific acanthocephalan redescribed from an unusual host, Mugil cephalus (Mugilidae), in the Arabian Gulf, with notes on histopathology and metal analysis

PubMed Central

Amin, Omar M.; Heckmann, Richard A.; Bannai, Majid A.

2018-01-01

Cavisoma magnum (Southwell, 1927) Van Cleave, 1931 was originally described from a sea bass, Serranus sp. and spotted surgeonfish, Ctenochaetus strigosus (Perciformes) off Sri Lanka before its more recent redescription from milkfish in the Philippines in 1995. These reports were based on only light infections of their host fishes. Of the few flathead grey mullets, Mugil cephalus (Mugilidae), that we examined in the Arabian Gulf, one fish was infected with 1,450 worms. One milkfish, Chanos chanos (Chanidae), from the same location in the Arabian Gulf, was also heavily infected with specimens of C. magnum. The descriptions of this unique large worm are revised and for the first time, we provide SEM images, new systematic observations, metal analysis of hooks showing extremely high levels of sulfur, and histopathology in the mullet intestinal tissue. Adjustments and corrections of previous descriptive accounts are made. The histopathology studies show extensive damage to the host intestinal tissue including epithelial necrosis, hemorrhaging and worm encapsulation. There is an extensive amount of host connective tissue surrounding the worm. Results of x-ray analysis displayed high levels of sulfur in proboscis hooks, especially at the tips and edges of these attachment structures. PMID:29424340

Leptospira interrogans Binds to Cadherins

PubMed Central

Evangelista, Karen; Franco, Ricardo; Schwab, Andrew; Coburn, Jenifer

2014-01-01

Leptospirosis, caused by pathogenic species of Leptospira, is the most widespread zoonosis and has emerged as a major public health problem worldwide. The adhesion of pathogenic Leptospira to host cells, and to extracellular matrix (ECM) components, is likely to be necessary for the ability of leptospires to penetrate, disseminate and persist in mammalian host tissues. Previous work demonstrated that pathogenic L. interrogans binds to host cells more efficiently than to ECM. Using two independent screening methods, mass spectrometry and protein arrays, members of the cadherin family were identified as potential L. interrogans receptors on mammalian host surfaces. We focused our investigation on vascular endothelial (VE)-cadherin, which is widely expressed on endothelia and is primarily responsible for endothelial cell-cell adhesion. Monolayers of EA.hy926 and HMEC-1 endothelial cells produce VE-cadherin, bind L. interrogans in vitro, and are disrupted upon incubation with the bacteria, which may reflect the endothelial damage seen in vivo. Dose-dependent and saturable binding of L. interrogans to the purified VE-cadherin receptor was demonstrated and pretreatment of purified receptor or endothelial cells with function-blocking antibody against VE-cadherin significantly inhibited bacterial attachment. The contribution of VE-cadherin to leptospiral adherence to host endothelial cell surfaces is biologically significant because VE-cadherin plays an important role in maintaining the barrier properties of the vasculature. Attachment of L. interrogans to the vasculature via VE-cadherin may result in vascular damage, facilitating the escape of the pathogen from the bloodstream into different tissues during disseminated infection, and may contribute to the hemorrhagic manifestations of leptospirosis. This work is first to describe a mammalian cell surface protein as a receptor for L. interrogans. PMID:24498454

Infestation of gill copepod Lernanthropus latis (Copepoda: Lernanthropidae) and its effect on cage-cultured Asian sea bass Lates calcarifer.

PubMed

Kua, B C; Noraziah, M R; Nik Rahimah, A R

2012-09-01

Twenty Asian sea bass Lates calcarifer from a floating cage in Bt. Tambun, Penang were examined for the presence of parasitic gill copepod, Lernanthropus latis. The prevalence of L. latis was 100% with the intensity of infection ranging from 1 to 18 parasites per host or 3.75 of mean intensity. Female parasites having oblong cephalothorax and egg-strings were seen mainly on the entire gill of examined Asian sea bass. The infected gill of Asian sea bass was pale and had eccessive mucus production. Under light and scanning electron microscopies (SEM), L. latis was seen grasping or holding tightly to the gill filament using their antenna, maxilla and maxilliped. These structures are characteristically prehensile and uncinate for the parasite to attach onto the host tissue. The damage was clearly seen under SEM as the hooked end of the antenna was embedded into the gill filament. The parasite also has the mandible which is styliform with eight teeth on the inner margin. The pathological effects such as erosion, haemorrhages, hyperplasia and necrosis along the secondary lamellae of gill filaments were seen and more severe at the attachment site. The combined actions of the antenna, maxilla and maxilliped together with the mandible resulted in extensive damage as L. latis attached and fed on the host tissues.

SpxA1 and SpxA2 Act Coordinately To Fine-Tune Stress Responses and Virulence in Streptococcus pyogenes.

PubMed

Port, Gary C; Cusumano, Zachary T; Tumminello, Paul R; Caparon, Michael G

2017-03-28

SpxA is a unique transcriptional regulator highly conserved among members of the phylum Firmicutes that binds RNA polymerase and can act as an antiactivator. Why some Firmicutes members have two highly similar SpxA paralogs is not understood. Here, we show that the SpxA paralogs of the pathogen Streptococcus pyogenes , SpxA1 and SpxA2, act coordinately to regulate virulence by fine-tuning toxin expression and stress resistance. Construction and analysis of mutants revealed that SpxA1 - mutants were defective for growth under aerobic conditions, while SpxA2 - mutants had severely attenuated responses to multiple stresses, including thermal and oxidative stresses. SpxA1 - mutants had enhanced resistance to the cationic antimicrobial molecule polymyxin B, while SpxA2 - mutants were more sensitive. In a murine model of soft tissue infection, a SpxA1 - mutant was highly attenuated. In contrast, the highly stress-sensitive SpxA2 - mutant was hypervirulent, exhibiting more extensive tissue damage and a greater bacterial burden than the wild-type strain. SpxA1 - attenuation was associated with reduced expression of several toxins, including the SpeB cysteine protease. In contrast, SpxA2 - hypervirulence correlated with toxin overexpression and could be suppressed to wild-type levels by deletion of speB These data show that SpxA1 and SpxA2 have opposing roles in virulence and stress resistance, suggesting that they act coordinately to fine-tune toxin expression in response to stress. SpxA2 - hypervirulence also shows that stress resistance is not always essential for S. pyogenes pathogenesis in soft tissue. IMPORTANCE For many pathogens, it is generally assumed that stress resistance is essential for pathogenesis. For Streptococcus pyogenes , environmental stress is also used as a signal to alter toxin expression. The amount of stress likely informs the bacterium of the strength of the host's defense response, allowing it to adjust its toxin expression to produce the ideal amount of tissue damage, balancing between too little damage, which will result in its elimination, and too much damage, which will debilitate the host. Here we identify components of a genetic circuit involved in stress resistance and toxin expression that has a fine-tuning function in tissue damage. The circuit consists of two versions of the protein SpxA that regulate transcription and are highly similar but have opposing effects on the severity of soft tissue damage. These results will help us understand how virulence is fine-tuned in other pathogens that have two SpxA proteins. Copyright © 2017 Port et al.

The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease.

PubMed

Chen, Yuanyuan; Zhao, Ye; Cheng, Qiao; Wu, Depei; Liu, Haiyan

2015-01-01

The mammalian intestinal microbiota is a complex ecosystem that plays an important role in host immune responses. Recent studies have demonstrated that alterations in intestinal microbiota composition are linked to multiple inflammatory diseases in humans, including acute graft-versus-host disease (aGVHD). aGVHD is one of the major obstacles in allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by tissue damage in the gastrointestinal (GI) tract, liver, lung, and skin. Here, we review the current understanding of the role of intestinal microbiota in the control of immune responses during aGVHD. Additionally, the possibility of using probiotic strains for potential treatment or prevention of aGVHD will be discussed.

The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease

PubMed Central

Chen, Yuanyuan; Zhao, Ye; Cheng, Qiao; Wu, Depei; Liu, Haiyan

2015-01-01

The mammalian intestinal microbiota is a complex ecosystem that plays an important role in host immune responses. Recent studies have demonstrated that alterations in intestinal microbiota composition are linked to multiple inflammatory diseases in humans, including acute graft-versus-host disease (aGVHD). aGVHD is one of the major obstacles in allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by tissue damage in the gastrointestinal (GI) tract, liver, lung, and skin. Here, we review the current understanding of the role of intestinal microbiota in the control of immune responses during aGVHD. Additionally, the possibility of using probiotic strains for potential treatment or prevention of aGVHD will be discussed. PMID:26090477

Control of Mucosal Candidiasis in the Zebrafish Swim Bladder Depends on Neutrophils That Block Filament Invasion and Drive Extracellular-Trap Production

PubMed Central

Gratacap, Remi L.; Scherer, Allison K.; Seman, Brittany G.

2017-01-01

ABSTRACT Candida albicans is a ubiquitous mucosal commensal that is normally prevented from causing acute or chronic invasive disease. Neutrophils contribute to protection in oral infection but exacerbate vulvovaginal candidiasis. To dissect the role of neutrophils during mucosal candidiasis, we took advantage of a new, transparent zebrafish swim bladder infection model. Intravital microscopic tracking of individual animals revealed that the blocking of neutrophil recruitment leads to rapid mortality in this model through faster disease progression. Conversely, artificial recruitment of neutrophils during early infection reduces disease pressure. Noninvasive longitudinal tracking showed that mortality is a consequence of C. albicans breaching the epithelial barrier and invading surrounding tissues. Accordingly, we found that a hyperfilamentous C. albicans strain breaches the epithelial barrier more frequently and causes mortality in immunocompetent zebrafish. A lack of neutrophils at the infection site is associated with less fungus-associated extracellular DNA and less damage to fungal filaments, suggesting that neutrophil extracellular traps help to protect the epithelial barrier from C. albicans breach. We propose a homeostatic model where C. albicans disease pressure is balanced by neutrophil-mediated damage of fungi, maintaining this organism as a commensal while minimizing the risk of damage to host tissue. The unequaled ability to dissect infection dynamics at a high spatiotemporal resolution makes this zebrafish model a unique tool for understanding mucosal host-pathogen interactions. PMID:28607100

The Immune Interplay between the Host and the Pathogen in Aspergillus fumigatus Lung Infection

PubMed Central

Sales-Campos, Helioswilton; Tonani, Ludmilla; Cardoso, Cristina Ribeiro Barros; Kress, Márcia Regina Von Zeska

2013-01-01

The interplay between Aspergillus fumigatus and the host immune response in lung infection has been subject of studies over the last years due to its importance in immunocompromised patients. The multifactorial virulence factors of A. fumigatus are related to the fungus biological characteristics, for example, structure, ability to grow and adapt to high temperatures and stress conditions, besides capability of evading the immune system and causing damage to the host. In this context, the fungus recognition by the host innate immunity occurs when the pathogen disrupts the natural and chemical barriers followed by the activation of acquired immunity. It seems clear that a Th1 response has a protective role, whereas Th2 reactions are often associated with higher fungal burden, and Th17 response is still controversial. Furthermore, a fine regulation of the effector immunity is required to avoid excessive tissue damage associated with fungal clearance, and this role could be attributed to regulatory T cells. Finally, in this work we reviewed the aspects involved in the complex interplay between the host immune response and the pathogen virulence factors, highlighting the immunological issues and the importance of its better understanding to the development of novel therapeutic approaches for invasive lung aspergillosis. PMID:23984400

Relative Contributions of Various Cellular Mechanisms to Loss of Algae during Cnidarian Bleaching.

PubMed

Bieri, Tamaki; Onishi, Masayuki; Xiang, Tingting; Grossman, Arthur R; Pringle, John R

2016-01-01

When exposed to stress such as high seawater temperature, corals and other cnidarians can bleach due to loss of symbiotic algae from the host tissue and/or loss of pigments from the algae. Although the environmental conditions that trigger bleaching are reasonably well known, its cellular and molecular mechanisms are not well understood. Previous studies have reported the occurrence of at least four different cellular mechanisms for the loss of symbiotic algae from the host tissue: in situ degradation of algae, exocytic release of algae from the host, detachment of host cells containing algae, and death of host cells containing algae. The relative contributions of these several mechanisms to bleaching remain unclear, and it is also not known whether these relative contributions change in animals subjected to different types and/or durations of stresses. In this study, we used a clonal population of the small sea anemone Aiptasia, exposed individuals to various precisely controlled stress conditions, and quantitatively assessed the several possible bleaching mechanisms in parallel. Under all stress conditions tested, except for acute cold shock at 4°C, expulsion of intact algae from the host cells appeared to be by far the predominant mechanism of bleaching. During acute cold shock, in situ degradation of algae and host-cell detachment also became quantitatively significant, and the algae released under these conditions appeared to be severely damaged.

Relative Contributions of Various Cellular Mechanisms to Loss of Algae during Cnidarian Bleaching

PubMed Central

Bieri, Tamaki; Onishi, Masayuki; Xiang, Tingting; Grossman, Arthur R.; Pringle, John R

2016-01-01

When exposed to stress such as high seawater temperature, corals and other cnidarians can bleach due to loss of symbiotic algae from the host tissue and/or loss of pigments from the algae. Although the environmental conditions that trigger bleaching are reasonably well known, its cellular and molecular mechanisms are not well understood. Previous studies have reported the occurrence of at least four different cellular mechanisms for the loss of symbiotic algae from the host tissue: in situ degradation of algae, exocytic release of algae from the host, detachment of host cells containing algae, and death of host cells containing algae. The relative contributions of these several mechanisms to bleaching remain unclear, and it is also not known whether these relative contributions change in animals subjected to different types and/or durations of stresses. In this study, we used a clonal population of the small sea anemone Aiptasia, exposed individuals to various precisely controlled stress conditions, and quantitatively assessed the several possible bleaching mechanisms in parallel. Under all stress conditions tested, except for acute cold shock at 4°C, expulsion of intact algae from the host cells appeared to be by far the predominant mechanism of bleaching. During acute cold shock, in situ degradation of algae and host-cell detachment also became quantitatively significant, and the algae released under these conditions appeared to be severely damaged. PMID:27119147

Too much of a good thing: How modulating LTB4 actions restore host defense in homeostasis or disease.

PubMed

Brandt, Stephanie L; Serezani, C Henrique

2017-10-01

The ability to regulate inflammatory pathways and host defense mechanisms is critical for maintaining homeostasis and responding to infections and tissue injury. While unbalanced inflammation is detrimental to the host; inadequate inflammation might not provide effective signals required to eliminate pathogens. On the other hand, aberrant inflammation could result in organ damage and impair host defense. The lipid mediator leukotriene B 4 (LTB 4 ) is a potent neutrophil chemoattractant and recently, its role as a dominant molecule that amplifies many arms of phagocyte antimicrobial effector function has been unveiled. However, excessive LTB 4 production contributes to disease severity in chronic inflammatory diseases such as diabetes and arthritis, which could potentially be involved in poor host defense in these groups of patients. In this review we discuss the cellular and molecular programs elicited during LTB 4 production and actions on innate immunity host defense mechanisms as well as potential therapeutic strategies to improve host defense. Copyright © 2017 Elsevier Ltd. All rights reserved.

Re-generation of tissue about an animal-based scaffold: AMS studies of the fate of the scaffold

NASA Astrophysics Data System (ADS)

Rickey, Frank A.; Elmore, David; Hillegonds, Darren; Badylak, Stephen; Record, Rae; Simmons-Byrd, Abby

2000-10-01

Small intestinal submucosa (SIS) is an unusual tissue, which shows great promise for the repair of damaged tissues in humans. When the SIS is used as a surgical implant, the porcine-derived material is not rejected by the host immune system, and in fact stimulates the constructive re-modeling of damaged tissue. In dogs, these SIS scaffolds have been used to grow new arteries, tendons, and urinary bladders. Moreover, the SIS scaffold tissue seems to disappear from the implant region after a few months. The fate of this SIS tissue is of considerable importance if it is to be used in human tissue repair. SIS is obtained from pigs. We have labeled the SIS in several pigs by intraveneous administration of 14C enriched proline from the age of three weeks until they reach market weight. The prepared SIS was then implanted in dogs as scaffolds for urinary bladder patches. During the remaining life of each dog, blood, urine and feces samples were collected on a regular schedule. AMS analyses of these specimens were performed to measure the elimination rate of the SIS. At different intervals, the dogs were sacrificed. Tissue samples were analyzed by AMS to determine the whole-body distribution of the labeled SIS.

Field Response of Dendroctonus frontalis (Coleoptera: Scolytinae) to Synthetic Semiochemicals in Chiapas, Mexico.

Treesearch

Benjamin Moreno; Jorge Macias; Brian Sullivan; Stephen Clarke

2008-01-01

Dendroctonus frontalis Zimmermann (Coleoptera: Scolytinae) is the most serious pestof pines (Pinus spp.) in Mexico. ConspeciÞcs are attracted to trees undergoing colonization by the  aggregation pheromone frontalin, which is synergized by odors of pine oleoresin released from beetle-damaged host tissue. Synthetic racemic frontalin combined with turpentine has been the...

Fungal Strategies to Evade the Host Immune Recognition.

PubMed

Hernández-Chávez, Marco J; Pérez-García, Luis A; Niño-Vega, Gustavo A; Mora-Montes, Héctor M

2017-09-23

The recognition of fungal cells by the host immune system is key during the establishment of a protective anti-fungal response. Even though the immune system has evolved a vast number of processes to control these organisms, they have developed strategies to fight back, avoiding the proper recognition by immune components and thus interfering with the host protective mechanisms. Therefore, the strategies to evade the immune system are as important as the virulence factors and attributes that damage the host tissues and cells. Here, we performed a thorough revision of the main fungal tactics to escape from the host immunosurveillance processes. These include the composition and organization of the cell wall, the fungal capsule, the formation of titan cells, biofilms, and asteroid bodies; the ability to undergo dimorphism; and the escape from nutritional immunity, extracellular traps, phagocytosis, and the action of humoral immune effectors.

The Pathogenesis of Staphylococcus aureus Eye Infections

PubMed Central

2018-01-01

Staphylococcus aureus is a major pathogen of the eye able to infect the tear duct, eyelid, conjunctiva, cornea, anterior and posterior chambers, and the vitreous chamber. Of these infections, those involving the cornea (keratitis) or the inner chambers of the eye (endophthalmitis) are the most threatening because of their potential to cause a loss in visual acuity or even blindness. Each of these ocular sites is protected by the constitutive expression of a variety of antimicrobial factors and these defenses are augmented by a protective host response to the organism. Such infections often involve a predisposing factor that weakens the defenses, such as the use of contact lenses prior to the development of bacterial keratitis or, for endophthalmitis, the trauma caused by cataract surgery or intravitreal injection. The structural carbohydrates of the bacterial surface induce an inflammatory response able to reduce the bacterial load, but contribute to the tissue damage. A variety of bacterial secreted proteins including alpha-toxin, beta-toxin, gamma-toxin, Panton-Valentine leukocidin and other two-component leukocidins mediate tissue damage and contribute to the induction of the inflammatory response. Quantitative animal models of keratitis and endophthalmitis have provided insights into the S. aureus virulence and host factors active in limiting such infections. PMID:29320451

Host-Derived CD70 Suppresses Murine Graft-versus-Host Disease by Limiting Donor T Cell Expansion and Effector Function.

PubMed

Leigh, Nicholas D; O'Neill, Rachel E; Du, Wei; Chen, Chuan; Qiu, Jingxin; Ashwell, Jonathan D; McCarthy, Philip L; Chen, George L; Cao, Xuefang

2017-07-01

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) may develop when donor-derived T cells recognize and damage genetically distinct normal host tissues. In addition to TCR signaling, costimulatory pathways are involved in T cell activation. CD27 is a TNFR family member expressed on T cells, and its ligand, CD70, is expressed on APCs. The CD27/CD70 costimulatory pathway was shown to be critical for T cell function and survival in viral infection models. However, the role of this pathway in allo-HCT is previously unknown. In this study, we have examined its contribution in GVHD pathogenesis. Surprisingly, Ab blockade of CD70 after allo-HCT significantly increases GVHD. Interestingly, whereas donor T cell- or bone marrow-derived CD70 plays no role in GVHD, host-derived CD70 inhibits GVHD as CD70 -/- hosts show significantly increased GVHD. This is evidenced by reduced survival, more severe weight loss, and increased histopathologic damage compared with wild-type hosts. In addition, CD70 -/- hosts have higher levels of proinflammatory cytokines TNF-α, IFN-γ, IL-2, and IL-17. Moreover, accumulation of donor CD4 + and CD8 + effector T cells is increased in CD70 -/- versus wild-type hosts. Mechanistic analyses suggest that CD70 expressed by host hematopoietic cells is involved in the control of alloreactive T cell apoptosis and expansion. Together, our findings demonstrate that host CD70 serves as a unique negative regulator of allogeneic T cell response by contributing to donor T cell apoptosis and inhibiting expansion of donor effector T cells. Copyright © 2017 by The American Association of Immunologists, Inc.

The oxygen reduction pathway and heat shock stress response are both required for Entamoeba histolytica pathogenicity.

PubMed

Olivos-García, Alfonso; Saavedra, Emma; Nequiz, Mario; Santos, Fabiola; Luis-García, Erika Rubí; Gudiño, Marco; Pérez-Tamayo, Ruy

2016-05-01

Several species belonging to the genus Entamoeba can colonize the mouth or the human gut; however, only Entamoeba histolytica is pathogenic to the host, causing the disease amoebiasis. This illness is responsible for one hundred thousand human deaths per year worldwide, affecting mainly underdeveloped countries. Throughout its entire life cycle and invasion of human tissues, the parasite is constantly subjected to stress conditions. Under in vitro culture, this microaerophilic parasite can tolerate up to 5 % oxygen concentrations; however, during tissue invasion the parasite has to cope with the higher oxygen content found in well-perfused tissues (4-14 %) and with reactive oxygen and nitrogen species derived from both host and parasite. In this work, the role of the amoebic oxygen reduction pathway (ORP) and heat shock response (HSP) are analyzed in relation to E. histolytica pathogenicity. The data suggest that in contrast with non-pathogenic E. dispar, the higher level of ORP and HSPs displayed by E. histolytica enables its survival in tissues by diminishing and detoxifying intracellular oxidants and repairing damaged proteins to allow metabolic fluxes, replication and immune evasion.

Do native parasitic plants cause more damage to exotic invasive hosts than native non-invasive hosts? An implication for biocontrol.

PubMed

Li, Junmin; Jin, Zexin; Song, Wenjing

2012-01-01

Field studies have shown that native, parasitic plants grow vigorously on invasive plants and can cause more damage to invasive plants than native plants. However, no empirical test has been conducted and the mechanism is still unknown. We conducted a completely randomized greenhouse experiment using 3 congeneric pairs of exotic, invasive and native, non-invasive herbaceous plant species to quantify the damage caused by parasitic plants to hosts and its correlation with the hosts' growth rate and resource use efficiency. The biomass of the parasitic plants on exotic, invasive hosts was significantly higher than on congeneric native, non-invasive hosts. Parasites caused more damage to exotic, invasive hosts than to congeneric, native, non-invasive hosts. The damage caused by parasites to hosts was significantly positively correlated with the biomass of parasitic plants. The damage of parasites to hosts was significantly positively correlated with the relative growth rate and the resource use efficiency of its host plants. It may be the mechanism by which parasitic plants grow more vigorously on invasive hosts and cause more damage to exotic, invasive hosts than to native, non-invasive hosts. These results suggest a potential biological control effect of native, parasitic plants on invasive species by reducing the dominance of invasive species in the invaded community.

Cavisoma magnum (Cavisomidae), a unique Pacific acanthocephalan redescribed from an unusual host, Mugil cephalus (Mugilidae), in the Arabian Gulf, with notes on histopathology and metal analysis.

PubMed

Amin, Omar M; Heckmann, Richard A; Bannai, Majid A

2018-01-01

Cavisoma magnum (Southwell, 1927) Van Cleave, 1931 was originally described from a sea bass, Serranus sp. and spotted surgeonfish, Ctenochaetus strigosus (Perciformes) off Sri Lanka before its more recent redescription from milkfish in the Philippines in 1995. These reports were based on only light infections of their host fishes. Of the few flathead grey mullets, Mugil cephalus (Mugilidae), that we examined in the Arabian Gulf, one fish was infected with 1,450 worms. One milkfish, Chanos chanos (Chanidae), from the same location in the Arabian Gulf, was also heavily infected with specimens of C. magnum. The descriptions of this unique large worm are revised and for the first time, we provide SEM images, new systematic observations, metal analysis of hooks showing extremely high levels of sulfur, and histopathology in the mullet intestinal tissue. Adjustments and corrections of previous descriptive accounts are made. The histopathology studies show extensive damage to the host intestinal tissue including epithelial necrosis, hemorrhaging and worm encapsulation. There is an extensive amount of host connective tissue surrounding the worm. Results of x-ray analysis displayed high levels of sulfur in proboscis hooks, especially at the tips and edges of these attachment structures. © O.M. Amin et al., published by EDP Sciences, 2018.

Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease

PubMed Central

Iyer, Shankar Subramanian; Cheng, Genhong

2012-01-01

Interleukin 10 (IL-10) is a cytokine with potent anti-inflammatory properties that plays a central role in limiting host immune response to pathogens, thereby preventing damage to the host and maintaining normal tissue homeostasis. Dysregulation of IL-10 is associated with enhanced immunopathology in response to infection as well as increased risk for development of many autoimmune diseases. Thus a fundamental understanding of IL-10 gene expression is critical for our comprehension of disease progression and resolution of host inflammatory response. In this review, we discuss modes of regulation of IL-10 gene expression in immune effector cell types, including signal transduction, epigenetics, promoter architecture, and post-transcriptional regulation, and how aberrant regulation contributes to immunopathology and disease progression. PMID:22428854

Macrobiota — helminths as active participants and partners of the microbiota in host intestinal homeostasis

PubMed Central

Gause, William C; Maizels, Rick M

2016-01-01

Important insights have recently been gained in our understanding of the intricate relationship in the intestinal milieu between the vertebrate host mucosal immune response, commensal bacteria, and helminths. Helminths are metazoan worms (macrobiota) and trigger immune responses that include potent regulatory components capable of controlling harmful inflammation, protecting barrier function and mitigating tissue damage. They can secrete a variety of products that directly affect immune regulatory function but they also have the capacity to influence the composition of microbiota, which can also then impact immune function. Conversely, changes in microbiota can affect susceptibility to helminth infection, indicating that crosstalk between these two disparate groups of endobiota can play an essential role in host intestinal immune function and homeostasis. PMID:27116368

Hypothesis: leukocyte endogenous mediator/endogenous pyrogen/lymphocyte-activating factor modulates the development of nonspecific and specific immunity and affects nutritional status.

PubMed

Powanda, M C; Beisel, W R

1982-04-01

We postulate that leukocyte endogenous mediator/endogenous pyrogen/lymphocyte-activating factor (LEM/EP/LAF) integrates the host's nonspecific and specific immune responses to infection by virtue of the panoply of physiological and metabolic activities it is capable of eliciting. The alterations in systemic metabolism modulated by LEM/EP/LAF, although apparently of value to the host in the defense against infection and the repair of tissue damage, result in negative nutrient balances. Severe infections, alone or in conjunction with injury, may result in malnutrition unless the patient is adequately nourished. Preexisting nutritional deficits can compromise host resistance to infection, in part by preventing production of LEM/EP/LAF. Additional studies of the sequelae of LEM/EP/LAF action and effects of nutrition on host resistance to infection appear warranted.

Complement factor H in host defense and immune evasion.

PubMed

Parente, Raffaella; Clark, Simon J; Inforzato, Antonio; Day, Anthony J

2017-05-01

Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.

High-throughput transcriptome analysis of ISAV-infected Atlantic salmon Salmo salar unravels divergent immune responses associated to head-kidney, liver and gills tissues.

PubMed

Valenzuela-Miranda, Diego; Boltaña, Sebastian; Cabrejos, Maria E; Yáñez, José M; Gallardo-Escárate, Cristian

2015-08-01

Infectious salmon anaemia virus (ISAV) is an orthomyxovirus causing high mortality in farmed Atlantic salmon (Salmo salar). The collective data from the Atlantic salmon-ISAV interactions, performed "in vitro" using various salmon cell lines and "in vivo" fish infected with different ISAV isolates, have shown a strong regulation of immune related transcripts during the infection. Despite this strong defence response, the majority of fish succumb to infections with ISAV. The deficient protection of the host against ISAV is in part due to virulence factors of the virus, which allow evade the host-defence machinery. As such, the viral replication is uninhibited and viral loads quickly spread to several tissues causing massive cellular damage before the host can develop an effective cell-mediated and humoral outcome. To interrogate the correlation of the viral replication with the host defence response, we used fish that have been infected by cohabitation with ISAV-injected salmons. Whole gene expression patterns were measured with RNA-seq using RNA extracted from Head-kidney, Liver and Gills. The results show divergent mRNA abundance of functional modules related to interferon pathway, adaptive/innate immune response and cellular proliferation/differentiation. Furthermore, gene regulation in distinct tissues during the infection process was independently controlled within the each tissue and the observed mRNA expression suggests high modulation of the ISAV-segment transcription. Importantly this is the first time that strong correlations between functional modules containing significant immune process with protein-protein affinities and viral-segment transcription have been made between different tissues of ISAV-infected fish. Copyright © 2015 Elsevier Ltd. All rights reserved.

Do Native Parasitic Plants Cause More Damage to Exotic Invasive Hosts Than Native Non-Invasive Hosts? An Implication for Biocontrol

PubMed Central

Li, Junmin; Jin, Zexin; Song, Wenjing

2012-01-01

Field studies have shown that native, parasitic plants grow vigorously on invasive plants and can cause more damage to invasive plants than native plants. However, no empirical test has been conducted and the mechanism is still unknown. We conducted a completely randomized greenhouse experiment using 3 congeneric pairs of exotic, invasive and native, non-invasive herbaceous plant species to quantify the damage caused by parasitic plants to hosts and its correlation with the hosts' growth rate and resource use efficiency. The biomass of the parasitic plants on exotic, invasive hosts was significantly higher than on congeneric native, non-invasive hosts. Parasites caused more damage to exotic, invasive hosts than to congeneric, native, non-invasive hosts. The damage caused by parasites to hosts was significantly positively correlated with the biomass of parasitic plants. The damage of parasites to hosts was significantly positively correlated with the relative growth rate and the resource use efficiency of its host plants. It may be the mechanism by which parasitic plants grow more vigorously on invasive hosts and cause more damage to exotic, invasive hosts than to native, non-invasive hosts. These results suggest a potential biological control effect of native, parasitic plants on invasive species by reducing the dominance of invasive species in the invaded community. PMID:22493703

Granulocytes in Helminth Infection - Who is Calling the Shots?

PubMed Central

Makepeace, BL; Martin, C; Turner, JD; Specht, S

2012-01-01

Helminths are parasitic organisms that can be broadly described as “worms” due to their elongated body plan, but which otherwise differ in shape, development, migratory routes and the predilection site of the adults and larvae. They are divided into three major groups: trematodes (flukes), which are leaf-shaped, hermaphroditic (except for blood flukes) flatworms with oral and ventral suckers; cestodes (tapeworms), which are segmented, hermaphroditic flatworms that inhabit the intestinal lumen; and nematodes (roundworms), which are dioecious, cylindrical parasites that inhabit intestinal and peripheral tissue sites. Helminths exhibit a sublime co-evolution with the host´s immune system that has enabled them to successfully colonize almost all multicellular species present in every geographical environment, including over two billion humans. In the face of this challenge, the host immune system has evolved to strike a delicate balance between attempts to neutralize the infectious assault versus limitation of damage to host tissues. Among the most important cell types during helminthic invasion are granulocytes: eosinophils, neutrophils and basophils. Depending on the specific context, these leukocytes may have pivotal roles in host protection, immunopathology, or facilitation of helminth establishment. This review provides an overview of the function of granulocytes in helminthic infections. PMID:22360486

Ultraviolet Radiation in Wound Care: Sterilization and Stimulation

PubMed Central

Gupta, Asheesh; Avci, Pinar; Dai, Tianhong; Huang, Ying-Ying; Hamblin, Michael R.

2013-01-01

Significance Wound care is an important area of medicine considering the increasing age of the population who may have diverse comorbidities. Light-based technology comprises a varied set of modalities of increasing relevance to wound care. While low-level laser (or light) therapy and photodynamic therapy both have wide applications in wound care, this review will concentrate on the use of ultraviolet (UV) radiation. Recent Advances UVC (200–280 nm) is highly antimicrobial and can be directly applied to acute wound infections to kill pathogens without unacceptable damage to host tissue. UVC is already widely applied for sterilization of inanimate objects. UVB (280–315 nm) has been directly applied to the wounded tissue to stimulate wound healing, and has been widely used as extracorporeal UV radiation of blood to stimulate the immune system. UVA (315–400 nm) has distinct effects on cell signaling, but has not yet been widely applied to wound care. Critical Issues Penetration of UV light into tissue is limited and optical technology may be employed to extend this limit. UVC and UVB can damage DNA in host cells and this risk must be balanced against beneficial effects. Chronic exposure to UV can be carcinogenic and this must be considered in planning treatments. Future Directions New high-technology UV sources, such as light-emitting diodes, lasers, and microwave-generated UV plasma are becoming available for biomedical applications. Further study of cellular signaling that occurs after UV exposure of tissue will allow the benefits in wound healing to be better defined. PMID:24527357

Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

PubMed Central

Kong, Eric F.; Tsui, Christina; Nguyen, M. Hong; Clancy, Cornelius J.; Fidel, Paul L.; Noverr, Mairi

2016-01-01

Historically, the nature and extent of host damage by a microbe were considered highly dependent on virulence attributes of the microbe. However, it has become clear that disease is a complex outcome which can arise because of pathogen-mediated damage, host-mediated damage, or both, with active participation from the host microbiota. This awareness led to the formulation of the damage response framework (DRF), a revolutionary concept that defined microbial virulence as a function of host immunity. The DRF outlines six classifications of host damage outcomes based on the microbe and the strength of the immune response. In this review, we revisit this concept from the perspective of Candida albicans, a microbial pathogen uniquely adapted to its human host. This fungus commonly colonizes various anatomical sites without causing notable damage. However, depending on environmental conditions, a diverse array of diseases may occur, ranging from mucosal to invasive systemic infections resulting in microbe-mediated and/or host-mediated damage. Remarkably, C. albicans infections can fit into all six DRF classifications, depending on the anatomical site and associated host immune response. Here, we highlight some of these diverse and site-specific diseases and how they fit the DRF classifications, and we describe the animal models available to uncover pathogenic mechanisms and related host immune responses. PMID:27430274

Histological Evaluation of a Chronically-implanted Electrocorticographic Electrode Grid in a Non-human Primate

PubMed Central

Degenhart, Alan D.; Eles, James; Dum, Richard; Mischel, Jessica L.; Smalianchuk, Ivan; Endler, Bridget; Ashmore, Robin C.; Tyler-Kabara, Elizabeth C.; Hatsopoulos, Nicholas G.; Wang, Wei; Batista, Aaron P.; Cui, X. Tracy

2016-01-01

Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically-implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. We implanted a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 days. Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation. These results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically-viable brain-machine interface systems. PMID:27351722

Histological evaluation of a chronically-implanted electrocorticographic electrode grid in a non-human primate

NASA Astrophysics Data System (ADS)

Degenhart, Alan D.; Eles, James; Dum, Richard; Mischel, Jessica L.; Smalianchuk, Ivan; Endler, Bridget; Ashmore, Robin C.; Tyler-Kabara, Elizabeth C.; Hatsopoulos, Nicholas G.; Wang, Wei; Batista, Aaron P.; Cui, X. Tracy

2016-08-01

Objective. Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. Approach. We implanted and recorded from a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 d. Main results. Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation. Significance. These results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically viable BMI systems.

Antimicrobial Histones and DNA Traps in Invertebrate Immunity

PubMed Central

Poirier, Aurore C.; Schmitt, Paulina; Rosa, Rafael D.; Vanhove, Audrey S.; Kieffer-Jaquinod, Sylvie; Rubio, Tristan P.; Charrière, Guillaume M.; Destoumieux-Garzón, Delphine

2014-01-01

Although antimicrobial histones have been isolated from multiple metazoan species, their role in host defense has long remained unanswered. We found here that the hemocytes of the oyster Crassostrea gigas release antimicrobial H1-like and H5-like histones in response to tissue damage and infection. These antimicrobial histones were shown to be associated with extracellular DNA networks released by hemocytes, the circulating immune cells of invertebrates, in response to immune challenge. The hemocyte-released DNA was found to surround and entangle vibrios. This defense mechanism is reminiscent of the neutrophil extracellular traps (ETs) recently described in vertebrates. Importantly, oyster ETs were evidenced in vivo in hemocyte-infiltrated interstitial tissues surrounding wounds, whereas they were absent from tissues of unchallenged oysters. Consistently, antimicrobial histones were found to accumulate in oyster tissues following injury or infection with vibrios. Finally, oyster ET formation was highly dependent on the production of reactive oxygen species by hemocytes. This shows that ET formation relies on common cellular and molecular mechanisms from vertebrates to invertebrates. Altogether, our data reveal that ET formation is a defense mechanism triggered by infection and tissue damage, which is shared by relatively distant species suggesting either evolutionary conservation or convergent evolution within Bilateria. PMID:25037219

Novel Strategies to Enhance Vaccine Immunity against Coccidioidomycosis

DTIC Science & Technology

2013-12-19

Mexico and Central and South America [1]. Coccidioides is a dimorphic ascomycetous fungus with distinct saprobic and parasitic phases and is classified in...lethal spore inoculum. However, sterile immunity was not achieved and pulmonary tissue damage associated with a persistent host inflammatory response...observation will translate to humans. A recent vector-based vaccine against tuberculosis intended to protect by eliciting strong CMI failed in humans despite

A Communications Link for an Implantable Electrode Array.

DTIC Science & Technology

1984-12-01

where the measuring technique does not effect the natural response, the researcher might begin to understand the process which provides pattern...the system does not damage the tissue or significantly alter natural functioning of the host I, Thereffore, techniques of encapsulation and trauma...following paragraphs gives a more thorough description of the problem. To provide a long term natural environment for the collection of

Immunopathology of highly virulent pathogens: insights from Ebola virus.

PubMed

Zampieri, Carisa A; Sullivan, Nancy J; Nabel, Gary J

2007-11-01

Ebola virus is a highly virulent pathogen capable of inducing a frequently lethal hemorrhagic fever syndrome. Accumulating evidence indicates that the virus actively subverts both innate and adaptive immune responses and triggers harmful inflammatory responses as it inflicts direct tissue damage. The host immune system is ultimately overwhelmed by a combination of inflammatory factors and virus-induced cell damage, particularly in the liver and vasculature, often leading to death from septic shock. We summarize the mechanisms of immune dysregulation and virus-mediated cell damage in Ebola virus-infected patients. Future approaches to prevention and treatment of infection will be guided by answers to unresolved questions about interspecies transmission, molecular mechanisms of pathogenesis, and protective adaptive and innate immune responses to Ebola virus.

Dynamics of Lung Defense in Pneumonia: Resistance, Resilience, and Remodeling

PubMed Central

Quinton, Lee J.; Mizgerd, Joseph P.

2015-01-01

Pneumonia is initiated by microbes in the lung, but physiological processes integrating responses across diverse cell types and organ systems dictate the outcome of respiratory infection. Resistance, or actions of the host to eradicate living microbes, in the lungs involves a combination of innate and adaptive immune responses triggered by air-space infection. Resilience, or the ability of the host tissues to withstand the physiologically damaging effects of microbial and immune activities, is equally complex, precisely regulated, and determinative. Both immune resistance and tissue resilience are dynamic and change throughout the lifetime, but we are only beginning to understand such remodeling and how it contributes to the incidence of severe pneumonias, which diminishes as childhood progresses and then increases again among the elderly. Here, we review the concepts of resistance, resilience, and remodeling as they apply to pneumonia, highlighting recent advances and current significant knowledge gaps. PMID:25148693

Basics of PD-1 in self-tolerance, infection, and cancer immunity.

PubMed

Chikuma, Shunsuke

2016-06-01

Successful cancer treatment requires understanding host immune response against tumor cells. PD-1 belongs to the CD28 superfamily of receptors that work as "checkpoints" of immune activation. PD-1 maintains immune self-tolerance to prevent autoimmunity and controls T-cell reaction during infection to prevent excessive tissue damage. Tumor cells that arise from normal tissue acquire mutations that can be targeted by lymphocytes. Accumulating lines of evidence suggest that tumor cells evade host immune attack by expressing physiological PD-1 ligands and stimulating PD-1 on the lymphocytes. Based on this idea, researchers have successfully demonstrated that systemic administration of monoclonal antibodies that inhibit the binding of PD-1 to the ligands reactivated T cells and augmented the anti-cancer immune response. In this review, I summarize the basics of T-cell biology and its regulation by PD-1 and discuss the current understanding and questions about this multifaceted molecule.

Cytosolic Double-Stranded DNA as a Damage-Associated Molecular Pattern Induces the Inflammatory Response in Rat Pancreatic Stellate Cells: A Plausible Mechanism for Tissue Injury-Associated Pancreatitis

PubMed Central

Nakamura, Taichi; Ito, Tetsuhide; Igarashi, Hisato; Uchida, Masahiko; Hijioka, Masayuki; Oono, Takamasa; Fujimori, Nao; Niina, Yusuke; Suzuki, Koichi; Jensen, Robert T.; Takayanagi, Ryoichi

2012-01-01

Pancreatitis is an inflammatory disease of unknown causes. There are many triggers causing pancreatitis, such as alcohol, common bile duct stone, virus and congenital or acquired stenosis of main pancreatic duct, which often involve tissue injuries. Pancreatitis often occurs in sterile condition, where the dead/dying pancreatic parenchymal cells and the necrotic tissues derived from self-digested-pancreas were observed. However, the causal relationship between tissue injury and pancreatitis and how tissue injury could induce the inflammation of the pancreas were not elucidated fully until now. This study demonstrates that cytosolic double-stranded DNA increases the expression of several inflammatory genes (cytokines, chemokines, type I interferon, and major histocompatibility complex) in rat pancreatic stellate cells. Furthermore, these increase accompanied the multiple signal molecules genes, such as interferon regulatory factors, nuclear factor-kappa B, low-molecular-weight protein 2, and transporter associated with antigen processing 1. We suggest that this phenomenon is a plausible mechanism that might explain how cell damage of the pancreas or tissue injury triggers acute, chronic, and autoimmune pancreatitis; it is potentially relevant to host immune responses induced during alcohol consumption or other causes. PMID:22550608

Consequences of immunopathology for pathogen virulence evolution and public health: malaria as a case study

PubMed Central

Long, Gráinne H; Graham, Andrea L

2011-01-01

Evolutionary theories explaining virulence—the fitness damage incurred by infected hosts—often focus on parasite strategies for within-host exploitation. However, much virulence can be caused by the host's own immune response: for example, pro-inflammatory cytokines, although essential for killing malaria parasites, also damage host tissue. Here we argue that immune-mediated virulence, or ‘immunopathology,’ may affect malaria virulence evolution and should be considered in the design of medical interventions. Our argument is based on the ability of immunopathology to disrupt positive virulence-transmission relationships assumed under the trade-off theory of virulence evolution. During rodent malaria infections, experimental reduction of inflammation using reagents approved for field use decreases virulence but increases parasite transmission potential. Importantly, rodent malaria parasites exhibit genetic diversity in the propensity to induce inflammation and invest in transmission-stage parasites in the presence of pro-inflammatory cytokines. If immunopathology positively correlates with malaria parasite density, theory suggests it could select for relatively low malaria virulence. Medical interventions which decrease immunopathology may therefore inadvertently select for increased malaria virulence. The fitness consequences to parasites of variations in immunopathology must be better understood in order to predict trajectories of parasite virulence evolution in heterogeneous host populations and in response to medical interventions. PMID:25567973

Helminth Infections: Recognition and Modulation of the Immune Response by Innate Immune Cells

PubMed Central

Motran, Claudia Cristina; Silvane, Leonardo; Chiapello, Laura Silvina; Theumer, Martin Gustavo; Ambrosio, Laura Fernanda; Volpini, Ximena; Celias, Daiana Pamela; Cervi, Laura

2018-01-01

The survival of helminths in the host over long periods of time is the result of a process of adaptation or dynamic co-evolution between the host and the parasite. However, infection with helminth parasites causes damage to the host tissues producing the release of danger signals that induce the recruitment of various cells, including innate immune cells such as macrophages (Mo), dendritic cells (DCs), eosinophils, basophils, and mast cells. In this scenario, these cells are able to secrete soluble factors, which orchestrate immune effector mechanisms that depend on the different niches these parasites inhabit. Here, we focus on recent advances in the knowledge of excretory-secretory products (ESP), resulting from helminth recognition by DCs and Mo. Phagocytes and other cells types such as innate lymphocyte T cells 2 (ILC2), when activated by ESP, participate in an intricate cytokine network to generate innate and adaptive Th2 responses. In this review, we also discuss the mechanisms of innate immune cell-induced parasite killing and the tissue repair necessary to assure helminth survival over long periods of time. PMID:29670630

Description and host relationships of Polymorphus spindlatus n. sp. (Acanthocephala: Polymorphidae) from the heron Nycticorax nycticorax in Peru.

PubMed

Amin, O M; Heckmann, R A

1991-04-01

Polymorphus spindlatus n. sp. is described from the black-crowned night heron, Nycticorax nycticorax, in Lake Titicaca, Peru. It is distinguished from all 27 known species of the subgenus Polymorphus by its spindle-shaped proboscis and its trunk shape, the anterior 2/3 of which is ovoid, tapering into a tubular posterior end. It resembles Polymorphus brevis (=Arhythmorhynchus brevis), which is, however, longer and considerably more slender, and has smaller and more numerous proboscis hooks per row and smaller eggs. It is separated also from Polymorphus swartzi, Polymorphus striatus, Polymorphus contortus, and Polymorphus cincli by its proboscis armature (usually 18 longitudinal rows of 11-13 hooks each), among other characters. Histopathological sections of host tissue show well defined localized damage including hemorrhaging with subsequent phagocyte cell migration (granular tissue). The lumen of the host intestine is obstructed and villi show compression. The proboscis of P. spindlatus extends through the intestinal mucosa and submucosa, displacing the smooth muscle layers of the muscularis externa. Fibrosis also was observed.

Apoplastic Sugar Extraction and Quantification from Wheat Leaves Infected with Biotrophic Fungi.

PubMed

Roman-Reyna, Veronica; Rathjen, John P

2017-01-01

Biotrophic fungi such as rusts modify the nutrient status of their hosts by extracting sugars. Hemibiotrophic and biotrophic fungi obtain nutrients from the cytoplasm of host cells and/or the apoplastic spaces. Uptake of nutrients from the cytoplasm is via intracellular hyphae or more complex structures such as haustoria. Apoplastic nutrients are taken up by intercellular hyphae. Overall the infection creates a sink causing remobilization of nutrients from local and distal tissues. The main mobile sugar in plants is sucrose which is absorbed via plant or fungal transporters once unloaded into the cytoplasm or the apoplast. Infection by fungal pathogens alters the apoplastic sugar contents and stimulates the influx of nutrients towards the site of infection as the host tissue transitions to sink. Quantification of solutes in the apoplast can help to understand the allocation of nutrients during infection. However, separation of apoplastic fluids from whole tissue is not straightforward and leakage from damaged cells can alter the results of the extraction. Here, we describe how variation in cytoplasmic contamination and infiltrated leaf volumes must be controlled when extracting apoplastic fluids from healthy and rust-infected wheat leaves. We show the importance of correcting the data for these parameters to measure sugar concentrations accurately.

Possibility of Aggravation of Tissue Sclerosis after Injection of Multipotent Mesenchymal Stromal Cells Near the Forming Cicatrix in the Experiment.

PubMed

Maiborodin, I V; Morozov, V V; Anikeev, A A; Figurenko, N F; Maslov, R V; Matveeva, V A; Chastikina, G A; Maiborodina, V I

2017-08-01

The peculiarities of tissue sclerosis after injection of autologous bone marrow multipotent mesenchymal stromal cells transfected with GFP gene and stained with Vybrant CM-Dil cell membrane dye were studied by light microscopy with luminescence. The surgical intervention consisting in ligation of the great vein was followed by tissue sclerotic transformation caused by direct damage and chronic inflammation caused by the presence of slowly resorbed ligature. Injection of stromal cells after this intervention led to formation of more extensive scar. This can attest to the possibility of stromal cells differentiation into connective tissue cells, fibroblasts, and stimulation of proliferation and collagen synthesis by host fibroblasts. A decrease in the volume of dense fibrous connective tissue due to scar reorganization at latter terms cannot not excluded.

Macrobiota - helminths as active participants and partners of the microbiota in host intestinal homeostasis.

PubMed

Gause, William C; Maizels, Rick M

2016-08-01

Important insights have recently been gained in our understanding of the intricate relationship in the intestinal milieu between the vertebrate host mucosal immune response, commensal bacteria, and helminths. Helminths are metazoan worms (macrobiota) and trigger immune responses that include potent regulatory components capable of controlling harmful inflammation, protecting barrier function and mitigating tissue damage. They can secrete a variety of products that directly affect immune regulatory function but they also have the capacity to influence the composition of microbiota, which can also then impact immune function. Conversely, changes in microbiota can affect susceptibility to helminth infection, indicating that crosstalk between these two disparate groups of endobiota can play an essential role in host intestinal immune function and homeostasis. Copyright © 2016. Published by Elsevier Ltd.

Neurotoxocarosis: marked preference of Toxocara canis for the cerebrum and T. cati for the cerebellum in the paratenic model host mouse.

PubMed

Janecek, Elisabeth; Beineke, Andreas; Schnieder, Thomas; Strube, Christina

2014-04-22

Infective larvae of the worldwide occurring zoonotic roundworm T. canis exhibit a marked affinity to the nervous tissues of paratenic hosts. In humans, most cases of neurotoxocarosis are considered to be caused by larvae of T. canis as T. cati larvae have rarely been found in the CNS in previous studies. However, direct comparison of studies is difficult as larval migration depends on a variety of factors including mouse strains and inoculation doses. Therefore, the present study aims to provide a direct comparison of both roundworm species in mice as a model for paratenic hosts with specific focus on the CNS during the acute and chronic phase of disease to provide a basis for further studies dealing with neurotoxocarosis. C57Bl/6J mice were infected with 2000 embryonated T. canis and T. cati eggs, respectively as well as Balb/c mice infected with T. cati eggs only. On 8 time points post infection, organs were removed and microscopically examined for respective larvae. Special focus was put on the CNS, including analysis of larval distribution in the cerebrum and cerebellum, right and left hemisphere as well as eyes and spinal cord. Additionally, brains of all infection groups as well as uninfected controls were examined histopathologically to characterize neurostructural damage. Significant differences in larval distribution were observed between and within the infection groups during the course of infection. As expected, significantly higher recovery rates of T. canis than T. cati larvae were determined in the brain. Surprisingly, significantly more T. canis larvae could be found in cerebra of infected mice whereas T. cati larvae were mainly located in the cerebellum. Structural damage in brain tissue could be observed in all infection groups, being more severe in brains of T. canis infected mice. The data obtained provides an extensive characterization of migrational routes of T. canis and T. cati in the paratenic host mouse in direct comparison. Even though to a lesser extent, structural damage in the brain was also caused by T. cati larvae and therefore, the potential as pathogenic agents should not be underestimated.

Neurotoxocarosis: marked preference of Toxocara canis for the cerebrum and T. cati for the cerebellum in the paratenic model host mouse

PubMed Central

2014-01-01

Background Infective larvae of the worldwide occurring zoonotic roundworm T. canis exhibit a marked affinity to the nervous tissues of paratenic hosts. In humans, most cases of neurotoxocarosis are considered to be caused by larvae of T. canis as T. cati larvae have rarely been found in the CNS in previous studies. However, direct comparison of studies is difficult as larval migration depends on a variety of factors including mouse strains and inoculation doses. Therefore, the present study aims to provide a direct comparison of both roundworm species in mice as a model for paratenic hosts with specific focus on the CNS during the acute and chronic phase of disease to provide a basis for further studies dealing with neurotoxocarosis. Methods C57Bl/6J mice were infected with 2000 embryonated T. canis and T. cati eggs, respectively as well as Balb/c mice infected with T. cati eggs only. On 8 time points post infection, organs were removed and microscopically examined for respective larvae. Special focus was put on the CNS, including analysis of larval distribution in the cerebrum and cerebellum, right and left hemisphere as well as eyes and spinal cord. Additionally, brains of all infection groups as well as uninfected controls were examined histopathologically to characterize neurostructural damage. Results Significant differences in larval distribution were observed between and within the infection groups during the course of infection. As expected, significantly higher recovery rates of T. canis than T. cati larvae were determined in the brain. Surprisingly, significantly more T. canis larvae could be found in cerebra of infected mice whereas T. cati larvae were mainly located in the cerebellum. Structural damage in brain tissue could be observed in all infection groups, being more severe in brains of T. canis infected mice. Conclusions The data obtained provides an extensive characterization of migrational routes of T. canis and T. cati in the paratenic host mouse in direct comparison. Even though to a lesser extent, structural damage in the brain was also caused by T. cati larvae and therefore, the potential as pathogenic agents should not be underestimated. PMID:24754900

Immune Modulation by Human Secreted RNases at the Extracellular Space.

PubMed

Lu, Lu; Li, Jiarui; Moussaoui, Mohammed; Boix, Ester

2018-01-01

The ribonuclease A superfamily is a vertebrate-specific family of proteins that encompasses eight functional members in humans. The proteins are secreted by diverse innate immune cells, from blood cells to epithelial cells and their levels in our body fluids correlate with infection and inflammation processes. Recent studies ascribe a prominent role to secretory RNases in the extracellular space. Extracellular RNases endowed with immuno-modulatory and antimicrobial properties can participate in a wide variety of host defense tasks, from performing cellular housekeeping to maintaining body fluid sterility. Their expression and secretion are induced in response to a variety of injury stimuli. The secreted proteins can target damaged cells and facilitate their removal from the focus of infection or inflammation. Following tissue damage, RNases can participate in clearing RNA from cellular debris or work as signaling molecules to regulate the host response and contribute to tissue remodeling and repair. We provide here an overall perspective on the current knowledge of human RNases' biological properties and their role in health and disease. The review also includes a brief description of other vertebrate family members and unrelated extracellular RNases that share common mechanisms of action. A better knowledge of RNase mechanism of actions and an understanding of their physiological roles should facilitate the development of novel therapeutics.

Contribution of neutrophils to acute lung injury.

PubMed

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

Does the Host Contribute to Modulation of Mycotoxin Production by Fruit Pathogens?

PubMed Central

Kumar, Dilip; Barad, Shiri; Sionov, Edward; Prusky, Dov B.

2017-01-01

Storage of freshly harvested fruit is a key factor in modulating their supply for several months after harvest; however, their quality can be reduced by pathogen attack. Fruit pathogens may infect their host through damaged surfaces, such as mechanical injuries occurring during growing, harvesting, and packing, leading to increased colonization as the fruit ripens. Of particular concern are fungal pathogens that not only macerate the host tissue but also secrete significant amounts of mycotoxins. Many studies have described the importance of physiological factors, including stage of fruit development, biochemical factors (ripening, C and N content), and environmental factors (humidity, temperature, water deficit) on the occurrence of mycotoxins. However, those factors usually show a correlative effect on fungal growth and mycotoxin accumulation. Recent reports have suggested that host factors can induce fungal metabolism, leading to the synthesis and accumulation of mycotoxins. This review describes the new vision of host-factor impact on the regulation of mycotoxin biosynthetic gene clusters underlying the complex regulation of mycotoxin accumulation in ripening fruit. PMID:28895896

Engineered Biomaterials to Enhance Stem Cell-Based Cardiac Tissue Engineering and Therapy.

PubMed

Hasan, Anwarul; Waters, Renae; Roula, Boustany; Dana, Rahbani; Yara, Seif; Alexandre, Toubia; Paul, Arghya

2016-07-01

Cardiovascular disease is a leading cause of death worldwide. Since adult cardiac cells are limited in their proliferation, cardiac tissue with dead or damaged cardiac cells downstream of the occluded vessel does not regenerate after myocardial infarction. The cardiac tissue is then replaced with nonfunctional fibrotic scar tissue rather than new cardiac cells, which leaves the heart weak. The limited proliferation ability of host cardiac cells has motivated investigators to research the potential cardiac regenerative ability of stem cells. Considerable progress has been made in this endeavor. However, the optimum type of stem cells along with the most suitable matrix-material and cellular microenvironmental cues are yet to be identified or agreed upon. This review presents an overview of various types of biofunctional materials and biomaterial matrices, which in combination with stem cells, have shown promises for cardiac tissue replacement and reinforcement. Engineered biomaterials also have applications in cardiac tissue engineering, in which tissue constructs are developed in vitro by combining stem cells and biomaterial scaffolds for drug screening or eventual implantation. This review highlights the benefits of using biomaterials in conjunction with stem cells to repair damaged myocardium and give a brief description of the properties of these biomaterials that make them such valuable tools to the field. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oxidative Stress and Antioxidant System in Periodontitis

PubMed Central

Wang, Yue; Andrukhov, Oleh; Rausch-Fan, Xiaohui

2017-01-01

Periodontitis is a common inflammatory disease, which is initiated by bacterial infection and subsequently progressed by aberrant host response. It can result in the destruction of teeth supporting tissues and have an influence on systemic health. When periodontitis occurs, reactive oxygen species, which are overproduced mostly by hyperactive neutrophils, could not be balanced by antioxidant defense system and cause tissues damage. This is characterized by increased metabolites of lipid peroxidation, DNA damage and protein damage. Local and systemic activities of antioxidants can also be influenced by periodontitis. Total antioxidant capacity, total oxidant status and oxidative stress index have been used to evaluate the oxidative stress associated with periodontitis. Studies have confirmed that inflammatory response in periodontitis is associated with an increased local and systemic oxidative stress and compromised antioxidant capacity. Our review focuses on increased oxidative stress in periodontal disease, specifically, on the relationship between the local and systemic biomarkers of oxidative stress and periodontitis and their association with the pathogenesis of periodontitis. Also, the relationship between periodontitis and systemic inflammation, and the effects of periodontal therapy on oxidative stress parameters will be discussed. PMID:29180965

The in vivo performance of plasmonic nanobubbles as cell theranostic agents in zebrafish hosting prostate cancer xenografts

PubMed Central

Wagner, Daniel S.; Delk, Nikki A.; Lukianova-Hleb, Ekaterina Y.; Hafner, Jason H.; Farach-Carson, Mary C.; Lapotko, Dmitri O.

2010-01-01

Cell theranostics is a new approach that unites diagnosis, therapy and confirmation (guidance) of the results of therapy in one single process at cell level, thus principally improving both the rapidity and precision of treatment. The ideal theranostic agent will support all three of the above functions in vivo with cellular resolution, allowing individual assessment of disease state and the elimination of diseased cells while leaving healthy cells intact. We have developed and evaluated plasmonic nanobubbles (PNBs) as an in vivo tunable theranostic cellular agent in zebrafish hosting prostate cancer xenografts. PNBs were selectively generated around gold nanoparticles in cancer cells in the zebrafish with short single laser pulses. By varying the energy of the laser pulse, we dynamically tuned the PNB size in a theranostic sequence of two PNBs: an initial small PNB detected a cancer cell through optical scattering, followed by a second bigger PNB, which mechanically ablated this cell without damage to surrounding tissue, while its optical scattering confirmed the destruction of the cell. Thus PNBs supported the diagnosis and guided ablation of individual human cancer cells in a living organism without damage to the host. PMID:20630586

The in vivo performance of plasmonic nanobubbles as cell theranostic agents in zebrafish hosting prostate cancer xenografts.

PubMed

Wagner, Daniel S; Delk, Nikki A; Lukianova-Hleb, Ekaterina Y; Hafner, Jason H; Farach-Carson, Mary C; Lapotko, Dmitri O

2010-10-01

Cell theranostics is a new approach that unites diagnosis, therapy and confirmation (guidance) of the results of therapy in one single process at cell level, thus principally improving both the rapidity and precision of treatment. The ideal theranostic agent will support all three of the above functions in vivo with cellular resolution, allowing individual assessment of disease state and the elimination of diseased cells while leaving healthy cells intact. We have developed and evaluated plasmonic nanobubbles (PNBs) as an in vivo tunable theranostic cellular agent in zebrafish hosting prostate cancer xenografts. PNBs were selectively generated around gold nanoparticles in cancer cells in the zebrafish with short single laser pulses. By varying the energy of the laser pulse, we dynamically tuned the PNB size in a theranostic sequence of two PNBs: an initial small PNB detected a cancer cell through optical scattering, followed by a second bigger PNB, which mechanically ablated this cell without damage to surrounding tissue, while its optical scattering confirmed the destruction of the cell. Thus PNBs supported the diagnosis and guided ablation of individual human cancer cells in a living organism without damage to the host. 2010 Elsevier Ltd. All rights reserved.

Pathogenesis of graft-versus-host disease: innate immunity amplifying acute alloimmune responses.

PubMed

Maeda, Yoshinobu

2013-09-01

In addition to reduced-intensity conditioning, which has expanded the eligibility for hematopoietic cell transplantation (HCT) to older patients, increased availability of alternative donors, including HLA-mismatched unrelated donors, has increased access to allogeneic HCT for more patients. However, acute graft-versus-host disease (GVHD) remains a lethal complication, even in HLA-matched donor-recipient pairs. The pathophysiology of GVHD depends on aspects of adaptive immunity and interactions between donor T-cells and host dendritic cells (DCs). Recent work has revealed that the role of other immune cells and endothelial cells and components of the innate immune response are also important. Tissue damage caused by the conditioning regimen leads to the release of exogenous and endogenous "danger signals". Exogenous danger signals called pathogen-associated molecular patterns and endogenous noninfectious molecules known as damage-associated molecular patterns (DAMPs) are responsible for initiating or amplifying acute GVHD by enhancing DC maturation and alloreactive T-cell responses. A significant association of innate immune receptor polymorphisms with outcomes, including GVHD severity, was observed in patients receiving allogeneic HCT. Understanding of the role of innate immunity in acute GVHD might offer new therapeutic approaches.

The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis.

PubMed

Hirayama, Daisuke; Iida, Tomoya; Nakase, Hiroshi

2017-12-29

Macrophages are effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators. In addition, macrophages play an important role in eliminating diseased and damaged cells through their programmed cell death. Generally, macrophages ingest and degrade dead cells, debris, tumor cells, and foreign materials. They promote homeostasis by responding to internal and external changes within the body, not only as phagocytes, but also through trophic, regulatory, and repair functions. Recent studies demonstrated that macrophages differentiate from hematopoietic stem cell-derived monocytes and embryonic yolk sac macrophages. The latter mainly give rise to tissue macrophages. Macrophages exist in all vertebrate tissues and have dual functions in host protection and tissue injury, which are maintained at a fine balance. Tissue macrophages have heterogeneous phenotypes in different tissue environments. In this review, we focused on the phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis for a better understanding of the role of tissue macrophages in several pathological conditions.

Plant-eriophyoid mite interactions: cellular biochemistry and metabolic responses induced in mite-injured plants. Part I.

PubMed

Petanović, Radmila; Kielkiewicz, Malgorzata

2010-07-01

This review is a comprehensive study of recent advances related to cytological, biochemical and physiological changes induced in plants in response to eriophyoid mite attack. It has been shown that responses of host plants to eriophyoids are variable. Most of the variability is due to individual eriophyoid mite-plant interactions. Usually, the direction and intensity of changes in eriophyoid-infested plant organs depend on mite genotype, density, or the feeding period, and are strongly differentiated relative to host plant species, cultivar, age and location. Although the mechanisms of changes elicited by eriophyoid mites within plants are not fully understood, in many cases the qualitative and quantitative biochemical status of mite-infested plants are known to affect the performance of consecutive herbivorous arthropods. In future, elucidation of the pathways from eriophyoid mite damage to plant gene activation will be necessary to clarify plant responses and to explain variation in plant tissue damage at the feeding and adjacent sites.

A Perspective on the Clinical Translation of Scaffolds for Tissue Engineering

PubMed Central

Webber, Matthew J.; Khan, Omar F.; Sydlik, Stefanie A.; Tang, Benjamin C.; Langer, Robert

2016-01-01

Scaffolds have been broadly applied within tissue engineering and regenerative medicine to regenerate, replace, or augment diseased or damaged tissue. For a scaffold to perform optimally, several design considerations must be addressed, with an eye toward the eventual form, function, and tissue site. The chemical and mechanical properties of the scaffold must be tuned to optimize the interaction with cells and surrounding tissues. For complex tissue engineering, mass transport limitations, vascularization, and host tissue integration are important considerations. As the tissue architecture to be replaced becomes more complex and hierarchical, scaffold design must also match this complexity to recapitulate a functioning tissue. We outline these design constraints and highlight creative and emerging strategies to overcome limitations and modulate scaffold properties for optimal regeneration. We also highlight some of the most advanced strategies that have seen clinical application and discuss the hurdles that must be overcome for clinical use and commercialization of tissue engineering technologies. Finally, we provide a perspective on the future of scaffolds as a functional contributor to advancing tissue engineering and regenerative medicine. PMID:25201605

A perspective on the clinical translation of scaffolds for tissue engineering.

PubMed

Webber, Matthew J; Khan, Omar F; Sydlik, Stefanie A; Tang, Benjamin C; Langer, Robert

2015-03-01

Scaffolds have been broadly applied within tissue engineering and regenerative medicine to regenerate, replace, or augment diseased or damaged tissue. For a scaffold to perform optimally, several design considerations must be addressed, with an eye toward the eventual form, function, and tissue site. The chemical and mechanical properties of the scaffold must be tuned to optimize the interaction with cells and surrounding tissues. For complex tissue engineering, mass transport limitations, vascularization, and host tissue integration are important considerations. As the tissue architecture to be replaced becomes more complex and hierarchical, scaffold design must also match this complexity to recapitulate a functioning tissue. We outline these design constraints and highlight creative and emerging strategies to overcome limitations and modulate scaffold properties for optimal regeneration. We also highlight some of the most advanced strategies that have seen clinical application and discuss the hurdles that must be overcome for clinical use and commercialization of tissue engineering technologies. Finally, we provide a perspective on the future of scaffolds as a functional contributor to advancing tissue engineering and regenerative medicine.

Laser damage threshold of gelatin and a copper phthalocyanine doped gelatin optical limiter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brant, M.C.; McLean, D.G.; Sutherland, R.L.

1996-12-31

The authors demonstrate optical limiting in a unique guest-host system which uses neither the typical liquid or solid host. Instead, they dope a gelatin gel host with a water soluble Copper (II) phthalocyaninetetrasulfonic acid, tetrasodium salt (CuPcTs). They report on the gelatin`s viscoelasticity, laser damage threshold, and self healing of this damage. The viscoelastic gelatin has mechanical properties quite different than a liquid or solid. The authors` laser measurements demonstrate that the single shot damage threshold of the undoped gelatin host increases with decreasing gelatin concentration. The gelatin also has a much higher laser damage threshold than a stiff acrylic.more » Unlike brittle solids, the soft gelatin self heals from laser induced damage. Optical limiting test also show the utility of a gelatin host doped with CuPcTs. The CuPcTs/gelatin matrix is not damaged at incident laser energies 5 times the single shot damage threshold of the gelatin host. However, at this high laser energy the CuPcTs is photo bleached at the beam waist. The authors repair photo bleached sites by annealing the CuPcTs/gelatin matrix.« less

Host-directed therapies for infectious diseases: current status, recent progress, and future prospects.

PubMed

Zumla, Alimuddin; Rao, Martin; Wallis, Robert S; Kaufmann, Stefan H E; Rustomjee, Roxana; Mwaba, Peter; Vilaplana, Cris; Yeboah-Manu, Dorothy; Chakaya, Jeremiah; Ippolito, Giuseppe; Azhar, Esam; Hoelscher, Michael; Maeurer, Markus

2016-04-01

Despite extensive global efforts in the fight against killer infectious diseases, they still cause one in four deaths worldwide and are important causes of long-term functional disability arising from tissue damage. The continuing epidemics of tuberculosis, HIV, malaria, and influenza, and the emergence of novel zoonotic pathogens represent major clinical management challenges worldwide. Newer approaches to improving treatment outcomes are needed to reduce the high morbidity and mortality caused by infectious diseases. Recent insights into pathogen-host interactions, pathogenesis, inflammatory pathways, and the host's innate and acquired immune responses are leading to identification and development of a wide range of host-directed therapies with different mechanisms of action. Host-directed therapeutic strategies are now becoming viable adjuncts to standard antimicrobial treatment. Host-directed therapies include commonly used drugs for non-communicable diseases with good safety profiles, immunomodulatory agents, biologics (eg monoclonal antibodies), nutritional products, and cellular therapy using the patient's own immune or bone marrow mesenchymal stromal cells. We discuss clinically relevant examples of progress in identifying host-directed therapies as adjunct treatment options for bacterial, viral, and parasitic infectious diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pathogenesis of Infection by Clinical and Environmental Strains of Vibrio vulnificus in Iron-Dextran-Treated Mice

PubMed Central

Starks, Angela M.; Schoeb, Trenton R.; Tamplin, Mark L.; Parveen, Salina; Doyle, Thomas J.; Bomeisl, Philip E.; Escudero, Gloria M.; Gulig, Paul A.

2000-01-01

Vibrio vulnificus is an opportunistic pathogen that contaminates oysters harvested from the Gulf of Mexico. In humans with compromising conditions, especially excess levels of iron in plasma and tissues, consumption of contaminated seafood or exposure of wounds to contaminated water can lead to systemic infection and disfiguring skin infection with extremely high mortality. V. vulnificus-associated diseases are noted for the rapid replication of the bacteria in host tissues, with extensive tissue damage. In this study we examined the virulence attributes of three virulent clinical strains and three attenuated oyster or seawater isolates in mouse models of systemic disease. All six V. vulnificus strains caused identical skin lesions in subcutaneously (s.c.) inoculated iron dextran-treated mice in terms of numbers of recovered CFU and histopathology; however, the inocula required for identical frequency and magnitude of infection were at least 350-fold higher for the environmental strains. At lethal doses, all strains caused s.c. skin lesions with extensive edema, necrosis of proximate host cells, vasodilation, and as many as 108 CFU/g, especially in perivascular regions. These data suggest that the differences between these clinical and environmental strains may be related to growth in the host or susceptibility to host defenses. In non-iron dextran-treated mice, strains required 105-fold-higher inocula to cause an identical disease process as with iron dextran treatment. These results demonstrate that s.c. inoculation of iron dextran-treated mice is a useful model for studying systemic disease caused by V. vulnificus. PMID:10992486

Role of gamma-delta T cells in host response against Staphylococcus aureus-induced pneumonia

PubMed Central

2012-01-01

Background Staphylococcus aureus is the major cause of hospital-acquired and community-acquired pneumonia. Host defense to S.aureus infection is largely mediated by the innate immune system. γδ T cells play an important role in innate immunity to many infectious diseases. However, less is known about the role of these cells during S.aureus-induced pneumonia. In this study, we examined the response and the role of γδ T cells to pulmonary S.aureus infection. Results Mice infected with S. aureus intranasally showed rapid γδ T cells accumulation in the lung. Deficiency of γδ T cells led to attenuated bacterial clearance and less tissue damage in lung compared with WT mice. Moreover, TCR-δ−/− mice exhibited impaired neutrophil recruitment and reduced cytokine production at the site of infection. The γδ T cells in response to pulmonary S. aureus infection mainly secreted IL-17 and γδ T cells deficiency reduced IL-17 production, which might regulate the production of neutrophil-inducing cytokine/chemokine in the S. aureus-infected lungs. Conclusions Accumulation of γδ T cells in the lungs to S. aureus infection is beneficial for bacteria clearance and also contributes to the tissue damage. These cells were the primary source of IL-17, which might influence the recruitment of neutrophils at the early stage of infection. PMID:22776294

Metformin: Candidate host-directed therapy for tuberculosis in diabetes and non-diabetes patients.

PubMed

Restrepo, Blanca I

2016-12-01

Despite major advances in tuberculosis (TB) control, TB continues to be a leading cause of death worldwide. The discovery of new anti-TB treatment drugs and regimens that target drug-sensitive and drug-resistant TB are being complemented with a search for adjunct host-directed therapies that synergize for Mycobacterium tuberculosis (Mtb) elimination. The goal of host-directed therapies is to boost immune mechanisms that diminish excess inflammation to reduce lung tissue damage and limit Mtb growth. Metformin is the most commonly-used medication for type 2 diabetes, and a candidate for host-directed therapy for TB. Preliminary data suggests metformin may be beneficial for TB control by reducing the deleterious inflammation associated with immune pathology and enhancing the anti-mycobacterial activity of immune cells. In this review I summarize current findings, knowledge gaps and the potential benefits as well as points of caution for using metformin as adjunct therapy for TB in patients with and without type 2 diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis.

PubMed

Kohlgruber, Ayano C; Gal-Oz, Shani T; LaMarche, Nelson M; Shimazaki, Moto; Duquette, Danielle; Nguyen, Hung N; Mina, Amir I; Paras, Tyler; Tavakkoli, Ali; von Andrian, Ulrich; Banks, Alexander S; Shay, Tal; Brenner, Michael B; Lynch, Lydia

2018-05-01

γδ T cells are situated at barrier sites and guard the body from infection and damage. However, little is known about their roles outside of host defense in nonbarrier tissues. Here, we characterize a highly enriched tissue-resident population of γδ T cells in adipose tissue that regulate age-dependent regulatory T cell (T reg ) expansion and control core body temperature in response to environmental fluctuations. Mechanistically, innate PLZF + γδ T cells produced tumor necrosis factor and interleukin (IL) 17 A and determined PDGFRα + and Pdpn + stromal-cell production of IL-33 in adipose tissue. Mice lacking γδ T cells or IL-17A exhibited decreases in both ST2 + T reg cells and IL-33 abundance in visceral adipose tissue. Remarkably, these mice also lacked the ability to regulate core body temperature at thermoneutrality and after cold challenge. Together, these findings uncover important physiological roles for resident γδ T cells in adipose tissue immune homeostasis and body-temperature control.

Pathogenetic aspects of uncomplicated urinary tract infection: recent advances.

PubMed

Fünfstück, R; Smith, J W; Tschäpe, H; Stein, G

1997-01-01

Urinary tract infections mostly are caused by Enterobacteriaceae; E. coli dominating in 80-90% for uncomplicated diseases. Microorganisms possessing the ability to colonize the uroepithelium (fimbriae/pili) and to cytotoxically damage cells and tissue (hemolysin) may initiate acute infection. Properties such as serum resistance, iron sequesteration, hydroxamate production and the presence of K-antigen are found in strains which persist in the host without initiating clinical symptoms. The ability of bacteria to adhere to cells of the epithelial boundary layer of the host organisms is of initial importance in the origin and progress of an infection. A variety of specific factors, e.g. glycolipids on the surface of the uroepithelium as well as cellular and humoral disorders of immunoreactions in the host determine the course of a disease. The immune response may ameliorate clinical symptoms and select urovirulent characteristics of the causative microorganism in recurrent diseases.

Denture-associated biofilm infection in three-dimensional oral mucosal tissue models.

PubMed

Morse, Daniel J; Wilson, Melanie J; Wei, Xiaoqing; Lewis, Michael A O; Bradshaw, David J; Murdoch, Craig; Williams, David W

2018-03-01

In vitro analyses of virulence, pathogenicity and associated host cell responses are important components in the study of biofilm infections. The Candida-related infection, denture-associated oral candidosis, affects up to 60 % of denture wearers and manifests as inflammation of palatal tissues contacting the denture-fitting surface. Commercially available three-dimensional tissue models can be used to study infection, but their use is limited for many academic research institutions, primarily because of the substantial purchase costs. The aim of this study was to develop and evaluate the use of in vitro tissue models to assess infections by biofilms on acrylic surfaces through tissue damage and Candida albicans virulence gene expression. In vitro models were compared against commercially available tissue equivalents (keratinocyte-only, SkinEthic; full-thickness, MatTek Corporation). An in vitro keratinocyte-only tissue was produced using a cancer-derived cell line, TR146, and a full-thickness model incorporating primary fibroblasts and immortalised normal oral keratinocytes was also generated. The in vitro full-thickness tissues incorporated keratinocytes and fibroblasts, and have potential for future further development and analysis. Following polymicrobial infection with biofilms on acrylic surfaces, both in-house developed models were shown to provide equivalent results to the SkinEthic and MatTek models in terms of tissue damage: a significant (P<0.05) increase in LDH activity for mixed species biofilms compared to uninfected control, and no significant difference (P>0.05) in the expression of most C. albicans virulence genes when comparing tissue models of the same type. Our results confirm the feasibility and suitability of using these alternative in vitro tissue models for such analyses.

Toxicity of Eosinophil MBP Is Repressed by Intracellular Crystallization and Promoted by Extracellular Aggregation

PubMed Central

Soragni, Alice; Yousefi, Shida; Stoeckle, Christina; Soriaga, Angela B.; Sawaya, Michael R.; Kozlowski, Evelyne; Schmid, Inès; Radonjic-Hoesli, Susanne; Boutet, Sebastien; Williams, Garth J.; Messerschmidt, Marc; Seibert, M. Marvin; Cascio, Duilio; Zatsepin, Nadia A.; Burghammer, Manfred; Riekel, Christian; Colletier, Jacques-Philippe; Riek, Roland; Eisenberg, David; Simon, Hans-Uwe

2016-01-01

SUMMARY Eosinophils are white blood cells that function in innate immunity and participate in the pathogenesis of various inflammatory and neoplastic disorders. Their secretory granules contain four cytotoxic proteins, including the eosinophil major basic protein (MBP-1). How MBP-1 toxicity is controlled within the eosinophil itself and activated upon extracellular release is unknown. Here we show how intragranular MBP-1 nanocrystals restrain toxicity, enabling its safe storage, and characterize them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity is triggered by granule acidification, followed by extracellular aggregation, which mediates the damage to pathogens and host cells. Larger non-toxic amyloid plaques are also present in tissues of eosinophilic patients in a feedback mechanism that likely limits tissue damage under pathological conditions of MBP-1 oversecretion. Our results suggest that MBP-1 aggregation is important for innate immunity and immunopathology mediated by eosinophils and clarify how its polymorphic self-association pathways regulate toxicity intra- and extracellularly. PMID:25728769

Evaluation of tissue engineered models of the oral mucosa to investigate oral candidiasis.

PubMed

Yadev, Nishant P; Murdoch, Craig; Saville, Stephen P; Thornhill, Martin H

2011-06-01

Candida albicans is a commensal organism that can be isolated from the majority of healthy individuals. However, in certain susceptible individuals C. albicans can become pathogenic leading to the mucocutaneous infection; oral candidiasis. Murine models and in vitro monolayer cultures have generated some data on the likely virulence and host factors that contribute to oral candidiasis but these models have limitations. Recently, tissue engineered oral mucosal models have been developed to mimic the normal oral mucosa but little information is available on their true representation. In this study, we assessed the histological features of three different tissue engineered oral mucosal models compared to the normal oral mucosa and analysed both cell damage and cytokine release following infection with C. albicans. Models comprised of normal oral keratinocytes and a fibroblast-containing matrix displayed more similar immunohistological and proliferation characteristics to normal mucosa, compared to models composed of an oral carcinoma cell line. Although all models were invaded and damaged by C. albicans in a similar manner, the cytokine response was much more pronounced in models containing normal keratinocytes. These data suggest that models based on normal keratinocytes atop a fibroblast-containing connective tissue will significantly aid in dissecting the molecular pathogenesis of oral candidiasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Leaf-morphology-assisted selection for resistance to two-spotted spider mite Tetranychus urticae Koch (Acari: Tetranychidae) in carnations (Dianthus caryophyllus L).

PubMed

Seki, Kousuke

2016-10-01

The development of a cultivar resistant to the two-spotted spider mite has provided both ecological and economic benefits to the production of cut flowers. This study aimed to clarify the mechanism of resistance to mites using an inbred population of carnations. In the resistant and susceptible plants selected from an inbred population, a difference was recognised in the thickness of the abaxial palisade tissue by microscopic examination of the damaged leaf. Therefore, it was assumed that mites displayed feeding preferences within the internal leaf structure of the carnation leaf. The suitability of the host plant for mites was investigated using several cultivars selected using an index of the thickness from the abaxial leaf surface to the spongy tissue. The results suggested that the cultivar associated with a thicker abaxial tissue lowered the intrinsic rate of natural increase of the mites. The cultivars with a thicker abaxial tissue of over 120 µm showed slight damage in the field test. The ability of mites to feed on the spongy tissue during an early life stage from hatching to adult emergence was critical. It was possible to select a cultivar that is resistant to mites under a real cultivation environment by observing the internal structure of the leaf. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Recovery from a near-lethal exposure to ultraviolet-C radiation in a scleractinian coral.

PubMed

Basti, David; Bricknell, Ian; Beane, Dawna; Bouchard, Deborah

2009-04-01

Hermatypic (reef building) corals live in an environment characterized by high ambient levels of photosynthetically active radiation (PAR) and ultraviolet radiation (UVR). Photoadaptive mechanisms have evolved to protect the sensitive cell structures of the host coral and their photosynthetic, endosymbiotic zooxanthellae. Environmental stressors may destabilize the coral-zooxanthellae system resulting in the expulsion of zooxanthellae and/or loss of photosynthetic pigment within zooxanthellae, causing a condition known as bleaching. It is estimated that 1% of the world's coral population is lost yearly, partly due to bleaching. Despite intensive research efforts, a single unified mechanism cannot explain this phenomenon. Although UVA and UVB cellular damage is well documented, UVC damage is rarely reported due to its almost complete absorption in the stratosphere. A small scale coral propagation system at the University of Maine was accidentally exposed to 15.5h of UVC radiation (253.7 nm) from a G15T8 germicidal lamp, resulting in a cumulative surface irradiance of 8.39 x 10(4) J m(-2). An experiment was designed to monitor the progression of UVC induced damage. Branch sections from affected scleractinian corals, Acropora yongei and Acropora formosa were submitted to histopathology to provide an historical record of tissue response. The death of gastrodermal cells and necrosis resulted in the release of intracellular zooxanthellae into the gastrovascular canals. Zooxanthellae were also injured as evidenced by pale coloration, increased vacuolization and loss of membrane integrity. The recovery of damaged coral tissue likely proceeds by re-epithelialization and zooxanthellae repopulation of gastrodermal cells by adjacent healthy tissue.

Comparison of the Antimicrobial Effect of Chlorhexidine and Saline for Irrigating a Contaminated Open Fracture Model

DTIC Science & Technology

2012-12-01

bacteria after irrigation, with aqueous CHG at a range of concentrations comparing irrigation with saline alone. Conclusions: This study does not support the...from high irrigation pressures and cytotoxic solutions has been shown to allow bacteria to thrive. We believe this is due to a “rebound” of bacteria ...physically removing bacteria with an active chemical antimicrobial effect without damaging host tissue. CHG was synthesized in the 1950s.6 It was quickly

Immune Ecosystem of Virus-Infected Host Tissues.

PubMed

Maarouf, Mohamed; Rai, Kul Raj; Goraya, Mohsan Ullah; Chen, Ji-Long

2018-05-06

Virus infected host cells serve as a central immune ecological niche during viral infection and replication and stimulate the host immune response via molecular signaling. The viral infection and multiplication process involves complex intracellular molecular interactions between viral components and the host factors. Various types of host cells are also involved to modulate immune factors in delicate and dynamic equilibrium to maintain a balanced immune ecosystem in an infected host tissue. Antiviral host arsenals are equipped to combat or eliminate viral invasion. However, viruses have evolved with strategies to counter against antiviral immunity or hijack cellular machinery to survive inside host tissue for their multiplication. However, host immune systems have also evolved to neutralize the infection; which, in turn, either clears the virus from the infected host or causes immune-mediated host tissue injury. A complex relationship between viral pathogenesis and host antiviral defense could define the immune ecosystem of virus-infected host tissues. Understanding of the molecular mechanism underlying this ecosystem would uncover strategies to modulate host immune function for antiviral therapeutics. This review presents past and present updates of immune-ecological components of virus infected host tissue and explains how viruses subvert the host immune surveillances.

Gastro-intestinal autoimmunity: preclinical experiences and successful therapy of fistulizing bowel diseases and gut Graft versus host disease by mesenchymal stromal cells.

PubMed

Voswinkel, Jan; Francois, Sabine; Gorin, Norbert-Claude; Chapel, Alain

2013-07-01

Mesenchymal stromal cells (MSC) are multipotent adult stem cells with the potential to regenerate tissue damage and inhibit inflammation and fibrosis in parallel. As they are non-immunogenic, MSC can be safely auto- and allotransplanted and consequently represent a therapeutic option for refractory connective tissue diseases and fistulizing colitis like Crohn's disease. Actually, there are more than 200 registered clinical trial sites for evaluating MSC therapy, 22 are on autoimmune diseases and 27 are actually recruiting bowel disease' patients. More than 1,500 patients with bowel diseases like Crohn's disease were treated in clinical trials by local as well as systemic MSC therapy. Phase I and II trials on fistula documented the feasibility and safety of MSC therapy, and a significant superiority compared to fibrin glue in fistulizing bowel diseases was demonstrated. Autologous as well as allogeneic use of Bone marrow as well as of adipose tissue-derived MSC are feasible. In refractory Graft versus host disease, especially in refractory gut Graft versus host diseases, encouraging results were reported using MSC. Systemic MSC therapy of refractory irradiation-induced colitis was safe and effective on pain, diarrhea, hemorrhage, inflammation and fistulization accompanied by modulation of the lymphocyte subsets toward an increase in T regulatory cells and a decrease in activated effector T cells. Mesenchymal stem cells represent a safe therapy for patients with refractory inflammatory bowel diseases.

Contributions of Neutrophils to Resolution of Mucosal Inflammation

PubMed Central

Colgan, Sean P.; Ehrentraut, Stefan F.; Glover, Louise E.; Kominsky, Douglas J.; Campbell, Eric L.

2014-01-01

Neutrophil (PMN) recruitment from the blood stream into surrounding tissues involves a regulated series of events central to acute responses in host defense. Accumulation of PMN within mucosal tissues have historically been considered pathognomonic features of both acute and chronic inflammatory conditions. Historically PMNs have been deemed necessary but detrimental when recruited, given the potential for tissue damage that results from a variety of mechanisms. Recent work, however, has altered our preconcieved notions of PMN contributions to inflammatory processes. In particular, significant evidence implicates a central role for the PMN in triggering inflammatory resolution. Such mechanisms involve both metabolic and biochemical crosstalk pathways during the intimate interactions of PMN with other cell types at inflammatory sites. Here, we highlight several recent examples of how PMN coordinate the resolution of ongoing inflammation, with a particular focus on the gastrointestinal mucosa. PMID:22968707

Good news–bad news: the Yin and Yang of immune privilege in the eye

PubMed Central

Forrester, John V.; Xu, Heping

2012-01-01

The eye and the brain are prototypical tissues manifesting immune privilege (IP) in which immune responses to foreign antigens, particularly alloantigens are suppressed, and even completely inhibited. Explanations for this phenomenon are numerous and mostly reflect our evolving understanding of the molecular and cellular processes underpinning immunological responses generally. IP is now viewed as a property of many tissues and the level of expression of IP varies not only with the tissue but with the nature of the foreign antigen and changes in the limited conditions under which privilege can operate as a mechanism of immunological tolerance. As a result, IP functions normally as a homeostatic mechanism preserving normal function in tissues, particularly those with highly specialized function and limited capacity for renewal such as the eye and brain. However, IP is relatively easily bypassed in the face of a sufficiently strong immunological response, and the privileged tissues may be at greater risk of collateral damage because its natural defenses are more easily breached than in a fully immunocompetent tissue which rapidly rejects foreign antigen and restores integrity. This two-edged sword cuts its swathe through the eye: under most circumstances, IP mechanisms such as blood–ocular barriers, intraocular immune modulators, induction of T regulatory cells, lack of lymphatics, and other properties maintain tissue integrity; however, when these are breached, various degrees of tissue damage occur from severe tissue destruction in retinal viral infections and other forms of uveoretinal inflammation, to less severe inflammatory responses in conditions such as macular degeneration. Conversely, ocular IP and tumor-related IP can combine to permit extensive tumor growth and increased risk of metastasis thus threatening the survival of the host. PMID:23230433

Negative regulators of the RIG-I-like receptor signaling pathway

PubMed Central

Quicke, Kendra M.; Diamond, Michael S.; Suthar, Mehul S.

2017-01-01

SUMMARY Upon recognition of specific molecular patterns on viruses, bacteria and fungi, host cells trigger an innate immune response, which culminates in the production of type I interferons (IFN), pro-inflammatory cytokines and chemokines, and restricts pathogen replication and spread within the host. At each stage of the immune response, there are stimulatory and inhibitory signals that regulate the magnitude, quality, and character of the response. Positive regulation promotes an antiviral state to control and eventually clear infection whereas negative regulation dampens inflammation and prevents immune-mediated tissue damage. An over-exuberant innate immune response can lead to the destruction of cells and tissues, and the development of spontaneous autoimmunity. The RIG-I-like receptors (RLRs) retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) belong to a family of cytosolic host RNA helicases that recognize distinct non-self RNA signatures and trigger innate immune responses against several RNA virus infections. The RLR signaling pathway is tightly regulated to achieve a well-orchestrated response aimed at maximizing antiviral immunity and minimizing immune-mediated pathology. This review highlights contemporary findings on negative regulators of the RLR signaling pathway, with specific focus on the proteins and biological processes that directly regulate RIG-I, MDA5 and MAVS function. PMID:28295214

Antioxidant genes of plants and fungal pathogens are distinctly regulated during disease development in different Rhizoctonia solani pathosystems.

PubMed

Samsatly, Jamil; Copley, Tanya R; Jabaji, Suha H

2018-01-01

Biotic stress, as a result of plant-pathogen interactions, induces the accumulation of reactive oxygen species in the cells, causing severe oxidative damage to plants and pathogens. To overcome this damage, both the host and pathogen have developed antioxidant systems to quench excess ROS and keep ROS production and scavenging systems under control. Data on ROS-scavenging systems in the necrotrophic plant pathogen Rhizoctonia solani are just emerging. We formerly identified vitamin B6 biosynthetic machinery of R. solani AG3 as a powerful antioxidant exhibiting a high ability to quench ROS, similar to CATALASE (CAT) and GLUTATHIONE S-TRANSFERASE (GST). Here, we provide evidence on the involvement of R. solani vitamin B6 biosynthetic pathway genes; RsolPDX1 (KF620111.1), RsolPDX2 (KF620112.1), and RsolPLR (KJ395592.1) in vitamin B6 de novo biosynthesis by yeast complementation assays. Since gene expression studies focusing on oxidative stress responses of both the plant and the pathogen following R. solani infection are very limited, this study is the first coexpression analysis of genes encoding vitamin B6, CAT and GST in plant and fungal tissues of three pathosystems during interaction of different AG groups of R. solani with their respective hosts. The findings indicate that distinct expression patterns of fungal and host antioxidant genes were correlated in necrotic tissues and their surrounding areas in each of the three R. solani pathosystems: potato sprout-R. solani AG3; soybean hypocotyl-R. solani AG4 and soybean leaves-R. solani AG1-IA interactions. Levels of ROS increased in all types of potato and soybean tissues, and in fungal hyphae following infection of R. solani AGs as determined by non-fluorescence and fluorescence methods using H2DCF-DA and DAB, respectively. Overall, we demonstrate that the co-expression and accumulation of certain plant and pathogen ROS-antioxidant related genes in each pathosystem are highlighted and might be critical during disease development from the plant's point of view, and in pathogenicity and developing of infection structures from the fungal point of view.

Antioxidant genes of plants and fungal pathogens are distinctly regulated during disease development in different Rhizoctonia solani pathosystems

PubMed Central

Samsatly, Jamil; Copley, Tanya R.

2018-01-01

Biotic stress, as a result of plant-pathogen interactions, induces the accumulation of reactive oxygen species in the cells, causing severe oxidative damage to plants and pathogens. To overcome this damage, both the host and pathogen have developed antioxidant systems to quench excess ROS and keep ROS production and scavenging systems under control. Data on ROS-scavenging systems in the necrotrophic plant pathogen Rhizoctonia solani are just emerging. We formerly identified vitamin B6 biosynthetic machinery of R. solani AG3 as a powerful antioxidant exhibiting a high ability to quench ROS, similar to CATALASE (CAT) and GLUTATHIONE S-TRANSFERASE (GST). Here, we provide evidence on the involvement of R. solani vitamin B6 biosynthetic pathway genes; RsolPDX1 (KF620111.1), RsolPDX2 (KF620112.1), and RsolPLR (KJ395592.1) in vitamin B6 de novo biosynthesis by yeast complementation assays. Since gene expression studies focusing on oxidative stress responses of both the plant and the pathogen following R. solani infection are very limited, this study is the first coexpression analysis of genes encoding vitamin B6, CAT and GST in plant and fungal tissues of three pathosystems during interaction of different AG groups of R. solani with their respective hosts. The findings indicate that distinct expression patterns of fungal and host antioxidant genes were correlated in necrotic tissues and their surrounding areas in each of the three R. solani pathosystems: potato sprout-R. solani AG3; soybean hypocotyl-R. solani AG4 and soybean leaves-R. solani AG1-IA interactions. Levels of ROS increased in all types of potato and soybean tissues, and in fungal hyphae following infection of R. solani AGs as determined by non-fluorescence and fluorescence methods using H2DCF-DA and DAB, respectively. Overall, we demonstrate that the co-expression and accumulation of certain plant and pathogen ROS-antioxidant related genes in each pathosystem are highlighted and might be critical during disease development from the plant’s point of view, and in pathogenicity and developing of infection structures from the fungal point of view. PMID:29466404

Response of host plants to periodical cicada oviposition damage.

PubMed

Flory, S Luke; Mattingly, W Brett

2008-06-01

Insect oviposition on plants is widespread across many systems, but studies on the response of host plants to oviposition damage are lacking. Although patterns of oviposition vary spatially and temporally, ovipositing insects that exhibit outbreak characteristics may have strong effects on host plants during peak abundance. Periodical cicadas (Magicicada spp.), in particular, may reduce the performance of host plants when they synchronously emerge in massive numbers to mate and oviposit on host plants. Here we provide the first experimental manipulation of host plant use by periodical cicadas to evaluate the impact of cicada oviposition on plant performance across a diversity of host species within an ecologically relevant setting. Using a randomized block design, we established a plantation of three native and three exotic host plant species common to the successional forests in which cicadas occur. During the emergence of Brood X in 2004, we employed a highly effective cicada exclusion treatment by netting half of the host plants within each block. We assessed multiple measures of host plant performance, including overall plant growth and the growth and reproduction of individual branches, across three growing seasons. Despite our thorough assessment of potential host plant responses to oviposition damage, cicada oviposition did not generally inhibit host plant performance. Oviposition densities on unnetted host plants were comparable to levels documented in other studies, reinforcing the ecological relevance of our results, which indicate that cicada oviposition damage did not generally reduce the performance of native or exotic host plants.

Exposure to persistent organic pollutants (POPs) and DNA damage as an indicator of environmental stress in fish of different feeding habits of Coatzacoalcos, Veracruz, Mexico.

PubMed

González-Mille, Donaji J; Ilizaliturri-Hernández, César A; Espinosa-Reyes, Guillermo; Costilla-Salazar, Rogelio; Díaz-Barriga, Fernando; Ize-Lema, Irina; Mejía-Saavedra, Jesús

2010-10-01

The region of Coatzacoalcos, Veracruz hosts one of the largest and most important industrial areas of Mexico and Latin America. Industrial development and rapid population growth, have triggered a severe impact on aquatic ecosystems of the region. The aim of this study was to determine the levels of POPs in sediment and in muscle tissue of five fish species from different trophic levels in downstream residents of the Coatzacoalcos River, and their integration with DNA damage in the fish, evaluated with the comet assay in whole blood as a biological indicator of stress, in order to obtain a baseline of the ecological condition of the region. The compounds detected in sediment and in muscle tissue were hexachlorobenzene (HCB), α-, β-, γ-hexachlorocyclohexane (HCH), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), mirex and polychlorinated biphenyls (PCBs). Sediment concentrations of these pollutants (except for mirex) exceeded the values of protection provided by international guidelines, suggesting a potential risk to aquatic life in the region. DNA damage recorded in the fish species is evidence of exposure to a mix of genotoxic pollutants, which combined with exposure to POPs, reflects the degree of environmental stress of aquatic organisms in the region. The results of this study show the importance of determining the presence of contaminants in the environment, the bioaccumulation in tissues and their effects on exposed organisms, providing an integrated approach in assessing the health of aquatic ecosystems.

Enhanced bioactive scaffolds for bone tissue regeneration

NASA Astrophysics Data System (ADS)

Karnik, Sonali

Bone injuries are commonly termed as fractures and they vary in their severity and causes. If the fracture is severe and there is loss of bone, implant surgery is prescribed. The response to the implant depends on the patient's physiology and implant material. Sometimes, the compromised physiology and undesired implant reactions lead to post-surgical complications. [4, 5, 20, 28] Efforts have been directed towards the development of efficient implant materials to tackle the problem of post-surgical implant failure. [ 15, 19, 24, 28, 32]. The field of tissue engineering and regenerative medicine involves the use of cells to form a new tissue on bio-absorbable or inert scaffolds. [2, 32] One of the applications of this field is to regenerate the damaged or lost bone by using stem cells or osteoprogenitor cells on scaffolds that can integrate in the host tissue without causing any harmful side effects. [2, 32] A variety of natural, synthetic materials and their combinations have been used to regenerate the damaged bone tissue. [2, 19, 30, 32, 43]. Growth factors have been supplied to progenitor cells to trigger a sequence of metabolic pathways leading to cellular proliferation, differentiation and to enhance their functionality. [56, 57] The challenge persists to supply these proteins, in the range of nano or even picograms, and in a sustained fashion over a period of time. A delivery system has yet to be developed that would mimic the body's inherent mechanism of delivering the growth factor molecules in the required amount to the target organ or tissue. Titanium is the most preferred metal for orthopedic and orthodontic implants. [28, 46, 48] Even though it has better osteogenic properties as compared to other metals and alloys, it still has drawbacks like poor integration into the surrounding host tissue leading to bone resorption and implant failure. [20, 28, 35] It also faces the problem of postsurgical infections that contributes to the implant failure. [26, 37]. The focus of this dissertation was to design and develop novel implant materials for coating titanium to improve its biological properties. These natural and/or semi-synthetic materials improved cellular adhesion, biological response to the scaffolds and prevented growth of bacteria when they were enhanced with growth factor and anti-infective loaded nanotubes. The implant materials showed promise when tested in vitro for cell proliferation, differentiation and bacterial growth inhibition.

The pathogenesis of measles.

PubMed

de Vries, Rory D; Mesman, Annelies W; Geijtenbeek, Teunis B H; Duprex, W Paul; de Swart, Rik L

2012-06-01

Measles is an important cause of childhood morbidity and mortality in developing countries. Measles virus (MV) is transmitted via the respiratory route and causes systemic disease. Over the last decade, identification of new cellular receptors and studies in animal models have challenged the historic concepts of measles pathogenesis. It is thought that MV enters the host by infection of alveolar macrophages and/or dendritic cells in the airways, and is amplified in local lymphoid tissues. Viremia mediated by infected CD150+ lymphocytes results in systemic dissemination. Infection of lymphocytes and dendritic cells in the respiratory submucosa facilitates basolateral infection of epithelial cells via the newly identified receptor Nectin-4. Concomitant and extensive epithelial damage may contribute to efficient transmission to the next host. Copyright © 2012 Elsevier B.V. All rights reserved.

An arsenal of magnetic nanoparticles; perspectives in the treatment of cancer.

PubMed

Karponis, Dimitrios; Azzawi, May; Seifalian, Alexander

2016-08-01

Nanomedicine is an emerging field, which constitutes a new direction in the treatment of cancer. Magnetic nanoparticles (MNPs) can circumvent vascular tissue to concentrate at the site of the tumor. Under the influence of an external, alternating magnetic field, MNPs generate high temperatures within the tumor and ablate malignant cells while inflicting minimal damage to healthy host tissue. Due to their theranostic properties, they constitute a promising candidate for the treatment of cancer. A critical review of the type, size and therapeutic effect of different MNPs is presented, following an appraisal of the literature in the last 5 years. This is a multibillion dollar industry, with a few studies moving to clinical trials within the next 5 years.

Mesenchymal stem cells and immunomodulation: current status and future prospects

PubMed Central

Gao, F; Chiu, S M; Motan, D A L; Zhang, Z; Chen, L; Ji, H-L; Tse, H-F; Fu, Q-L; Lian, Q

2016-01-01

The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them an invaluable cell type for the repair of tissue/ organ damage caused by chronic inflammation or autoimmune disorders. Although they hold great promise in the treatment of immune disorders such as graft versus host disease (GvHD) and allergic disorders, there remain many challenges to overcome before their widespread clinical application. An understanding of the biological properties of MSCs will clarify the mechanisms of MSC-based transplantation for immunomodulation. In this review, we summarize the preclinical and clinical studies of MSCs from different adult tissues, discuss the current hurdles to their use and propose the future development of pluripotent stem cell-derived MSCs as an approach to immunomodulation therapy. PMID:26794657

Enhancement of healing in osteochondral defects by collagen sponge implants.

PubMed

Speer, D P; Chvapil, M; Volz, R G; Holmes, M D

1979-10-01

Implants of porous, highly cross-linked collagen sponge (CS) were tested for their capacity to enhance the healing of osteochondral defects in rabbits. Comparison was made to the healing of similar defects with polyvinyl alcohol sponge (PVAS) implants and with no implants (CONT). Evaluation was carried out up to 44 weeks following implantation and included observation of host cellular response, biodegradability of implant, gross appearance of restored joint surface, collagenous architecture of repair tissue, and properties of the junctions of implants and host articular cartilage, subchondral bone, and medullary bone. Collagen sponge proved most effective in promoting healing of osteochondral defects with fibrous and fibrocartilaginous tissue over restored subchondral bone. Collagen sponge showed many desirable properties as a potential material for biologic resurfacing of damaged joints. These properties included porosity, biodegradability, biocompatability, ability to mechanically protect cells and matrix while directing cell ingrowth, and an available chemical technology for modifying its biomechanical and biological properties. Comparative analysis of results of healing of CS, PVAS, and CONT osteochondral defects suggest rational design criteria for implant materials to improve their effectiveness in restoration of articular surfaces.

The role of granulocyte macrophage-colony stimulating factor in gastrointestinal immunity to salmonellosis.

PubMed

Coon, C; Beagley, K W; Bao, S

2009-08-01

Human Salmonella infection, in particular, typhoid fever is a highly infectious disease that remains a major public health problem causing significant morbidity and mortality. The outcome of these infections depends on the host's immune response, particularly the actions of granulocytes and macrophages. Using a mouse model of human typhoid fever, with Salmonella typhimurium infection of wild type and granulocyte macrophage-colony stimulating factor (GM-CSF) knock out mice we show a delay in the onset of immune-mediated tissue damage in the spleens and livers of GM-CSF(-/-) mice. Furthermore, GM-CSF(-/-) mice have a prolonged sequestration of S. typhimurium in affected tissues despite an increased production of F4/80+ effector cells. Moreover in the absence of GM-CSF, a decrease in pro-inflammatory cytokine expression of tumor necrosis factor-alpha, interleukin-12 (IL-12) and IL-18 was found, which may alter the host's immune response to infection. GM-CSF appears to play an important role in the pathogenesis of Salmonellosis, and may contribute significantly to the development of protective gastrointestinal mucosal immune responses against oral pathogens.

Photoactivated methods for enabling cartilage-to-cartilage tissue fixation

NASA Astrophysics Data System (ADS)

Sitterle, Valerie B.; Roberts, David W.

2003-06-01

The present study investigates whether photoactivated attachment of cartilage can provide a viable method for more effective repair of damaged articular surfaces by providing an alternative to sutures, barbs, or fibrin glues for initial fixation. Unlike artificial materials, biological constructs do not possess the initial strength for press-fitting and are instead sutured or pinned in place, typically inducing even more tissue trauma. A possible alternative involves the application of a photosensitive material, which is then photoactivated with a laser source to attach the implant and host tissues together in either a photothermal or photochemical process. The photothermal version of this method shows potential, but has been almost entirely applied to vascularized tissues. Cartilage, however, exhibits several characteristics that produce appreciable differences between applying and refining these techniques when compared to previous efforts involving vascularized tissues. Preliminary investigations involving photochemical photosensitizers based on singlet oxygen and electron transfer mechanisms are discussed, and characterization of the photodynamic effects on bulk collagen gels as a simplified model system using FTIR is performed. Previous efforts using photothermal welding applied to cartilaginous tissues are reviewed.

Post-treatment Vascular Leakage and Inflammatory Responses around Brain Cysts in Porcine Neurocysticercosis

PubMed Central

Mahanty, Siddhartha; Orrego, Miguel Angel; Mayta, Holger; Marzal, Miguel; Cangalaya, Carla; Paredes, Adriana; Gonzales-Gustavson, Eloy; Arroyo, Gianfranco; Gonzalez, Armando E.; Guerra-Giraldez, Cristina; García, Hector H.; Nash, Theodore E.

2015-01-01

Cysticidal treatment of neurocysticercosis, an infection of humans and pig brains with Taenia solium, results in an early inflammatory response directed to cysts causing seizures and focal neurological manifestations. Treatment-induced pericystic inflammation and its association with blood brain barrier (BBB) dysfunction, as determined by Evans blue (EB) extravasation, was studied in infected untreated and anthelmintic-treated pigs. We compared the magnitude and extent of the pericystic inflammation, presence of EB-stained capsules, the level of damage to the parasite, expression of genes for proinflammatory and regulatory cytokines, chemokines, and tissue remodeling by quantitative PCR assays between treated and untreated infected pigs and between EB-stained (blue) and non stained (clear) cysts. Inflammatory scores were higher in pericystic tissues from EB-stained cysts compared to clear cysts from untreated pigs and also from anthelmintic-treated pigs 48 hr and 120 hr after treatment. The degree of inflammation correlated with the severity of cyst wall damage and both increased significantly at 120 hours. Expression levels of the proinflammatory genes for IL-6, IFN-γ, TNF-α were higher in EB-stained cysts compared to clear cysts and unaffected brain tissues, and were generally highest at 120 hr. Additionally, expression of some markers of immunoregulatory activity (IL-10, IL-2Rα) were decreased in EB-stained capsules. An increase in other markers for regulatory T cells (CTLA4, FoxP3) was found, as well as significant increases in expression of two metalloproteases, MMP1 and MMP2 at 48 hr and 120 hr post-treatment. We conclude that the increase in severity of the inflammation caused by treatment is accompanied by both a proinflammatory and a complex regulatory response, largely limited to pericystic tissues with compromised vascular integrity. Because treatment induced inflammation occurs in porcine NCC similar to that in human cases, this model can be used to investigate mechanisms involved in host damaging inflammatory responses and agents or modalities that may control damaging post treatment inflammation. PMID:25774662

The Schistosoma Granuloma: Friend or Foe?

PubMed Central

Hams, Emily; Aviello, Gabriella; Fallon, Padraic G.

2013-01-01

Infection of man with Schistosoma species of trematode parasite causes marked chronic morbidity. Individuals that become infected with Schistosomes may develop a spectrum of pathology ranging from mild cercarial dermatitis to severe tissue inflammation, in particular within the liver and intestines, which can lead to life threatening hepatosplenomegaly. It is well established that the etiopathology during schistosomiasis is primarily due to an excessive or unregulated inflammatory response to the parasite, in particular to eggs that become trapped in various tissue. The eggs forms the foci of a classical type 2 granulomatous inflammation, characterized by an eosinophil-rich, CD4+ T helper (Th) 2 cell dominated infiltrate with additional infiltration of alternatively activated macrophages (M2). Indeed the sequela of the type 2 perioval granuloma is marked fibroblast infiltration and development of fibrosis. Paradoxically, while the granuloma is the cause of pathology it also can afford some protection, whereby the granuloma minimizes collateral tissue damage in the liver and intestines. Furthermore, the parasite is exquisitely reliant on the host to mount a granulomatous reaction to the eggs as this inflammatory response facilitates the successful excretion of the eggs from the host. In this focused review we will address the conundrum of the S. mansoni granuloma acting as both friend and foe in inflammation during infection. PMID:23596444

Personalizing Stem Cell Research and Therapy: The Arduous Road Ahead or Missed Opportunity?

PubMed Central

Patel, S.A.; King, C.C.; Lim, P.K.; Habiba, U.; Dave, M.; Porecha, R.; Rameshwar, P.

2010-01-01

The euphoria of stem cell therapy has diminished, allowing scientists, clinicians and the general public to seriously re-examine how and what types of stem cells would effectively repair damaged tissue, prevent further tissue damage and/or replace lost cells. Importantly, there is a growing recognition that there are substantial person-to-person differences in the outcome of stem cell therapy. Even though the small molecule pharmaceuticals have long remained a primary focus of the personalized medicine research, individualized or targeted use of stem cells to suit a particular individual could help forecast potential failures of the therapy or identify, early on, the individuals who might benefit from stem cell interventions. This would however demand collaboration among several specialties such as pharmacology, immunology, genomics and transplantation medicine. Such transdisciplinary work could also inform how best to achieve efficient and predictable stem cell migration to sites of tissue damage, thereby facilitating tissue repair. This paper discusses the possibility of polarizing immune responses to rationalize and individualize therapy with stem cell interventions, since generalized “one-size-fits-all” therapy is difficult to achieve in the face of the diverse complexities posed by stem cell biology. We also present the challenges to stem cell delivery in the context of the host related factors. Although we focus on the mesenchymal stem cells in this paper, the overarching rationale can be extrapolated to other types of stem cells as well. Hence, the broader purpose of this paper is to initiate a dialogue within the personalized medicine community by expanding the scope of inquiry in the field from pharmaceuticals to stem cells and related cell-based health interventions. PMID:20563265

Retroperitoneal Actinomycosis: A Rare Sequela of an Infected Obstructing Ureteral Stone.

PubMed

Bearrick, Elizabeth; Dixon, Colby A; Rhein, Joshua; Borofsky, Michael S

2017-01-01

Background: Actinomycosis is a condition in which Actinomyces , a normal component of the oral and gastrointenstial flora, becomes pathogenic in the setting of damaged tissue, leading to widespread tissue destruction across fascial planes. Prior literature describing this condition is rare, particularly cases involving the retroperitoneum. In this study, we report a case of retroperitoneal actinomycosis caused by an infected, obstructing ureteral stone. Case Presentation: A 48-year-old woman with a history of substance abuse, malnutrition, and gastric bypass presented to the emergency room with a 3-week history of abdominal pain and fevers. Workup revealed a 9 mm obstructing right ureteral stone with associated perinephric fluid collection that was concerning for forniceal rupture. There was left hydronephrosis and a 3 mm lower pole renal calculus as well. The patient underwent emergent decompression where bilateral duplicated collecting systems were identified, requiring stenting of all four moieties to ensure maximal decompression in the setting of obstructive pyelonephritis. Urine cultures grew Escherichia coli and Candida . The patient continued to deteriorate despite culture appropriate antibiotic therapy; repeat scan revealed progression of her perinephric fluid collection into a loculated retroperitoneal abscess. A percutaneous drain was placed, and nearly half a liter of pus was evacuated. Fluid cultures grew Actinomyces , and she ultimately recovered after a prolonged course of antibiotics, including 1 month of intravenous therapy and an additional 6 months of oral treatment. All stones were ultimately removed via ureteroscopy. Conclusion: Actinomycosis is a rare invasive infection that is caused when the Actinomyces bacteria colonizes damaged tissue. We present the first reported case of urolithiasis inciting this process via tissue damage caused by obstruction and infection. Although rare, heightened suspicion is warranted among immunocompromised hosts who do not improve after decompression in such scenarios.

A murine experimental anthracycline extravasation model: pathology and study of the involvement of topoisomerase II alpha and iron in the mechanism of tissue damage.

PubMed

Thougaard, Annemette V; Langer, Seppo W; Hainau, Bo; Grauslund, Morten; Juhl, Birgitte Ravn; Jensen, Peter Buhl; Sehested, Maxwell

2010-02-28

The bisdioxopiperazine topoisomerase II catalytic inhibitor dexrazoxane has successfully been introduced into the clinic as an antidote to accidental anthracycline extravasation based on our preclinical mouse studies. The histology of this mouse extravasation model was investigated and found to be similar to findings in humans: massive necrosis in the subcutis, dermis and epidermis followed by sequestration and healing with granulation tissue, and a graft-versus-host-like reaction with hyperkeratotic and acanthotic keratinocytes, occasional apoptoses, epidermal invasion by lymphocytes and healing with dense dermal connective tissue. The extension of this fibrosis was quantified, and dexrazoxane intervention resulted in a statistically significant decrease in fibrosis extension, as also observed in the clinic. Several mechanisms have been proposed in anthracycline extravasation cytotoxicity, and we tested two major hypotheses: (1) interaction with topoisomerase II alpha and (2) the formation of tissue damaging reactive oxygen species following redox cycling of an anthracycline Fe(2+) complex. Dexrazoxane could minimise skin damage via both mechanisms, as it stops the catalytic activity of topoisomerase II alpha and thereby prevents access of anthracycline to the enzyme and thus cytotoxicity, and also acts as a strong iron chelator following opening of its two bisdioxopiperazine rings. Using the model of extravasation in a dexrazoxane-resistant transgenic mouse with a heterozygous mutation in the topoisomerase II alpha gene (Top2a(Y165S/+)), we found that dexrazoxane provided a protection against anthracycline-induced skin wounds that was indistinguishable from that found in wildtype mice. Thus, interaction with topoisomerase II alpha is not central in the pathogenesis of anthracycline-induced skin damage. In contrast to dexrazoxane, the iron-chelating bisdioxopiperazine ICRF-161 do not inhibit the catalytic cycle of topoisomerase II alpha. This compound was used to isolate and test the importance of iron in the wound pathogenesis. ICRF-161 was found ineffective in the treatment of anthracycline-induced skin damage, suggesting that iron does not play a dominant role in the genesis of wounds. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Mathematical Modeling of Early Cellular Innate and Adaptive Immune Responses to Ischemia/Reperfusion Injury and Solid Organ Allotransplantation

PubMed Central

Day, Judy D.; Metes, Diana M.; Vodovotz, Yoram

2015-01-01

A mathematical model of the early inflammatory response in transplantation is formulated with ordinary differential equations. We first consider the inflammatory events associated only with the initial surgical procedure and the subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host as well as the donor graft. These events release damage-associated molecular pattern molecules (DAMPs), thereby initiating an acute inflammatory response. In simulations of this model, resolution of inflammation depends on the severity of the tissue damage caused by these events and the patient’s (co)-morbidities. We augment a portion of a previously published mathematical model of acute inflammation with the inflammatory effects of T cells in the absence of antigenic allograft mismatch (but with DAMP release proportional to the degree of graft damage prior to transplant). Finally, we include the antigenic mismatch of the graft, which leads to the stimulation of potent memory T cell responses, leading to further DAMP release from the graft and concomitant increase in allograft damage. Regulatory mechanisms are also included at the final stage. Our simulations suggest that surgical injury and I/R-induced graft damage can be well-tolerated by the recipient when each is present alone, but that their combination (along with antigenic mismatch) may lead to acute rejection, as seen clinically in a subset of patients. An emergent phenomenon from our simulations is that low-level DAMP release can tolerize the recipient to a mismatched allograft, whereas different restimulation regimens resulted in an exaggerated rejection response, in agreement with published studies. We suggest that mechanistic mathematical models might serve as an adjunct for patient- or sub-group-specific predictions, simulated clinical studies, and rational design of immunosuppression. PMID:26441988

Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells

PubMed Central

Sato, Hiromi

2017-01-01

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection. PMID:28750011

Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells.

PubMed

Sato, Hiromi; Coburn, Jenifer

2017-07-01

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection.

Intravascular detection of Giardia trophozoites in naturally infected mice. An electron microscopic study.

PubMed

el-Shewy, K A; Eid, R A

2003-06-01

During routine transmission electron microscopic (TEM) examination of mice naturally infected with Giardia muris, an intense infection with Giardia trophozoites was demonstrated within intestinal and renal tissues. Examination of randomly taken sections from these heavily infected tissues revealed marked deep affection with mixed pathology. Duodenal sections were found loaded with Giardia trophozoites in intimate contact with necrotic gut cells. Some of these trophozoites were detected within central lacteal of damaged villi and nearby blood vessels. Interestingly, and for the first time to be demonstrated, morphologically identical G. muris trophozoite was detected in a renal blood vessel. An intense cellular immune reaction was obviously demonstrated with remarkable interaction between giant macrophages and the trophozoites particulates. Involvement of deep tissues by Giardia trophozoites and their presence within vascular channels could open up questions about the possible invasive and disseminative behavior of G. muris, particularly in heavily and naturally infected hosts.

The morphology and histopathology of Nephridiacanthus major (Acanthocephala: Oligacanthorhynchidae) from hedgehogs in Iran.

PubMed

Heckmann, Richard A; Amin, Omar M; Halajian, Ali; El-Naggar, Atif M

2013-02-01

The morphology of Nephridiacanthus major (Bremser 1811 in Westrumb 1821) Golvan, 1962 collected from the long-eared hedgehog Hemiechinus auritus (Gmelin 1770) and the Eastern European hedgehog Erinaceus concolor Martin, 1838 (Erinaceidae) is described using SEM for the first time. This acanthocephalan was previously described from hedgehogs in Europe, Asia, and Africa. Measurements of specimens from Iran, Bulgaria, Germany, Central Asia, Morocco, and Egypt show considerable variations in the size of the trunk, proboscis, proboscis hooks and receptacle, and eggs. The SEM studies add new perspectives to its morphology. Features observed for the first time include the near terminal position and shape of the female gonopore and orifice, among others. Histopathological studies for this species are reported for the first time. Tissue sections show extensive damage near the proboscis with hemorrhaging and formation of collagenous connective tissue, compression of the intestinal mucosa, obstruction of intestinal lumen, and extensive necrosis of host epithelial tissue.

What’s the Damage? The Impact of Pathogens on Pathways that Maintain Host Genome Integrity

PubMed Central

Weitzman, Matthew D.; Weitzman, Jonathan B.

2014-01-01

Maintaining genome integrity and transmission of intact genomes is critical for cellular, organismal, and species survival. Cells can detect damaged DNA, activate checkpoints, and either enable DNA repair or trigger apoptosis to eliminate the damaged cell. Aberrations in these mechanisms lead to somatic mutations and genetic instability, which are hallmarks of cancer. Considering the long history of host-microbe coevolution, an impact of microbial infection on host genome integrity is not unexpected, and emerging links between microbial infections and oncogenesis further reinforce this idea. In this review, we compare strategies employed by viruses, bacteria, and parasites to alter, subvert, or otherwise manipulate host DNA damage and repair pathways. We highlight how microbes contribute to tumorigenesis by directly inducing DNA damage, inactivating checkpoint controls, or manipulating repair processes. We also discuss indirect effects resulting from inflammatory responses, changes in cellular metabolism, nuclear architecture, and epigenome integrity, and the associated evolutionary tradeoffs. PMID:24629335

Self-healing pH-sensitive poly[(methyl vinyl ether)-alt-(maleic acid)]-based supramolecular hydrogels formed by inclusion complexation between cyclodextrin and adamantane.

PubMed

Ma, Xiaoe; Zhou, Naizhen; Zhang, Tianzhu; Hu, Wanjun; Gu, Ning

2017-04-01

Self-healing materials are of interest for drug delivery, cell and gene therapy, tissue engineering, and other biomedical applications. In this work, on the base of biocompatible polymer poly(methyl vinyl ether-alt-maleic acid) (P(MVE-alt-MA)), host polymer β-cyclodextrin-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-β-CD) and guest polymer adamantane-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-Ad) were first prepared. Then through taking advantage of the traditional host-guest interaction of β-cyclodextrin and adamantane, a novel self-healing pH-sensitive physical P(MVE-alt-MA)-g-β-CD/P(MVE-alt-MA)-g-Ad supramolecular hydrogels were obtained after simply mixing the aqueous solution of host polymer and guest polymer. This kind of supramolecular hydrogels not only possess pH-sensitivity, but also possess the ability to repair themselves after being damaged. Copyright © 2016 Elsevier B.V. All rights reserved.

Immunotherapy against cancer-related viruses

PubMed Central

Tashiro, Haruko; Brenner, Malcolm K

2017-01-01

Approximately 12% of all cancers worldwide are associated with viral infections. To date, eight viruses have been shown to contribute to the development of human cancers, including Epstein-Barr virus (EBV), Hepatitis B and C viruses, and Human papilloma virus, among others. These DNA and RNA viruses produce oncogenic effects through distinct mechanisms. First, viruses may induce sustained disorders of host cell growth and survival through the genes they express, or may induce DNA damage response in host cells, which in turn increases host genome instability. Second, they may induce chronic inflammation and secondary tissue damage favoring the development of oncogenic processes in host cells. Viruses like HIV can create a more permissive environment for cancer development through immune inhibition, but we will focus on the previous two mechanisms in this review. Unlike traditional cancer therapies that cannot distinguish infected cells from non-infected cells, immunotherapies are uniquely equipped to target virus-associated malignancies. The targeting and functioning mechanisms associated with the immune response can be exploited to prevent viral infections by vaccination, and can also be used to treat infection before cancer establishment. Successes in using the immune system to eradicate established malignancy by selective recognition of virus-associated tumor cells are currently being reported. For example, numerous clinical trials of adoptive transfer of ex vivo generated virus-specific T cells have shown benefit even for established tumors in patients with EBV-associated malignancies. Additional studies in other virus-associated tumors have also been initiated and in this review we describe the current status of immunotherapy for virus-associated malignancies and discuss future prospects. PMID:28008927

Reduced Leukocyte Infiltration in Absence of Eosinophils Correlates with Decreased Tissue Damage and Disease Susceptibility in ΔdblGATA Mice during Murine Neurocysticercosis.

PubMed

Mishra, Pramod K; Li, Qun; Munoz, Luis E; Mares, Chris A; Morris, Elizabeth G; Teale, Judy M; Cardona, Astrid E

2016-06-01

Neurocysticercosis (NCC) is one of the most common helminth parasitic diseases of the central nervous system (CNS) and the leading cause of acquired epilepsy worldwide. NCC is caused by the presence of the metacestode larvae of the tapeworm Taenia solium within brain tissues. NCC patients exhibit a long asymptomatic phase followed by a phase of symptoms including increased intra-cranial pressure and seizures. While the asymptomatic phase is attributed to the immunosuppressive capabilities of viable T. solium parasites, release of antigens by dying organisms induce strong immune responses and associated symptoms. Previous studies in T. solium-infected pigs have shown that the inflammatory response consists of various leukocyte populations including eosinophils, macrophages, and T cells among others. Because the role of eosinophils within the brain has not been investigated during NCC, we examined parasite burden, disease susceptibility and the composition of the inflammatory reaction in the brains of infected wild type (WT) and eosinophil-deficient mice (ΔdblGATA) using a murine model of NCC in which mice were infected intracranially with Mesocestoides corti, a cestode parasite related to T. solium. In WT mice, we observed a time-dependent induction of eosinophil recruitment in infected mice, contrasting with an overall reduced leukocyte infiltration in ΔdblGATA brains. Although, ΔdblGATA mice exhibited an increased parasite burden, reduced tissue damage and less disease susceptibility was observed when compared to infected WT mice. Cellular infiltrates in infected ΔdblGATA mice were comprised of more mast cells, and αβ T cells, which correlated with an abundant CD8+ T cell response and reduced CD4+ Th1 and Th2 responses. Thus, our data suggest that enhanced inflammatory response in WT mice appears detrimental and associates with increased disease susceptibility, despite the reduced parasite burden in the CNS. Overall reduced leukocyte infiltration due to absence of eosinophils correlates with attenuated tissue damage and longer survival of ΔdblGATA mice. Therefore, our study suggests that approaches to clear NCC will require strategies to tightly control the host immune response while eradicating the parasite with minimal damage to brain tissue.

Reduced Leukocyte Infiltration in Absence of Eosinophils Correlates with Decreased Tissue Damage and Disease Susceptibility in ΔdblGATA Mice during Murine Neurocysticercosis

PubMed Central

Mishra, Pramod K.; Li, Qun; Munoz, Luis E.; Mares, Chris A.; Morris, Elizabeth G.; Teale, Judy M.; Cardona, Astrid E.

2016-01-01

Neurocysticercosis (NCC) is one of the most common helminth parasitic diseases of the central nervous system (CNS) and the leading cause of acquired epilepsy worldwide. NCC is caused by the presence of the metacestode larvae of the tapeworm Taenia solium within brain tissues. NCC patients exhibit a long asymptomatic phase followed by a phase of symptoms including increased intra-cranial pressure and seizures. While the asymptomatic phase is attributed to the immunosuppressive capabilities of viable T. solium parasites, release of antigens by dying organisms induce strong immune responses and associated symptoms. Previous studies in T. solium-infected pigs have shown that the inflammatory response consists of various leukocyte populations including eosinophils, macrophages, and T cells among others. Because the role of eosinophils within the brain has not been investigated during NCC, we examined parasite burden, disease susceptibility and the composition of the inflammatory reaction in the brains of infected wild type (WT) and eosinophil-deficient mice (ΔdblGATA) using a murine model of NCC in which mice were infected intracranially with Mesocestoides corti, a cestode parasite related to T. solium. In WT mice, we observed a time-dependent induction of eosinophil recruitment in infected mice, contrasting with an overall reduced leukocyte infiltration in ΔdblGATA brains. Although, ΔdblGATA mice exhibited an increased parasite burden, reduced tissue damage and less disease susceptibility was observed when compared to infected WT mice. Cellular infiltrates in infected ΔdblGATA mice were comprised of more mast cells, and αβ T cells, which correlated with an abundant CD8+ T cell response and reduced CD4+ Th1 and Th2 responses. Thus, our data suggest that enhanced inflammatory response in WT mice appears detrimental and associates with increased disease susceptibility, despite the reduced parasite burden in the CNS. Overall reduced leukocyte infiltration due to absence of eosinophils correlates with attenuated tissue damage and longer survival of ΔdblGATA mice. Therefore, our study suggests that approaches to clear NCC will require strategies to tightly control the host immune response while eradicating the parasite with minimal damage to brain tissue. PMID:27332553

Alcohol and the Intestine

PubMed Central

Patel, Sheena; Behara, Rama; Swanson, Garth R.; Forsyth, Christopher B.; Voigt, Robin M.; Keshavarzian, Ali

2015-01-01

Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. However, a subset of alcoholics without any of these predisposing factors can develop alcohol-mediated organ injury. The gastrointestinal tract (GI) could be an important source of inflammation in alcohol-mediated organ damage. The purpose of review was to evaluate mechanisms of alcohol-induced endotoxemia (including dysbiosis and gut leakiness), and highlight the predisposing factors for alcohol-induced dysbiosis and gut leakiness to endotoxins. Barriers, including immunologic, physical, and biochemical can regulate the passage of toxins into the portal and systemic circulation. In addition, a host of environmental interactions including those influenced by circadian rhythms can impact alcohol-induced organ pathology. There appears to be a role for therapeutic measures to mitigate alcohol-induced organ damage by normalizing intestinal dysbiosis and/or improving intestinal barrier integrity. Ultimately, the inflammatory process that drives progression into organ damage from alcohol appears to be multifactorial. Understanding the role of the intestine in the pathogenesis of alcoholic liver disease can pose further avenues for pathogenic and treatment approaches. PMID:26501334

Risk-rating Saratoga Spittlebug Damage by Abundance of Alternate-host Plants

Treesearch

Louis F. Wilson

1971-01-01

The potential damage of the Saratoga spittlebug to red pine can be predicted by comparing the percentage of ground occupied by sweet-fern with the percentage of ground cover occupied by other nymphal host plants. A risk-rating graph is used to estimate potential damage.

Chemically modified tetracyclines an emerging host modulator in chronic periodontitis patients: A randomized, double-blind, placebo-controlled, clinical trial.

PubMed

Alyousef, Abdullah A; Divakar, Darshan Devang; Muzaheed

2017-09-01

Although periodontal diseases are caused by some of the specific pathogens, most of the tissue damage is caused by the host reaction to disease and not actually by the infections. Therefore, host modulatory therapy (HMT) has advanced benefit for the treatment of periodontitis, which works basically by reducing tissue destruction and regeneration in periodontium by altering the critical aspects of host response regulation and up regulating defensive regenerative responses. The present study was conducted with the goal to test an innovative therapeutic option using chemically modified tetracycline in patients affected with generalized, moderate and severe chronic periodontitis. We assumed that CMT might have the potential to provoke an assessable clinical result and pharmacologically impede the level inflammatory flow. CMT (incyclinide) treated group had significantly higher CAL (clinical attachment) values than Placebo Control suggesting an improved CAL in CMT treatment. Host modulation therapy width incyclinide can be as an adjunct to conventional nonsurgical therapies without antimicrobial resistance. Progress was noticed in the clinical parameters but not the serum CRP level in our study establishing the role of CMTs in controlling chronic periodontitis. Also CMT treatment indicates its role in anti-inflammatory process as it inhibited IL-12 and TNF alpha but IL-10 level was not affected. However, more randomized placebo-controlled clinical trials with large sample size are required in order to authenticate the usage of CMTs in chronic periodontitis treatment. Based on this understanding, exploration of the novel, low-cost synthetic inhibitors that can be used as potential therapeutic agents, has been tested. Copyright © 2017 Elsevier Ltd. All rights reserved.

Why do larval helminths avoid the gut of intermediate hosts?

PubMed

Parker, G A; Ball, M A; Chubb, J C

2009-10-07

In complex life cycles, larval helminths typically migrate from the gut to exploit the tissues of their intermediate hosts. Yet the definitive host's gut is overwhelmingly the most favoured site for adult helminths to release eggs. Vertebrate nematodes with one-host cycles commonly migrate to a site in the host away from the gut before returning to the gut for reproduction; those with complex cycles occupy sites exclusively in the intermediate host's tissues or body spaces, and may or may not show tissue migration before (typically) returning to the gut in the definitive host. We develop models to explain the patterns of exploitation of different host sites, and in particular why larval helminths avoid the intermediate host's gut, and adult helminths favour it. Our models include the survival costs of migration between sites, and maximise fitness (=expected lifetime number of eggs produced by a given helminth propagule) in seeking the optimal strategy (host gut versus host tissue exploitation) under different growth, mortality, transmission and reproductive rates in the gut and tissues (i.e. sites away from the gut). We consider the relative merits of the gut and tissues, and conclude that (i) growth rates are likely to be higher in the tissues, (ii) mortality rates possibly higher in the gut (despite the immunological inertness of the gut lumen), and (iii) that there are very high benefits to egg release in the gut. The models show that these growth and mortality relativities would account for the common life history pattern of avoidance of the intermediate host's gut because the tissues offer a higher growth rate/mortality rate ratio (discounted by the costs of migration), and make a number of testable predictions. Though nematode larvae in paratenic hosts usually migrate to the tissues, unlike larvae in intermediates, they sometimes remain in the gut, which is predicted since in paratenics mortality rate and migration costs alone determine the site to be exploited.

Plasma bacterial and mitochondrial DNA distinguish bacterial sepsis from sterile systemic inflammatory response syndrome and quantify inflammatory tissue injury in nonhuman primates.

PubMed

Sursal, Tolga; Stearns-Kurosawa, Deborah J; Itagaki, Kiyoshi; Oh, Sun-Young; Sun, Shiqin; Kurosawa, Shinichiro; Hauser, Carl J

2013-01-01

Systemic inflammatory response syndrome (SIRS) is a fundamental host response common to bacterial infection and sterile tissue injury. Systemic inflammatory response syndrome can cause organ dysfunction and death, but its mechanisms are incompletely understood. Moreover, SIRS can progress to organ failure or death despite being sterile or after control of the inciting infection. Biomarkers discriminating between sepsis, sterile SIRS, and postinfective SIRS would therefore help direct care. Circulating mitochondrial DNA (mtDNA) is a damage-associated molecular pattern reflecting cellular injury. Circulating bacterial 16S DNA (bDNA) is a pathogen-associated pattern (PAMP) reflecting ongoing infection. We developed quantitative polymerase chain reaction assays to quantify these markers, and predicting their plasma levels might help distinguish sterile injury from infection. To study these events in primates, we assayed banked serum from Papio baboons that had undergone a brief challenge of intravenous Bacillus anthracis delta Sterne (modified to remove toxins) followed by antibiotics (anthrax) that causes organ failure and death. To investigate the progression of sepsis to "severe" sepsis and death, we studied animals where anthrax was pretreated with drotrecogin alfa (activated protein C), which attenuates sepsis in baboons. We also contrasted lethal anthrax bacteremia against nonlethal E. coli bacteremia and against sterile tissue injury from Shiga-like toxin 1. Bacterial DNA and mtDNA levels in timed samples were correlated with blood culture results and assays of organ function. Sterile injury by Shiga-like toxin 1 increased mtDNA, but bDNA was undetectable: consistent with the absence of infection. The bacterial challenges caused parallel early bDNA and mtDNA increases, but bDNA detected pathogens even after bacteria were undetectable by culture. Sublethal E. coli challenge only caused transient rises in mtDNA consistent with a self-limited injury. In lethal anthrax challenge (n = 4), bDNA increased transiently, but mtDNA levels remained elevated until death, consistent with persistent septic tissue damage after bacterial clearance. Critically, activated protein C pretreatment (n = 4) allowed mtDNA levels to decay after bacterial clearance with sparing of organ function and survival. In summary, host tissue injury correlates with mtDNA whether infective or sterile. Mitochondrial DNA and bDNA polymerase chain reactions can quantify tissue injury incurred by septic or sterile mechanisms and suggest the source of SIRS of unknown origin.

Plasma Bacterial and Mitochondrial DNA Distinguish Bacterial Sepsis from Sterile SIRS and Quantify Inflammatory Tissue Injury in Nonhuman Primates

PubMed Central

Sursal, Tolga; Stearns-Kurosawa, Deborah J; Itagaki, Kiyoshi; Oh, Sun-Young; Sun, Shiqin; Kurosawa, Shinichiro; Hauser, Carl J

2012-01-01

Systemic inflammatory response syndrome (SIRS) is a fundamental host response common to bacterial infection and sterile tissue injury. SIRS can cause organ dysfunction and death but its mechanisms are incompletely understood. Moreover, SIRS can progress to organ failure or death despite being sterile or after control of the inciting infection. Biomarkers discriminating between sepsis, sterile SIRS and post-infective SIRS would therefore help direct care. Circulating mitochondrial DNA (mtDNA) is a damage-associated molecular pattern (DAMP) reflecting cellular injury. Circulating bacterial 16S-DNA (bDNA) is a pathogen-associated pattern (PAMP) reflecting ongoing infection. We developed qPCR assays to quantify these markers and predicted their plasma levels might help distinguish sterile injury from infection. To study these events in primates we assayed banked serum from papio baboons that had undergone a brief challenge of intravenous Bacillus anthracis deltaSterne (modified to remove toxins) followed by antibiotics (anthrax) that causes organ failure and death. To investigate the progression of sepsis to “severe” sepsis and death we studied animals where anthrax was pretreated with drotrecogin alfa (aPC), which attenuates sepsis in baboons. We also contrasted lethal anthrax bacteremia against non-lethal E.coli bacteremia and against sterile tissue injury from Shiga-like toxin-1 (Stx1). bDNA and mtDNA levels in timed samples were correlated with blood culture results and assays of organ function. Sterile injury by Stx1 increased mtDNA but bDNA was undetectable: consistent with the absence of infection. The bacterial challenges caused parallel early bDNA and mtDNA increases, but bDNA detected pathogens even after bacteria were undetectable by culture. Sub-lethal E.coli challenge only caused transient rises in mtDNA consistent with a self-limited injury. In lethal anthrax challenge (n=4) bDNA increased transiently but mtDNA levels remained elevated until death, consistent with persistent septic tissue damage after bacterial clearance. Critically, aPC pre-treatment (n=4) allowed mtDNA levels to decay after bacterial clearance with sparing of organ function and survival. In summary, host tissue injury correlates with mtDNA whether infective or sterile. mtDNA and bDNA PCRs can quantify tissue injury incurred by septic or sterile mechanisms and suggest the source of SIRS of unknown origin. PMID:23247122

Chronic infection and the origin of adaptive immune system.

PubMed

Usharauli, David

2010-08-01

It has been speculated that the rise of the adaptive immune system in jawed vertebrates some 400 million years ago gave them a superior protection to detect and defend against pathogens that became more elusive and/or virulent to the host that had only innate immune system. First, this line of thought implies that adaptive immune system was a new, more sophisticated layer of host defense that operated independently of the innate immune system. Second, the natural consequence of this scenario would be that pathogens would have exercised so strong an evolutionary pressure that eventually no host could have afforded not to have an adaptive immune system. Neither of these arguments is supported by the facts. First, new experimental evidence has firmly established that operation of adaptive immune system is critically dependent on the ability of the innate immune system to detect invader-pathogens and second, the absolute majority of animal kingdom survives just fine with only an innate immune system. Thus, these data raise the dilemma: If innate immune system was sufficient to detect and protect against pathogens, why then did adaptive immune system develop in the first place? In contrast to the innate immune system, the adaptive immune system has one important advantage, precision. By precision I mean the ability of the defense system to detect and remove the target, for example, infected cells, without causing unwanted bystander damage of surrounding tissue. While the target precision per se is not important for short-term immune response, it becomes a critical factor when the immune response is long-lasting, as during chronic infection. In this paper I would like to propose new, "toxic index" hypothesis where I argue that the need to reduce the collateral damage to the tissue during chronic infection(s) was the evolutionary pressure that led to the development of the adaptive immune system. Copyright 2010 Elsevier Ltd. All rights reserved.

Host response biomarkers in the diagnosis of sepsis: a general overview.

PubMed

Parlato, Marianna; Cavaillon, Jean-Marc

2015-01-01

Critically ill patients who display a systemic inflammatory response syndrome (SIRS) are prone to develop nosocomial infections. The challenge remains to distinguish as early as possible among SIRS patients those who are developing sepsis. Following a sterile insult, damage-associated molecular patterns (DAMPs) released by damaged tissues and necrotic cells initiate an inflammatory response close to that observed during sepsis. During sepsis, pathogen-associated molecular patterns (PAMPs) trigger the release of host mediators involved in innate immunity and inflammation through identical receptors as DAMPs. In both clinical settings, a compensatory anti-inflammatory response syndrome (CARS) is concomitantly initiated. The exacerbated production of pro- or anti-inflammatory mediators allows their detection in biological fluids and particularly within the bloodstream. Some of these mediators can be used as biomarkers to decipher among the patients those who developed sepsis, and eventually they can be used as prognosis markers. In addition to plasma biomarkers, the analysis of some surface markers on circulating leukocytes or the study of mRNA and miRNA can be helpful. While there is no magic marker, a combination of few biomarkers might offer a high accuracy for diagnosis.

[Application of silk-based tissue engineering scaffold for tendon / ligament regeneration].

PubMed

Hu, Yejun; Le, Huihui; Jin, Zhangchu; Chen, Xiao; Yin, Zi; Shen, Weiliang; Ouyang, Hongwei

2016-03-01

Tendon/ligament injury is one of the most common impairments in sports medicine. The traditional treatments of damaged tissue repair are unsatisfactory, especially for athletes, due to lack of donor and immune rejection. The strategy of tissue engineering may break through these limitations, and bring new hopes to tendon/ligament repair, even regeneration. Silk is a kind of natural biomaterials, which has good biocompatibility, wide range of mechanical properties and tunable physical structures; so it could be applied as tendon/ligament tissue engineering scaffolds. The silk-based scaffold has robust mechanical properties; combined with other biological ingredients, it could increase the surface area, promote more cell adhesion and improve the biocompatibility. The potential clinical application of silk-based scaffold has been confirmed by in vivo studies on tendon/ligament repairing, such as anterior cruciate ligament, medial collateral ligament, achilles tendon and rotator cuff. To develop novel biomechanically stable and host integrated tissue engineered tendon/ligament needs more further micro and macro studies, combined with product development and clinical application, which will give new hope to patients with tendon/ligament injury.

Regulatory T cells in the control of host-microorganism interactions (*).

PubMed

Belkaid, Yasmine; Tarbell, Kristin

2009-01-01

Each microenvironment requires a specific set of regulatory elements that are finely and constantly tuned to maintain local homeostasis. Various populations of regulatory T cells contribute to the maintenance of this equilibrium and establishment of controlled immune responses. In particular, regulatory T cells limit the magnitude of effector responses, which may result in failure to adequately control infection. However, regulatory T cells also help limit collateral tissue damage caused by vigorous antimicrobial immune responses against pathogenic microbes as well as commensals. In this review, we describe various situations in which the balance between regulatory T cells and effector immune functions influence the outcome of host-microorganism coexistence and discuss current hypotheses and points of polemic associated with the origin, target, and antigen specificity of both endogenous and induced regulatory T cells during these interactions.

Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System.

PubMed

Withers, David R; Hepworth, Matthew R

2017-01-01

The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of "exogenous" signals, such as dietary metabolites and commensal microbes, and "endogenous" host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a "communications hub" in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell-cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.

Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

PubMed Central

Withers, David R.; Hepworth, Matthew R.

2017-01-01

The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases. PMID:29085366

Clinical Implications of Oral Candidiasis: Host Tissue Damage and Disseminated Bacterial Disease

PubMed Central

Kong, Eric F.; Kucharíková, Sona; Peters, Brian M.; Shirtliff, Mark E.

2014-01-01

The clinical significance of polymicrobial interactions, particularly those between commensal species with high pathogenic potential, remains largely understudied. Although the dimorphic fungal species Candida albicans and the bacterium Staphylococcus aureus are common cocolonizers of humans, they are considered leading opportunistic pathogens. Oral candidiasis specifically, characterized by hyphal invasion of oral mucosal tissue, is the most common opportunistic infection in HIV+ and immunocompromised individuals. In this study, building on our previous findings, a mouse model was developed to investigate whether the onset of oral candidiasis predisposes the host to secondary staphylococcal infection. The findings demonstrated that in mice with oral candidiasis, subsequent exposure to S. aureus resulted in systemic bacterial infection with high morbidity and mortality. Histopathology and scanning electron microscopy of tongue tissue from moribund animals revealed massive C. albicans hyphal invasion coupled with S. aureus deep tissue infiltration. The crucial role of hyphae in the process was demonstrated using a non-hypha-producing and a noninvasive hypha-producing mutant strains of C. albicans. Further, in contrast to previous findings, S. aureus dissemination was aided but not contingent upon the presence of the Als3p hypha-specific adhesion. Importantly, impeding development of mucosal C. albicans infection by administering antifungal fluconazole therapy protected the animals from systemic bacterial disease. The combined findings from this study demonstrate that oral candidiasis may constitute a risk factor for disseminated bacterial disease warranting awareness in terms of therapeutic management of immunocompromised individuals. PMID:25422264

Clinical implications of oral candidiasis: host tissue damage and disseminated bacterial disease.

PubMed

Kong, Eric F; Kucharíková, Sona; Van Dijck, Patrick; Peters, Brian M; Shirtliff, Mark E; Jabra-Rizk, Mary Ann

2015-02-01

The clinical significance of polymicrobial interactions, particularly those between commensal species with high pathogenic potential, remains largely understudied. Although the dimorphic fungal species Candida albicans and the bacterium Staphylococcus aureus are common cocolonizers of humans, they are considered leading opportunistic pathogens. Oral candidiasis specifically, characterized by hyphal invasion of oral mucosal tissue, is the most common opportunistic infection in HIV(+) and immunocompromised individuals. In this study, building on our previous findings, a mouse model was developed to investigate whether the onset of oral candidiasis predisposes the host to secondary staphylococcal infection. The findings demonstrated that in mice with oral candidiasis, subsequent exposure to S. aureus resulted in systemic bacterial infection with high morbidity and mortality. Histopathology and scanning electron microscopy of tongue tissue from moribund animals revealed massive C. albicans hyphal invasion coupled with S. aureus deep tissue infiltration. The crucial role of hyphae in the process was demonstrated using a non-hypha-producing and a noninvasive hypha-producing mutant strains of C. albicans. Further, in contrast to previous findings, S. aureus dissemination was aided but not contingent upon the presence of the Als3p hypha-specific adhesion. Importantly, impeding development of mucosal C. albicans infection by administering antifungal fluconazole therapy protected the animals from systemic bacterial disease. The combined findings from this study demonstrate that oral candidiasis may constitute a risk factor for disseminated bacterial disease warranting awareness in terms of therapeutic management of immunocompromised individuals. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Intravital imaging of the immune responses during liver-stage malaria infection: An improved approach for fixing the liver.

PubMed

Akbari, Masoud; Kimura, Kazumi; Houts, James T; Yui, Katsuyuki

2016-10-01

The host-parasite relationship is one of the main themes of modern parasitology. Recent revolutions in science, including the development of various fluorescent proteins/probes and two-photon microscopy, have made it possible to directly visualize and study the mechanisms underlying the interaction between the host and pathogen. Here, we describe our method of preparing and setting-up the liver for our experimental approach of using intravital imaging to examine the interaction between Plasmodium berghei ANKA and antigen-specific CD8 + T cells during the liver-stage of the infection in four dimensions. Since the liver is positioned near the diaphragm, neutralization of respiratory movements is critical during the imaging process. In addition, blood circulation and temperature can be affected by the surgical exposure due to the anatomy and tissue structure of the liver. To control respiration, we recommend anesthesia with isoflurane inhalation at 1% during the surgery. In addition, our protocol introduces a cushion of gauze around the liver to avoid external pressure on the liver during intravital imaging using an inverted microscope, which makes it possible to image the liver tissue for long periods with minimal reduction in the blood circulation and with minimal displacement and tissue damage. The key point of this method is to reduce respiratory movements and external pressure on the liver tissue during intravital imaging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: immunity interruptus

PubMed Central

Behar, Samuel M.; Carpenter, Stephen M.; Booty, Matthew G.; Barber, Daniel L.; Jayaraman, Pushpa

2014-01-01

Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease – the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage. PMID:25311810

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: immunity interruptus.

PubMed

Behar, Samuel M; Carpenter, Stephen M; Booty, Matthew G; Barber, Daniel L; Jayaraman, Pushpa

2014-12-01

Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease--the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hsp-72, a candidate prognostic indicator of heatstroke.

PubMed

Dehbi, Mohammed; Baturcam, Engin; Eldali, Abdelmoneim; Ahmed, Maqbool; Kwaasi, Aaron; Chishti, Muhammad Azhar; Bouchama, Abderrezak

2010-09-01

Exposure of rats to environmental heat enhances the expression of heat shock protein-72 (Hsp-72) in most of their organs proportionally to heat stress severity. Pre-induction or over-expression of Hsp-72 prevents organ damage and lethality, suggesting that heat shock proteins (Hsps) may have a pathogenic role in this condition. We investigated the expression profile of Hsps in baboons subjected to environmental heat stress until the core temperature attained 42.5 degrees C (moderate heatstroke) or occurrence of hypotension associated with core temperature > or = 43.5 degrees C (severe heatstroke). Western blot analysis demonstrated a differential induction of Hsp-72 among organs of heat-stressed animals with the highest induction in the liver and the lowest in lung. Hsp-60 and Hsc-70 expression was similar between control and heat-stressed animals. ELISA studies indicated a marked release of Hsp-72 into the circulation of baboons with severe heatstroke with a peak at 24 h post-heatstroke onset and remained sustained up to 72 h. Hsp-72 release was not associated with core temperature or systolic blood pressure, but correlated with markers of liver, myocardium, and skeletal muscle tissue necrosis. Non-survivors displayed significantly higher Hsp-72 levels than survivors. No Hsp-60 was detected in the circulation. These findings add further evidence that increased expression of Hsp-72 may be an important component of the host response to severe heatstroke. They also suggest that extracellular Hsp-72 is a marker of multiple organs tissue damage. Whether extracellular Hsp-72 plays a role in the host immune response to heat stress merits further studies.

Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

PubMed

Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

2015-01-01

The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

A Novel Biopsy Method for Isolating Neural Stem Cells from the Subventricular Zone of the Adult Rat Brain for Autologous Transplantation in CNS Injuries.

PubMed

Aligholi, Hadi; Hassanzadeh, Gholamreza; Gorji, Ali; Azari, Hassan

2016-01-01

Despite all attempts the problem of regeneration in damaged central nervous system (CNS) has remained challenging due to its cellular complexity and highly organized and sophisticated connections. In this regard, stem cell therapy might serve as a viable therapeutic approach aiming either to support the damaged tissue and hence to reduce the subsequent neurological dysfunctions and impairments or to replace the lost cells and re-establish damaged circuitries. Adult neural stem/progenitor cells (NS/PCs) are one of the outstanding cell sources that can be isolated from the subventricular zone (SVZ) of the lateral ventricles. These cells can differentiate into neurons, astrocytes, and oligodendrocytes. Implanting autologous NS/PCs will greatly benefit the patients by avoiding immune rejection after implantation, better survival, and integration with the host tissue. Developing safe and efficient methods in small animal models will provide us with the opportunity to optimize procedures required to achieve successful human autologous NS/PC transplantation in near future. In this chapter, a highly controlled and safe biopsy method for harvesting stem cell containing tissue from the SVZ of adult rat brain is introduced. Then, isolation and expansion of NS/PCs from harvested specimen as well as the techniques to verify proliferation and differentiation capacity of the resulting NS/PCs are discussed. Finally, a method for assessing the biopsy lesion volume in the brain is described. This safe biopsy method in rat provides a unique tool to study autologous NS/PC transplantation in different CNS injury models.

Changes in plant growth and seed production in wild lima bean in response to herbivory are attenuated by parasitoids.

PubMed

Cuny, Maximilien A C; Gendry, Johanna; Hernández-Cumplido, Johnattan; Benrey, Betty

2018-03-29

Lima bean plants (Phaseolus lunatus) exhibit compensatory growth responses to herbivory. Among the various factors that have been identified to affect plant compensatory growth are the extent and type of tissue damage, the herbivore's feeding mode and the time of damage. Another factor that can greatly impact plant responses to herbivory, but has been largely ignored in previous studies, is the action of parasitoids. In most cases, parasitoids halt or slow down the development of herbivorous hosts, which, can result in decreased leaf damage, thereby affecting plant responses and ultimately plant fitness. Here, we investigated the effects of two koinobiont parasitoids on the amount of leaf damage inflicted by the Southern armyworm Spodoptera latifascia to wild lima bean, and the consequences of this for plant growth and seed production in the field. We specifically tested the hypothesis that the action of parasitoids will reduce plant damage and that this reduction will alter plant growth responses and seed production. Indeed, we found that in the presence of parasitoids plants suffered less damage than plants with only herbivores. As a consequence, compensatory growth was reduced and more and heavier seeds were produced earlier in the season, compared to plants exposed to only herbivores.

Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity

PubMed Central

Garcia, Emmanuel; Becker, Veronika G. C.; McCullough, Danielle J.; Stabley, John N.; Gittemeier, Elizabeth M.; Opoku-Acheampong, Alexander B.; Sieman, Dietmar W.

2016-01-01

Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10−9 to 10−4 M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. PMID:27125846

Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.

PubMed

Garcia, Emmanuel; Becker, Veronika G C; McCullough, Danielle J; Stabley, John N; Gittemeier, Elizabeth M; Opoku-Acheampong, Alexander B; Sieman, Dietmar W; Behnke, Bradley J

2016-07-01

Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. Copyright © 2016 the American Physiological Society.

Variability in leaf damage among cultivars of lychee, host of Myllocerus undecimpustulatus undatus Marshall adults

USDA-ARS?s Scientific Manuscript database

The Sri Lankan weevil has imposed heavy damage on the canopy of various ornamental and fruit trees since it was first detected in South Florida in 2000. One of the more heavily damaged fruit trees is lychee, Litchi chinensis (Sapindales: Sapindaceae). As part of a study to better understand host cho...

Deformation and reperfusion damages and their accumulation in subcutaneous tissues during loading and unloading: a theoretical modeling of deep tissue injuries.

PubMed

Mak, Arthur F T; Yu, Yanyan; Kwan, Linda P C; Sun, Lei; Tam, Eric W C

2011-11-21

Deep tissue injuries (DTI) involve damages in the subcutaneous tissues under intact skin incurred by prolonged excessive epidermal loadings. This paper presents a new theoretical model for the development of DTI, broadly based on the experimental evidence in the literatures. The model covers the loading damages implicitly inclusive of both the direct mechanical and ischemic injuries, and the additional reperfusion damages and the competing healing processes during the unloading phase. Given the damage accumulated at the end of the loading period, the relative strength of the reperfusion and the healing capacity of the involved tissues system, the model provides a description of the subsequent damage evolution during unloading. The model is used to study parametrically the scenario when reperfusion damage dominates over healing upon unloading and the opposite scenario when the loading and subsequent reperfusion damages remain small relative to the healing capacity of the tissues system. The theoretical model provides an integrated understanding of how tissue damage may further build-up paradoxically even with unloading, how long it would take for the loading and reperfusion damages in the tissues to become fully recovered, and how such loading and reperfusion damages, if not given sufficient time for recovery, may accumulate over multiple loading and unloading cycles, leading to clinical deep tissues ulceration. Copyright © 2011 Elsevier Ltd. All rights reserved.

Nanoceramics on osteoblast proliferation and differentiation in bone tissue engineering.

PubMed

Sethu, Sai Nievethitha; Namashivayam, Subhapradha; Devendran, Saravanan; Nagarajan, Selvamurugan; Tsai, Wei-Bor; Narashiman, Srinivasan; Ramachandran, Murugesan; Ambigapathi, Moorthi

2017-05-01

Bone, a highly dynamic connective tissue, consist of a bioorganic phase comprising osteogenic cells and proteins which lies over an inorganic phase predominantly made of CaPO 4 (biological apatite). Injury to bone can be due to mechanical, metabolic or inflammatory agents also owing pathological conditions like fractures, osteomyelitis, osteolysis or cysts may arise in enameloid, chondroid, cementum, or chondroid bone which forms the intermediate tissues of the body. Bone tissue engineering (BTE) applies bioactive scaffolds, host cells and osteogenic signals for restoring damaged or diseased tissues. Various bioceramics used in BTE can be bioactive (like glass ceramics and hydroxyapatite bioactive glass), bioresorbable (like tricalcium phosphates) or bioinert (like zirconia and alumina). Limiting the size of these materials to nano-scale has resulted in a higher surface area to volume ratio thereby improving multi-functionality, solubility, surface catalytic activity, high heat and electrical conductivity. Nanoceramics have been found to induce osteoconduction, osteointegration, osteogenesis and osteoinduction. The present review aims at summarizing the interactions of nanoceramics and osteoblast/stem cells for promoting the proliferation and differentiation of the osteoblast cells by nanoceramics as superior bone substitutes in bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Resiniferatoxin modulates the Th1 immune response and protects the host during intestinal nematode infection.

PubMed

Muñoz-Carrillo, J L; Contreras-Cordero, J F; Muñoz-López, J L; Maldonado-Tapia, C H; Muñoz-Escobedo, J J; Moreno-García, M A

2017-09-01

In the early stage of the intestinal phase of Trichinella spiralis infection, the host triggers a Th1-type immune response with the aim of eliminating the parasite. However, this response damages the host which favours the survival of the parasite. In the search for novel pharmacological strategies that inhibit the Th1 immune response and assist the host against T. spiralis infection, a recent study showed that resiniferatoxin had anti-inflammatory activity contributed to the host in T. spiralis infection. In this study, we evaluated whether RTX modulates the host immune response through the inhibition of Th1 cytokines in the intestinal phase. In addition, it was determined whether the treatment with RTX affects the infectivity of T. spiralis-L1 and the development of the T. spiralis life cycle. Our results show that RTX decreased serum levels of IL-12, INF-γ, IL-1β, TNF-α and parasite burden on muscle tissue. It was observed that T. spiralis-L1 treated with RTX decreased their infectivity affecting the development of the T. spiralis life cycle in mouse. These results demonstrate that RTX is able to inhibit the production of Th1 cytokines, contributing to the defence against T. spiralis, which places it as a potential drug modulator of the immune response. © 2017 John Wiley & Sons Ltd.

Small bite, large impact-saliva and salivary molecules in the medicinal leech, Hirudo medicinalis

NASA Astrophysics Data System (ADS)

Hildebrandt, Jan-Peter; Lemke, Sarah

2011-12-01

Blood-sucking leeches have been used for medical purposes in humans for hundreds of years. Accordingly, one of the most prominent species has been named Hirudo medicinalis by Carl Linne in 1758. Feeding on vertebrate blood poses some serious problems to blood-sucking ectoparasites, as they have to penetrate the body surface of the host and to suppress the normal reactions of the host to such injuries (swelling, pain, inflammation) to remain undetected during the feeding period. Furthermore, the parasites have to take measures to inhibit the normal reactions in host tissues to blood vessel damage, namely hemostasis and blood coagulation (platelet aggregation and activation, activation of thrombin and formation of fibrin clots). During evolution, leeches have acquired the ability to control these processes in their hosts by transferring various bioactive substances to the host. These substances are supposedly produced in unicellular salivary gland cells and injected into the wound at the feeding site through tiny salivary ductule openings in the jaws that the leech uses to slice open the host body surface and to cut blood vessels in the depth of the wound. This review summarizes current knowledge about the salivary gland cells and the biological effects of individual saliva components as well as hints to the potential usefulness of some of these compounds for medical purposes.

NK1.1+ cells promote sustained tissue injury and inflammation after trauma with hemorrhagic shock.

PubMed

Chen, Shuhua; Hoffman, Rosemary A; Scott, Melanie; Manson, Joanna; Loughran, Patricia; Ramadan, Mostafa; Demetris, Anthony J; Billiar, Timothy R

2017-07-01

Various cell populations expressing NK1.1 contribute to innate host defense and systemic inflammatory responses, but their role in hemorrhagic shock and trauma remains uncertain. NK1.1 + cells were depleted by i.p. administration of anti-NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL-6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h. The number of NK cells, NKT cells, neutrophils, and macrophages in liver, as well as intracellular staining for TNF-α, IFN-γ, and MCP-1 in liver cell populations were determined by flow cytometry. Control mice subjected to HS/T exhibited end organ damage manifested by marked increases in circulating ALT, AST, and MCP-1 levels, as well as histologic evidence of hepatic necrosis and gut injury. Although NK1.1 + cell-depleted mice exhibited a similar degree of organ damage as nondepleted animals at 6 h, NK1.1 + cell depletion resulted in marked suppression of both liver and gut injury by 24 h after HS/T. These findings indicate that NK1.1 + cells contribute to the persistence of inflammation leading to end organ damage in the liver and gut. © Society for Leukocyte Biology.

Treatment with a New Peroxisome Proliferator-Activated Receptor Gamma Agonist, Pyridinecarboxylic Acid Derivative, Increases Angiogenesis and Reduces Inflammatory Mediators in the Heart of Trypanosoma cruzi-Infected Mice.

PubMed

Penas, Federico Nicolás; Carta, Davide; Dmytrenko, Ganna; Mirkin, Gerado A; Modenutti, Carlos Pablo; Cevey, Ágata Carolina; Rada, Maria Jimena; Ferlin, Maria Grazia; Sales, María Elena; Goren, Nora Beatriz

2017-01-01

Trypanosoma cruzi infection induces an intense inflammatory response in diverse host tissues. The immune response and the microvascular abnormalities associated with infection are crucial aspects in the generation of heart damage in Chagas disease. Upon parasite uptake, macrophages, which are involved in the clearance of infection, increase inflammatory mediators, leading to parasite killing. The exacerbation of the inflammatory response may lead to tissue damage. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent nuclear transcription factor that exerts important anti-inflammatory effects and is involved in improving endothelial functions and proangiogenic capacities. In this study, we evaluated the intermolecular interaction between PPARγ and a new synthetic PPARγ ligand, HP 24 , using virtual docking. Also, we showed that early treatment with HP 24 , decreases the expression of NOS2, a pro-inflammatory mediator, and stimulates proangiogenic mediators (vascular endothelial growth factor A, CD31, and Arginase I) both in macrophages and in the heart of T. cruzi -infected mice. Moreover, HP 24 reduces the inflammatory response, cardiac fibrosis and the levels of inflammatory cytokines (TNF-α, interleukin 6) released by macrophages of T. cruzi -infected mice. We consider that PPARγ agonists might be useful as coadjuvants of the antiparasitic treatment of Chagas disease, to delay, reverse, or preclude the onset of heart damage.

Identification of Cell-Binding Adhesins of Leptospira interrogans

PubMed Central

Evangelista, Karen V.; Hahn, Beth; Wunder, Elsio A.; Ko, Albert I.; Haake, David A.; Coburn, Jenifer

2014-01-01

Leptospirosis is a globally distributed bacterial infectious disease caused by pathogenic members of the genus Leptospira. Infection can lead to illness ranging from mild and non-specific to severe, with jaundice, kidney and liver dysfunction, and widespread endothelial damage. The adhesion of pathogenic Leptospira species (spp.), the causative agent of leptospirosis, to host tissue components is necessary for infection and pathogenesis. While it is well-established that extracellular matrix (ECM) components play a role in the interaction of the pathogen with host molecules, we have shown that pathogenic Leptospira interrogans binds to host cells more efficiently than to ECM components. Using in vitro phage display to select for phage clones that bind to EA.hy926 endothelial cells, we identified the putative lipoproteins LIC10508 and LIC13411, and the conserved hypothetical proteins LIC12341 and LIC11574, as candidate L. interrogans sv. Copenhageni st. Fiocruz L1–130 adhesins. Recombinant LIC11574, but not its L. biflexa homologue LBF1629, exhibited dose-dependent binding to both endothelial and epithelial cells. In addition, LIC11574 and LIC13411 bind to VE-cadherin, an endothelial cell receptor for L. interrogans. Extraction of bacteria with the non-ionic detergent Triton X-114 resulted in partitioning of the candidate adhesins to the detergent fraction, a likely indication that these proteins are outer membrane localized. All candidate adhesins were recognized by sera obtained from leptospirosis patients but not by sera from healthy individuals as assessed by western blot. This work has identified bacterial adhesins that are potentially involved in L. interrogans infection of the mammalian host, and through cadherin binding, may contribute to dissemination and vascular damage. Our findings may be of value in leptospirosis control and prevention, with the bacterial adhesins potentially serving as targets for development of diagnostics, therapeutics, and vaccines. PMID:25275630

Engineering functional and histological regeneration of vascularized skeletal muscle.

PubMed

Gilbert-Honick, Jordana; Iyer, Shama R; Somers, Sarah M; Lovering, Richard M; Wagner, Kathryn; Mao, Hai-Quan; Grayson, Warren L

2018-05-01

Tissue engineering strategies to treat patients with volumetric muscle loss (VML) aim to recover the structure and contractile function of lost muscle tissue. Here, we assessed the capacity of novel electrospun fibrin hydrogel scaffolds seeded with murine myoblasts to regenerate the structure and function of damaged muscle within VML defects to the mouse tibialis anterior muscle. The electrospun fibrin scaffolds provide pro-myogenic alignment and stiffness cues, myomimetic hierarchical structure, suturability, and scale-up capabilities. Myoblast-seeded scaffolds enabled remarkable muscle regeneration with high myofiber and vascular densities after 2 and 4 weeks, mimicking that of native skeletal muscle, while acellular scaffolds lacked muscle regeneration. Both myoblast-seeded and acellular scaffolds fully recovered muscle contractile function to uninjured values after 2 and 4 weeks. Electrospun scaffolds pre-vascularized with co-cultured human endothelial cells and human adipose-derived stem cells implanted into VML defects for 2 weeks anastomosed with host vasculature and were perfused with host red blood cells. These data demonstrate the significant potential of electrospun fibrin scaffolds seeded with myoblasts to fully regenerate the structure and function of volumetric muscle defects and these scaffolds offer a promising treatment option for patients with VML. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of the Specific Toxin in Helminthosporium victoriae on Host Cell Membranes 1

PubMed Central

Samaddar, K. R.; Scheffer, R. P.

1968-01-01

Helminthosporium victoriae toxin, which affects only hosts of the toxin-producing fungus, causes loss of electrolytes from roots, leaves, and coleoptiles of treated plants. Root hair cells lost the ability to plasmolyze after 20 minutes exposure to toxin in solution; comparable resistant cells retained plasmolytic ability during 3 hours exposure. Toxin stopped uptake of exogenous amino acids and Pi by susceptible but not by resistant tissue. Incorporation of 32P into organic-P and 14C-amino acids into protein was blocked in susceptible but not in resistant tissue. Apparent free space increased in susceptible but not in resistant roots. The increase was evident within 30 minutes, and reached 80% free space after 2 hours exposure to toxin. When cell wall-free protoplasts were exposed to 0.16 μg toxin/ml, protoplasmic streaming stopped and all plasma membranes of susceptible protoplasts broke within 1 hour. Resistant protoplasts were not affected significantly. Data support the hypothesis of a primary lesion of toxin in the plasma membrane. Effects on synthesis could result from lack of transport of exogenous solutes to sites of synthesis. It is possible that all other observed effects of toxin are secondary to membrane damage. PMID:16656731

Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization.

PubMed

Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru

2016-09-01

Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY-dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage.

Exploiting bacterial drug resistance: a single construct for the diagnosis and treatment of drug resistant infections

NASA Astrophysics Data System (ADS)

Sallum, Ulysses W.; Zheng, Xiang; Verma, Sarika; Hasan, Tayyaba

2009-06-01

β-lactamase enzyme-activated photosensitizer (β-LEAP). We aim to exploit drug resistance mechanisms to selectively release photosensitizers (PSs) for a specific photodynamic antimicrobial effect and reduced host tissue damage. Consequently, the fluorescence emission intensity of the PSs increases and allows for the detection of enzyme activity. In this work we sought to evaluate β-LEAP for use as a sensitive molecular probe. We have reported the enzyme specific antibacterial action of β-LEAP. Here we report the use of β-LEAP for the rapid functional definition of a β-lactamase.

A20-binding inhibitor of NF-κB (ABIN1) controls Toll-like receptor-mediated CCAAT/enhancer-binding protein β activation and protects from inflammatory disease.

PubMed

Zhou, Jingran; Wu, Ruiqiong; High, Anthony A; Slaughter, Clive A; Finkelstein, David; Rehg, Jerold E; Redecke, Vanessa; Häcker, Hans

2011-11-01

Toll-like receptors (TLRs) are expressed on innate immune cells and trigger inflammation upon detection of pathogens and host tissue injury. TLR-mediated proinflammatory-signaling pathways are counteracted by partially characterized anti-inflammatory mechanisms that prevent exaggerated inflammation and host tissue damage as manifested in inflammatory diseases. We biochemically identified a component of TLR-signaling pathways, A20-binding inhibitor of NF-κB (ABIN1), which recently has been linked by genome-wide association studies to the inflammatory diseases systemic lupus erythematosus and psoriasis. We generated ABIN1-deficient mice to study the function of ABIN1 in vivo and during TLR activation. Here we show that ABIN1-deficient mice develop a progressive, lupus-like inflammatory disease characterized by expansion of myeloid cells, leukocyte infiltrations in different parenchymatous organs, activated T and B lymphocytes, elevated serum Ig levels, and the appearance of autoreactive antibodies. Kidneys develop glomerulonephritis and proteinuria, reflecting tissue injury. Surprisingly, ABIN1-deficient macrophages exhibit normal regulation of major proinflammatory signaling pathways and mediators but show selective deregulation of the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) and its target genes, such as colony-stimulating factor 3 (Csf3), nitric oxide synthase, inducible (Nos2), and S100 calcium-binding protein A8 (S100a8). Their gene products, which are intimately linked to innate immune cell expansion (granulocyte colony-stimulating factor), cytotoxicity (inducible nitric oxide synthase), and host factor-derived inflammation (S100A8), may explain, at least in part, the inflammatory phenotype observed. Together, our data reveal ABIN1 as an essential anti-inflammatory component of TLR-signaling pathways that controls C/EBPβ activity.

Tissue Damage Signaling Is a Prerequisite for Protective Neutrophil Recruitment to Microbial Infection in Zebrafish.

PubMed

Huang, Cong; Niethammer, Philipp

2018-05-15

Tissue damage and infection are deemed likewise triggers of innate immune responses. But whereas neutrophil responses to microbes are generally protective, neutrophil recruitment into damaged tissues without infection is deleterious. Why neutrophils respond to tissue damage and not just to microbes is unknown. Is it a flaw of the innate immune system that persists because evolution did not select against it, or does it provide a selective advantage? Here we dissect the contribution of tissue damage signaling to antimicrobial immune responses in a live vertebrate. By intravital imaging of zebrafish larvae, a powerful model for innate immunity, we show that prevention of tissue damage signaling upon microbial ear infection abrogates leukocyte chemotaxis and reduces animal survival, at least in part, through suppression of cytosolic phospholipase A 2 (cPla 2 ), which integrates tissue damage- and microbe-derived cues. Thus, microbial cues are insufficient, and damage signaling is essential for antimicrobial neutrophil responses in zebrafish. Copyright © 2018 Elsevier Inc. All rights reserved.

Antibiofilm agents: A new perspective for antimicrobial strategy.

PubMed

Li, Xi-Hui; Lee, Joon-Hee

2017-10-01

Biofilms are complex microbial architectures that attach to surfaces and encase microorganisms in a matrix composed of self-produced hydrated extracellular polymeric substances (EPSs). In biofilms, microorganisms become much more resistant to antimicrobial treatments, harsh environmental conditions, and host immunity. Biofilm formation by microbial pathogens greatly enhances survival in hosts and causes chronic infections that result in persistent inflammation and tissue damages. Currently, it is believed over 80% of chronic infectious diseases are mediated by biofilms, and it is known that conventional antibiotic medications are inadequate at eradicating these biofilm-mediated infections. This situation demands new strategies for biofilm-associated infections, and currently, researchers focus on the development of antibiofilm agents that are specific to biofilms, but are nontoxic, because it is believed that this prevents the development of drug resistance. Here, we review the most promising antibiofilm agents undergoing intensive research and development.

Host-Cell Survival and Death During Chlamydia Infection

PubMed Central

Ying, Songmin; Pettengill, Matthew; Ojcius, David M.; Häcker, Georg

2008-01-01

Different Chlamydia trachomatis strains are responsible for prevalent bacterial sexually-transmitted disease and represent the leading cause of preventable blindness worldwide. Factors that predispose individuals to disease and mechanisms by which chlamydiae cause inflammation and tissue damage remain unclear. Results from recent studies indicate that prolonged survival and subsequent death of infected cells and their effect on immune effector cells during chlamydial infection may be important in determining the outcome. Survival of infected cells is favored at early times of infection through inhibition of the mitochondrial pathway of apoptosis. Death at later times displays features of both apoptosis and necrosis, but pro-apoptotic caspases are not involved. Most studies on chlamydial modulation of host-cell death until now have been performed in cell lines. The consequences for pathogenesis and the immune response will require animal models of chlamydial infection, preferably mice with targeted deletions of genes that play a role in cell survival and death. PMID:18843378

Pathogenicity and ultrastructural studies of the mode of penetration by Phoma strasseri in peppermint stems and rhizomes.

PubMed

Zimowska, Beata

2012-01-01

Pathogenicity and ultrastructural investigation of the inoculation of peppermint stems and rhizomes with Phoma strasseri conidia was undertaken using scanning and transmission electron microscopy to examine the host-parasite relationship. Pathogenicity experiments demonstrated that all tested P. strasseri isolates had infected the stems and rhizomes of peppermint. Of all inoculation methods, direct placement of colonized agar plugs on damaged epidermis and soaking stems and rhizomes in conidial suspension were the most effective. The behavior of the conidia deposited on the stems and rhizomes was investigated at different time intervals after inoculation: 6, 16, 24, 36 and 48 h. Conidia produced an appressorium directly at the end of a short germ tube. Appressoria were formed over the cuticle, but never over stomata. Direct penetration to host tissue through the cuticle was observed. The spore and hyphae were covered with a mucilaginous sheath.

Extracts from Hericium erinaceus relieve inflammatory bowel disease by regulating immunity and gut microbiota.

PubMed

Diling, Chen; Xin, Yang; Chaoqun, Zheng; Jian, Yang; Xiaocui, Tang; Jun, Chen; Ou, Shuai; Yizhen, Xie

2017-10-17

Hericium erinaceus (HE), a traditional edible mushroom, is known as a medicine food homology to ameliorate gastrointestinal diseases. To investigate whether HE is clinically effective in alleviating inflammatory bowel disease (IBD), HE extracts (polysaccharide, alcoholic extracts and whole extracts were prepared using solvent extraction methods) were administrated for 2 weeks in rats with IBD induced by trinitro-benzene-sulfonic acid (TNBS) enema (150 mg/kg). Significant clinical and histological changes in IBD rats were identified, including damage activity, common morphous and tissue damage index scores in colonic mucosa and myeloperoxidase (MPO) activity. The damage activity, common morphous and tissue damage index scores in colonic mucosa ( P <0.05) were improved, MPO activities were decreased. Inflammatory factors were also differentially expressed in colonic mucosa in IBD rats, including serum cytokines, Foxp3 and interleukin (IL)-10 were increased while NF-κB p65 and tumor necrosis factor (TNF)-α were decreased ( P <0.05), and T cells were activated ( P <0.05), especially in the alcohol extracts-treated group. We also found that the structure of gut microbiota of the H. erinaceus extracts-treated groups changed significantly by compared with the model group. Further studies revealed that the polysaccharides in HE extracts may play a prebiotic role, whereas the alcoholic extracts show bactericidin-like and immunomodulatory effects. Taken together, we demonstrated that H. erinaceus extracts could promote the growth of beneficial gut bacteria and improve the host immunity in vivo IBD model, which shows clinical potential in relieving IBD by regulating gut microbiota and immune system.

Extracts from Hericium erinaceus relieve inflammatory bowel disease by regulating immunity and gut microbiota

PubMed Central

Diling, Chen; Xin, Yang; Chaoqun, Zheng; Jian, Yang; Xiaocui, Tang; Jun, Chen; Ou, Shuai; Yizhen, Xie

2017-01-01

Hericium erinaceus (HE), a traditional edible mushroom, is known as a medicine food homology to ameliorate gastrointestinal diseases. To investigate whether HE is clinically effective in alleviating inflammatory bowel disease (IBD), HE extracts (polysaccharide, alcoholic extracts and whole extracts were prepared using solvent extraction methods) were administrated for 2 weeks in rats with IBD induced by trinitro-benzene-sulfonic acid (TNBS) enema (150 mg/kg). Significant clinical and histological changes in IBD rats were identified, including damage activity, common morphous and tissue damage index scores in colonic mucosa and myeloperoxidase (MPO) activity. The damage activity, common morphous and tissue damage index scores in colonic mucosa (P <0.05) were improved, MPO activities were decreased. Inflammatory factors were also differentially expressed in colonic mucosa in IBD rats, including serum cytokines, Foxp3 and interleukin (IL)-10 were increased while NF-κB p65 and tumor necrosis factor (TNF)-α were decreased (P <0.05), and T cells were activated (P <0.05), especially in the alcohol extracts-treated group. We also found that the structure of gut microbiota of the H. erinaceus extracts-treated groups changed significantly by compared with the model group. Further studies revealed that the polysaccharides in HE extracts may play a prebiotic role, whereas the alcoholic extracts show bactericidin-like and immunomodulatory effects. Taken together, we demonstrated that H. erinaceus extracts could promote the growth of beneficial gut bacteria and improve the host immunity in vivo IBD model, which shows clinical potential in relieving IBD by regulating gut microbiota and immune system. PMID:29156761

Neutrophils: Beneficial and Harmful Cells in Septic Arthritis

PubMed Central

Boff, Daiane; Crijns, Helena; Teixeira, Mauro M.

2018-01-01

Septic arthritis is an inflammatory joint disease that is induced by pathogens such as Staphylococcus aureus. Infection of the joint triggers an acute inflammatory response directed by inflammatory mediators including microbial danger signals and cytokines and is accompanied by an influx of leukocytes. The recruitment of these inflammatory cells depends on gradients of chemoattractants including formylated peptides from the infectious agent or dying cells, host-derived leukotrienes, complement proteins and chemokines. Neutrophils are of major importance and play a dual role in the pathogenesis of septic arthritis. On the one hand, these leukocytes are indispensable in the first-line defense to kill invading pathogens in the early stage of disease. However, on the other hand, neutrophils act as mediators of tissue destruction. Since the elimination of inflammatory neutrophils from the site of inflammation is a prerequisite for resolution of the acute inflammatory response, the prolonged stay of these leukocytes at the inflammatory site can lead to irreversible damage to the infected joint, which is known as an important complication in septic arthritis patients. Thus, timely reduction of the recruitment of inflammatory neutrophils to infected joints may be an efficient therapy to reduce tissue damage in septic arthritis. PMID:29401737

Late Multiple Organ Surge in Interferon-Regulated Target Genes Characterizes Staphylococcal Enterotoxin B Lethality

PubMed Central

Ferreyra, Gabriela A.; Elinoff, Jason M.; Demirkale, Cumhur Y.; Starost, Matthew F.; Buckley, Marilyn; Munson, Peter J.; Krakauer, Teresa; Danner, Robert L.

2014-01-01

Background Bacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) challenge was investigated in six tissues. Results The earliest responses and largest number of affected genes occurred in peripheral blood mononuclear cells (PBMC), spleen, and lung tissues with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney, and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Nine of the 85 genes were subsequently confirmed by RT-PCR in every tissue/organ at 24 h. These 85 transcripts, up-regulated in all tissues, annotated to the interferon (IFN)/antiviral-response and included genes belonging to the DNA/RNA sensing system, DNA damage repair, the immunoproteasome, and the ER/metabolic stress-response and apoptosis pathways. Overall, this shared program was identified as a type I and II interferon (IFN)-response and the promoters of these genes were highly enriched for IFN regulatory matrices. Several genes whose secreted products induce the IFN pathway were up-regulated at early time points in PBMCs, spleen, and/or lung. Furthermore, IFN regulatory factors including Irf1, Irf7 and Irf8, and Zbp1, a DNA sensor/transcription factor that can directly elicit an IFN innate immune response, participated in this host-wide SEB signature. Conclusion Global gene-expression changes across multiple organs implicated a host-wide IFN-response in SEB-induced death. Therapies aimed at IFN-associated innate immunity may improve outcome in toxic shock syndromes. PMID:24551153

Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by 19F- and diffusion-MRI

PubMed Central

Bible, Ellen; Dell’Acqua, Flavio; Solanky, Bhavana; Balducci, Anthony; Crapo, Peter; Badylak, Stephen F.; Ahrens, Eric T.; Modo, Michel

2012-01-01

Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based 1H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a 19F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on 1H-MRI scans. Twenty percent of cells labeled with the 19F-agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T2- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively. PMID:22244696

Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches

PubMed Central

Toyoshima, Koh-ei; Asakawa, Kyosuke; Ishibashi, Naoko; Toki, Hiroshi; Ogawa, Miho; Hasegawa, Tomoko; Irié, Tarou; Tachikawa, Tetsuhiko; Sato, Akio; Takeda, Akira; Tsuji, Takashi

2012-01-01

Organ replacement regenerative therapy is purported to enable the replacement of organs damaged by disease, injury or aging in the foreseeable future. Here we demonstrate fully functional hair organ regeneration via the intracutaneous transplantation of a bioengineered pelage and vibrissa follicle germ. The pelage and vibrissae are reconstituted with embryonic skin-derived cells and adult vibrissa stem cell region-derived cells, respectively. The bioengineered hair follicle develops the correct structures and forms proper connections with surrounding host tissues such as the epidermis, arrector pili muscle and nerve fibres. The bioengineered follicles also show restored hair cycles and piloerection through the rearrangement of follicular stem cells and their niches. This study thus reveals the potential applications of adult tissue-derived follicular stem cells as a bioengineered organ replacement therapy. PMID:22510689

Aspergillosis.

PubMed

Bodey, G P; Vartivarian, S

1989-05-01

Aspergillus spores are ubiquitous in the environment and may become concentrated in hospital ventilation systems. Colonization in normal hosts can lead to allergic diseases ranging from asthma to allergic bronchopulmonary aspergillosis. Normal hosts rarely develop invasive disease, which is primarily an infection of severely immunocompromised patients. The major predisposing factors for infection include prolonged neutropenia, chronic administration of adrenal corticosteroids, the insertion of prosthetic devices, and tissue damage due to prior infection or trauma. Since Aspergillus spp. are respiratory pathogens, the most common form of infection is pneumonia followed by sinusitis. Patients with preexistant cavitary disease may develop noninvasive aspergillomas. Most infections are caused by Aspergillus fumigatus. The organism is capable of invading across all natural barriers, including cartilage and bone. It has a propensity for invading blood vessels causing thrombosis and infarction. The diagnosis of pulmonary infection is usually difficult to establish because the organism is seldom cultured from sputum and can represent contamination in some cases. Therapy is immunocompromised hosts is less than satisfactory and amphotericin B is the only agent with significant activity. There is anecdotal evidence to suggest that the addition of 5-fluorocytosine to amphotericin B may be beneficial.

Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering.

PubMed

Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Dusséaux, Antoine; Hung, Clark T; Ateshian, Gerard A

2016-02-06

This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process.

Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering

PubMed Central

Nims, Robert J.; Durney, Krista M.; Cigan, Alexander D.; Hung, Clark T.; Ateshian, Gerard A.

2016-01-01

This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process. PMID:26855751

Fatigue Damage of Collagenous Tissues: Experiment, Modeling and Simulation Studies

PubMed Central

Martin, Caitlin; Sun, Wei

2017-01-01

Mechanical fatigue damage is a critical issue for soft tissues and tissue-derived materials, particularly for musculoskeletal and cardiovascular applications; yet, our understanding of the fatigue damage process is incomplete. Soft tissue fatigue experiments are often difficult and time-consuming to perform, which has hindered progress in this area. However, the recent development of soft-tissue fatigue-damage constitutive models has enabled simulation-based fatigue analyses of tissues under various conditions. Computational simulations facilitate highly controlled and quantitative analyses to study the distinct effects of various loading conditions and design features on tissue durability; thus, they are advantageous over complex fatigue experiments. Although significant work to calibrate the constitutive models from fatigue experiments and to validate predictability remains, further development in these areas will add to our knowledge of soft-tissue fatigue damage and will facilitate the design of durable treatments and devices. In this review, the experimental, modeling, and simulation efforts to study collagenous tissue fatigue damage are summarized and critically assessed. PMID:25955007

Functional fabrication of recombinant human collagen-phosphorylcholine hydrogels for regenerative medicine applications.

PubMed

Mirazul Islam, M; Cėpla, Vytautas; He, Chaoliang; Edin, Joel; Rakickas, Tomas; Kobuch, Karin; Ruželė, Živilė; Bruce Jackson, W; Rafat, Mehrdad; Lohmann, Chris P; Valiokas, Ramūnas; Griffith, May

2015-01-01

The implant-host interface is a critical element in guiding tissue or organ regeneration. We previously developed hydrogels comprising interpenetrating networks of recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) as substitutes for the corneal extracellular matrix that promote endogenous regeneration of corneal tissue. To render them functional for clinical application, we have now optimized their composition and thereby enhanced their mechanical properties. We have demonstrated that such optimized RHCIII-MPC hydrogels are suitable for precision femtosecond laser cutting to produce complementing implants and host surgical beds for subsequent tissue welding. This avoids the tissue damage and inflammation associated with manual surgical techniques, thereby leading to more efficient healing. Although we previously demonstrated in clinical testing that RHCIII-based implants stimulated cornea regeneration in patients, the rate of epithelial cell coverage of the implants needs improvement, e.g. modification of the implant surface. We now show that our 500μm thick RHCIII-MPC constructs comprising over 85% water are suitable for microcontact printing with fibronectin. The resulting fibronectin micropatterns promote cell adhesion, unlike the bare RHCIII-MPC hydrogel. Interestingly, a pattern of 30μm wide fibronectin stripes enhanced cell attachment and showed the highest mitotic rates, an effect that potentially can be utilized for faster integration of the implant. We have therefore shown that laboratory-produced mimics of naturally occurring collagen and phospholipids can be fabricated into robust hydrogels that can be laser profiled and patterned to enhance their potential function as artificial substitutes of donor human corneas. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The Unexpected Tuners: Are LncRNAs Regulating Host Translation during Infections?

PubMed Central

Knap, Primoz; Tebaldi, Toma; Di Leva, Francesca; Biagioli, Marta; Dalla Serra, Mauro; Viero, Gabriella

2017-01-01

Pathogenic bacteria produce powerful virulent factors, such as pore-forming toxins, that promote their survival and cause serious damage to the host. Host cells reply to membrane stresses and ionic imbalance by modifying gene expression at the epigenetic, transcriptional and translational level, to recover from the toxin attack. The fact that the majority of the human transcriptome encodes for non-coding RNAs (ncRNAs) raises the question: do host cells deploy non-coding transcripts to rapidly control the most energy-consuming process in cells—i.e., host translation—to counteract the infection? Here, we discuss the intriguing possibility that membrane-damaging toxins induce, in the host, the expression of toxin-specific long non-coding RNAs (lncRNAs), which act as sponges for other molecules, encoding small peptides or binding target mRNAs to depress their translation efficiency. Unravelling the function of host-produced lncRNAs upon bacterial infection or membrane damage requires an improved understanding of host lncRNA expression patterns, their association with polysomes and their function during this stress. This field of investigation holds a unique opportunity to reveal unpredicted scenarios and novel approaches to counteract antibiotic-resistant infections. PMID:29469820

Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity.

PubMed

Collins, Kelsey H; Herzog, Walter; MacDonald, Graham Z; Reimer, Raylene A; Rios, Jaqueline L; Smith, Ian C; Zernicke, Ronald F; Hart, David A

2018-01-01

Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i.e., muscle, bone, tendon, and joints) that result from obesity-associated metabolic disturbances are less frequently interrogated. As musculoskeletal diseases can lead to the worsening of MetS, this underscores the imminent need to understand the cause and effect relations between the two, and the convergence between inflammatory pathways that contribute to MSK damage. Muscle mass is a key predictor of longevity in older adults, and obesity-induced sarcopenia is a significant risk factor for adverse health outcomes. Muscle is highly plastic, undergoes regular remodeling, and is responsible for the majority of total body glucose utilization, which when impaired leads to insulin resistance. Furthermore, impaired muscle integrity, defined as persistent muscle loss, intramuscular lipid accumulation, or connective tissue deposition, is a hallmark of metabolic dysfunction. In fact, many common inflammatory pathways have been implicated in the pathogenesis of the interrelated tissues of the musculoskeletal system (e.g., tendinopathy, osteoporosis, and osteoarthritis). Despite these similarities, these diseases are rarely evaluated in a comprehensive manner. The aim of this review is to summarize the common pathways that lead to musculoskeletal damage and disease that result from and contribute to MetS. We propose the overarching hypothesis that there is a central role for muscle damage with chronic exposure to an obesity-inducing diet. The inflammatory consequence of diet and muscle dysregulation can result in dysregulated tissue repair and an imbalance toward negative adaptation, resulting in regulatory failure and other musculoskeletal tissue damage. The commonalities support the conclusion that musculoskeletal pathology with MetS should be evaluated in a comprehensive and integrated manner to understand risk for other MSK-related conditions. Implications for conservative management strategies to regulate MetS are discussed, as are future research opportunities.

Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity

PubMed Central

Collins, Kelsey H.; Herzog, Walter; MacDonald, Graham Z.; Reimer, Raylene A.; Rios, Jaqueline L.; Smith, Ian C.; Zernicke, Ronald F.; Hart, David A.

2018-01-01

Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i.e., muscle, bone, tendon, and joints) that result from obesity-associated metabolic disturbances are less frequently interrogated. As musculoskeletal diseases can lead to the worsening of MetS, this underscores the imminent need to understand the cause and effect relations between the two, and the convergence between inflammatory pathways that contribute to MSK damage. Muscle mass is a key predictor of longevity in older adults, and obesity-induced sarcopenia is a significant risk factor for adverse health outcomes. Muscle is highly plastic, undergoes regular remodeling, and is responsible for the majority of total body glucose utilization, which when impaired leads to insulin resistance. Furthermore, impaired muscle integrity, defined as persistent muscle loss, intramuscular lipid accumulation, or connective tissue deposition, is a hallmark of metabolic dysfunction. In fact, many common inflammatory pathways have been implicated in the pathogenesis of the interrelated tissues of the musculoskeletal system (e.g., tendinopathy, osteoporosis, and osteoarthritis). Despite these similarities, these diseases are rarely evaluated in a comprehensive manner. The aim of this review is to summarize the common pathways that lead to musculoskeletal damage and disease that result from and contribute to MetS. We propose the overarching hypothesis that there is a central role for muscle damage with chronic exposure to an obesity-inducing diet. The inflammatory consequence of diet and muscle dysregulation can result in dysregulated tissue repair and an imbalance toward negative adaptation, resulting in regulatory failure and other musculoskeletal tissue damage. The commonalities support the conclusion that musculoskeletal pathology with MetS should be evaluated in a comprehensive and integrated manner to understand risk for other MSK-related conditions. Implications for conservative management strategies to regulate MetS are discussed, as are future research opportunities. PMID:29527173

α7 Nicotinic Acetylcholine Receptor (α7nAChR) Expression in Bone Marrow–Derived Non–T Cells Is Required for the Inflammatory Reflex

PubMed Central

Olofsson, Peder S; Katz, David A; Rosas-Ballina, Mauricio; Levine, Yaakov A; Ochani, Mahendar; Valdés-Ferrer, Sergio I; Pavlov, Valentin A; Tracey, Kevin J; Chavan, Sangeeta S

2012-01-01

The immune response to infection or injury coordinates host defense and tissue repair, but also has the capacity to damage host tissues. Recent advances in understanding protective mechanisms have found neural circuits that suppress release of damaging cytokines. Stimulation of the vagus nerve protects from excessive cytokine production and ameliorates experimental inflammatory disease. This mechanism, the inflammatory reflex, requires the α7 nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel expressed on macrophages, lymphocytes, neurons and other cells. To investigate cell-specific function of α7nAChR in the inflammatory reflex, we created chimeric mice by cross-transferring bone marrow between wild-type (WT) and α7nAChR-deficient mice. Deficiency of α7nAChR in bone marrow–derived cells significantly impaired vagus nerve–mediated regulation of tumor necrosis factor (TNF), whereas α7nAChR deficiency in neurons and other cells had no significant effect. In agreement with recent work, the inflammatory reflex was not functional in nude mice, because functional T cells are required for the integrity of the pathway. To investigate the role of T-cell α7nAChR, we adoptively transferred α7nAChR-deficient or WT T cells to nude mice. Transfer of WT and α7nAChR-deficient T cells restored function, indicating that α7nAChR expression on T cells is not necessary for this pathway. Together, these results indicate that α7nAChR expression in bone marrow–derived non–T cells is required for the integrity of the inflammatory reflex. PMID:22183893

Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix

PubMed Central

Kuo, Kuan-Chih; Lin, Ruei-Zeng; Tien, Han-Wen; Wu, Pei-Yun; Li, Yen-Cheng; Melero-Martin, Juan M.; Chen, Ying-Chieh

2015-01-01

Tissue engineering promises to restore or replace diseased or damaged tissue by creating functional and transplantable artificial tissues. The development of artificial tissues with large dimensions that exceed the diffusion limitation will require nutrients and oxygen to be delivered via perfusion instead of diffusion alone over a short time period. One approach to perfusion is to vascularize engineered tissues, creating a de novo three-dimensional (3D) microvascular network within the tissue construct. This significantly shortens the time of in vivo anastomosis, perfusion and graft integration with the host. In this study, we aimed to develop injectable allogeneic collagen-phenolic hydroxyl (collagen-Ph) hydrogels that are capable of controlling a wide range of physicochemical properties, including stiffness, water absorption and degradability. We tested whether collagen-Ph hydrogels could support the formation of vascularized engineered tissue graft by human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSC) in vivo. First, we studied the growth of adherent ECFCs and MSCs on or in the hydrogels. To examine the potential formation of functional vascular networks in vivo, a liquid pre-polymer solution of collagen-Ph containing human ECFCs and MSCs, horseradish peroxidase and hydrogen peroxide was injected into the subcutaneous space or abdominal muscle defect of an immunodeficient mouse before gelation, to form a 3D cell-laden polymerized construct. These results showed that extensive human ECFC-lined vascular networks can be generated within 7 days, the engineered vascular density inside collagen-Ph hydrogel constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with the existing vasculature to further support the survival of host muscle tissues. Finally, optimized conditions of the cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse after 1 month of implantation. PMID:26348142

Thicker host tissues moderate light stress in a cnidarian endosymbiont.

PubMed

Dimond, James L; Holzman, Benjamin J; Bingham, Brian L

2012-07-01

The susceptibility of algal-cnidarian holobionts to environmental stress is dependent on attributes of both host and symbiont, but the role of the host is often unclear. We examined the influence of the host on symbiont light stress, comparing the photophysiology of the chlorophyte symbiont Elliptochloris marina in two species of sea anemones in the genus Anthopleura. After 3 months of acclimation in outdoor tanks, polyp photoprotective contraction behavior was similar between the two host species, but photochemical efficiency was 1.5 times higher in A. xanthogrammica than in A. elegantissima. Maximum relative electron transport rates, derived from rapid light curves, were 1.5 times higher in A. xanthogrammica than in A. elegantissima when symbionts were inside intact tissues, but were not significantly different between host species upon removal of outer (epidermis and mesoglea) tissue layers from symbiont-containing gastrodermal cells. Tissues of A. xanthogrammica were 1.8 times thicker than those of A. elegantissima, with outer tissue layers attenuating 1.6 times more light. We found no significant differences in light absorption properties per unit volume of tissue, confirming the direct effect of tissue thickness on light attenuation. The thicker tissues of A. xanthogrammica thus provide a favorable environment for E. marina - a relatively stress-susceptible symbiont - and may explain its higher prevalence and expanded range in A. xanthogrammica along the Pacific coast of North America. Our findings also support a photoprotective role for thicker host tissues in reef corals that has long been thought to influence variability in bleaching susceptibility among coral taxa.

An experimental test of the effects of behavioral and immunological defenses against vectors: do they interact to protect birds from blood parasites?

PubMed Central

2014-01-01

Background Blood-feeding arthropods can harm their hosts in many ways, such as through direct tissue damage and anemia, but also by distracting hosts from foraging or watching for predators. Blood-borne pathogens transmitted by arthropods can further harm the host. Thus, effective behavioral and immunological defenses against blood-feeding arthropods may provide important fitness advantages to hosts if they reduce bites, and in systems involving pathogen transmission, if they lower pathogen transmission rate. Methods We tested whether Rock Pigeons (Columba livia) have effective behavioral and immunological defenses against a blood-feeding hippoboscid fly (Pseudolynchia canariensis) and, if so, whether the two defenses interact. The fly vectors the blood parasite Haemoproteus columbae; we further tested whether these defenses reduced the transmission success of blood parasites when birds were exposed to infected flies. We compared four experimental treatments in which hosts had available both purported defenses, only one of the defenses, or no defenses against the flies. Results We found that preening and immunological defenses were each effective in decreasing the survival and reproductive success of flies. However, the two defenses were additive, rather than one defense enhancing or decreasing the effectiveness of the other defense. Neither defense reduced the prevalence of H. columbae, nor the intensity of infection in birds exposed to infected flies. Conclusions Flies experience reduced fitness when maintained on hosts with immunological or preening defenses. This suggests that if vectors are given a choice among hosts, they may choose hosts that are less defended, which could impact pathogen transmission in a system where vectors can choose among hosts. PMID:24620737

Dying dangerously: Necrotic cell death and chronic inflammation promote tumor growth.

PubMed

Lotze, Michael T; Demarco, Richard A

2004-12-01

Extract: We all shudder about untimely deaths or those that we were not prepared for. As such we perceive such "unscheduled" deaths as dangerous. Similarly, apoptotic death (literally falling leaves) or the programmed cell death of cells in multicellular organisms ranging from slime mold and simple worms through to mammals, has a level of tidiness and well-orchestrated activities with literally hundreds if not thousands of gene products employed with either the primary or secondary purpose of coordinating the orderly death of cells throughout life. During inflammation of any sort, driven by tissue damage or injury or infection by pathogens (virus, bacteria, and parasites), apoptotic death similarly serves to quickly rid the host of damaged cells, promote removal and digestion of the infected cell, and prepare the way for tissue remodeling and repair. When this goes awry, for example during periods of chronic inflammation, tissues are subjected to the contrasting needs of driving apoptotic death whilst maintaining the barrier function of the epithelia (such as skin cells) as well as the selective permeability of mucosal sites (i.e., areas where mucus is secreted to protect the cells from their surroundings, such as gut cells protecting themselves from the gastric acids). Prudently, they need to limit and husband local resources sufficiently for the maintenance of tissue integrity and renewal. It is our provocative and novel contention that cancer in adults (and not children) most often arises in a setting of chronic inflammation and disordered cell death rather than one associated primarily with disordered cell growth as it is popularly imagined by scientists, clinicians, and the general public.

Small Molecular, Macromolecular and Cellular Chloramines React with Thiocyanate to Give the Human Defense Factor Hypothiocyanite†

PubMed Central

Xulu, Bheki A.; Ashby, Michael T.

2010-01-01

Thiocyanate reacts non-catalytically with myeloperoxidase-derived HOCl to produce hypothiocyanite (OSCN−), thereby potentially limiting the propensity of HOCl to inflict host tissue damage that can lead to inflammatory diseases. However, the efficiency with which SCN− captures HOCl in vivo depends on the concentration of SCN− relative to other chemical targets. In blood plasma, where the concentration of SCN− is relatively low, proteins may be the principal initial targets of HOCl, and chloramines are a significant product. Chloramines eventually decompose to irreversibly damage proteins. In the present study, we demonstrate that SCN− reacts efficiently with chloramines in small molecules, in proteins, and in Escherichia coli cells to give OSCN− and the parent amine. Remarkably, OSCN− reacts faster than SCN− with chloramines. These reactions of SCN− and OSCN− with chloramines may repair some of the damage that is inflicted on protein amines by HOCl. Our observations are further evidence for the importance of secondary reactions during the redox cascades that are associated with oxidative stress by hypohalous acids. PMID:20085320

Oxidative stress damage as a detrimental factor in preterm birth pathology.

PubMed

Menon, Ramkumar

2014-01-01

Normal term and spontaneous preterm births (PTB) are documented to be associated with oxidative stress (OS), and imbalances in the redox system (balance between pro- and antioxidant) have been reported in the maternal-fetal intrauterine compartments. The exact mechanism of labor initiation either at term or preterm by OS is still unclear, and this lack of understanding can partially be blamed for failure of antioxidant supplementation trials in PTB prevention. Based on recent findings from our laboratory, we postulate heterogeneity in host OS response. The physiologic (at term) and pathophysiologic (preterm) pathways of labor are not mediated by OS alone but by OS-induced damage to intrauterine tissues, especially fetal membranes of the placenta. OS damage affects all major cellular elements in the fetal cells, and this damage promotes fetal cell senescence (aging). The aging of the fetal cells is predominated by p38 mitogen activated kinase (p38MAPK) pathways. Senescing cells generate biomolecular signals that are uterotonic, triggering labor process. The aging of fetal cells is normal at term. However, aging is premature in PTB, especially in those PTBs complicated by preterm premature rupture of the membranes, where elements of redox imbalances and OS damage are more dominant. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor. This review highlights the mechanisms involved in senescence development at term and preterm by OS damage and provides insight into novel fetal signals of labor initiation pathways.

Oxidative Stress Damage as a Detrimental Factor in Preterm Birth Pathology

PubMed Central

Menon, Ramkumar

2014-01-01

Normal term and spontaneous preterm births (PTB) are documented to be associated with oxidative stress (OS), and imbalances in the redox system (balance between pro- and antioxidant) have been reported in the maternal–fetal intrauterine compartments. The exact mechanism of labor initiation either at term or preterm by OS is still unclear, and this lack of understanding can partially be blamed for failure of antioxidant supplementation trials in PTB prevention. Based on recent findings from our laboratory, we postulate heterogeneity in host OS response. The physiologic (at term) and pathophysiologic (preterm) pathways of labor are not mediated by OS alone but by OS-induced damage to intrauterine tissues, especially fetal membranes of the placenta. OS damage affects all major cellular elements in the fetal cells, and this damage promotes fetal cell senescence (aging). The aging of the fetal cells is predominated by p38 mitogen activated kinase (p38MAPK) pathways. Senescing cells generate biomolecular signals that are uterotonic, triggering labor process. The aging of fetal cells is normal at term. However, aging is premature in PTB, especially in those PTBs complicated by preterm premature rupture of the membranes, where elements of redox imbalances and OS damage are more dominant. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor. This review highlights the mechanisms involved in senescence development at term and preterm by OS damage and provides insight into novel fetal signals of labor initiation pathways. PMID:25429290

Studying tumor growth in Drosophila using the tissue allograft method.

PubMed

Rossi, Fabrizio; Gonzalez, Cayetano

2015-10-01

This protocol describes a method to allograft Drosophila larval tissue into adult fly hosts that can be used to assay the tumorigenic potential of mutant tissues. The tissue of interest is dissected, loaded into a fine glass needle and implanted into a host. Upon implantation, nontransformed tissues do not overgrow beyond their normal size, but malignant tumors grow without limit, are invasive and kill the host. By using this method, Drosophila malignant tumors can be transplanted repeatedly, for years, and therefore they can be aged beyond the short life span of flies. Because several hosts can be implanted using different pieces from a single tumor, the method also allows the tumor mass to be increased to facilitate further studies that may require large amounts of tissue (i.e., genomics, proteomics and so on). This method also provides an operational definition of hyperplastic, benign and malignant growth. The injection procedure itself requires only ∼1 d. Tumor development can then be monitored until the death of the implanted hosts.

Changes in optical properties during heating of ex vivo liver tissues

NASA Astrophysics Data System (ADS)

Nagarajan, Vivek Krishna; Gogineni, Venkateshwara R.; White, Sarah B.; Yu, Bing

2017-02-01

Thermal ablation is the use of heat to induce cell death through coagulative necrosis. Ideally, complete ablation of tumor cells with no damage to surrounding critical structures such as blood vessels, nerves or even organs is desired. Ablation monitoring techniques are often employed to ensure optimal tumor ablation. In thermal tissue ablation, tissue damage is known to be dependent on the temperature and time of exposure. Aptly, current methods for monitoring ablation rely profoundly on local tissue temperature and duration of heating to predict the degree of tissue damage. However, such methods do not take into account the microstructural and physiological changes in tissues as a result of thermocoagulation. Light propagation within biological tissues is known to be dependent on the tissue microstructure and physiology. During tissue denaturation, changes in tissue structure alter light propagations in tissue which could be used to directly assess the extent of thermal tissue damage. We report the use of a spectroscopic system for monitoring the tissue optical properties during heating of ex vivo liver tissues. We observed that during tissue denaturation, continuous changes in wavelength-averaged μa(λ) and μ's(λ) followed a sigmoidal trend and are correlated with damage predicted by Arrhenius model.

Necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia.

PubMed

Singh, Anju; Periasamy, Sivakumar; Malik, Meenakshi; Bakshi, Chandra Shekhar; Stephen, Laurie; Ault, Jeffrey G; Mannella, Carmen A; Sellati, Timothy J

2017-01-01

Infection with Francisella tularensis ssp. tularensis ( Ft ) strain SchuS4 causes an often lethal disease known as tularemia in rodents, non-human primates, and humans. Ft subverts host cell death programs to facilitate their exponential replication within macrophages and other cell types during early respiratory infection (⩽72 h). The mechanism(s) by which cell death is triggered remains incompletely defined, as does the impact of Ft on mitochondria, the host cell's organellar 'canary in a coal mine'. Herein, we reveal that Ft infection of host cells, particularly macrophages and polymorphonuclear leukocytes, drives necroptosis via a receptor-interacting protein kinase 1/3-mediated mechanism. During necroptosis mitochondria and other organelles become damaged. Ft -induced mitochondrial damage is characterized by: (i) a decrease in membrane potential and consequent mitochondrial oncosis or swelling, (ii) increased generation of superoxide radicals, and (iii) release of intact or damaged mitochondria into the lung parenchyma. Host cell recognition of and response to released mitochondria and other damage-associated molecular patterns engenders a sepsis-like syndrome typified by production of TNF, IL-1 β , IL-6, IL-12p70, and IFN- γ during late-phase tularemia (⩾72 h), but are absent early during infection.

Free-living pathogens: life-history constraints and strain competition.

PubMed

Caraco, Thomas; Wang, Ing-Nang

2008-02-07

Many pathogen life histories include a free-living stage, often with anatomical and physiological adaptations promoting persistence outside of host tissues. More durable particles presumably require that the pathogen metabolize more resources per particle. Therefore, we hypothesize functional dependencies, pleiotropic constraints, between the rate at which free-living particles decay outside of host tissues and other pathogen traits, including virulence, the probability of infecting a host upon contact, and pathogen reproduction within host tissues. Assuming that pathogen strains compete for hosts preemptively, we find patterns in trait dependencies predicting whether or not strain competition favors a highly persistent free-living stage.

Quantification of change in vocal fold tissue stiffness relative to depth of artificial damage.

PubMed

Rohlfs, Anna-Katharina; Schmolke, Sebastian; Clauditz, Till; Hess, Markus; Müller, Frank; Püschel, Klaus; Roemer, Frank W; Schumacher, Udo; Goodyer, Eric

2017-10-01

To quantify changes in the biomechanical properties of human excised vocal folds with defined artificial damage. The linear skin rheometer (LSR) was used to obtain a series of rheological measurements of shear modulus from the surface of 30 human cadaver vocal folds. The tissue samples were initially measured in a native condition and then following varying intensities of thermal damage. Histological examination of each vocal fold was used to determine the depth of artificial alteration. The measured changes in stiffness were correlated with the depth of cell damage. For vocal folds in a pre-damage state the shear modulus values ranged from 537 Pa to 1,651 Pa (female) and from 583 Pa to 1,193 Pa (male). With increasing depth of damage from the intermediate layer of the lamina propria (LP), tissue stiffness increased consistently (compared with native values) following application of thermal damage to the vocal folds. The measurement showed an increase of tissue stiffness when the depth of tissue damage was extending from the intermediate LP layer downwards. Changes in the elastic characteristics of human vocal fold tissue following damage at defined depths were demonstrated in an in vitro experiment. In future, reproducible in vivo measurements of elastic vocal fold tissue alterations may enable phonosurgeons to infer the extent of subepithelial damage from changes in surface elasticity.

Genome-Wide Comparison of Magnaporthe Species Reveals a Host-Specific Pattern of Secretory Proteins and Transposable Elements

PubMed Central

Gowda, Malali

2016-01-01

Blast disease caused by the Magnaporthe species is a major factor affecting the productivity of rice, wheat and millets. This study was aimed at generating genomic information for rice and non-rice Magnaporthe isolates to understand the extent of genetic variation. We have sequenced the whole genome of the Magnaporthe isolates, infecting rice (leaf and neck), finger millet (leaf and neck), foxtail millet (leaf) and buffel grass (leaf). Rice and finger millet isolates infecting both leaf and neck tissues were sequenced, since the damage and yield loss caused due to neck blast is much higher as compared to leaf blast. The genome-wide comparison was carried out to study the variability in gene content, candidate effectors, repeat element distribution, genes involved in carbohydrate metabolism and SNPs. The analysis of repeat element footprints revealed some genes such as naringenin, 2-oxoglutarate 3-dioxygenase being targeted by Pot2 and Occan, in isolates from different host species. Some repeat insertions were host-specific while other insertions were randomly shared between isolates. The distributions of repeat elements, secretory proteins, CAZymes and SNPs showed significant variation across host-specific lineages of Magnaporthe indicating an independent genome evolution orchestrated by multiple genomic factors. PMID:27658241

An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia

PubMed Central

Periasamy, Sivakumar; Avram, Dorina; McCabe, Amanda; MacNamara, Katherine C.; Sellati, Timothy J.; Harton, Jonathan A.

2016-01-01

Inhalation of Francisella tularensis (Ft) causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection. PMID:27015566

Host range expansion and increased damage potential of Euwallacea nr. fornicatus (Coleoptera: Curculionidae) in Florida

USDA-ARS?s Scientific Manuscript database

Ambrosia beetles in the Euwallacea nr. fornicatus complex (Coleoptera: Curculionidae) vector Fusarium spp. fungi pathogenic to susceptible hosts, including avocado. The Florida avocado production area in Miami-Dade County was surveyed for E. nr. fornicatus upon observations of initial damage in 2016...

Mycophenolic acid induces differentiation of Toxoplasma gondii RH strain tachyzoites into bradyzoites and formation of cyst-like structure in vitro.

PubMed

Castro-Elizalde, Kitzia N; Hernández-Contreras, Pedro; Ramírez-Flores, Carlos J; González-Pozos, Sirenia; Gómez de León, Carmen T; Mondragón-Castelán, Mónica; Mondragón-Flores, Ricardo

2018-02-01

The biochemical and structural changes that occur during the conversion of Toxoplasma gondii tachyzoites to bradyzoites and the formation of tissue cyst are not well understood. Maintaining cells infected with T. gondii type II and III strains under stress conditions induces the tachyzoite-bradyzoite in vitro differentiation, along with the formation of cyst-like structures. However, due to the long exposure to such conditions required to induce the differentiation, the severe damages in the host cell and the low encystation frequency, it has been difficult to dissect in more detail these processes. Here, we successfully induced the in vitro formation of Toxoplasma cysts-like structures from tachyzoites of the type I RH strain by treating with mycophenolic acid, an inhibitor of the inosine monophosphate dehydrogenase. Mycophenolic acid is a drug widely used for HXGPRT positive selection of Toxoplasma mutant strains along with xanthine incubation in the culture medium; under such conditions, formation of tissue cysts has not been reported. We show that the exposure of extracellular tachyzoites to mycophenolic acid in absence of xanthine, followed by host cell invasion, triggered their differentiation into cyst-like structures. The differential expression of CST1, BAG1, and SAG1 molecules, as well as the structural modifications of infected cells, was characterized during the formation of cyst-like structures in vitro. These findings will allow the characterization of signaling pathways involved in tachyzoite to bradyzoite conversion and formation of tissue cysts.

Immunology of Cryptococcal Infections: Developing a Rational Approach to Patient Therapy

PubMed Central

Elsegeiny, Waleed; Marr, Kieren A.; Williamson, Peter R.

2018-01-01

Cryptococcal meningoencephalitis is responsible for upwards of 15% of HIV-related deaths worldwide and is currently the most common cause of non-viral meningitis in the US, affecting both previously healthy and people with immune suppression caused by cancer chemotherapy, transplantation, and biologic therapies. Despite a continued 30–50% attributable mortality, recommended therapeutic strategies have remained largely unchanged since the 1950s. Recent murine models and human studies examining the role of the immune system in both susceptibility to the infection as well as host damage have begun to influence patient care decisions. The Damage Framework Response, originally proposed in 1999, was recently used to discuss dichotomous etiologies of host damage in cryptococcal disease. These include patients suffering microbiological damage with low host immunity (especially those immunosuppressed with HIV) and those having low (live) microbiological burden but high immune-mediated damage (HIV-related immune reconstitution syndrome and non-HIV-related postinfectious inflammatory response syndrome). Cryptococcal disease in previously healthy hosts, albeit rare, has been known for a long time. Immunophenotyping and dendritic cell-T cell signaling studies on cerebral spinal fluid of these rare patients reveal immune capacity for recognition and T-cell activation pathways including increased levels of HLA-DR and CD56. However, despite effective T-cell signals, brain biopsy and autopsy specimens demonstrated an M2 alternative macrophage polarization and poor phagocytosis of fungal cells. These studies expand the paradigm for cryptococcal disease susceptibility to include a prominent role for immune-mediated damage and suggest a need for careful individual consideration of immune activation during therapy of cryptococcal disease in diverse hosts. PMID:29670625

Immunology of Cryptococcal Infections: Developing a Rational Approach to Patient Therapy.

PubMed

Elsegeiny, Waleed; Marr, Kieren A; Williamson, Peter R

2018-01-01

Cryptococcal meningoencephalitis is responsible for upwards of 15% of HIV-related deaths worldwide and is currently the most common cause of non-viral meningitis in the US, affecting both previously healthy and people with immune suppression caused by cancer chemotherapy, transplantation, and biologic therapies. Despite a continued 30-50% attributable mortality, recommended therapeutic strategies have remained largely unchanged since the 1950s. Recent murine models and human studies examining the role of the immune system in both susceptibility to the infection as well as host damage have begun to influence patient care decisions. The Damage Framework Response, originally proposed in 1999, was recently used to discuss dichotomous etiologies of host damage in cryptococcal disease. These include patients suffering microbiological damage with low host immunity (especially those immunosuppressed with HIV) and those having low (live) microbiological burden but high immune-mediated damage (HIV-related immune reconstitution syndrome and non-HIV-related postinfectious inflammatory response syndrome). Cryptococcal disease in previously healthy hosts, albeit rare, has been known for a long time. Immunophenotyping and dendritic cell-T cell signaling studies on cerebral spinal fluid of these rare patients reveal immune capacity for recognition and T-cell activation pathways including increased levels of HLA-DR and CD56. However, despite effective T-cell signals, brain biopsy and autopsy specimens demonstrated an M2 alternative macrophage polarization and poor phagocytosis of fungal cells. These studies expand the paradigm for cryptococcal disease susceptibility to include a prominent role for immune-mediated damage and suggest a need for careful individual consideration of immune activation during therapy of cryptococcal disease in diverse hosts.

Barbiturate euthanasia solution-induced tissue artifact in nonhuman primates.

PubMed

Grieves, J L; Dick, E J; Schlabritz-Loutsevich, N E; Butler, S D; Leland, M M; Price, S E; Schmidt, C R; Nathanielsz, P W; Hubbard, G B

2008-06-01

Barbiturate euthanasia solutions are a humane and approved means of euthanasia. Overdosing causes significant tissue damage in a variety of laboratory animals. One hundred seventeen non-human primates (NHP) representing 7 species including 12 fetuses euthanized for humane and research reasons by various vascular routes with Euthasol, Sodium Pentobarbital, Fatal Plus, Beuthanasia D, or Euthanasia 5 were evaluated for euthanasia-induced tissue damage. Lungs and livers were histologically graded for hemolysis, vascular damage, edema, and necrosis. Severity of tissue damage was analyzed for differences on the basis of agent, age, sex, dose, and injection route. Severity of tissue damage was directly related to dose and the intracardiac injection route, but did not differ by species, sex, and agent used. When the recommended dose of agent was used, tissue damage was generally reduced, minimal, or undetectable. Barbiturate-induced artifacts in NHPs are essentially the same as in other laboratory species.

Histopathological changes on the gills of asp (Aspius aspius) and European catfish (Silurus glanis) caused by Lamproglena pulchella and a Lamproglena sp. (Copepoda: Lernaeidae), respectively.

PubMed

Molnár, K; Avenant-Oldewage, A; Sellyei, B; Varga, Á; Székely, C

2018-01-01

In a parasitology survey of Hungarian fishes, heavy infections of parasitic copepods Lamproglena pulchella and a Lamproglena sp. were found in the gills of the asp and the European catfish, respectively. Individuals of both fish species were emaciated and infected with hundreds of Lamproglena. Copepods located close to the tip of gill filaments and formed a depression at the attachment sites. In histological sections, cell degenerations and local haemorrhages were present adjacent to the maxillipeds and where the maxillary claws pierced the gill tissue. Around maxillae and in the midgut of the Lamproglena, damaged piscine blood cells and remains of the gill tissue were observed. Host reaction was expressed by proliferation of epithelioid cells, increase in both number and size of goblet and mast cells and formation of giant cells. © 2017 John Wiley & Sons Ltd.

Pro-resolution therapeutics for cardiovascular diseases.

PubMed

Heinz, Justin; Marinello, Michael; Fredman, Gabrielle

2017-09-01

Studies over the last couple of decades suggest that failed resolution of a chronic inflammatory response is an important driving force in the progression of atherosclerosis. Resolution of inflammation is mediated in part by lipid-derived specialized pro-resolving mediators (SPMs) such as lipoxins, resolvins, protectins and maresins. The major functions of SPMs are to quell inflammation and repair tissue damage in a manner that does not compromise host defense. An imbalance between SPMs and pro-inflammatory mediators like leukotriene B 4 (LTB 4 ) are associated with several prevalent human diseases, including atherosclerosis. Because atherosclerosis is marked by persistent, unresolved inflammation and arterial tissue injury, SPMs have garnered immense interest as a potential treatment strategy. This mini review will highlight recent advances in the application of SPMs in atherosclerosis as well as the ability of SPMs to control several of the risk factors associated with cardiovascular diseases. Copyright © 2017. Published by Elsevier Inc.

The Resistance of Certain Tissues to Invasion

PubMed Central

Eisenstein, Reuben; Sorgente, Nino; Soble, Lawrence W.; Miller, Alexander; Kuettner, Klaus E.

1973-01-01

If puppy tissues are explanted onto the chick chorioallantoic membrane, those tissues which normally have a blood supply are rapidly invaded by vascularized mesenchyme of host origin. Hyaline cartilage, a tissue virtually devoid of blood vessels, is impenetrable by proliferating mesenchyme of the host, while calcified cartilage, which normally is vascularized, is penetrable. The stroma of the cornea, another normally avascular tissue, is readily penetrable, but Descemet's membrane forms a barrier to invasion by host tissues. The experimental system used permits the design of experiments in which the study of factors responsible for the resistance of tissues such as cartilage to invasion can be undertaken. ImagesFig 1Fig 2Fig 3Fig 4 PMID:4129060

Variability in the intensity of nematode larvae from gastrointestinal tissues of a natural herbivore.

PubMed

van Kuren, Andrew T; Boag, Brian; Hruban, Emilie; Cattadori, Isabella M

2013-04-01

The migration of infective nematode larvae into the tissues of their hosts has been proposed as a mechanism of reducing larval mortality and increase parasite lifetime reproductive success. Given that individual hosts differ in the level of exposure, strength of immune response and physiological conditions we may expect the number of larvae in tissue to vary both between and within hosts. We used 2 gastrointestinal nematode species common in the European rabbit (Oryctolagus cuniculus) and examined how the number of larvae in the tissue changed with the immune response, parasite intensity-dependent constraints in the lumen and seasonal weather factors, in rabbits of different age, sex and breeding status. For both nematode species, larvae from the gastrointestinal tissue exhibited strong seasonal and host age-related patterns with fewer larvae recovered in summer compared to winter and more in adults than in juveniles. The number of larvae of the 2 nematodes was positively associated with intensity of parasite infection in the lumen and antibody responses while it was negatively related with air temperature and rainfall. Host sex, reproductive status and co-infection with the second parasite species contributed to increase variability between hosts. We concluded that heterogeneities in host conditions are a significant cause of variability of larval abundance in the gastrointestinal tissues. These findings can have important consequences for the dynamics of nematode infections and how parasite's life-history strategies adjust to host changes.

What Is a Host? Incorporating the Microbiota into the Damage-Response Framework

PubMed Central

Pirofski, Liise-anne

2014-01-01

Since proof of the germ theory of disease in the late 19th century, a major focus of the fields of microbiology and infectious diseases has been to seek differences between pathogenic and nonpathogenic microbes and the role that the host plays in microbial pathogenesis. Remarkably, despite the increasing recognition that host immunity plays a role in microbial pathogenesis, there has been little discussion about what constitutes a host. Historically, hosts have been viewed in the context of their fitness or immunological status and characterized by adjectives such as immune, immunocompetent, immunosuppressed, immunocompromised, or immunologically impaired. However, in recent years it has become apparent that the microbiota has profound effects on host homeostasis and susceptibility to microbial diseases in addition to its effects on host immunity. This raises the question of how to incorporate the microbiota into defining a host. This definitional problem is further complicated because neither host nor microbial properties are adequate to predict the outcome of host-microbe interaction because this outcome exhibits emergent properties. In this essay, we revisit the damage-response framework (DRF) of microbial pathogenesis and demonstrate how it can incorporate the rapidly accumulating information being generated by the microbiome revolution. We use the tenets of the DRF to put forth the following definition of a host: a host is an entity that houses an associated microbiome/microbiota and interacts with microbes such that the outcome results in damage, benefit, or indifference, thus resulting in the states of symbiosis, colonization, commensalism, latency, and disease. PMID:25385796

Distribution of O-Acetylated Sialic Acids among Target Host Tissues for Influenza Virus

PubMed Central

Barnard, Karen N.; Ossiboff, Robert J.; Khedri, Zahra; Feng, Kurtis H.; Yu, Hai; Chen, Xi; Varki, Ajit

2017-01-01

ABSTRACT Sialic acids (Sias) are important glycans displayed on the cells and tissues of many different animals and are frequent targets for binding and modification by pathogens, including influenza viruses. Influenza virus hemagglutinins bind Sias during the infection of their normal hosts, while the encoded neuraminidases and/or esterases remove or modify the Sia to allow virion release or to prevent rebinding. Sias naturally occur in a variety of modified forms, and modified Sias can alter influenza virus host tropisms through their altered interactions with the viral glycoproteins. However, the distribution of modified Sia forms and their effects on pathogen-host interactions are still poorly understood. Here we used probes developed from viral Sia-binding proteins to detect O-acetylated (4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl) Sias displayed on the tissues of some natural or experimental hosts for influenza viruses. These modified Sias showed highly variable displays between the hosts and tissues examined. The 9-O-acetyl (and 7,9-) modified Sia forms were found on cells and tissues of many hosts, including mice, humans, ferrets, guinea pigs, pigs, horses, dogs, as well as in those of ducks and embryonated chicken egg tissues and membranes, although in variable amounts. The 4-O-acetyl Sias were found in the respiratory tissues of fewer animals, being primarily displayed in the horse and guinea pig, but were not detected in humans or pigs. The results suggest that these Sia variants may influence virus tropisms by altering and selecting their cell interactions. IMPORTANCE Sialic acids (Sias) are key glycans that control or modulate many normal cell and tissue functions while also interacting with a variety of pathogens, including many different viruses. Sias are naturally displayed in a variety of different forms, with modifications at several positions that can alter their functional interactions with pathogens. In addition, Sias are often modified or removed by enzymes such as host or pathogen esterases or sialidases (neuraminidases), and Sia modifications can alter those enzymatic activities to impact pathogen infections. Sia chemical diversity in different hosts and tissues likely alters the pathogen-host interactions and influences the outcome of infection. Here we explored the display of 4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl modified Sia forms in some target tissues for influenza virus infection in mice, humans, birds, guinea pigs, ferrets, swine, horses, and dogs, which encompass many natural and laboratory hosts of those viruses. PMID:28904995

Modeling conduction in host-graft interactions between stem cell grafts and cardiomyocytes.

PubMed

Chen, Michael Q; Yu, Jin; Whittington, R Hollis; Wu, Joseph C; Kovacs, Gregory T A; Giovangrandi, Laurent

2009-01-01

Cell therapy has recently made great strides towards aiding heart failure. However, while transplanted cells may electromechanically integrate into host tissue, there may not be a uniform propagation of a depolarization wave between the heterogeneous tissue boundaries. A model using microelectrode array technology that maps the electrical interactions between host and graft tissues in co-culture is presented and sheds light on the effects of having a mismatch of conduction properties at the boundary. Skeletal myoblasts co-cultured with cardiomyocytes demonstrated that conduction velocity significantly decreases at the boundary despite electromechanical coupling. In an attempt to improve the uniformity of conduction with host cells, differentiating human embryonic stem cells (hESC) were used in co-culture. Over the course of four to seven days, synchronous electrical activity was observed at the hESC boundary, implying differentiation and integration. Activity did not extend far past the boundary, and conduction velocity was significantly greater than that of the host tissue, implying the need for other external measures to properly match the conduction properties between host and graft tissue.

Thermal damage produced by high-irradiance continuous wave CO2 laser cutting of tissue.

PubMed

Schomacker, K T; Walsh, J T; Flotte, T J; Deutsch, T F

1990-01-01

Thermal damage produced by continuous wave (cw) CO2 laser ablation of tissue in vitro was measured for irradiances ranging from 360 W/cm2 to 740 kW/cm2 in order to investigate the extent to which ablative cooling can limit tissue damage. Damage zones thinner than 100 microns were readily produced using single pulses to cut guinea pig skin as well as bovine cornea, aorta, and myocardium. Multiple pulses can lead to increased damage. However, a systematic decrease in damage with irradiance, predicted theoretically by an evaporation model of ablation, was not observed. The damage-zone thickness was approximately constant around the periphery of the cut, consistent with the existence of a liquid layer which stores heat and leads to tissue damage, and with a model of damage and ablation recently proposed by Zweig et al.

Free-living pathogens: life-history constraints and strain competition

PubMed Central

Caraco, Thomas; Wang, Ing-Nang

2008-01-01

Many pathogen life histories include a free-living stage, often with anatomical and physiological adaptations promoting persistence outside of host tissues. More durable particles presumably require that the pathogen metabolize more resources per particle. Therefore, we hypothesize functional dependencies, pleiotropic constraints, between the rate at which free-living particles decay outside of host tissues and other pathogen traits, including virulence, the probability of infecting a host upon contact, and pathogen reproduction within host tissues. Assuming that pathogen strains compete for hosts preemptively, we find patterns in trait dependencies predicting whether or not strain competition favors a highly persistent free-living stage. PMID:18062992

Chemical variability and leaf damage among lychee varieties, host of the Sri Lanka weevil, Myllocerus undecimpustulatus undatus Marchall

USDA-ARS?s Scientific Manuscript database

Chemical Variability and leaf damages among lychee varieties, host of the Sri Lanka weevil Myllocerus undecimpustulatus undatus Marshall. Jerome Niogret, Nancy Epsky, Paul Kendra, Peter Teal The Sri Lanka weevil Myllocerus undercimpustulatus undatus Marshall is serious economic pest in India and P...

ENHANCED BINDING OF AUTOLOGOUS RED CELLS TO THE MACROPHAGE PLASMA MEMBRANE AS A SENSITIVE INDICATOR OF POLLUTANT DAMAGE

EPA Science Inventory

The alveolar macrophage (AM) represents the primary line of defense in host protection against inhaled infectious organisms. Following exposure to oxidant gases, the ability of the host to resist airborne bacterial infection is severely impaired, and damage to the AM defense syst...

Aspergillus flavus induced alterations in tear protein profile reveal pathogen-induced host response to fungal infection.

PubMed

Kandhavelu, Jeyalakshmi; Demonte, Naveen Luke; Namperumalsamy, Venkatesh Prajna; Prajna, Lalitha; Thangavel, Chitra; Jayapal, Jeya Maheshwari; Kuppamuthu, Dharmalingam

2017-01-30

Aspergillus flavus and Fusarium sp. are primary causative agents of keratitis that results in corneal tissue damage leading to vision loss particularly in individuals from the tropical parts of the world. Proteins in the tear film collected from control and keratitis patients was profiled and compared. A total of 1873 proteins from control and 1400 proteins from patient tear were identified by mass spectrometry. While 847 proteins were found to be glycosylated in the patient tear, only 726 were glycosylated in control tear. And, some of the tear proteins showed alterations in their glycosylation pattern after infection. Complement system proteins, proteins specific for neutrophil extracellular traps and proteins involved in would healing were found only in the patient tear. The presence of these innate immune system proteins in the tear film of patients supports the previous data indicating the involvement of neutrophil and complement pathways in antifungal defense. High levels of wound healing proteins in keratitis patient tear implied activation of tissue repair during infection. The early appearance of the host defense proteins and wound healing response indicates that tear proteins could be used as an early marker system for monitoring the progression of pathogenesis. Identification of negative regulators of the above defense pathways in keratitis tear indicates an intricate balance of pro and anti-defense mechanisms operating in fungal infection of the eye. Tear proteins from control and mycotic keratitis patients were separated into glycoproteins and non-glycosylated proteins and then identified by mass spectrometry. Tear proteins from keratitis patients showed alteration in the glycosylation pattern indicating the alteration of glycosylation machinery due to infection. Neutrophil extracellular traps specific proteins, complement pathway proteins, as well as wound healing proteins, were found only in patient tear showing the activation of antifungal defense in the patient tear. Negative regulators of these defense pathways were also found in patient tear indicating a fine balance between pathogen clearance and host tissue destruction during fungal infection depending upon the individual specific host - pathogen interaction. This understanding could be used to predict the progression and outcome of infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Olfactory responses of banana weevil predators to volatiles from banana pseudostem tissue and synthetic pheromone.

PubMed

Tinzaara, W; Gold, C S; Dicke, M; van Huis, A

2005-07-01

As a response to attack by herbivores, plants can emit a variety of volatile substances that attract natural enemies of these insect pests. Predators of the banana weevil, Cosmopolites sordidus (Germar) (Coleoptera: Curculionidae) such as Dactylosternum abdominale (Coleoptera: Hydrophilidae) and Pheidole megacephala (Hymenoptera: Formicidae), are normally found in association with weevil-infested rotten pseudostems and harvested stumps. We investigated whether these predators are attracted to such environments in response to volatiles produced by the host plant, by the weevil, or by the weevil plant complex. We evaluated predator responses towards volatiles from banana pseudostem tissue (synomones) and the synthetic banana weevil aggregation pheromone Cosmolure+ in a two-choice olfactometer. The beetle D. abdominale was attracted to fermenting banana pseudostem tissue and Cosmolure+, whereas the ant P. megacephala was attracted only to fermented pseudostem tissue. Both predators were attracted to banana pseudostem tissue that had been damaged by weevil larvae irrespective of weevil presence. Adding pheromone did not enhance predator response to volatiles from pseudostem tissue fed on by weevils. The numbers of both predators recovered with pseudostem traps in the field from banana mats with a pheromone trap were similar to those in pseudostem traps at different distance ranges from the pheromone. Our study shows that the generalist predators D. abdominale and P. megacephala use volatiles from fermented banana pseudostem tissue as the major chemical cue when searching for prey.

Immunologic alterations and the pathogenesis of organ failure in the ICU.

PubMed

Opal, Steven M

2011-10-01

Rapid and marked alterations of innate and adaptive immunity typify the host response to systemic infection and acute inflammatory states. Immune dysfunction contributes to the development of organ failure in most patients with critical illness. The molecular mechanisms by which microbial pathogens and tissue injury activate myeloid cells and prime cellular and humoral immunity are increasingly understood. An early and effective immune response to microbial invasion is essential to mount an effective antimicrobial response. However, unchecked and nonresolving inflammation can induce diffuse vasodilation, increased capillary permeability, microvascular damage, coagulation activation, and organ dysfunction. Control of the inflammatory response to limit tissue damage, yet retain the antimicrobial responses in critically ill patients with severe infection, has been sought for decades. Anti-inflammatory approaches might be beneficial in some patients but detrimental in others. It is now clear that a state of sepsis-induced immune suppression can follow the immune activation phase of sepsis. In carefully selected patients, a better therapeutic strategy might be to provide immunoadjuvants to reconstitute immune function in intensive care unit (ICU) patients. Proresolving agents are also in development to terminate acute inflammatory reactions without immune suppression. This brief review summarizes the current understanding of the fundamental immune alterations in critical illness that lead to organ failure in critical illness. © Thieme Medical Publishers.

Proteomic analysis of the action of the Mycobacterium ulcerans toxin mycolactone: targeting host cells cytoskeleton and collagen.

PubMed

Gama, José B; Ohlmeier, Steffen; Martins, Teresa G; Fraga, Alexandra G; Sampaio-Marques, Belém; Carvalho, Maria A; Proença, Fernanda; Silva, Manuel T; Pedrosa, Jorge; Ludovico, Paula

2014-08-01

Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. The tissue damage characteristic of BU lesions is known to be driven by the secretion of the potent lipidic exotoxin mycolactone. However, the molecular action of mycolactone on host cell biology mediating cytopathogenesis is not fully understood. Here we applied two-dimensional electrophoresis (2-DE) to identify the mechanisms of mycolactone's cellular action in the L929 mouse fibroblast proteome. This revealed 20 changed spots corresponding to 18 proteins which were clustered mainly into cytoskeleton-related proteins (Dync1i2, Cfl1, Crmp2, Actg1, Stmn1) and collagen biosynthesis enzymes (Plod1, Plod3, P4ha1). In line with cytoskeleton conformational disarrangements that are observed by immunofluorescence, we found several regulators and constituents of both actin- and tubulin-cytoskeleton affected upon exposure to the toxin, providing a novel molecular basis for the effect of mycolactone. Consistent with these cytoskeleton-related alterations, accumulation of autophagosomes as well as an increased protein ubiquitination were observed in mycolactone-treated cells. In vivo analyses in a BU mouse model revealed mycolactone-dependent structural changes in collagen upon infection with M. ulcerans, associated with the reduction of dermal collagen content, which is in line with our proteomic finding of mycolactone-induced down-regulation of several collagen biosynthesis enzymes. Our results unveil the mechanisms of mycolactone-induced molecular cytopathogenesis on exposed host cells, with the toxin compromising cell structure and homeostasis by inducing cytoskeleton alterations, as well as disrupting tissue structure, by impairing the extracellular matrix biosynthesis.

Enhanced susceptibility of irradiated tumor vessels to vascular endothelial growth factor receptor tyrosine kinase inhibition.

PubMed

Zips, Daniel; Eicheler, Wolfgang; Geyer, Peter; Hessel, Franziska; Dörfler, Annegret; Thames, Howard D; Haberey, Martin; Baumann, Michael

2005-06-15

Previous experiments with PTK787/ZK222584, a specific inhibitor of vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, using irradiated human FaDu squamous cell carcinoma in nude mice, suggested that radiation-damaged tumor vessels are more sensitive to VEGFR inhibition. To test this hypothesis, the tumor transplantation site (i.e., the right hind leg of nude mice) was irradiated 10 days before transplantation of FaDu to induce radiation damage in the host tissue. FaDu tumors vascularized by radiation-damaged blood vessels appeared later, grew at a slower rate, and showed more necrosis and a smaller vessel area per central tumor section than controls. PTK787/ZK222584 at a daily dose of 50 mg/kg body weight had no impact on growth of control tumors. In contrast, tumors vascularized by radiation-damaged vessels responded to PTK787/ZK222584 with longer latency and slower growth rate than controls, and a trend toward further increase in necrosis, indicating that irradiated tumor vessels are more susceptible to VEGFR inhibition than unirradiated vessels. Although not proving causality, expression analysis of VEGF and VEGFR2 shows that enhanced sensitivity of irradiated vessels to a specific inhibitor of VEGFR tyrosine kinases correlates with increased expression of the molecular target.

Exploiting Advanced Hydrogel Technologies to Address Key Challenges in Regenerative Medicine

PubMed Central

Gentleman, Eileen

2018-01-01

Regenerative medicine aims to tackle a panoply of challenges, from repairing focal damage to articular cartilage to preventing pathological tissue remodelling after myocardial infarction. Hydrogels are water-swollen networks formed from synthetic or naturally derived polymers, and are emerging as important tools to address these challenges. Recent advances in hydrogel chemistries are enabling researchers to create hydrogels that can act as 3D ex vivo tissue models, allowing them to explore fundamental questions in cell biology by replicating tissues’ dynamic and non-linear physical properties. Enabled by emerging techniques such as 3D bioprinting, cell-laden hydrogels are also being developed with highly controlled tissue-specific architectures, vasculature, and biological functions that together can direct tissue repair. Moreover, advanced in situ forming and acellular hydrogels are increasingly finding use as delivery vehicles for bioactive compounds and in mediating host cell response. Here, we review advances in the design and fabrication of hydrogels for regenerative medicine. We also address how controlled chemistries are allowing for precise engineering of spatial and time-dependent properties in hydrogels with a look to how these materials will eventually translate to clinical applications. PMID:29316363

Scalloped and Yorkie are required for cell cycle re-entry of quiescent cells after tissue damage.

PubMed

Meserve, Joy H; Duronio, Robert J

2015-08-15

Regeneration of damaged tissues typically requires a population of active stem cells. How damaged tissue is regenerated in quiescent tissues lacking a stem cell population is less well understood. We used a genetic screen in the developing Drosophila melanogaster eye to investigate the mechanisms that trigger quiescent cells to re-enter the cell cycle and proliferate in response to tissue damage. We discovered that Hippo signaling regulates compensatory proliferation after extensive cell death in the developing eye. Scalloped and Yorkie, transcriptional effectors of the Hippo pathway, drive Cyclin E expression to induce cell cycle re-entry in cells that normally remain quiescent in the absence of damage. Ajuba, an upstream regulator of Hippo signaling that functions as a sensor of epithelial integrity, is also required for cell cycle re-entry. Thus, in addition to its well-established role in modulating proliferation during periods of tissue growth, Hippo signaling maintains homeostasis by regulating quiescent cell populations affected by tissue damage. © 2015. Published by The Company of Biologists Ltd.

Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

PubMed Central

Gardner, Jameson K.; Herbst-Kralovetz, Melissa M.

2016-01-01

The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies. PMID:27834891

Evidence for a cost of immunity when the crustacean Daphnia magna is exposed to the bacterial pathogen Pasteuria ramosa.

PubMed

Little, Tom J; Killick, Stuart C

2007-11-01

The deployment of the immune system has the obvious potential to ameliorate infection outcomes, but immune responses can also harm hosts by either damaging host tissues or monopolizing resources, leading to enhanced mortality. To gain insight into such a 'cost of immunity' when the crustacean Daphnia magna is challenged with the bacterium Pasteuria ramosa, we measured survivorship among hosts that resisted infection following exposure to various strains and doses of the parasite. In the first of two experiments, these exposures were: single exposures with relatively non-aggressive strains, double exposures with non-aggressive strains, and exposure to aggressive strains. Mortality increased across this gradient of exposure. In a second experiment, we varied the dose of the most aggressive P. ramosa strain and found that resisting infection when a large dose was applied resulted in greater mortality than when a medium or low dose was applied. Assuming that resistance is accomplished with an immune response, and that more aggressive parasites and/or larger doses of parasites are more immunostimulatory, these data are compatible with a cost of immunity. Indeed, in terms of survival, resisting parasites can be more harmful than infection.

Adenovirus Core Protein VII Downregulates the DNA Damage Response on the Host Genome

PubMed Central

Avgousti, Daphne C.; Della Fera, Ashley N.; Otter, Clayton J.; Herrmann, Christin; Pancholi, Neha J.

2017-01-01

ABSTRACT Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier to successful infection. The adenovirus genome is packaged with protein VII, a virally encoded histone-like core protein that is suggested to protect incoming viral genomes from detection by the cellular DNA damage machinery. We showed that protein VII localizes to host chromatin during infection, leading us to hypothesize that protein VII may affect DNA damage responses on the cellular genome. Here we show that protein VII at cellular chromatin results in a significant decrease in accumulation of phosphorylated H2AX (γH2AX) following irradiation, indicating that protein VII inhibits DDR signaling. The oncoprotein SET was recently suggested to modulate the DDR by affecting access of repair proteins to chromatin. Since protein VII binds SET, we investigated a role for SET in DDR inhibition by protein VII. We show that knockdown of SET partially rescues the protein VII-induced decrease in γH2AX accumulation on the host genome, suggesting that SET is required for inhibition. Finally, we show that knockdown of SET also allows ATM to localize to incoming viral genomes bound by protein VII during infection with a mutant lacking early region E4. Together, our data suggest that the protein VII-SET interaction contributes to DDR evasion by adenovirus. Our results provide an additional example of a strategy used by adenovirus to abrogate the host DDR and show how viruses can modify cellular processes through manipulation of host chromatin. IMPORTANCE The DNA damage response (DDR) is a cellular network that is crucial for maintaining genome integrity. DNA viruses replicating in the nucleus challenge the resident genome and must overcome cellular responses, including the DDR. Adenoviruses are prevalent human pathogens that can cause a multitude of diseases, such as respiratory infections and conjunctivitis. Here we describe how a small adenovirus core protein that localizes to host chromatin during infection can globally downregulate the DDR. Our study focuses on key players in the damage signaling pathway and highlights how viral manipulation of chromatin may influence access of DDR proteins to the host genome. PMID:28794020

Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix.

PubMed

Kuo, Kuan-Chih; Lin, Ruei-Zeng; Tien, Han-Wen; Wu, Pei-Yun; Li, Yen-Cheng; Melero-Martin, Juan M; Chen, Ying-Chieh

2015-11-01

Tissue engineering promises to restore or replace diseased or damaged tissue by creating functional and transplantable artificial tissues. The development of artificial tissues with large dimensions that exceed the diffusion limitation will require nutrients and oxygen to be delivered via perfusion instead of diffusion alone over a short time period. One approach to perfusion is to vascularize engineered tissues, creating a de novo three-dimensional (3D) microvascular network within the tissue construct. This significantly shortens the time of in vivo anastomosis, perfusion and graft integration with the host. In this study, we aimed to develop injectable allogeneic collagen-phenolic hydroxyl (collagen-Ph) hydrogels that are capable of controlling a wide range of physicochemical properties, including stiffness, water absorption and degradability. We tested whether collagen-Ph hydrogels could support the formation of vascularized engineered tissue graft by human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSC) in vivo. First, we studied the growth of adherent ECFCs and MSCs on or in the hydrogels. To examine the potential formation of functional vascular networks in vivo, a liquid pre-polymer solution of collagen-Ph containing human ECFCs and MSCs, horseradish peroxidase and hydrogen peroxide was injected into the subcutaneous space or abdominal muscle defect of an immunodeficient mouse before gelation, to form a 3D cell-laden polymerized construct. These results showed that extensive human ECFC-lined vascular networks can be generated within 7 days, the engineered vascular density inside collagen-Ph hydrogel constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with the existing vasculature to further support the survival of host muscle tissues. Finally, optimized conditions of the cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse after 1 month of implantation. We reported a method for preparing autologous extracellular matrix scaffolds, murine collagen-Ph hydrogels, and demonstrated its suitability for use in supporting human progenitor cell-based formation of 3D vascular networks in vitro and in vivo. Results showed extensive human vascular networks can be generated within 7 days, engineered vascular density inside collagen-Ph constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with existing vasculature to further support the survival of host muscle tissues. Moreover, optimized conditions of cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Modeling Soft Tissue Damage and Failure Using a Combined Particle/Continuum Approach.

PubMed

Rausch, M K; Karniadakis, G E; Humphrey, J D

2017-02-01

Biological soft tissues experience damage and failure as a result of injury, disease, or simply age; examples include torn ligaments and arterial dissections. Given the complexity of tissue geometry and material behavior, computational models are often essential for studying both damage and failure. Yet, because of the need to account for discontinuous phenomena such as crazing, tearing, and rupturing, continuum methods are limited. Therefore, we model soft tissue damage and failure using a particle/continuum approach. Specifically, we combine continuum damage theory with Smoothed Particle Hydrodynamics (SPH). Because SPH is a meshless particle method, and particle connectivity is determined solely through a neighbor list, discontinuities can be readily modeled by modifying this list. We show, for the first time, that an anisotropic hyperelastic constitutive model commonly employed for modeling soft tissue can be conveniently implemented within a SPH framework and that SPH results show excellent agreement with analytical solutions for uniaxial and biaxial extension as well as finite element solutions for clamped uniaxial extension in 2D and 3D. We further develop a simple algorithm that automatically detects damaged particles and disconnects the spatial domain along rupture lines in 2D and rupture surfaces in 3D. We demonstrate the utility of this approach by simulating damage and failure under clamped uniaxial extension and in a peeling experiment of virtual soft tissue samples. In conclusion, SPH in combination with continuum damage theory may provide an accurate and efficient framework for modeling damage and failure in soft tissues.

Modeling Soft Tissue Damage and Failure Using a Combined Particle/Continuum Approach

PubMed Central

Rausch, M. K.; Karniadakis, G. E.; Humphrey, J. D.

2016-01-01

Biological soft tissues experience damage and failure as a result of injury, disease, or simply age; examples include torn ligaments and arterial dissections. Given the complexity of tissue geometry and material behavior, computational models are often essential for studying both damage and failure. Yet, because of the need to account for discontinuous phenomena such as crazing, tearing, and rupturing, continuum methods are limited. Therefore, we model soft tissue damage and failure using a particle/continuum approach. Specifically, we combine continuum damage theory with Smoothed Particle Hydrodynamics (SPH). Because SPH is a meshless particle method, and particle connectivity is determined solely through a neighbor list, discontinuities can be readily modeled by modifying this list. We show, for the first time, that an anisotropic hyperelastic constitutive model commonly employed for modeling soft tissue can be conveniently implemented within a SPH framework and that SPH results show excellent agreement with analytical solutions for uniaxial and biaxial extension as well as finite element solutions for clamped uniaxial extension in 2D and 3D. We further develop a simple algorithm that automatically detects damaged particles and disconnects the spatial domain along rupture lines in 2D and rupture surfaces in 3D. We demonstrate the utility of this approach by simulating damage and failure under clamped uniaxial extension and in a peeling experiment of virtual soft tissue samples. In conclusion, SPH in combination with continuum damage theory may provide an accurate and efficient framework for modeling damage and failure in soft tissues. PMID:27538848

Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure.

PubMed

Mielczarek, Ewelina; Blaszkowska, Joanna

2016-08-01

Trichomonas vaginalis, which colonizes the genitourinary tract of men and women, is a sexually transmitted parasite causing symptomatic or asymptomatic trichomoniasis. The host-parasite relationship is very complex, and clinical symptoms cannot likely be attributed to a single pathogenic effect. Among the many factors responsible for interactions between T. vaginalis and host tissues, contact-dependent and contact-independent mechanisms are important in pathogenicity, as is the immune response. This review focuses on the potential virulence properties of T. vaginalis and its role in female and male infertility. It highlights the association between T. vaginalis infection and serious adverse health consequences experienced by women, including infertility, preterm birth and low-birth-weight infants. Long-term clinical observations and results of in vitro experimental studies indicate that in men, trichomoniasis has been also associated with infertility through inflammatory damage to the genitourinary tract or interference with sperm function. These results contribute significantly to improving our knowledge of the role of parasitic virulence factors in the development of infection and its role in human infertility.

Does defibrotide prophylaxis decrease the risk of acute graft versus host disease following allogeneic hematopoietic cell transplantation?

PubMed

Tekgündüz, Emre; Kaya, Ali Hakan; Bozdağ, Sinem Civriz; Koçubaba, Şerife; Kayıkçı, Ömür; Namdaroğlu, Sinem; Uğur, Bilge; Akpınar, Seval; Batgi, Hikmetullah; Bekdemir, Filiz; Altuntaş, Fevzi

2016-02-01

There is some preliminary evidence, that veno-occlusive disease prophylaxis with defibrotide (DF) may also have a role in decreasing risk of acute graft-versus-host disease (aGvHD) by preventing tissue damage. In this study, we aimed to investigate the role of DF prophylaxis on the development of aGvHD at D+180. One hundred ninety-five consecutive adult patients receiving allogeneic HCT were retrospectively evaluated in 3 groups: no DF, DF/post-HCT (DF D+1 to D+14) and DF/pre-HCT (DF for 14 days concurrently with conditioning). The total (p: 0.057) and grades III/IV (p: 0.051) aGvHD rates at D+180 were 46.5%, 40%, 25.5% and 15.5%, 11.2%, 0% in patients on no DF, DF/post-HCT and DF/pre-HCT. DF may have a role in decreasing incidence and severity of aGvHD, especially if used concurrently with conditioning regimen. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative proteomic analysis of proteins expression changes in the mammary tissue of cows infected with Escherichia coli mastitis.

PubMed

Zhao, Xiao-wei; Yang, Yong-xin; Huang, Dong-wei; Cheng, Guang-long; Zhao, Hui-ling

2015-01-01

Cows infected with Escherichia (E.) coli usually experience severe clinical symptoms, including damage to mammary tissues, reduced milk yield, and altered milk composition. In order to investigate the host response to E. coli infection and discover novel markers for mastitis treatment, mammary tissue samples were collected from healthy cows and bovines with naturally occurring severe E. coli mastitis. Changes of mammary tissue proteins were examined using two-dimensional gel electrophoresis and label-free proteomic approaches. A total of 95 differentially expressed proteins were identified. Of these, 56 proteins were categorized according to molecular function, cellular component, and biological processes. The most frequent biological processes influenced by the proteins were response to stress, transport, and establishment of localization. Furthermore, a network analysis of the proteins with altered expression in mammary tissues demonstrated that these factors are predominantly involved with binding and structural molecule activities. Vimentin and a-enolase were central "functional hubs" in the network. Based on results from the present study, disease-induced alterations of protein expression in mammary glands and potential markers for the effective treatment of E. coli mastitis were identified. These data have also helped elucidate defense mechanisms that protect the mammary glands and promote the pathogenesis of E. coli mastitis.

Comparative proteomic analysis of proteins expression changes in the mammary tissue of cows infected with Escherichia coli mastitis

PubMed Central

Zhao, Xiao-wei; Huang, Dong-wei; Cheng, Guang-long; Zhao, Hui-ling

2015-01-01

Cows infected with Escherichia (E.) coli usually experience severe clinical symptoms, including damage to mammary tissues, reduced milk yield, and altered milk composition. In order to investigate the host response to E. coli infection and discover novel markers for mastitis treatment, mammary tissue samples were collected from healthy cows and bovines with naturally occurring severe E. coli mastitis. Changes of mammary tissue proteins were examined using two-dimensional gel electrophoresis and label-free proteomic approaches. A total of 95 differentially expressed proteins were identified. Of these, 56 proteins were categorized according to molecular function, cellular component, and biological processes. The most frequent biological processes influenced by the proteins were response to stress, transport, and establishment of localization. Furthermore, a network analysis of the proteins with altered expression in mammary tissues demonstrated that these factors are predominantly involved with binding and structural molecule activities. Vimentin and α-enolase were central "functional hubs" in the network. Based on results from the present study, disease-induced alterations of protein expression in mammary glands and potential markers for the effective treatment of E. coli mastitis were identified. These data have also helped elucidate defense mechanisms that protect the mammary glands and promote the pathogenesis of E. coli mastitis. PMID:25549220

Toll-like receptor signaling in cell proliferation and survival

PubMed Central

Li, Xinyan; Jiang, Song; Tapping, Richard I.

2009-01-01

Toll-like receptors (TLRs) are important sensors of foreign microbial components as well as products of damaged or inflamed self tissues. Upon sensing these molecules, TLRs initiate a series of downstream signaling events that drive cellular responses including the production of cytokines, chemokines and other inflammatory mediators. This outcome results from the intracellular assembly of protein complexes that drive phosphorylation and other signaling cascades ultimately leading to chromatin remodeling and transcription factor activation. In addition to driving inflammatory responses, TLRs also regulate cell proliferation and survival which serves to expand useful immune cells and integrate inflammatory responses and tissue repair processes. In this context, central TLR signaling molecules, such as the mitogen-activated protein kinases (MAPK) and phosphoinositide 3-kinase (PI3K), play key roles. In addition, four major groups of transcription factors which are targets of TLR activation also control cell fate. This review focuses on the role of TLR signaling as it relates to cell proliferation and survival. This topic not only has important implications for understanding host defense and tissue repair, but also cancer which is often associated with conditions of chronic inflammation. PMID:19775907

A quantitative multiplex nuclease protection assay reveals immunotoxicity gene expression profiles in the rabbit model for vaginal drug safety evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fichorova, Raina N., E-mail: rfichorova@rics.bwh.harvard.edu; Mendonca, Kevin; Yamamoto, Hidemi S.

Any vaginal product that alters the mucosal environment and impairs the immune barrier increases the risk of sexually transmitted infections, especially HIV infection, which thrives on mucosal damage and inflammation. The FDA-recommended rabbit vaginal irritation (RVI) model serves as a first line selection tool for vaginal products; however, for decades it has been limited to histopathology scoring, insufficient to select safe anti-HIV microbicides. In this study we incorporate to the RVI model a novel quantitative nuclease protection assay (qNPA) to quantify mRNA levels of 25 genes representing leukocyte differentiation markers, toll-like receptors (TLR), cytokines, chemokines, epithelial repair, microbicidal and vascularmore » markers, by designing two multiplex arrays. Tissue sections were obtained from 36 rabbits (6 per treatment arm) after 14 daily applications of a placebo gel, saline, 4% nonoxynol-9 (N-9), and three combinations of the anti-HIV microbicides tenofovir (TFV) and UC781 in escalating concentrations (highest: 10% TFV + 2.5%UC781). Results showed that increased expression levels of toll-like receptor (TLR)-4, interleukin (IL)-1β, CXCL8, epithelial membrane protein (EMP)-1 (P < 0.05), and decreased levels of TLR2 (P < 0.05), TLR3 and bactericidal permeability increasing protein (BPI) (P < 0.001) were associated with cervicovaginal mucosal alteration (histopathology). Seven markers showed a significant linear trend predicting epithelial damage (up with CD4, IL-1β, CXCL8, CCL2, CCL21, EMP1 and down with BPI). Despite the low tissue damage RVI scores, the high-dose microbicide combination gel caused activation of HIV host cells (SLC and CD4) while N-9 caused proinflammatory gene upregulation (IL-8 and TLR4) suggesting a potential for increasing risk of HIV via different mechanisms depending on the chemical nature of the test product. - Highlights: • A transcriptome nuclease protection assay assessed microbicides for vaginal safety. • Biomarkers were correlated with histopathology in paraffin-embedded rabbit tissues. • Compounds differed by effects on putative pathways of increased risk of HIV. • Nonsoxynol-9 caused inflammatory tissue damage involving TLR4 and IL-8. • An antiretroviral combination stimulated immune cells evidenced by SLC and CD4.« less

Exo-erythrocytic development of avian malaria and related haemosporidian parasites.

PubMed

Valkiūnas, Gediminas; Iezhova, Tatjana A

2017-03-03

Avian malaria parasites (Plasmodium spp.) and related haemosporidians (Haemosporida) are responsible for diseases which can be severe and even lethal in avian hosts. These parasites cause not only blood pathology, but also damage various organs due to extensive exo-erythrocytic development all over the body, which is not the case during Plasmodium infections in mammals. However, exo-erythrocytic development (tissue merogony or schizogony) remains the most poorly investigated part of life cycle in all groups of wildlife haemosporidian parasites. In spite of remarkable progress in studies of genetic diversity, ecology and evolutionary biology of avian haemosporidians during the past 20 years, there is not much progress in understanding patterns of exo-erythrocytic development in these parasites. The purpose of this review is to overview the main information on exo-erythrocytic development of avian Plasmodium species and related haemosporidian parasites as a baseline for assisting academic and veterinary medicine researchers in morphological identification of these parasites using tissue stages, and to define future research priorities in this field of avian malariology. The data were considered from peer-reviewed articles and histological material that was accessed in zoological collections in museums of Australia, Europe and the USA. Articles describing tissue stages of avian haemosporidians were included from 1908 to the present. Histological preparations of various organs infected with the exo-erythrocytic stages of different haemosporidian parasites were examined. In all, 229 published articles were included in this review. Exo-erythrocytic stages of avian Plasmodium, Fallisia, Haemoproteus, Leucocytozoon, and Akiba species were analysed, compared and illustrated. Morphological characters of tissue stages that can be used for diagnostic purposes were specified. Recent molecular studies combined with histological research show that avian haemosporidians are more virulent than formerly believed. The exo-erythrocytic stages can cause severe disease, especially in non-adapted avian hosts, suggesting the existence of a group of underestimated malignant infections. The development of a given haemosporidian strain can be markedly different in different avian hosts, resulting in significantly different virulence. A methodology combining the traditional histology techniques with molecular diagnostic tools is essential to speed research in this field of avian malariology.

A mosquito 2-Cys peroxiredoxin protects against nitrosative and oxidative stresses associated with malaria parasite infection

PubMed Central

Peterson, Tina M.L.; Luckhart, Shirley

2008-01-01

Malaria parasite infection in anopheline mosquitoes induces nitrosative and oxidative stresses that limit parasite development, but also damage mosquito tissues in proximity to the response. Based on these observations, we proposed that cellular defenses in the mosquito may be induced to minimize self-damage. Specifically, we hypothesized that peroxiredoxins (Prxs), enzymes known to detoxify reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), protect mosquito cells. We identified an Anopheles stephensi 2-Cys Prx ortholog of Drosophila melanogaster Prx-4783, which protects fly cells against oxidative stresses. To assess function, AsPrx-4783 was overexpressed in D. melanogaster (S2) and in A. stephensi (MSQ43) cells and silenced in MSQ43 cells with RNA interference before treatment with various ROS and RNOS. Our data revealed that AsPrx-4783 and DmPrx-4783 differ in host cell protection and that AsPrx-4783 protects A. stephensi cells against stresses that are relevant to malaria parasite infection in vivo, namely nitric oxide (NO), hydrogen peroxide, nitroxyl, and peroxynitrite. Further, AsPrx-4783 expression is induced in the mosquito midgut by parasite infection at times associated with peak nitrosative and oxidative stresses. Hence, whereas the NO-mediated defense response is toxic to both host and parasite, AsPrx-4783 may shift the balance in favor of the mosquito. PMID:16540402

Histological survey of symbionts and other conditions of pod razor clam Ensis siliqua (Linnaeus, 1758) in Galicia (NW Spain).

PubMed

Ruiz, Maite; Darriba, Susana; Rodríguez, Rosana; López, Carmen

2013-01-01

The aim of the present study was to carry out a survey of parasites and other conditions affecting pod razor clam populations, Ensis siliqua, in two beds from Galicia (NW Spain). In Galicia, the production of E. siliqua has increased in recent years due to the development of specific plans for its exploitation, however few and quite recent pathological studies have been carried out in this species. The results of this study showed the presence of different protozoa as the more prevalent group, especially Nematopsis sp. gregarines, unidentified branchial protozoa, renal coccidia and Trichodina sp. ciliates. Larval stages of trematodes and neoplastic disorders were also observed with lower prevalences. Furthermore, an ultrastructural analysis of two types of unidentified basophilic inclusions, both found in the digestive gland, revealed the presence of icosahedral viral particles and prokaryotic organisms, respectively. None of the parasites detected in E. siliqua from this study was notifiable to the World Organisation for Animal Health (OIE) and the majority of the symbionts and conditions observed in their tissues did not cause host damage. Nevertheless, parasites like bucephalid digenean sporocysts, viral inclusions, prokaryotic infections, disseminated neoplasm or germinoma detected in some samples could cause moderate or severe damage to the host depending on the intensity of infection. Copyright © 2012 Elsevier Inc. All rights reserved.

Modeling electrical power absorption and thermally-induced biological tissue damage.

PubMed

Zohdi, T I

2014-01-01

This work develops a model for thermally induced damage from high current flow through biological tissue. Using the first law of thermodynamics, the balance of energy produced by the current and the energy absorbed by the tissue are investigated. The tissue damage is correlated with an evolution law that is activated upon exceeding a temperature threshold. As an example, the Fung material model is used. For certain parameter choices, the Fung material law has the ability to absorb relatively significant amounts of energy, due to its inherent exponential response character, thus, to some extent, mitigating possible tissue damage. Numerical examples are provided to illustrate the model's behavior.

Non-Fourier based thermal-mechanical tissue damage prediction for thermal ablation.

PubMed

Li, Xin; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

2017-01-02

Prediction of tissue damage under thermal loads plays important role for thermal ablation planning. A new methodology is presented in this paper by combing non-Fourier bio-heat transfer, constitutive elastic mechanics as well as non-rigid motion of dynamics to predict and analyze thermal distribution, thermal-induced mechanical deformation and thermal-mechanical damage of soft tissues under thermal loads. Simulations and comparison analysis demonstrate that the proposed methodology based on the non-Fourier bio-heat transfer can account for the thermal-induced mechanical behaviors of soft tissues and predict tissue thermal damage more accurately than classical Fourier bio-heat transfer based model.

Non-Fourier based thermal-mechanical tissue damage prediction for thermal ablation

PubMed Central

Li, Xin; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

2017-01-01

ABSTRACT Prediction of tissue damage under thermal loads plays important role for thermal ablation planning. A new methodology is presented in this paper by combing non-Fourier bio-heat transfer, constitutive elastic mechanics as well as non-rigid motion of dynamics to predict and analyze thermal distribution, thermal-induced mechanical deformation and thermal-mechanical damage of soft tissues under thermal loads. Simulations and comparison analysis demonstrate that the proposed methodology based on the non-Fourier bio-heat transfer can account for the thermal-induced mechanical behaviors of soft tissues and predict tissue thermal damage more accurately than classical Fourier bio-heat transfer based model. PMID:27690290

Peroxiredoxins are important for the regulation of hydrogen peroxide concentrations in ticks and tick cell line.

PubMed

Kusakisako, Kodai; Hernandez, Emmanuel Pacia; Talactac, Melbourne Rio; Yoshii, Kentaro; Umemiya-Shirafuji, Rika; Fujisaki, Kozo; Tanaka, Tetsuya

2018-03-17

Ticks are obligate hematophagous ectoparasites, as they need to feed blood from vertebrate hosts for development. Host blood contains high levels of iron. Host-derived iron may lead to high levels of reactive oxygen species (ROS), including hydrogen peroxide (H 2 O 2 ). Since a high concentration of H 2 O 2 causes serious damage to organisms, this molecule is known to be a harmful chemical compound for aerobic organisms. On the other hand, the transparent method is compatible with chemical fluorescent probes. Therefore, we tried to establish the visualizing method for H 2 O 2 in unfed tick tissues. The combination method of a chemical fluorescent probe (BES-H 2 O 2 -Ac) with the transparent method, Scale, demonstrated in unfed tick tissues that H 2 O 2 and paraquat could induce oxidative stress in the tissues, such as the midgut and ovary. In addition, an H 2 O 2 detection method using BES-H 2 O 2 -Ac was established in Ixodes scapularis embryo-derived cell line (ISE6) in vitro to evaluate the antioxidant activity of peroxiredoxins (PRXs), H 2 O 2 scavenging enzymes, against H 2 O 2 in the cells. The effects of paraquat in ISE6 cells were also observed in the PRXs gene-silenced ISE6 cells. A high intensity of H 2 O 2 fluorescence induced by paraquat was observed in the PRX gene-knockdowned cells. These results suggest that H 2 O 2 and paraquat act as an H 2 O 2 inducer, and PRX genes are important for the regulation of the H 2 O 2 concentration in unfed ticks and ISE6 cells. Therefore, this study contributes to the search for H 2 O 2 visualization in ticks and tick cell line and furthers understanding of the tick's oxidative stress induced by H 2 O 2 . Copyright © 2018 Elsevier GmbH. All rights reserved.

Relative binding affinity of carboxylate-, phosphonate-, and bisphosphonate-functionalized gold nanoparticles targeted to damaged bone tissue

NASA Astrophysics Data System (ADS)

Ross, Ryan D.; Cole, Lisa E.; Roeder, Ryan K.

2012-10-01

Functionalized Au NPs have received considerable recent interest for targeting and labeling cells and tissues. Damaged bone tissue can be targeted by functionalizing Au NPs with molecules exhibiting affinity for calcium. Therefore, the relative binding affinity of Au NPs surface functionalized with either carboxylate ( l-glutamic acid), phosphonate (2-aminoethylphosphonic acid), or bisphosphonate (alendronate) was investigated for targeted labeling of damaged bone tissue in vitro. Targeted labeling of damaged bone tissue was qualitatively verified by visual observation and backscattered electron microscopy, and quantitatively measured by the surface density of Au NPs using field-emission scanning electron microscopy. The surface density of functionalized Au NPs was significantly greater within damaged tissue compared to undamaged tissue for each functional group. Bisphosphonate-functionalized Au NPs exhibited a greater surface density labeling damaged tissue compared to glutamic acid- and phosphonic acid-functionalized Au NPs, which was consistent with the results of previous work comparing the binding affinity of the same functionalized Au NPs to synthetic hydroxyapatite crystals. Targeted labeling was enabled not only by the functional groups but also by the colloidal stability in solution. Functionalized Au NPs were stabilized by the presence of the functional groups, and were shown to remain well dispersed in ionic (phosphate buffered saline) and serum (fetal bovine serum) solutions for up to 1 week. Therefore, the results of this study suggest that bisphosphonate-functionalized Au NPs have potential for targeted delivery to damaged bone tissue in vitro and provide motivation for in vivo investigation.

Assessment of penetrating thermal tissue damage/spread associated with PhotonBlade™, Valleylab™ Pencil, Valleylab™ EDGE™ Coated Pencil, PlasmaBlade® 3.0S and PlasmaBlade® 4.0 for intraoperative tissue dissection using the fresh extirpated porcine muscle model

NASA Astrophysics Data System (ADS)

Bennett, Haydon E.; Taylor, Scott D.; Fugett, James H.; Shrout, Joshua L.; Davison, Paul O.; Ryan, S. Eric; Coad, James E.

2017-02-01

Penetrating thermal tissue damage/spread is an important aspect of many electrosurgical devices and correlates with effective tissue cutting, hemostasis, preservation of adjacent critical structures and tissue healing. This study compared the thermal damage/spread associated with the PhotonBlade, Valleylab Pencil, Valleylab EDGE Coated Pencil, PlasmaBlade 3.0S and PlasmaBlade 4.0, when performing a single pass dynamic tissue cut in fresh extirpated porcine longissimus muscle. These devices were used in a fashion that emulated their use in the clinical setting. Each device's thermal damage/spread, at Minimum, Median and Maximum power input settings, was assessed with nitroblue tetrazolium viability staining in the WVU Pathology Laboratory for Translational Medicine. The thermal damage/spread associated with the PhotonBlade was compared with the other devices tested based on the individual treatment results (n=179 cuts combined). In summary, the PhotonBlade overall demonstrated the least penetrating thermal tissue damage/spread, followed by the PlasmaBlade 4.0, then Valleylab Pencil and PlasmaBlade 3.0S and then Valleylab EDGE Coated Pencil in order of increasing thermal damage/spread depths.

Metagonimoides oregonensis (Heterophyidae: Digenea) infection in Pleurocerid snails and Desmognathus quadramaculatus salamander larvae in Southern Appalachian streams.

PubMed

Belden, Lisa K; Peterman, William E; Smith, Stephen A; Brooks, Lauren R; Benfield, E F; Black, Wesley P; Yang, Zhaomin; Wojdak, Jeremy M

2012-08-01

Metagonimoides oregonensis (Heterophyidae) is a little-known digenetic trematode that uses raccoons and possibly mink as definitive hosts, and stream snails and amphibians as intermediate hosts. Some variation in the life cycle and adult morphology in western and eastern populations has been previously noted. In the southern Appalachians, Pleurocera snails and stream salamanders, e.g., Desmognathus spp., are used as intermediate hosts in the life cycle. We completed a series of studies in this system examining some aspects of larval trematode morphology and first and second intermediate host use. Molecular sequencing of the 28S rDNA of cercariae in our survey placed them clearly within the heterophyid family. However, light and scanning electron microscopy revealed both lateral and dorso-ventral finfolds on the cercariae in our region, whereas original descriptions of M. oregonensis cercariae from the west coast indicate only a dorso-ventral finfold, so further work on the systematics of this group may be warranted. A survey of first intermediate host, Pleurocera proxima, from 7 streams in the region identified only M. oregonensis, virgulate-type cercariae, and cotylomicrocercous-type cercariae in the streams, with M. oregonensis having the highest prevalence, and the only type present that use amphibians as second intermediate hosts. Based on clearing and staining of 6 Desmognathus quadramaculatus salamander larvae, we found that individual salamanders could have over 600 metacercariae, which form between muscle fibers throughout the body. Histological observations suggest that the metacercariae do not cause excessive tissue damage or inflammation, and likely persist through metamorphosis, thereby transmitting potentially large numbers of worms to definitive host raccoons foraging along streams.

Screening host proteins required for bacterial adherence after H9N2 virus infection.

PubMed

Ma, Li-Li; Sun, Zhen-Hong; Xu, Yu-Lin; Wang, Shu-Juan; Wang, Hui-Ning; Zhang, Hao; Hu, Li-Ping; Sun, Xiao-Mei; Zhu, Lin; Shang, Hong-Qi; Zhu, Rui-Liang; Wei, Kai

2018-01-01

H9N2 subtype low pathogenic avian influenza virus (LPAIV) is distributed worldwide and causes great economic losses in the poultry industry, especially when complicated with other bacterial infections. Tissue damages caused by virus infection provide an opportunity for bacteria invasion, but this mechanism is not sufficient for low pathogenic strains. Moreover, although H9N2 virus infection was demonstrated to promote bacterial infection in several studies, its mechanism remained unclear. In this study, infection experiments in vivo and in vitro demonstrated that the adhesion of Escherichia coli (E. coli) to host cells significantly increased after H9N2 virus infection, and this increase was not caused by pathological damages. Subsequently, we constructed a late chicken embryo infection model and used proteomics techniques to analyze the expression of proteins associated with bacterial adhesion after H9N2 virus infection. A total of 279 significantly differential expressed proteins were detected through isobaric tags for relative and absolute quantitation (iTRAQ) coupled with nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) analysis. The results of Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that differentially expressed proteins were enriched in host innate immunity; cell proliferation, differentiation, and apoptosis; and pathogenicity-related signaling pathways. Finally, we screened out several proteins, such as TGF-β1, integrins, cortactin, E-cadherin, vinculin, and fibromodulin, which were probably associated with bacterial adhesion. The study analyzed the mechanism of secondary bacterial infection induced by H9N2 virus infection from a novel perspective, which provided theoretical and data support for investigating the synergistic infection mechanism between the H9N2 virus and bacteria. Copyright © 2017 Elsevier B.V. All rights reserved.

Thermal modeling of lesion growth with radiofrequency ablation devices

PubMed Central

Chang, Isaac A; Nguyen, Uyen D

2004-01-01

Background Temperature is a frequently used parameter to describe the predicted size of lesions computed by computational models. In many cases, however, temperature correlates poorly with lesion size. Although many studies have been conducted to characterize the relationship between time-temperature exposure of tissue heating to cell damage, to date these relationships have not been employed in a finite element model. Methods We present an axisymmetric two-dimensional finite element model that calculates cell damage in tissues and compare lesion sizes using common tissue damage and iso-temperature contour definitions. The model accounts for both temperature-dependent changes in the electrical conductivity of tissue as well as tissue damage-dependent changes in local tissue perfusion. The data is validated using excised porcine liver tissues. Results The data demonstrate the size of thermal lesions is grossly overestimated when calculated using traditional temperature isocontours of 42°C and 47°C. The computational model results predicted lesion dimensions that were within 5% of the experimental measurements. Conclusion When modeling radiofrequency ablation problems, temperature isotherms may not be representative of actual tissue damage patterns. PMID:15298708

Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

PubMed Central

Calvo, Jennifer A.; Moroski-Erkul, Catherine A.; Lake, Annabelle; Eichinger, Lindsey W.; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T.; Christiani, David C.; Meira, Lisiane B.; Samson, Leona D.

2013-01-01

Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag −/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage. PMID:23593019

Tissue-Resident Macrophages in Fungal Infections.

PubMed

Xu, Shengjie; Shinohara, Mari L

2017-01-01

Invasive fungal infections result in high morbidity and mortality. Host organs targeted by fungal pathogens vary depending on the route of infection and fungal species encountered. Cryptococcus neoformans infects the respiratory tract and disseminates throughout the central nervous system. Candida albicans infects mucosal tissues and the skin, and systemic Candida infection in rodents has a tropism to the kidney. Aspergillus fumigatus reaches distal areas of the lung once inhaled by the host. Across different tissues in naïve hosts, tissue-resident macrophages (TRMs) are one of the most populous cells of the innate immune system. Although they function to maintain homeostasis in a tissue-specific manner during steady state, TRMs may function as the first line of defense against invading pathogens and may regulate host immune responses. Thus, in any organs, TRMs are uniquely positioned and specifically programmed to function. This article reviews the current understanding of the roles of TRMs during major fungal infections.

Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders.

PubMed

Kaminsky, Natalie; Bihari, Ofer; Kanner, Sivan; Barzilai, Ari

2016-06-01

The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a "hostile" environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit. Copyright © 2016 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

Shifts in stable-isotope signatures confirm parasitic relationship of freshwater mussel glochidia attached to host fish

USGS Publications Warehouse

Fritts, Mark W.; Fritts, Andrea K.; Carleton, Scott A.; Bringolf, Robert B.

2013-01-01

The parasitic nature of the association between glochidia of unionoidean bivalves and their host fish (i.e. the role of fish hosts in providing nutritional resources to the developing glochidia) is still uncertain. While previous work has provided descriptions of development of glochidia on fish hosts, earlier studies have not explicitly documented the flow of nutrition from the host fish to the juvenile mussel. Therefore, our objective was to use stable isotope analysis to quantitatively document nutrient flow between fish and glochidia. Glochidia were collected from nine adult Lampsilis cardium and used to inoculate Micropterus salmoides(n = 27; three fish per maternal mussel) that produced juvenile mussels for the experiment. Adult mussel tissue samples, glochidia, transformed juvenile mussels and fish gill tissues were analysed for δ15N and δ13C isotope ratios. We used a linear mixing model to estimate the fraction of juvenile mussel tissue derived from the host fish's tissue during attachment. Our analyses indicate a distinct shift in both C and N isotopic ratios from the glochidial stage to the juvenile stage during mussel attachment and development. Linear mixing model analysis indicated that 57.4% of the δ15N in juvenile tissues were obtained from the host fish. This work provides novel evidence that larval unionoideans are true parasites that derive nutrition from host fish during their metamorphosis into the juvenile stage.

Examination of epithelial tissue cytokine response to natural peste des petits ruminants virus (PPRV) infection in sheep and goats by immunohistochemistry.

PubMed

Atmaca, H T; Kul, O

2012-01-01

In this study, we aimed to evaluate expression of IL-4, IL-10, TNF-α, IFN-γ and iNOS in lingual, buccal mucosa and lung epithelial tissue using immunoperoxidase technique and to compare with the tissues of control animals. The tissues used in the study were collected from 17 PPRV-affected and 5 healthy sheep and goats. In PPRV positive animals, the lungs, lingual and buccal mucosa had significantly higher iNOS, IFN-γ and TNF-α expressions compared to control group animals. There was no significant difference between PPRV positive and control groups for IL-4 and IL-10 expressions of epithelial tissues. In conclusion, the epithelial tissues infected by PPRV showed significant iNOS, IFN-γ and TNF-α expressions and they might play an important role in the initiation and regulation of cytokine response, as they take place in the first host barrier to be in contact with PPRV. It is suggested that the more epithelial damage produced by PPRV the more cytokine response may result in the infected epithelial cells. The first demonstration of iNOS expression and epithelial cytokine response to PPRV in natural cases is important because it may contribute to an early initiation of systemic immunity against PPRV infection, in addition to direct elimination of the virus during the initial epithelial phase of the infection.

FACTORS INFLUENCING HOST-VIRUS INTERACTIONS

PubMed Central

Boring, William D.; Angevine, D. Murray; Walker, Duard L.

1955-01-01

A study was made of the pathogenesis of infection due to the Conn.-5 strain of Coxsackie virus in 4 to 5 day old infant mice, untreated adult mice, and adult mice treated with cortisone. The quantitative distribution of virus and the evolution of lesions in different tissues were followed for the first 7 days of the infection. Virus dissemination was prompt and widespread via the blood in all groups. In 4 to 5 day old infant mice viral multiplication and cellular injury occurred in many organs and tissues, while in untreated adult mice these processes were largely limited to the pancreas, even though infecting virus appeared to be equally available to other tissues from the blood. Treatment of adult mice with a single injection of 2.5 mg. cortisone resulted in viral multiplication and tissue damage in several sites in addition to the pancreas, the most marked occurring in the liver and heart. In a consideration of possible mechanisms involved, it was thought unlikely that the differences in the course of the disease in the three groups could be attributed solely to differences in the specific immune response. It is suggested that developmental changes in cells and tissues, perhaps related to cellular metabolism and alterable by cortisone administration, are the major factors determining the location and extent of viral multiplication and tissue injury in this infection in mice. PMID:13271687

Decay-Accelerating Factor Mitigates Controlled Hemorrhage-Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine

DTIC Science & Technology

2011-07-01

Decay-Accelerating Factor Mitigates Controlled Hemorrhage- Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine Jurandir J. Dalle...DAF treatment improved hemorrhage- induced hyperkalemia . The protective effects of DAF appear to be related to its ability to reduce tissue complement...Decay-accelerating factor mitigates controlled hemorrhage-instigated intestinal and lung tissue damage and hyperkalemia in swine 5a. CONTRACT NUMBER

Dynamic reciprocity in cell-scaffold interactions.

PubMed

Mauney, Joshua R; Adam, Rosalyn M

2015-03-01

Tissue engineering in urology has shown considerable promise. However, there is still much to understand, particularly regarding the interactions between scaffolds and their host environment, how these interactions regulate regeneration and how they may be enhanced for optimal tissue repair. In this review, we discuss the concept of dynamic reciprocity as applied to tissue engineering, i.e. how bi-directional signaling between implanted scaffolds and host tissues such as the bladder drives the process of constructive remodeling to ensure successful graft integration and tissue repair. The impact of scaffold content and configuration, the contribution of endogenous and exogenous bioactive factors, the influence of the host immune response and the functional interaction with mechanical stimulation are all considered. In addition, the temporal relationships of host tissue ingrowth, bioactive factor mobilization, scaffold degradation and immune cell infiltration, as well as the reciprocal signaling between discrete cell types and scaffolds are discussed. Improved understanding of these aspects of tissue repair will identify opportunities for optimization of repair that could be exploited to enhance regenerative medicine strategies for urology in future studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Dissociation of Tissue Destruction and Bacterial Expansion during Bubonic Plague

PubMed Central

Guinet, Françoise; Avé, Patrick; Filali, Sofia; Huon, Christèle; Savin, Cyril; Huerre, Michel; Fiette, Laurence; Carniel, Elisabeth

2015-01-01

Activation and/or recruitment of the host plasmin, a fibrinolytic enzyme also active on extracellular matrix components, is a common invasive strategy of bacterial pathogens. Yersinia pestis, the bubonic plague agent, expresses the multifunctional surface protease Pla, which activates plasmin and inactivates fibrinolysis inhibitors. Pla is encoded by the pPla plasmid. Following intradermal inoculation, Y. pestis has the capacity to multiply in and cause destruction of the lymph node (LN) draining the entry site. The closely related, pPla-negative, Y. pseudotuberculosis species lacks this capacity. We hypothesized that tissue damage and bacterial multiplication occurring in the LN during bubonic plague were linked and both driven by pPla. Using a set of pPla-positive and pPla-negative Y. pestis and Y. pseudotuberculosis strains in a mouse model of intradermal injection, we found that pPla is not required for bacterial translocation to the LN. We also observed that a pPla-cured Y. pestis caused the same extensive histological lesions as the wild type strain. Furthermore, the Y. pseudotuberculosis histological pattern, characterized by infectious foci limited by inflammatory cell infiltrates with normal tissue density and follicular organization, was unchanged after introduction of pPla. However, the presence of pPla enabled Y. pseudotuberculosis to increase its bacterial load up to that of Y. pestis. Similarly, lack of pPla strongly reduced Y. pestis titers in LNs of infected mice. This pPla-mediated enhancing effect on bacterial load was directly dependent on the proteolytic activity of Pla. Immunohistochemistry of Pla-negative Y. pestis-infected LNs revealed extensive bacterial lysis, unlike the numerous, apparently intact, microorganisms seen in wild type Y. pestis-infected preparations. Therefore, our study demonstrates that tissue destruction and bacterial survival/multiplication are dissociated in the bubo and that the primary action of Pla is to protect bacteria from destruction rather than to alter the tissue environment to favor Y. pestis propagation in the host. PMID:26484539

Dissociation of Tissue Destruction and Bacterial Expansion during Bubonic Plague.

PubMed

Guinet, Françoise; Avé, Patrick; Filali, Sofia; Huon, Christèle; Savin, Cyril; Huerre, Michel; Fiette, Laurence; Carniel, Elisabeth

2015-10-01

Activation and/or recruitment of the host plasmin, a fibrinolytic enzyme also active on extracellular matrix components, is a common invasive strategy of bacterial pathogens. Yersinia pestis, the bubonic plague agent, expresses the multifunctional surface protease Pla, which activates plasmin and inactivates fibrinolysis inhibitors. Pla is encoded by the pPla plasmid. Following intradermal inoculation, Y. pestis has the capacity to multiply in and cause destruction of the lymph node (LN) draining the entry site. The closely related, pPla-negative, Y. pseudotuberculosis species lacks this capacity. We hypothesized that tissue damage and bacterial multiplication occurring in the LN during bubonic plague were linked and both driven by pPla. Using a set of pPla-positive and pPla-negative Y. pestis and Y. pseudotuberculosis strains in a mouse model of intradermal injection, we found that pPla is not required for bacterial translocation to the LN. We also observed that a pPla-cured Y. pestis caused the same extensive histological lesions as the wild type strain. Furthermore, the Y. pseudotuberculosis histological pattern, characterized by infectious foci limited by inflammatory cell infiltrates with normal tissue density and follicular organization, was unchanged after introduction of pPla. However, the presence of pPla enabled Y. pseudotuberculosis to increase its bacterial load up to that of Y. pestis. Similarly, lack of pPla strongly reduced Y. pestis titers in LNs of infected mice. This pPla-mediated enhancing effect on bacterial load was directly dependent on the proteolytic activity of Pla. Immunohistochemistry of Pla-negative Y. pestis-infected LNs revealed extensive bacterial lysis, unlike the numerous, apparently intact, microorganisms seen in wild type Y. pestis-infected preparations. Therefore, our study demonstrates that tissue destruction and bacterial survival/multiplication are dissociated in the bubo and that the primary action of Pla is to protect bacteria from destruction rather than to alter the tissue environment to favor Y. pestis propagation in the host.

The in vitro and in vivo biocompatibility evaluation of electrospun recombinant spider silk protein/PCL/gelatin for small caliber vascular tissue engineering scaffolds.

PubMed

Xiang, Ping; Wang, Shan-Shan; He, Meng; Han, Yong-He; Zhou, Zhi-Hua; Chen, Deng-Long; Li, Min; Ma, Lena Q

2018-03-01

Recombinant spider silk protein (pNSR32) and gelatin (Gt) were demonstrated to enhance cytocompatibility of electrospun pNSR32/PCL/Gt scaffold. However, its potential pro-inflammatory effects and interactions with tissue and blood are unknown. In this study, the physicochemical properties and in vitro and in vivo biocompatibility of such scaffolds were evaluated. The results showed that the pNSR32/PCL/Gt scaffold possessed larger average fiber diameters, wider fiber diameter distribution and faster degradation rate than that of pNSR32/PCL and PCL scaffolds. The addition of pNSR32 and Gt had little influence on the hemolysis and plasma re-calcification time, but prolonged kinetic clotting time and reduced the platelet adhesion. The Il-6 and Tnf-α mRNA expression levels were up-regulated in macrophages seeded on the PCL and pNSR32/PCL scaffolds. The lowest release of IL-6 and TNF-α appeared in the pNSR32/PCL/Gt scaffold. Histological results revealed that the PCL and pNSR32/PCL scaffolds elicited severe host tissue responses after implantation, while prominent ingrowth of host cells were observed in the pNSR32/PCL and pNSR32/PCL/Gt scaffolds. The comet assay and bone marrow micronucleus test demonstrated that the pNSR32/PCL/Gt scaffold did not increase the frequency of DNA damage or bone marrow micronucleus. In short, this study confirmed that the pNSR32/PCL/Gt scaffold exhibited better blood and tissue compatibility than pNSR32/PCL and PCL scaffolds. No induction of genotoxicity and inflammatory factor releases makes the pNSR32/PCL/Gt scaffold a good candidate for engineering small diameter vascular tissue. Copyright © 2017. Published by Elsevier B.V.

Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by (19)F- and diffusion-MRI.

PubMed

Bible, Ellen; Dell'Acqua, Flavio; Solanky, Bhavana; Balducci, Anthony; Crapo, Peter M; Badylak, Stephen F; Ahrens, Eric T; Modo, Michel

2012-04-01

Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based (1)H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a (19)F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on (1)H-MRI scans. Twenty percent of cells labeled with the (19)F agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T(2)- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively. Copyright © 2011 Elsevier Ltd. All rights reserved.

Use of Green Fluorescent Protein-Transgenic Strains to Study Pathogenic and Nonpathogenic Lifestyles in Colletotrichum acutatum.

PubMed

Horowitz, Sigal; Freeman, Stanley; Sharon, Amir

2002-07-01

ABSTRACT Colletotrichum acutatum, which causes anthracnose disease on strawberry, can also persist on several other plant species without causing disease symptoms. The genetic and molecular bases that determine pathogenic and nonpathogenic lifestyles in C. acutatum are unclear. We developed a transformation system for C. acutatum by electroporation of germinating conidia, and transgenic isolates that express the green fluorescent protein (GFP) were produced. Details of the pathogenic and nonpathogenic lifestyles of C. acutatum were determined by using GFP-transgenic isolates. Major differences between colonization-mediating processes of strawberry and of other plants were observed. On the main host, strawberry, the germinating conidia formed branched, thick hyphae, and large numbers of appressoria were produced that were essential for plant penetration. In strawberry, the fungus developed rapidly, filling the mesophyll with dense mycelium that invaded the cells and caused necrosis of the tissue. In nonpathogenic interactions on pepper, eggplant, and tomato, the conidia germinated, producing thin, straight germ tubes. Appressoria were produced but failed to germinate and penetrate leaf tissue, resulting in epiphytic growth without invasion of the plant. Penetration of the plant occurred only several days after inoculation and was restricted to the intercellular spaces of the first cell layers of infected tissue without causing any visible damage. Much of the new fungal biomass continued to develop on the surface of inoculated organs in the nonpathogenic interaction. The differences in fungal development on strawberry compared with the other plant species suggest that signal molecules, which may be present only in strawberry, trigger appressorial germination and penetration of the primary host.

Recent Advances in Tissue Engineering Strategies for the Treatment of Joint Damage.

PubMed

Stephenson, Makeda K; Farris, Ashley L; Grayson, Warren L

2017-08-01

While the clinical potential of tissue engineering for treating joint damage has yet to be realized, research and commercialization efforts in the field are geared towards overcoming major obstacles to clinical translation, as well as towards achieving engineered grafts that recapitulate the unique structures, function, and physiology of the joint. In this review, we describe recent advances in technologies aimed at obtaining biomaterials, stem cells, and bioreactors that will enable the development of effective tissue-engineered treatments for repairing joint damage. 3D printing of scaffolds is aimed at improving the mechanical structure and microenvironment necessary for bone regeneration within a damaged joint. Advances in our understanding of stem cell biology and cell manufacturing processes are informing translational strategies for the therapeutic use of allogeneic and autologous cells. Finally, bioreactors used in combination with cells and biomaterials are promising strategies for generating large tissue grafts for repairing damaged tissues in pre-clinical models. Together, these advances along with ongoing research directions are making tissue engineering increasingly viable for the treatment of joint damage.

Phototoxicity to the retina: mechanisms of damage.

PubMed

Glickman, Randolph D

2002-01-01

Light damage to the retina occurs through three general mechanisms involving thermal, mechanical, or photochemical effects. The particular mechanism activated depends on the wavelength and exposure duration of the injuring light. The transitions between the various light damage mechanism may overlap to some extent. Energy confinement is a key concept in understanding or predicting the type of damage mechanism produced by a given light exposure. As light energy (either from a laser or an incoherent source) is deposited in the retina, its penetration through, and its absorption in, various tissue compartments is determined by its wavelength. Strongly absorbing tissue components will tend to "concentrate" the light energy. The effect of absorbed light energy largely depends on the rate of energy deposition, which is correlated with the exposure duration. If the rate of energy deposition is too low to produce an appreciable temperature increase in the tissue, then any resulting tissue damage necessarily occurs because of chemical (oxidative) reactions induced by absorption of energetic photons (photochemical damage). If the rate of energy deposition is faster than the rate of thermal diffusion (thermal confinement), then the temperature of the exposed tissue rises. If a critical temperature is reached (typically about 10 degrees C above basal), then thermal damage occurs. If the light energy is deposited faster than mechanical relaxation can occur (stress confinement), then a thermoelastic pressure wave is produced, and tissue is disrupted by shear forces or by cavitation-nonlinear effects. Very recent evidence suggests that ultrashort laser pulses can produce tissue damage through nonlinear and photochemical mechanisms; the latter because of two-photon excitation of cellular chromophores. In addition to tissue damage caused directly by light absorption, light toxicity can be produced by the presence of photosensitizing agents. Drugs excited to reactive states by ultraviolet (UV) or visible light produce damage by type I (free radical) and type II (oxygen dependent) mechanisms. Some commonly used drugs, such as certain antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and psychotherapeutic agents, as well as some popular herbal medicines, can produce ocular phototoxicity. Specific cellular effects and damage end points characteristic of light damage mechanisms are described.

Variation in host resistance and pathogen selective value in the interaction between Pinus sylvestris and the fungus Crumenulopsis sororia.

PubMed

Ennos, R A; McConnell, K C

2003-09-01

There have been many studies of plant pathogen evolution in systems showing gene-for-gene control of host resistance. However little is known about situations, exemplified by Scots pine, Pinus sylvestris, and its fungal pathogen Crumenulopsis sororia, where variation in host resistance is quantitative. In a field experiment genetically marked isolates of C. sororia from three natural populations were reciprocally inoculated on 1- and 2-year-old branch tissue of P. sylvestris in the three sites from which they had been collected. Quantitative variation in host resistance was measured by comparing the performance of the same inocula on different host populations, individuals and tissues. The selective value of isolates derived from different populations was estimated by comparing the frequency of genotypes in lesion re-isolations with those in the initial inoculum mixtures. Host resistance varied significantly among populations, individuals within populations and between 1- and 2-year-old branch tissue of P. sylvestris. Large differences in the relative selective values of C. sororia isolates from different populations were detected. The selective value of pathogens was independent of the host population on which they were inoculated. However, their selective value did depend on the age of the tissue on which they grew. The implications of these results for modelling evolution in pathogen-host interactions that lack gene-for-gene determination of host resistance are discussed.

Cryptococcus neoformans-induced macrophage lysosome damage crucially contributes to fungal virulence1

PubMed Central

Davis, Michael J.; Eastman, Alison J.; Qiu, Yafeng; Gregorka, Brian; Kozel, Thomas R.; Osterholzer, John J.; Curtis, Jeffrey L.; Swanson, Joel A.; Olszewski, Michal A.

2015-01-01

Upon ingestion by macrophages, Cryptococcus neoformans (Cn) can survive and replicate intracellularly unless the macrophages become classically activated. The mechanism enabling intracellular replication is not fully understood; neither are the mechanisms which allow classical activation to counteract replication. Cn-induced lysosome damage was observed in infected murine bone marrow-derived macrophages, increased with time and required yeast viability. To demonstrate lysosome damage in the infected host, we developed a novel flow-cytometric method for measuring lysosome damage. Increased lysosome damage was found in Cn-containing lung cells compared to Cn–free cells. Among Cn-containing myeloid cells, recently recruited cells displayed lower damage than resident cells, consistent with the protective role of recruited macrophages. The magnitude of lysosome damage correlated with increased Cn replication. Experimental induction of lysosome damage increased Cn replication. Activation of macrophages with IFN-γ abolished macrophage lysosome damage and enabled increased killing of Cn. We conclude that induction of lysosome damage is an important Cn survival strategy and that classical activation of host macrophages counters replication by preventing damage. Thus, therapeutic strategies which decrease lysosomal damage, or increase resistance to such damage, could be valuable in treating cryptococcal infections. PMID:25637026

Apoptosis Modulation in the Immune System Reveals a Role of Neutrophils in Tissue Damage in a Murine Model of Chlamydial Genital Infection.

PubMed

Zortel, Tom; Schmitt-Graeff, Annette; Kirschnek, Susanne; Häcker, Georg

2018-05-05

Chlamydial infection frequently causes damage to the female genital tract. The precise mechanisms of chlamydial clearance and tissue damage are unknown, but studies suggest immunopathology with a particular role of neutrophils. The goal of this study was to understand the contribution of the immune system, in particular neutrophils. Using Chlamydia muridarum, we infected mice with a prolonged immune response due to expression of B-cell lymphoma 2 (Bcl-2) in hematopoietic cells (Bcl-2 mice), and mice where mature neutrophils are lacking due to the deletion of Myeloid cell leukemia 1 (Mcl-1) in myeloid cells (LysM-cre-mcl-1-flox mice; Mcl-1 mice). We monitored bacterial clearance, cellular infiltrate, and long-term tissue damage. Both mutant strains showed slightly delayed clearance of the acute infection. Bcl-2 mice had a strongly increased inflammatory infiltrate concerning almost all cell lineages. The infection of Bcl-2 mice caused increased tissue damage. The loss of neutrophils in Mcl-1 mice was associated with substantial quantitative and qualitative alterations of the inflammatory infiltrate. Mcl-1 mice had higher chlamydial burden and reduced tissue damage, including lower incidence of hydrosalpinx and less uterine dilation. Inhibition of apoptosis in the hematopoietic system increases inflammation and tissue damage. Neutrophils have broad functions, including a role in chlamydial clearance and in tissue destruction.

HOST-PARASITE FACTORS IN GROUP A STREPTOCOCCAL INFECTIONS

PubMed Central

Watson, Dennis W.

1960-01-01

The factors present in streptococcal lesion extracts (SLE) which enhanced the lethal and tissue-damaging properties of Gram-negative bacterial endotoxins and streptolysin O were identified with the scarlet fever group of toxins. Toxic manifestations attributed to this group of toxins included lethality, cardiotoxic and other tissue damage, enhancement of toxicity, and pyrogenicity. Of these, the measurement of febrile response in American Dutch rabbits was the most useful parameter of toxicity. In rabbits, repeated daily intravenous injections of 0.125 Lf of a purified erythrogenic toxin immunizes specifically against the pyrogenic activity; this technique was used to type the toxins and to distinguish them from exogenous and endogenous pyrogens; non-specific pyrogens, such as streptococcal endotoxin, were not found in SLE. All types of the Lancefield Group A streptococci tested produced one or or more immunologically distinct toxins in vivo in contrast to Groups B and C which did not produce them; toxins A and B, previously distinguished by neutralization of rash-inducing activity in the skin, were produced in vivo. The A toxin was the most common, as indicated by its presence in extracts prepared with Types 28, 12, 17, and 10 (NY-5); B toxin was found in 10 (NY-5) and 19. A new toxin, designated C, was obtained from a Type 18. In American Dutch rabbits, purified toxin at a concentration of 15 Lf (900,000 STD) neither gave a Dick test nor prepared the skin for the local Shwartzman reaction; by this route, however, in contrast to classical endotoxins, they enhance the lethal and tissue-damaging properties of sublethal doses of these and other toxins. These properties of the immunologic distinct exotoxins as demonstrated in American Dutch rabbits suggest by analogy their importance in the pathogenesis of streptococcal disease in man. Evidence that might implicate them in sequelae, in addition to scarlet fever, is discussed. PMID:13783427

Injury and immune response: applying the danger theory to mosquitoes

PubMed Central

Moreno-García, Miguel; Recio-Tótoro, Benito; Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

2014-01-01

The insect immune response can be activated by the recognition of both non-self and molecular by-products of tissue damage. Since pathogens and tissue damage usually arise at the same time during infection, the specific mechanisms of the immune response to microorganisms, and to tissue damage have not been unraveled. Consequently, some aspects of damage caused by microorganisms in vector-borne arthropods have been neglected. We herein reassess the Anopheles–Plasmodium interaction, incorporating Matzinger’s danger/damage hypothesis and George Salt’s injury assumptions. The invasive forms of the parasite cross the peritrophic matrix and midgut epithelia to reach the basal lamina and differentiate into an oocyst. The sporozoites produced in the oocyst are released into the hemolymph, and from there enter the salivary gland. During parasite development, wounds to midgut tissue and the basement membrane are produced. We describe the response of the different compartments where the parasite interacts with the mosquito. In the midgut, the response includes the expression of antimicrobial peptides, production of reactive oxygen species, and possible activation of midgut regenerative cells. In the basal membrane, wound repair mainly involves the production of molecules and the recruitment of hemocytes. We discuss the susceptibility to damage in tissues, and how the place and degree of damage may influence the differential response and the expression of damage associated molecular patterns (DAMPs). Knowledge about damage caused by parasites may lead to a deeper understanding of the relevance of tissue damage and the immune response it generates, as well as the origins and progression of infection in this insect–parasite interaction. PMID:25250040

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes.

PubMed

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications.

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes

PubMed Central

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications. PMID:28078052

Evaluation of the tissue reaction to a new bilayered collagen matrix in vivo and its translation to the clinic.

PubMed

Ghanaati, Shahram; Schlee, Markus; Webber, Matthew J; Willershausen, Ines; Barbeck, Mike; Balic, Ela; Görlach, Christoph; Stupp, Samuel I; Sader, Robert A; Kirkpatrick, C James

2011-02-01

This study evaluates a new collagen matrix that is designed with a bilayered structure in order to promote guided tissue regeneration and integration within the host tissue. This material induced a mild tissue reaction when assessed in a murine model and was well integrated within the host tissue, persisting in the implantation bed throughout the in vivo study. A more porous layer was rapidly infiltrated by host mesenchymal cells, while a layer designed to be a barrier allowed cell attachment and host tissue integration, but at the same time remained impermeable to invading cells for the first 30 days of the study. The tissue reaction was favorable, and unlike a typical foreign body response, did not include the presence of multinucleated giant cells, lymphocytes, or granulation tissue. In the context of translation, we show preliminary results from the clinical use of this biomaterial applied to soft tissue regeneration in the treatment of gingival tissue recession and exposed roots of human teeth. Such a condition would greatly benefit from guided tissue regeneration strategies. Our findings demonstrate that this material successfully promoted the ingrowth of gingival tissue and reversed gingival tissue recession. Of particular importance is the fact that the histological evidence from these human studies corroborates our findings in the murine model, with the barrier layer preventing unspecific tissue ingrowth, as the scaffold becomes infiltrated by mesenchymal cells from adjacent tissue into the porous layer. Also in the clinical situation no multinucleated giant cells, no granulation tissue and no evidence of a marked inflammatory response were observed. In conclusion, this bilayered matrix elicits a favorable tissue reaction, demonstrates potential as a barrier for preferential tissue ingrowth, and achieves a desirable therapeutic result when applied in humans for soft tissue regeneration.

Probing multi-scale mechanical damage in connective tissues using X-ray diffraction.

PubMed

Bianchi, Fabio; Hofmann, Felix; Smith, Andrew J; Thompson, Mark S

2016-11-01

The accumulation of microstructural collagen damage following repetitive loading is linked to painful and debilitating tendon injuries. As a hierarchical, semi-crystalline material, collagen mechanics can be studied using X-ray diffraction. The aim of the study was to describe multi-structural changes in tendon collagen following controlled plastic damage (5% permanent strain). We used small angle X-ray scattering (SAXS) to interrogate the spacing of collagen molecules within a fibril, and wide angle X-ray scattering (WAXS) to measure molecular strains under macroscopic loading. Simultaneous recordings of SAXS and WAXS patterns, together with whole-tissue strain in physiologically hydrated rat-tail tendons were made during increments of in situ tensile loading. Results showed that while tissue level modulus was unchanged, fibril modulus decreased significantly, and molecular modulus significantly increased. Further, analysis of higher order SAXS peaks suggested structural changes in the gap and overlap regions, possibly localising the damage to molecular cross-links. Our results provide new insight into the fundamental damage processes at work in collagenous tissues and point to new directions for their mitigation and repair. This article reports the first in situ loading synchrotron studies on mechanical damage in collagenous tissues. We provide new insight into the nano- and micro-structural mechanisms of damage processes. Pre-damaged tendons showed differential alteration of moduli at macro, micro and nano-scales as measured using X-ray scattering techniques. Detailed analysis of higher order diffraction peaks suggested damage is localised to molecular cross-links. The results are consistent with previous X-ray scattering studies of tendons and also with recent thermal stability studies on damaged material. Detailed understanding of damage mechanisms is essential in the development of new therapies promoting tissue repair. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effect of mechanical damage on emission of volatile organic compounds from plant leaves and implications for evaluation of host plant specificity of prospective biological control agents of weeds

USDA-ARS?s Scientific Manuscript database

Assessment of host plant specificity is a critical step in the evaluation of classical biological control agents of weeds, which is necessary for avoiding possible damage to nontarget plants. Volatile organic compounds (VOC) emitted by plants likely play an important role in determining which plant...

Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases

PubMed Central

Walker, Naomi F.; Clark, Simon O.; Oni, Tolu; Andreu, Nuria; Tezera, Liku; Singh, Shivani; Saraiva, Luísa; Pedersen, Bernadette; Kelly, Dominic L.; Tree, Julia A.; D'Armiento, Jeanine M.; Meintjes, Graeme; Mauri, Francesco A.; Williams, Ann; Wilkinson, Robert J.; Friedland, Jon S.

2012-01-01

Rationale: Tuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for more than 30 years. Tuberculosis (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined and no current antituberculous therapy reduces host tissue damage. Objectives: To investigate MMP activity in patients with TB with and without HIV coinfection and to determine the potential of doxycycline to inhibit MMPs and decrease pathology. Methods: Concentrations of MMPs and cytokines were analyzed by Luminex array in a prospectively recruited cohort of patients. Modulation of MMP secretion and Mycobacterium tuberculosis growth by doxycycline was studied in primary human cells and TB-infected guinea pigs. Measurements and Main Results: HIV coinfection decreased MMP concentrations in induced sputum of patients with TB. MMPs correlated with clinical markers of tissue damage, further implicating dysregulated protease activity in TB-driven pathology. In contrast, cytokine concentrations were no different. Doxycycline, a licensed MMP inhibitor, suppressed TB-dependent MMP-1 and -9 secretion from primary human macrophages and epithelial cells by inhibiting promoter activation. In the guinea pig model, doxycycline reduced lung TB colony forming units after 8 weeks in a dose-dependent manner compared with untreated animals, and in vitro doxycycline inhibited mycobacterial proliferation. Conclusions: HIV coinfection in patients with TB reduces concentrations of immunopathogenic MMPs. Doxycycline decreases MMP activity in a cellular model and suppresses mycobacterial growth in vitro and in guinea pigs. Adjunctive doxycycline therapy may reduce morbidity and mortality in TB. PMID:22345579

Solexa sequencing and custom microRNA chip reveal repertoire of microRNAs in mammary gland of bovine suffering from natural infectious mastitis.

PubMed

Ju, Zhihua; Jiang, Qiang; Liu, Gang; Wang, Xiuge; Luo, Guojing; Zhang, Yan; Zhang, Jibin; Zhong, Jifeng; Huang, Jinming

2018-02-01

Identification of microRNAs (miRNAs), target genes and regulatory networks associated with innate immune and inflammatory responses and tissue damage is essential to elucidate the molecular and genetic mechanisms for resistance to mastitis. In this study, a combination of Solexa sequencing and custom miRNA chip approaches was used to profile the expression of miRNAs in bovine mammary gland at the late stage of natural infection with Staphylococcus aureus, a widespread mastitis pathogen. We found 383 loci corresponding to 277 known and 49 putative novel miRNAs, two potential mitrons and 266 differentially expressed miRNAs in the healthy and mastitic cows' mammary glands. Several interaction networks and regulators involved in mastitis susceptibility, such as ALCAM, COL1A1, APOP4, ITIH4, CRP and fibrinogen alpha (FGA), were highlighted. Significant down-regulation and location of bta-miR-26a, which targets FGA in the mastitic mammary glands, were validated using quantitative real-time PCR, in situ hybridization and dual-luciferase reporter assays. We propose that the observed miRNA variations in mammary glands of mastitic cows are related to the maintenance of immune and defense responses, cell proliferation and apoptosis, and tissue injury and healing during the late stage of infection. Furthermore, the effect of bta-miR-26a in mastitis, mediated at least in part by enhancing FGA expression, involves host defense, inflammation and tissue damage. © 2018 Stichting International Foundation for Animal Genetics.

Mucosal immunology of HIV infection.

PubMed

Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S

2013-07-01

Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection, but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of 'symbiotic' intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high-level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4(+) T-cell responses, binding anti-bodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Furthermore, immune therapies specifically directed toward boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mucosal Immunology of HIV Infection

PubMed Central

Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S.

2013-01-01

Summary Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of ‘symbiotic’ intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4+ T-cell responses, binding antibodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Further, immune therapies specifically directed towards boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients. PMID:23772612

IL-17A promotes neutrophilic inflammation and disturbs acute wound healing in skin.

PubMed

Takagi, Naoyuki; Kawakami, Kazuyoshi; Kanno, Emi; Tanno, Hiromasa; Takeda, Atsushi; Ishii, Keiko; Imai, Yoshimichi; Iwakura, Yoichiro; Tachi, Masahiro

2017-02-01

In the wound healing process, neutrophils are the first inflammatory cells to move to the wound tissues. They sterilize wounds by killing microbes, and they stimulate other immune cells to protect the host from infection. In contrast, neutrophil-derived proteases cause damage to host tissues, so neutrophils play dual opposite roles in wound healing. Interleukin-17A (IL-17A) is a proinflammatory cytokine that promotes the recruitment of these cells. The role of this cytokine in the wound healing process is not fully clarified. In the present study, therefore, we examined how defect in IL-17A production affected the wound healing in skin. IL-17A-knockout (KO) mice showed promoted wound closure, myofibroblast differentiation and collagen deposition and decreased the neutrophil accumulation compared with wild-type (WT) mice. In contrast, the administration of recombinant IL-17A led to delayed wound closure, low collagen deposition and accelerated neutrophilic accumulation. In addition, the treatment of IL-17A-administered mice with a neutrophil elastase inhibitor improved the wound repair to the same level as that of WT mice. These results indicated that IL-17A hampered the wound healing process and suggested that neutrophilic inflammation caused by IL-17A may be associated with impaired wound healing in skin. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The characterization of neural tissue ablation rate and corresponding heat affected zone of a 2 micron Tm3+ doped fiber laser(Conference Presentation)

NASA Astrophysics Data System (ADS)

Marques, Andrew J.; Jivraj, Jamil; Reyes, Robnier; Ramjist, Joel; Gu, Xijia J.; Yang, Victor X. D.

2017-02-01

Tissue removal using electrocautery is standard practice in neurosurgery since tissue can be cut and cauterized simultaneously. Thermally mediated tissue ablation using lasers can potentially possess the same benefits but with increased precision. However, given the critical nature of the spine, brain, and nerves, the effects of direct photo-thermal interaction on neural tissue needs to be known, yielding not only high precision of tissue removal but also increased control of peripheral heat damage. The proposed use of lasers as a neurosurgical tool requires that a common ground is found between ablation rates and resulting peripheral heat damage. Most surgical laser systems rely on the conversion of light energy into heat resulting in both desirable and undesirable thermal damage to the targeted tissue. Classifying the distribution of thermal energy in neural tissue, and thus characterizing the extent of undesirable thermal damage, can prove to be exceptionally challenging considering its highly inhomogenous composition when compared to other tissues such as muscle and bone. Here we present the characterization of neural tissue ablation rate and heat affected zone of a 1.94 micron thulium doped fiber laser for neural tissue ablation. In-Vivo ablation of porcine cerebral cortex is performed. Ablation volumes are studied in association with laser parameters. Histological samples are taken and examined to characterize the extent of peripheral heat damage.

Evaluation of DNA damage induced by gamma radiation in gill and muscle tissues of Cyprinus carpio and their relative sensitivity.

PubMed

M K, Praveen Kumar; Shyama, Soorambail K; D'Costa, Avelyno; Kadam, Samit B; Sonaye, Bhagatsingh Harisingh; Chaubey, Ramesh Chandra

2017-10-01

The effect of radiation on the aquatic environment is of major concern in recent years. Limited data is available on the genotoxicity of gamma radiation on different tissues of aquatic organisms. Hence, the present investigation was carried out to study the DNA damage induced by gamma radiation in the gill and muscle tissues and their relative sensitivity using the comet assay in the freshwater teleost fish, common carp (Cyprinus carpio). The comet assay was optimized and validated in common carp using cyclophosphamide (CP), a reference genotoxic agent. The fish were exposed (acute) to various doses of gamma radiation (2, 4, 6, 8 and 10Gy) and samplings (gill and muscle tissue) were done at regular intervals (24, 48 and 72h) to assess the DNA damage. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA for all doses of gamma radiation in both tissues. We also observed a dose-related increase and a time-dependent decrease of DNA damage. In comparison, DNA damage showed different sensitivity among the tissues at different doses. This shows that a particular dose may have different effects on different tissues which could be due to physiological factors of the particular tissue. Our study also suggests that the gills and muscle of fish are sensitive and reliable tissues for evaluating the genotoxic effects of reference and environmental agents, using the comet assay. Copyright © 2017. Published by Elsevier Inc.

Campylobacter jejuni host tissue tropism: a consequence of its low-carb lifestyle?

PubMed

Thompson, Stuart A; Gaynor, Erin C

2008-11-13

Mechanisms underlying virulence properties of Campylobacter jejuni have historically been difficult to identify. In this issue of Cell Host & Microbe, Hofreuter et al. (2008) show that C. jejuni's ability to metabolize glutamine, glutathione, and asparagine affects its ability to colonize specific host tissues. These findings reflect the emerging theme of bacterial physiology directly impacting pathogenesis.

Cellular and molecular interactions of mesenchymal stem cells in innate immunity.

PubMed

Spaggiari, Grazia Maria; Moretta, Lorenzo

2013-01-01

In recent years, human mesenchymal stem/stromal cells (MSC) have attracted major attention for their possible clinical applications. In addition to their tissue regenerative capacity, they display immune-modulatory properties for which they have been used in the treatment of acute graft-versus-host disease and autoimmune diseases. Various studies have analyzed the inhibitory effect exerted by MSC on cells belonging to acquired or to innate immunity. In this context, MSC have been shown to inhibit proliferation and function of natural killer (NK) cells and to hinder the generation of dendritic cells and macrophages, thus interfering with inflammatory processes and with the generation of type I immune responses. In addition, MSC promote the differentiation of regulatory cells and participate in the regeneration of tissues damaged as a consequence of the inflammatory process. Different molecular mechanisms are involved in the immunosuppressive effect. Further investigation on the biology of MSC and on the regulatory events involved in their functional activities can help to optimize their use in clinical practice.

Skin Fungi from Colonization to Infection.

PubMed

de Hoog, Sybren; Monod, Michel; Dawson, Tom; Boekhout, Teun; Mayser, Peter; Gräser, Yvonne

2017-07-01

Humans are exceptional among vertebrates in that their living tissue is directly exposed to the outside world. In the absence of protective scales, feathers, or fur, the skin has to be highly effective in defending the organism against the gamut of opportunistic fungi surrounding us. Most (sub)cutaneous infections enter the body by implantation through the skin barrier. On intact skin, two types of fungal expansion are noted: (A) colonization by commensals, i.e., growth enabled by conditions prevailing on the skin surface without degradation of tissue, and (B) infection by superficial pathogens that assimilate epidermal keratin and interact with the cellular immune system. In a response-damage framework, all fungi are potentially able to cause disease, as a balance between their natural predilection and the immune status of the host. For this reason, we will not attribute a fixed ecological term to each species, but rather describe them as growing in a commensal state (A) or in a pathogenic state (B).

Migrating Myeloid Cells Sense Temporal Dynamics of Chemoattractant Concentrations.

PubMed

Petrie Aronin, Caren E; Zhao, Yun M; Yoon, Justine S; Morgan, Nicole Y; Prüstel, Thorsten; Germain, Ronald N; Meier-Schellersheim, Martin

2017-11-21

Chemoattractant-mediated recruitment of hematopoietic cells to sites of pathogen growth or tissue damage is critical to host defense and organ homeostasis. Chemotaxis is typically considered to rely on spatial sensing, with cells following concentration gradients as long as these are present. Utilizing a microfluidic approach, we found that stable gradients of intermediate chemokines (CCL19 and CXCL12) failed to promote persistent directional migration of dendritic cells or neutrophils. Instead, rising chemokine concentrations were needed, implying that temporal sensing mechanisms controlled prolonged responses to these ligands. This behavior was found to depend on G-coupled receptor kinase-mediated negative regulation of receptor signaling and contrasted with responses to an end agonist chemoattractant (C5a), for which a stable gradient led to persistent migration. These findings identify temporal sensing as a key requirement for long-range myeloid cell migration to intermediate chemokines and provide insights into the mechanisms controlling immune cell motility in complex tissue environments. Published by Elsevier Inc.

Sarcocystis and Its Complications in Camels (Camelus dromedarius) of Eastern Provinces of Iran

PubMed Central

Valinezhad, Akbar; Ahmadi, Nasrollah

2008-01-01

The prevalence of Sarcocystis spp. was investigated by gross and histopathological examinations in 250 camels (Camelus dromedarius) slaughtered from 2002 to 2005 in the Mashhad Slaughterhouse, eastern Iran. Samples were taken from the diaphragm, heart, tongue, esophagus and masseter muscles for histopathological studies. No macroscopic sarcocysts were found in the samples at gross inspection. Sarcocysts were detected in 209 of 250 (83.6%) examined camels at histopathological level. The infection rate of the esophagus, heart, masseter muscles, diaphragm, and tongue was 58.8%, 48.0%, 46.8%, 41.6%, and 28.0%, respectively. There was no significant difference in the rate of infection between male (85.8%) and female (81.0%) camels. The tissue response to vital cysts was minimal; however, reaction to the degenerating cysts was severe and caused tissue damages resulting in hyperemia, hemorrhages, mononuclear cell infiltration, necrotic changes, and fibrosis. The wild and domestic carnivores especially dogs may be the final hosts of Sarcocystis spp. in this area. PMID:19127328

Clinical imaging in regenerative medicine

PubMed Central

Naumova, Anna V; Modo, Michel; Moore, Anna; Murry, Charles E; Frank, Joseph A

2014-01-01

In regenerative medicine, clinical imaging is indispensable for characterizing damaged tissue and for measuring the safety and efficacy of therapy. However, the ability to track the fate and function of transplanted cells with current technologies is limited. Exogenous contrast labels such as nanoparticles give a strong signal in the short term but are unreliable long term. Genetically encoded labels are good both short- and long-term in animals, but in the human setting they raise regulatory issues related to the safety of genomic integration and potential immunogenicity of reporter proteins. Imaging studies in brain, heart and islets share a common set of challenges, including developing novel labeling approaches to improve detection thresholds and early delineation of toxicity and function. Key areas for future research include addressing safety concerns associated with genetic labels and developing methods to follow cell survival, differentiation and integration with host tissue. Imaging may bridge the gap between cell therapies and health outcomes by elucidating mechanisms of action through longitudinal monitoring. PMID:25093889

γδ T cells in homeostasis and host defence of epithelial barrier tissues

PubMed Central

Nielsen, Morten M.; Witherden, Deborah A.; Havran, Wendy L.

2018-01-01

Epithelial surfaces line the body and provide a critical interface between the body and the external environment which is essential to maintaining the symbiotic relationship between the host and the microbiome. Tissue-resident epithelial γδ T cells represent a major T cell population in epithelia and are ideally positioned to perform barrier surveillance and aid in tissue homeostasis and repair. In this review we focus on the intraepithelial γδ compartment in the two largest epithelial tissues in the body, namely the epidermis and intestine, and provide a comprehensive overview of the crucial contributions of intraepithelial γδ cells at these sites to tissue integrity and repair, host homeostasis and host protection in the context of the symbiotic relationship with the microbiome and during pathogen clearance. Finally, we address epithelia-specific butyrophilin-like molecules and touch upon their emerging role in selectively shaping and regulating epidermal and intestinal γδ T cell repertoires. PMID:28920588

Herbivory modifies conifer phenology: induced amelioration by a specialist folivore.

PubMed

Carroll, Allan L; Quiring, Dan T

2003-06-01

Herbivory by Zeiraphera canadensis Mut. & Free. (Lepidoptera: Tortricidae), an early season folivore of white spruce [ Picea glauca(Moench) Voss], has been associated with a shift in the timing of bud burst by its host during the subsequent year. We tested the hypothesis that a herbivory-induced shift in the phenology of bud development improves the window for colonisation of white spruce buds by Z. canadensis. Feeding on cortical tissue of elongating shoots caused the destruction of apical buds and an interruption of apical dominance in the year following herbivory. White spruce compensated for damage with the activation of dormant buds; mainly at proximal positions along shoots. As a result, half of all active buds on previously damaged branches were located immediately adjacent egg sites (i.e. previous year's bud scales), whereas <10% of active buds on intact shoots were situated there. More than 40% of newly emerged larvae colonised the basal buds of damaged shoots versus just 10% for intact shoots. Previous herbivory also influenced the initiation of bud burst. All buds flushed 2 days earlier on damaged shoots and date of bud burst was inversely correlated to bud density, indicating that short damaged shoots with large numbers of buds were stronger sinks for nutrients required for bud development. Egg hatch was best synchronized with early bursting buds on damaged branches. As a consequence, 89% of first-instar larvae successfully colonised buds on damaged branches while only 55% were successful on undamaged branches. Improved survival of larvae in the year following herbivory was a direct result of the evolved response by white spruce to the interruption of apical dominance. The pattern of herbivory by Z. canadensis may have evolved as a strategy to enhance the quality of white spruce for their offspring.

Mechanisms and use of neural transplants for brain repair.

PubMed

Dunnett, Stephen B; Björklund, Anders

2017-01-01

Under appropriate conditions, neural tissues transplanted into the adult mammalian brain can survive, integrate, and function so as to influence the behavior of the host, opening the prospect of repairing neuronal damage, and alleviating symptoms associated with neuronal injury or neurodegenerative disease. Alternative mechanisms of action have been postulated: nonspecific effects of surgery; neurotrophic and neuroprotective influences on disease progression and host plasticity; diffuse or locally regulated pharmacological delivery of deficient neurochemicals, neurotransmitters, or neurohormones; restitution of the neuronal and glial environment necessary for proper host neuronal support and processing; promoting local and long-distance host and graft axon growth; formation of reciprocal connections and reconstruction of local circuits within the host brain; and up to full integration and reconstruction of fully functional host neuronal networks. Analysis of neural transplants in a broad range of anatomical systems and disease models, on simple and complex classes of behavioral function and information processing, have indicated that all of these alternative mechanisms are likely to contribute in different circumstances. Thus, there is not a single or typical mode of graft function; rather grafts can and do function in multiple ways, specific to each particular context. Consequently, to develop an effective cell-based therapy, multiple dimensions must be considered: the target disease pathogenesis; the neurodegenerative basis of each type of physiological dysfunction or behavioral symptom; the nature of the repair required to alleviate or remediate the functional impairments of particular clinical relevance; and identification of a suitable cell source or delivery system, along with the site and method of implantation, that can achieve the sought for repair and recovery. © 2017 Elsevier B.V. All rights reserved.

Copper Acquisition and Utilization in Fungi.

PubMed

Smith, Aaron D; Logeman, Brandon L; Thiele, Dennis J

2017-09-08

Fungal cells colonize and proliferate in distinct niches, from soil and plants to diverse tissues in human hosts. Consequently, fungi are challenged with the goal of obtaining nutrients while simultaneously elaborating robust regulatory mechanisms to cope with a range of availability of nutrients, from scarcity to excess. Copper is essential for life but also potentially toxic. In this review we describe the sophisticated homeostatic mechanisms by which fungi acquire, utilize, and control this biochemically versatile trace element. Fungal pathogens, which can occupy distinct host tissues that have their own intrinsic requirements for copper homeostasis, have evolved mechanisms to acquire copper to successfully colonize the host, disseminate to other tissues, and combat host copper bombardment mechanisms that would otherwise mitigate virulence.

3D virtual histology at the host/parasite interface: visualisation of the master manipulator, Dicrocoelium dendriticum, in the brain of its ant host.

PubMed

Martín-Vega, Daniel; Garbout, Amin; Ahmed, Farah; Wicklein, Martina; Goater, Cameron P; Colwell, Douglas D; Hall, Martin J R

2018-06-05

Some parasites are able to manipulate the behaviour of their hosts to their own advantage. One of the most well-established textbook examples of host manipulation is that of the trematode Dicrocoelium dendriticum on ants, its second intermediate host. Infected ants harbour encysted metacercariae in the gaster and a non-encysted metacercaria in the suboesophageal ganglion (SOG); however, the mechanisms that D. dendriticum uses to manipulate the ant behaviour remain unknown, partly because of a lack of a proper and direct visualisation of the physical interface between the parasite and the ant brain tissue. Here we provide new insights into the potential mechanisms that this iconic manipulator uses to alter its host's behaviour by characterising the interface between D. dendriticum and the ant tissues with the use of non-invasive micro-CT scanning. For the first time, we show that there is a physical contact between the parasite and the ant brain tissue at the anteriormost part of the SOG, including in a case of multiple brain infection where only the parasite lodged in the most anterior part of the SOG was in contact with the ant brain tissue. We demonstrate the potential of micro-CT to further understand other parasite/host systems in parasitological research.

Evaluation of roadside greenbelt trees damage caused by strangler plants in Bogor

NASA Astrophysics Data System (ADS)

Danniswari, Dibyanti; Nasrullah, Nizar

2017-10-01

Certain plants are called stranglers (hemiepiphyte) because they grow on host trees and slowly choking the host, which often results in the host’s death. The existence of strangler plants on roadside greenbelt trees is quite common in Bogor, but they may cause tree’s failure and threaten users’ safety. To prevent such hazard, evaluation of roadside greenbelt trees damage caused by strangler plants is important. This study was directed to analyse the vegetation of strangler plants in Bogor, to assess the damage caused by stranglers, and to compose strangled trees maintenance recommendations. This study was conducted in March to May 2014 by doing survey at five major roads in Bogor, which were Jalan Ahmad Yani, Jalan Sudirman, Jalan Pemuda, Jalan Semeru, and Jalan Juanda. The results showed that strangler species found in Bogor are Ficus benjamina, Ficus glauca, Ficus elastica, and Schefflera actinophylla. The most common species in Bogor is F. benjamina. Host trees that tend to be preferred by strangler plants are trees with large trunk, many branches, and medium to high height. The maintenance for every strangled tree is different according to the damage level, mild to severe damage could be treated by strangler root cutting to tree logging, respectively.

Re-education begins at home: an overview of the discovery of in vivo-active small molecule modulators of endogenous stem cells.

PubMed

Um, JungIn; Lee, Ji-Hyung; Jung, Da-Woon; Williams, Darren R

2018-04-01

Degenerative diseases, such as Alzheimer's disease, heart disease and arthritis cause great suffering and are major socioeconomic burdens. An attractive treatment approach is stem cell transplantation to regenerate damaged or destroyed tissues. However, this can be problematic. For example, donor cells may not functionally integrate into the host tissue. An alternative methodology is to deliver bioactive agents, such as small molecules, directly into the diseased tissue to enhance the regenerative potential of endogenous stem cells. Areas covered: In this review, the authors discuss the necessity of developing these small molecules to treat degenerative diseases and survey progress in their application as therapeutics. They describe both the successes and caveats of developing small molecules that target endogenous stem cells to induce tissue regeneration. This article is based on literature searches which encompass databases for biomedical research and clinical trials. These small molecules are also categorized per their target disease and mechanism of action. Expert opinion: The development of small molecules targeting endogenous stem cells is a high-profile research area. Some compounds have made the successful transition to the clinic. Novel approaches, such as modulating the stem cell niche or targeted delivery to disease sites, should increase the likelihood of future successes in this field.

Expression Profile of DNA Damage Signaling Genes in Proton Exposed Mouse Brain

NASA Astrophysics Data System (ADS)

Ramesh, Govindarajan; Wu, Honglu

Exposure of living systems to radiation results in a wide assortment of lesions, the most signif-icant of is damage to genomic DNA which induce several cellular functions such as cell cycle arrest, repair, apoptosis etc. The radiation induced DNA damage investigation is one of the im-portant area in biology, but still the information available regarding the effects of proton is very limited. In this report, we investigated the differential gene expression pattern of DNA damage signaling genes particularly, damaged DNA binding, repair, cell cycle arrest, checkpoints and apoptosis using quantitative real-time RT-PCR array in proton exposed mouse brain tissues. The expression profiles showed significant changes in DNA damage related genes in 2Gy proton exposed mouse brain tissues as compared with control brain tissues. Furthermore, we also show that significantly increased levels of apoptotic related genes, caspase-3 and 8 activities in these cells, suggesting that in addition to differential expression of DNA damage genes, the alteration of apoptosis related genes may also contribute to the radiation induced DNA damage followed by programmed cell death. In summary, our findings suggest that proton exposed brain tissue undergo severe DNA damage which in turn destabilize the chromatin stability.

Transient Receptor Potential Channel 1 Deficiency Impairs Host Defense and Proinflammatory Responses to Bacterial Infection by Regulating Protein Kinase Cα Signaling.

PubMed

Zhou, Xikun; Ye, Yan; Sun, Yuyang; Li, Xuefeng; Wang, Wenxue; Privratsky, Breanna; Tan, Shirui; Zhou, Zongguang; Huang, Canhua; Wei, Yu-Quan; Birnbaumer, Lutz; Singh, Brij B; Wu, Min

2015-08-01

Transient receptor potential channel 1 (TRPC1) is a nonselective cation channel that is required for Ca(2+) homeostasis necessary for cellular functions. However, whether TRPC1 is involved in infectious disease remains unknown. Here, we report a novel function for TRPC1 in host defense against Gram-negative bacteria. TRPC1(-/-) mice exhibited decreased survival, severe lung injury, and systemic bacterial dissemination upon infection. Furthermore, silencing of TRPC1 showed decreased Ca(2+) entry, reduced proinflammatory cytokines, and lowered bacterial clearance. Importantly, TRPC1 functioned as an endogenous Ca(2+) entry channel critical for proinflammatory cytokine production in both alveolar macrophages and epithelial cells. We further identified that bacterium-mediated activation of TRPC1 was dependent on Toll-like receptor 4 (TLR4), which induced endoplasmic reticulum (ER) store depletion. After activation of phospholipase Cγ (PLC-γ), TRPC1 mediated Ca(2+) entry and triggered protein kinase Cα (PKCα) activity to facilitate nuclear translocation of NF-κB/Jun N-terminal protein kinase (JNK) and augment the proinflammatory response, leading to tissue damage and eventually mortality. These findings reveal that TRPC1 is required for host defense against bacterial infections through the TLR4-TRPC1-PKCα signaling circuit. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Toll-like Receptor-mediated Down-regulation of the Deubiquitinase Cylindromatosis (CYLD) Protects Macrophages from Necroptosis in Wild-derived Mice*

PubMed Central

Schworer, Stephen A.; Smirnova, Irina I.; Kurbatova, Irina; Bagina, Uliana; Churova, Maria; Fowler, Trent; Roy, Ananda L.; Degterev, Alexei; Poltorak, Alexander

2014-01-01

Pathogen recognition by the innate immune system initiates the production of proinflammatory cytokines but can also lead to programmed host cell death. Necroptosis, a caspase-independent cell death pathway, can contribute to the host defense against pathogens or cause damage to host tissues. Receptor-interacting protein (RIP1) is a serine/threonine kinase that integrates inflammatory and necroptotic responses. To investigate the mechanisms of RIP1-mediated activation of immune cells, we established a genetic screen on the basis of RIP1-mediated necroptosis in wild-derived MOLF/EiJ mice, which diverged from classical laboratory mice over a million years ago. When compared with C57BL/6, MOLF/EiJ macrophages were resistant to RIP1-mediated necroptosis induced by Toll-like receptors. Using a forward genetic approach in a backcross panel of mice, we identified cylindromatosis (CYLD), a deubiquitinase known to act directly on RIP1 and promote necroptosis in TNF receptor signaling, as the gene conferring the trait. We demonstrate that CYLD is required for Toll-like receptor-induced necroptosis and describe a novel mechanism by which CYLD is down-regulated at the transcriptional level in MOLF/EiJ macrophages to confer protection from necroptosis. PMID:24706750

Echinococcus granulosus equinus: an ultrastructural study of murine tissue response to hydatid cysts.

PubMed

Richards, K S; Arme, C; Bridges, J F

1983-06-01

Peritoneal hydatids of Echinococcus granulosus equinus of 9 months standing in BALB/c mice occurred as free cysts or cysts within cyst masses. Both showed wide variation in size and in host tissue response, and all had a well-developed laminated layer separating the host tissue response from the germinal layer. In the smallest cyst-mass cysts the host tissue response was present as remnants of the initial cellular attack involving eosinophils. Slightly larger cyst-mass cysts possessed a primary macrophage invasion which phagocytosed the remnants of the initial attack and also, though to little effect, the laminated layer material. In the largest cyst-mass cysts a second macrophage invasion, of monocyte origin, had commenced and transformation stages of these cells to macrophages were observed. No fibroblasts surrounded individual cyst-mass cysts but they were present around the cyst mass, encapsulating it and possibly preventing further host cell invasion. Thus, the host tissue response around individual cyst-mass cysts remained 'preserved' at an early stage such as existed at the time of encapsulation. Small free cysts showed a primary macrophage invasion and transformation stages of cells of a secondary infiltration of peritoneal origin. Peripheral to the macrophages were fibroblasts demonstrating limited fibrinogenesis, and each cyst was surrounded by a layer of mesothelial cells. Large free cysts, also delimited by a mesothelial layer, possessed peripheral connective tissue, a deep fibrous layer and a monolayer of very compressed macrophages lying adjacent to the laminated layer. It is emphasized that an understanding of the host tissue response in cysts of different sizes and from different locations is an essential pre-requisite for the design of experimental studies.

Parasite Removal, but Not Herbivory, Deters Future Parasite Attachment on Tomato

PubMed Central

Tjiurutue, Muvari Connie; Palmer-Young, Evan C.; Adler, Lynn S.

2016-01-01

Plants face many antagonistic interactions that occur sequentially. Often, plants employ defense strategies in response to the initial damage that are highly specific and can affect interactions with subsequent antagonists. In addition to herbivores and pathogens, plants face attacks by parasitic plants, but we know little about how prior herbivory compared to prior parasite attachment affects subsequent host interactions. If host plants can respond adaptively to these different damage types, we predict that prior parasitism would have a greater deterrent effect on subsequent parasites than would prior herbivory. To test the effects of prior parasitism and prior herbivory on subsequent parasitic dodder (Cuscuta spp.) preference, we conducted two separate greenhouse studies with tomato hosts (Solanum lycopersicum). In the first experiment, we tested the effects of previous dodder attachment on subsequent dodder preference on tomato hosts using three treatments: control plants that had no previous dodder attachment; dodder-removed plants that had an initial dodder seedling attached, removed and left in the same pot to simulate parasite death; and dodder-continuous plants with an initial dodder seedling that remained attached. In the second experiment, we tested the effects of previous caterpillar damage (Spodoptera exigua) and mechanical damage on future dodder attachment on tomato hosts. Dodder attached most slowly to tomato hosts that had dodder plants previously attached and then removed, compared to control plants or plants with continuous dodder attachment. In contrast, herbivory did not affect subsequent dodder attachment rate. These results indicate that dodder preference depended on the identity and the outcome of the initial attack, suggesting that early-season interactions have the potential for profound impacts on subsequent community dynamics. PMID:27529694

The Bacteroides fragilis cell envelope: quarterback, linebacker, coach-or all three?

PubMed

Pumbwe, Lilian; Skilbeck, Christopher A; Wexler, Hannah M

2006-01-01

Bacteroides fragilis is an anaerobic commensal constituting only 1-2% of the micro-flora of the human gastrointestinal tract, yet it is the predominant anaerobic isolate in cases of intraabdominal sepsis and bacteremia. B. fragilis can play two roles in the host: in its role as friendly commensal, it must be able to establish itself in the host intestinal mucosa, to utilize and process polysaccharides for use by the host, and to resist the noxious effects of bile salts. In its role as pathogen, it must be able to attach itself to the site of infection, evade killing mechanisms by host defense, withstand antimicrobial treatment and produce factors that damage host tissue. The cell envelope of B. fragilis, likewise, must be able to function in the roles of aggressor, defender and strategist in allowing the organism to establish itself in the host--whether as friend or foe. Recent studies of the genomes and proteomes of the genus Bacteroides suggest that these organisms have evolved strategies to survive and dominate in the overcrowded gastrointestinal neighborhood. Analysis of the proteomes of B. fragilis and Bacteroides thetaiotaomicron demonstrates both a tremendous capacity to use a wide range of dietary polysaccharides, and the capacity to create variable surface antigenicities by multiple DNA inversion systems. The latter characteristic is particularly pronounced in the species B. fragilis, which is more frequently found at the mucosal surface (i.e., often the site of attack by host defenses). The B. fragilis cell envelope undergoes major protein expression and ultrastructural changes in response to stressors such as bile or antimicrobial agents. These agents may also act as signals for attachment and colonization. Thus the bacterium manages its surface characteristics to enable it to bind to its target, to use the available nutrients, and to avoid or evade hostile forces (host-derived or external) in its multiple roles.

Effect of Habitat Conditions and Plant Traits on Leaf Damage in the Carduoideae Subfamily

PubMed Central

Münzbergová, Zuzana; Skuhrovec, Jiří

2013-01-01

Plant traits are the key factors that determine herbivore foraging selection. The traits serving as defense traits against herbivores represent a wide range of traits, such as chemical, physiological, morphological and life-history traits. While many studies considered plant defense traits at the within-species scale, much less is known from comparisons of a wide range of closely related species. The aim of this study was to identify factors responsible for the intensity of leaf damage in the Carduoideae subfamily of Asteraceae, which hosts many invasive species and thus is potential candidate plant species that could be controlled by biological control. Specifically, we wanted to see the relative importance of habitat characteristics, plant size and plants traits in determining the degree of folivory. The study identified several defense traits able to explain differences in herbivory between species after accounting for differences in the habitats in which the species occur and the plant size. Specifically, the most important traits were traits related to the quality of the leaf tissue expressed as the content of phosphorus, water and specific leaf area, which suggests that the leaf quality had a more important effect on the degree of herbivory than the presence of specific defense mechanisms such as spines and hair. Leaf quality is thus a candidate factor that drives herbivore choice when selecting which plant to feed on and should be considered when assessing the danger that a herbivore will switch hosts when introduced to a new range. PMID:23717643

Histopathology of nymphal pentastomid infections (Sebekia mississippiensis) in paratenic hosts.

PubMed

Boyce, W M; Kazacos, E A

1991-02-01

The histopathologic alterations occurring in mice, hamsters, turtles, and a frog were described following experimental infection with nymphs of Sebekia mississippiensis. Initially, nymphal migration caused traumatic tissue damage and hemorrhage characteristic of larva migrans. Subsequent inflammatory responses included cellular infiltration with eosinophils, macrophages, and lymphocytes, and fibrotic encapsulation of the nymphs. Dead nymphs were surrounded by a necrotic granulomatous response similar to that reported previously in humans and other animals. Differences were not seen in animals given single or multiple infections, but mice and hamsters exhibited a more marked inflammatory response than turtles. Overall, the histopathologic response to nymphal infections resembled those seen in infections resulting from ingestion of eggs, and both sources of infection should be considered in epidemiologic investigations of naturally occurring pentastomiasis.

Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo.

PubMed

Brönnimann, Daniel; Bouchet, Audrey; Schneider, Christoph; Potez, Marine; Serduc, Raphaël; Bräuer-Krisch, Elke; Graber, Werner; von Gunten, Stephan; Laissue, Jean Albert; Djonov, Valentin

2016-09-19

Our goal was the visualizing the vascular damage and acute inflammatory response to micro- and minibeam irradiation in vivo. Microbeam (MRT) and minibeam radiation therapies (MBRT) are tumor treatment approaches of potential clinical relevance, both consisting of parallel X-ray beams and allowing the delivery of thousands of Grays within tumors. We compared the effects of microbeams (25-100 μm wide) and minibeams (200-800 μm wide) on vasculature, inflammation and surrounding tissue changes during zebrafish caudal fin regeneration in vivo. Microbeam irradiation triggered an acute inflammatory response restricted to the regenerating tissue. Six hours post irradiation (6 hpi), it was infiltrated by neutrophils and fli1a(+) thrombocytes adhered to the cell wall locally in the beam path. The mature tissue was not affected by microbeam irradiation. In contrast, minibeam irradiation efficiently damaged the immature tissue at 6 hpi and damaged both the mature and immature tissue at 48 hpi. We demonstrate that vascular damage, inflammatory processes and cellular toxicity depend on the beam width and the stage of tissue maturation. Minibeam irradiation did not differentiate between mature and immature tissue. In contrast, all irradiation-induced effects of the microbeams were restricted to the rapidly growing immature tissue, indicating that microbeam irradiation could be a promising tumor treatment tool.

Parametric study of irreversible electroporation with different needle electrodes: electrical and thermal analysis.

PubMed

Nickfarjam, Abolfazl; Firoozabadi, S Mohammad P

2014-08-01

Irreversible electroporation (IRE) is a new tumour ablation method used in cancer treatment procedures. In a successful IRE treatment it is crucial to impose minimum thermal damage to the tumour and its surrounding healthy tissue, while subjecting the entire tumour to a strong electric field. Here we present a 3D model of a subcutaneous tumour in a four-layer skin using a geometry-based finite element approach. Four common needle electrode configurations were studied in this paper. The study evaluated six essential factors which are important in the electrical and thermal distributions in tumour and normal tissue. The results revealed that a hexagonal 3 × 3 geometry provides the maximum electrical coverage of the tumour, compared to other electrode configurations. However, in some cases the hexagonal 2 × 2 geometry can ablate the entire tumour with less damage to normal tissue. We found that the deeper insertion of 2- and 4-electrode geometries can lead to more damage to healthy tissue. The results also indicate that the insertion of the electrodes into tumour tissue can increase thermal damage dramatically due to existing large electrical conductivity. These findings suggest that needle electrodes should not be placed within the tumour tissue if the goal is to prevent thermal damage. This method can be used as a trade-off between electric field coverage in tumour tissue and thermal damage to both tumour and normal tissue.

Compartmentalized and systemic control of tissue immunity by commensals

PubMed Central

Belkaid, Yasmine; Naik, Shruti

2013-01-01

The body is composed of various tissue microenvironments with finely tuned local immunosurveillance systems, many of which are in close apposition with distinct commensal niches. Mammals have formed an evolutionary partnership with the microbiota that is critical for metabolism, tissue development and host defense. Despite our growing understanding of the impact of this host-microbe alliance on immunity in the gastrointestinal tract, the extent to which individual microenvironments are controlled by resident microbiota remains unclear. In this Perspective we discuss how resident commensals outside the gastrointestinal tract can control unique physiological niches and the potential implications of the dialog between these commensals and the host for the establishment of immune homeostasis, protective responses and tissue pathology. PMID:23778791

Roles of oxidative stress in synchrotron radiation X-ray-induced testicular damage of rodents

PubMed Central

Ma, Yingxin; Nie, Hui; Sheng, Caibin; Chen, Heyu; Wang, Ban; Liu, Tengyuan; Shao, Jiaxiang; He, Xin; Zhang, Tingting; Zheng, Chaobo; Xia, Weiliang; Ying, Weihai

2012-01-01

Synchrotron radiation (SR) X-ray has characteristic properties such as coherence and high photon flux, which has excellent potential for its applications in medical imaging and cancer treatment. However, there is little information regarding the mechanisms underlying the damaging effects of SR X-ray on biological tissues. Oxidative stress plays an important role in the tissue damage induced by conventional X-ray, while the role of oxidative stress in the tissue injury induced by SR X-ray remains unknown. In this study we used the male gonads of rats as a model to study the roles of oxidative stress in SR X-ray-induced tissue damage. Exposures of the testes to SR X-ray at various radiation doses did not significantly increase the lipid peroxidation of the tissues, assessed at one day after the irradiation. No significant decreases in the levels of GSH or total antioxidation capacity were found in the SR X-ray-irradiated testes. However, the SR X-ray at 40 Gy induced a marked increase in phosphorylated H2AX – a marker of double-strand DNA damage, which was significantly decreased by the antioxidant N-acetyl cysteine (NAC). NAC also attenuated the SR X-ray-induced decreases in the cell layer number of seminiferous tubules. Collectively, our observations have provided the first characterization of SR X-ray-induced oxidative damage of biological tissues: SR X-ray at high doses can induce DNA damage and certain tissue damage during the acute phase of the irradiation, at least partially by generating oxidative stress. However, SR X-ray of various radiation doses did not increase lipid peroxidation. PMID:22837810

Cytocompatibility, antibacterial activity and biodegradability of self-assembling beta-hairpin peptide-based hydrogels for tissue regenerative applications

NASA Astrophysics Data System (ADS)

Salick, Daphne Ann

Every year, millions of people suffer from tissue loss or failure. One approach to repair damaged or diseased tissue is through tissue/organ transplantation. However, one of the major problems which exist with this approach is that there are more people in need of a transplant than there are donors. Over the past several decades, scientists and doctors have come together to find a way to overcome this challenge. This collaboration has led to the development of biomimetic scaffolds, which closely mimic the desired tissue of interest to act as a substitute for the unfunctional tissue, with hopes to improve the quality of life. The Schneider and Pochan labs have developed a biomimetic scaffold using self-assembling beta-hairpin peptides. The self-assembly event can be triggered in response to physiological conditions, which is dictated by the monomer, to form non covalently crosslinked mechanically rigid hydrogels. In vitro studies showed that hydrogels were cytocompatible and may not elicit a pro-inflammatory response from murine macrophages. These material properties show promise for the use of these hydrogels in tissue engineering. When implanting a material into a host, a major concern is the introduction of infection. Infection, if not prevented or halted, results in poor tissue integration and function, ultimately leading to implant removal from the host. Interestingly, the beta-hairpin hydrogels were shown to exhibit antibacterial properties against pathogens commonly found in hospital environments. This inherently antibacterial hydrogel is advantageous because it may help decrease or diminish bacterial contamination when implanted in vivo, which may help to increase the success of implants. Also, a unique and exciting feature of these peptide-based hydrogels is their ability to shear-thin and self-heal. Hydrogels can be directly formed in a syringe and be subsequently delivered to a tissue defect in a minimally invasive manner where they will recover to their original mechanical rigidity. The resultant syringe-delivered gel was also shown to possess antibacterial properties. Aside from the material's inherent antibacterial activity, these peptide-based scaffolds display degradation that can be controlled using an exogenously added enzyme. This suggests that by using peptide design, the gel network degradation can be controlled to allow for the proper formation of functional tissue. The work described in this thesis shows these described attributes, as well as, the potential of these peptide-based gels for use as tissue substitutes.

Comparison of ferromagnetic induction and bipolar electrosurgery and suction in corticotomies in pig cerebrum.

PubMed

Bowers, Christian A; Burns, Greg; Salzman, Karen; McGill, Lawrence; MacDonald, Joel D

2015-04-01

The effects of newer energy-based surgical dissection and coagulation modalities on cerebral tissue have not been investigated. Several instruments have been developed to address the limitations of traditional electrosurgical instruments in the nervous system. We compared the effects of standard bipolar electrocautery and suction (BPS) with those of a new ferromagnetic induction (FMI) device in corticotomies of pig cerebral tissue as assessed by magnetic resonance imaging (MRI) and histological analysis. Three adult pigs underwent bilateral corticotomies (3 cm long×1 cm deep) using both FMI and BPS. The acute cerebral tissue edema created by each method was measured on coronal volumetric T2-weighted MRI sequences immediately after surgery. A lateral thermal "damage index" was calculated by dividing the width of the visible T2 tissue edema by the measured depth. The radiographic damage indices with each method were compared statistically. Histological analysis of each incision was conducted to compare the extent of tissue damage. MRI showed that the mean radiographic damage index of each corticotomy was significantly lower with the FMI (0.30 ± 0.02 (0.28-0.32)) than with the BPS method (0.54 ± 0.11 (0.42-0.64)) (p = 0.02). Histological analysis suggested a correlation with the radiographic findings as the FMI tissue samples demonstrated less adjacent tissue damage than BPS. FMI appeared to cause less adjacent tissue damage than the BPS method in pig cerebral tissue based on quantitative radiographic and qualitative histological analysis. Future studies are needed to investigate the clinical implications of energy-based surgical dissection on cerebral tissue. Copyright © 2015 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Metabolism links bacterial biofilms and colon carcinogenesis

PubMed Central

Johnson, Caroline H.; Dejea, Christine M.; Edler, David; Hoang, Linh T.; Santidrian, Antonio F.; Felding, Brunhilde H.; Cho, Kevin; Wick, Elizabeth C.; Hechenbleikner, Elizabeth M.; Uritboonthai, Winnie; Goetz, Laura; Casero, Robert A.; Pardoll, Drew M.; White, James R.; Patti, Gary J.; Sears, Cynthia L.; Siuzdak, Gary

2015-01-01

SUMMARY Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N1, N12-diacetylspermine in both biofilm positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N1, N12-diacetylspermine levels to those seen in biofilm negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome, to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression. PMID:25959674

Metabolism links bacterial biofilms and colon carcinogenesis.

PubMed

Johnson, Caroline H; Dejea, Christine M; Edler, David; Hoang, Linh T; Santidrian, Antonio F; Felding, Brunhilde H; Ivanisevic, Julijana; Cho, Kevin; Wick, Elizabeth C; Hechenbleikner, Elizabeth M; Uritboonthai, Winnie; Goetz, Laura; Casero, Robert A; Pardoll, Drew M; White, James R; Patti, Gary J; Sears, Cynthia L; Siuzdak, Gary

2015-06-02

Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N(1), N(12)-diacetylspermine in both biofilm-positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N(1), N(12)-diacetylspermine levels to those seen in biofilm-negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression. Copyright © 2015 Elsevier Inc. All rights reserved.

Coral disease physiology: the impact of Acroporid white syndrome on Symbiodinium

NASA Astrophysics Data System (ADS)

Roff, G.; Kvennefors, E. C. E.; Ulstrup, K. E.; Fine, M.; Hoegh-Guldberg, O.

2008-06-01

Acroporid white syndrome, a disease-like syndrome from the Great Barrier Reef, results from degenerative host tissue at lesion borders. Tissue preceding lesion borders appears visually healthy, but it is currently unclear whether the endosymbiotic zooxanthellae ( Symbiodinium) are physiologically impacted. Compared to healthy colonies, this study found no significant differences in symbiont density, mitotic index or chlorophyll a content in tissue bordering (0 cm), and 8 cm away from white syndrome lesions. Using chlorophyll a fluorescence techniques, the border tissue did not appear to be photosynthetically compromised, and Symbiodinium extracted from this area were photosynthetically competent. Transmission electron microscopy revealed extensive degeneration of host tissues surrounding symbionts in affected areas, however, Symbiodinium cells were structurally intact with no sign of in situ degradation. Collectively, these results suggest that Symbiodinium at white syndrome lesion borders exist in a dynamic intra-cellular state during active host tissue loss, yet remain physiologically uncompromised.

Using synchrotron X-ray phase-contrast micro-computed tomography to study tissue damage by laser irradiation.

PubMed

Robinson, Alan M; Stock, Stuart R; Soriano, Carmen; Xiao, Xianghui; Richter, Claus-Peter

2016-11-01

The aim of this study was to determine if X-ray micro-computed tomography could be used to locate and characterize tissue damage caused by laser irradiation and to describe its advantages over classical histology for this application. A surgical CO 2 laser, operated in single pulse mode (100 milliseconds) at different power settings, was used to ablate different types of cadaveric animal tissues. Tissue samples were then harvested and imaged with synchrotron X-ray phase-contrast and micro-computed tomography to generate stacks of virtual sections of the tissues. Subsequently, Fiji (ImageJ) software was used to locate tissue damage, then to quantify volumes of laser ablation cones and thermal coagulation damage from 3D renderings of tissue image stacks. Visual comparisons of tissue structures in X-ray images with those visible by classic light microscopy histology were made. We demonstrated that micro-computed tomography could be used to rapidly identify areas of surgical laser ablation, vacuolization, carbonization, and thermally coagulated tissue. Quantification and comparison of the ablation crater, which represents the volume of ablated tissue, and the thermal coagulation zone volumes were performed faster than we could by classical histology. We demonstrated that these procedures can be performed on fresh hydrated and non-sectioned plastic embedded tissue. We demonstrated that the application of non-destructive micro-computed tomography to the visualization and analysis of laser induced tissue damage without tissue sectioning is possible. This will improve evaluation of new surgical lasers and their corresponding effect on tissues. Lasers Surg. Med. 48:866-877, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Porites white patch syndrome: associated viruses and disease physiology

NASA Astrophysics Data System (ADS)

Lawrence, S. A.; Davy, J. E.; Wilson, W. H.; Hoegh-Guldberg, O.; Davy, S. K.

2015-03-01

In recent decades, coral reefs worldwide have undergone significant changes in response to various environmental and anthropogenic impacts. Among the numerous causes of reef degradation, coral disease is one factor that is to a large extent still poorly understood. Here, we characterize the physiology of white patch syndrome (WPS), a disease affecting poritid corals on the Great Barrier Reef. WPS manifests as small, generally discrete patches of tissue discolouration. Physiological analysis revealed that chlorophyll a content was significantly lower in lesions than in healthy tissues, while host protein content remained constant, suggesting that host tissue is not affected by WPS. This was confirmed by transmission electron microscope (TEM) examination, which showed intact host tissue within lesions. TEM also revealed that Symbiodinium cells are lost from the host gastrodermis with no apparent harm caused to the surrounding host tissue. Also present in the electron micrographs were numerous virus-like particles (VLPs), in both coral and Symbiodinium cells. Small (<50 nm diameter) icosahedral VLPs were significantly more abundant in coral tissue taken from diseased colonies, and there was an apparent, but not statistically significant, increase in abundance of filamentous VLPs in Symbiodinium cells from diseased colonies. There was no apparent increase in prokaryotic or eukaryotic microbial abundance in diseased colonies. Taken together, these results suggest that viruses infecting the coral and/or its resident Symbiodinium cells may be the causative agents of WPS.

Submucosal injection of normal saline may prevent tissue damage from argon plasma coagulation: an experimental study using resected porcine esophagus, stomach, and colon.

PubMed

Fujishiro, Mitsuhiro; Yahagi, Naohisa; Nakamura, Masanori; Kakushima, Naomi; Kodashima, Shinya; Ono, Satoshi; Kobayashi, Katsuya; Hashimoto, Takuhei; Yamamichi, Nobutake; Tateishi, Ayako; Shimizu, Yasuhito; Oka, Masashi; Ichinose, Masao; Omata, Masao

2006-10-01

Argon plasma coagulation (APC) is considered to be a safe thermocoagulation technique, but some reports show perforation and deformity during and after APC. In this study, we investigated the usefulness of prior submucosal injection for APC. APC over the mucosa was performed on fresh resected porcine esophagus, stomach, and colon with prior submucosal injection of normal saline (injection group) and without it (control group). The depth of tissue damage increased linearly with pulse duration up to the shallower submucosal layer in both groups. After that, tissue damage in the injection group remained confined to the shallower submucosal layer under any condition, whereas that in the control group continued to extend. The tissue damages of the injection groups were significantly (P<0.05) shallower than those of the control groups that reached the deeper submucosal layer in all the organs. Submucosal injection of normal saline before the application of APC may limit tissue damage and prevent perforation and deformity.

Classification of Foreign Body Reactions due to Industrial Silicone Injection.

PubMed

Harlim, Ago; Kanoko, Mpu; Aisah, Siti

2018-05-02

A foreign body reaction (FBR) is a typical tissue response to a biomaterial that has been injected or implanted in human body tissue. There has been a lack of data on the classification of foreign body reaction to silicone injection, which can describe the pattern of body tissue responses to silicone. Determine the foreign body reaction to silicone injection. We modified the classification proposed by Duranti and colleagues, which has categorized a FBR to hyaluronic acid injection into a new classification of an FBR to silicone injection. A cohort study of 31 women suffering from silicone-induced granulomas on their chin was conducted. Granulomatous tissue and submental skin were stained with hematoxylin-eosin and evaluated. Our data revealed that there were at least 7 categories of FBRs to silicone injection that could be developed. Categories 1 to 4 showed inflammatory activity, and categories 5 to 8 showed tissue repair by fibrosis. Using histopathological staining, we are able to sequence the steps of body reactions to silicone injection. Initial inflammatory reaction is then replaced by fibrosis process repairing the damaged tissues. The process depends on the host immune tolerance.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Modulation of Experimental Herpes Encephalitis-Associated Neurotoxicity through Sulforaphane Treatment

PubMed Central

Schachtele, Scott J.; Hu, Shuxian; Lokensgard, James R.

2012-01-01

Reactive oxygen species (ROS) produced by brain-infiltrating macrophages and neutrophils, as well as resident microglia, are pivotal to pathogen clearance during viral brain infection. However, unchecked free radical generation is also responsible for damage to and cytotoxicity of critical host tissue bystander to primary infection. These unwanted effects of excessive ROS are combated by local cellular production of antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutathione peroxidase 1 (Gpx1). In this study, we showed that experimental murine herpes encephalitis triggered robust ROS production, as well as an opposing upregulation of the antioxidants HO-1 and Gpx1. This antioxidant response was insufficient to prevent tissue damage, neurotoxicity, and mortality associated with viral brain infection. Previous studies corroborate our data supporting astrocytes as the major antioxidant producer in brain cell cultures exposed to HSV-1 stimulated microglia. We hypothesized that stimulating opposing antioxidative responses in astrocytes, as well as neurons, would mitigate the effects of ROS-mediated neurotoxicity both in vitro and during viral brain infection in vivo. Here, we demonstrate that the addition of sulforaphane, a potent stimulator of antioxidant responses, enhanced HO-1 and Gpx1 expression in astrocytes through the activation of nuclear factor-E2-related factor 2 (Nrf2). Additionally, sulforaphane treatment was found to be effective in reducing neurotoxicity associated with HSV-stimulated microglial ROS production. Finally, intraperitoneal injections of sulforaphane into mice during active HSV infection reduced neuroinflammation via a decrease in brain-infiltrating leukocytes, macrophage- and neutrophil-produced ROS, and MHCII-positive, activated microglia. These data support a key role for astrocyte-produced antioxidants in modulating oxidative stress and neuronal damage in response to viral infection. PMID:22558388

Mechanical stimulation enhances integration in an in vitro model of cartilage repair.

PubMed

Theodoropoulos, John S; DeCroos, Amritha J N; Petrera, Massimo; Park, Sam; Kandel, Rita A

2016-06-01

(1) To characterize the effects of mechanical stimulation on the integration of a tissue-engineered construct in terms of histology, biochemistry and biomechanical properties; (2) to identify whether cells of the implant or host tissue were critical to implant integration; and (3) to study cells believed to be involved in lateral integration of tissue-engineered cartilage to host cartilage. We hypothesized that mechanical stimulation would enhance the integration of the repair implant with host cartilage in an in vitro integration model. Articular cartilage was harvested from 6- to 9-month-old bovine metacarpal-phalangeal joints. Constructs composed of tissue-engineered cartilage implanted into host cartilage were placed in spinner bioreactors and maintained on a magnetic stir plate at either 0 (static control) or 90 (experimental) rotations per minute (RPM). The constructs from both the static and spinner bioreactors were harvested after either 2 or 4 weeks of culture and evaluated histologically, biochemically, biomechanically and for gene expression. The extent and strength of integration between tissue-engineered cartilage and native cartilage improved significantly with both time and mechanical stimulation. Integration did not occur if the implant was not viable. The presence of stimulation led to a significant increase in collagen content in the integration zone between host and implant at 2 weeks. The gene profile of cells in the integration zone differs from host cartilage demonstrating an increase in the expression of membrane type 1 matrix metalloproteinase (MT1-MMP), aggrecan and type II collagen. This study shows that the integration of in vitro tissue-engineered implants with host tissue improves with mechanical stimulation. The findings of this study suggests that consideration should be given to implementing early loading (mechanical stimulation) into future in vivo studies investigating the long-term viability and integration of tissue-engineered cartilage for the treatment of cartilage injuries. This could simply be done through the use of continuous passive motion (CPM) in the post-operative period or through a more complex and structured rehabilitation program with a gradual increase in forces across the joint over time.

Postoperative morbidity and histopathologic characteristics of tonsillar tissue following coblation tonsillectomy in children: a prospective randomized single-blind study.

PubMed

Roje, Zeljka; Racić, Goran; Dogas, Zoran; Pisac, Valdi Pesutić; Timms, Michael

2009-03-01

The aim of this prospective randomized single blind study was to determine the depth of thermal damage to tonsillar tissue due to coblation, and to compare it with thermal damage to tonsillar tissue following conventional tonsillectomy; to correlate the depth of thermal damage to tonsillar tissue with the parameters of postoperative morbidity, to compare intraoperative blood loss, postoperative pain severity, time to resuming normal physical activity, and incidence of postoperative bleeding between two groups of tonsillectomized children aged up to 16 years. 72 children aged 3-16 years scheduled for tonsillectomy randomly assigned into two groups submitted either to conventional tonsillectomy with bipolar diathermy coagulation or to coblation tonsillectomy, with a 14-day follow up. Statistically significant differences were observed in the depth of thermal damage to tonsillar tissue (p < 0.001), intraoperative blood loss (p < 0.004), in postoperative pain severity (p < 0.05) and in time to resuming normal physical activity between the two groups (p < 0.001). There was no case of reactionary or secondary bleeding in either group. In this paper for the first time we have correlated postoperative morbidity and thermal tissue damage: less thermal damage is associated with less postoperative morbidity.

Duration of plant damage by host larvae affects attraction of two parasitoid species (Microplitis croceipes and Cotesia marginiventris) to cotton: implications for interspecific competition.

PubMed

Morawo, Tolulope; Fadamiro, Henry

2014-12-01

Volatile organic compounds (VOCs) released by herbivore-damaged plants can guide parasitoids to their hosts. The quantity and quality of VOC blends emitted by plants may be affected by the duration of plant damage by herbivores, which could have potential ramifications on the recruitment of competing parasitoids. We used two parasitoid species, Microplitis croceipes and Cotesia marginiventris (Hymenoptera: Braconidae), to address the question of whether duration of plant damage affects parasitoid use of plant VOCs for host location. Both wasp species are larval endoparasitoids of Heliothis virescens (Lepidoptera: Noctuidae), an important pest of cotton. Attraction of the two parasitoid species to odors emitted by undamaged (UD), fresh (6 h infestation) damage (FD), and old (24 h infestation) damage (OD) cotton plants infested by H. virescens larvae was investigated using a headspace volatile collection system coupled with four-choice olfactometer bioassay. Both sexes of M. croceipes showed a preference for FD- and OD-plant odors over UD-plants. On the other hand, more C. marginiventris females were attracted to UD- and FD-plants than to OD-plants. GC/MS analyses showed qualitative and quantitative differences in the VOC profiles of UD, FD, and OD-plants, which may explain the observed preferences of the parasitoids. These results suggest a temporal partitioning in the recruitment of M. croceipes and C. marginiventris to H. virescens-damaged cotton, and may have potential implications for interspecific competition between the two parasitoid species.

Use of Transcriptional Profiling to Delineate the Initial Response of Mice to Intravaginal Herpes Simplex Virus Type 2 Infection

PubMed Central

Harvey, Stephen A. K.; Phillips, Jaclyn M.; Vicetti Miguel, Rodolfo D.; Melan, Melissa A.; Quispe Calla, Nirk E.; Hendricks, Robert L.

2013-01-01

Abstract Intravaginal (ivag) infection of mice with herpes simplex virus type 2 (HSV-2) causes genital tissue damage, quickly followed by development of fatal encephalopathy. To delineate initial host responses generated by HSV-2 infection, here oligonucleotide microarrays compared gene expression in vaginal tissue from uninfected mice and mice 1, 2, 3, 4, 5, 6, or 7 days after ivag infection with 104 pfu HSV-2. While comparison of mRNA expression in uninfected and HSV-infected vaginal tissue detected few changes during the first 2 days post infection (dpi), there were 156 genes whose expression was first significantly altered 3 dpi that remained significantly modified at all later time points examined. These 156 genes were significantly enriched in canonical pathways associated with interferon (IFN) signaling, activation of IFN elements by intracellular pattern recognition receptors, and antiviral immunity induced by cytosolic RIG-like receptors. Evaluation of this gene set with the National Center for Biotechnology Information Gene and INTERFEROME databases corroborated pathway analysis, as function of most (53%) were linked to IFN-mediated host immunity. In the final set of experiments, ivag administration of the Toll-like receptor 3 agonist polyinosinic: polycytidylic acid (poly I:C) 24 h before ivag HSV-2 infection reduced the incidence of genital pathology and encephalopathy, while these poly I:C-treated mice were subsequently protected from ocular HSV-2 challenge lethal to uninfected controls. The latter results imply that the exuberant antiviral immunity produced in our experimental model is simply formed too late to prevent viral replication and dissemination, and that poly I:C-induced formation of an antiviral state protecting against primary ivag infection also permits development of HSV-specific protective immunity. PMID:23638732

A self-harm series and its relationship with childhood adversity among adolescents in mainland China: a cross-sectional study.

PubMed

Han, Azhu; Wang, Gengfu; Xu, Geng; Su, Puyu

2018-02-01

Self-harm (SH) is an emerging problem among Chinese adolescents. The present study aimed to measure the prevalence of SH behaviours and to explore the relationship between childhood adversity and different SH subtypes among Chinese adolescents. A total of 5726 middle school students were randomly selected in three cities of Anhui province, China, using a stratified cluster sampling method. SH was categorized into five subtypes (highly lethal self-harm, less lethal self-harm with visible tissue damage, self-harm without visible tissue damage, self-harmful behaviours with latency damage and psychological self-harm). Multivariate logistic regression was used to explore the relationships between childhood adversity and different subtypes of adolescent SH. The prevalence rates of highly lethal self-harm, less lethal self-harm with visible tissue damage, self-harm without visible tissue damage, self-harmful behaviours with latency damage and psychological self-harm were 6.1, 20.4, 32.0, 20.0 and 23.0%, respectively. Childhood sexual abuse and physical peer victimization were associated with each SH subtype with adjusted odds ratios (AORs) ranging from 1.23 to 1.76. Highly lethal self-harm was associated with childhood physical peer victimization, sexual abuse, emotional abuse, and emotional neglect. The less lethal SH subtypes (i.e., less lethal self-harm with visible tissue damage, self-harm without visible tissue damage, self-harmful behaviours with latency damage and psychological self-harm) were associated with childhood peer victimization, family life stress event scores and childhood sexual abuse. A high prevalence of SH exists among Chinese adolescents. The association of childhood adversity with SH merits serious attention in both future research and preventive interventions.

Parameter estimation and sensitivity analysis in an agent-based model of Leishmania major infection

PubMed Central

Jones, Douglas E.; Dorman, Karin S.

2009-01-01

Computer models of disease take a systems biology approach toward understanding host-pathogen interactions. In particular, data driven computer model calibration is the basis for inference of immunological and pathogen parameters, assessment of model validity, and comparison between alternative models of immune or pathogen behavior. In this paper we describe the calibration and analysis of an agent-based model of Leishmania major infection. A model of macrophage loss following uptake of necrotic tissue is proposed to explain macrophage depletion following peak infection. Using Gaussian processes to approximate the computer code, we perform a sensitivity analysis to identify important parameters and to characterize their influence on the simulated infection. The analysis indicates that increasing growth rate can favor or suppress pathogen loads, depending on the infection stage and the pathogen’s ability to avoid detection. Subsequent calibration of the model against previously published biological observations suggests that L. major has a relatively slow growth rate and can replicate for an extended period of time before damaging the host cell. PMID:19837088

Quorum sensing and Bacterial Pathogenicity: From Molecules to Disease

PubMed Central

Deep, Antariksh; Chaudhary, Uma; Gupta, Varsha

2011-01-01

Quorum sensing in prokaryotic biology refers to the ability of a bacterium to sense information from other cells in the population when they reach a critical concentration (i.e. a Quorum) and communicate with them. The “language” used for this intercellular communication is based on small, self-generated signal molecules called as autoinducers. Quorum sensing is thought to afford pathogenic bacteriaa mechanism to minimize host immune responses by delaying theproduction of tissue-damaging virulence factors until sufficientbacteria have amassed and are prepared to overwhelm host defensemechanisms and establish infection. Quorum sensing systems are studied in a large number of gram-negative bacterial species belonging to α, β, and γ subclasses of proteobacteria. Among the pathogenic bacteria, Pseudomonas aeruginosa is perhaps the best understood in terms of the virulence factors regulated and the role the Quorum sensing plays in pathogenicity. Presently, Quorum sensing is considered as a potential novel target for antimicrobial therapy to control multi/all drug-resistant infections. This paper reviews Quorum sensing in gram positive and gram negative bacteria and its role in biofilm formation. PMID:21701655

Acute graft-versus-host disease: a bench-to-bedside update.

PubMed

Holtan, Shernan G; Pasquini, Marcelo; Weisdorf, Daniel J

2014-07-17

Over the past 5 years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response, and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need. © 2014 by The American Society of Hematology.

Caterpillar mimicry by plant galls as a visual defense against herbivores.

PubMed

Yamazaki, Kazuo

2016-09-07

Plant galls, induced by arthropods and various other organisms have an intimate relationship with host plants, and gall-inducers have limited mobility. In addition to their own photosynthesis, galls are resource sinks rich with nutrients, with neighboring plant organs commonly serving as external photosynthate sources. Galls, if not well defended, may therefore be attractive food sources for herbivores. Galls produced by some aphids, jumping plant lice, thrips, and gall midges in Japan, Palearctic region and in the Middle East visually resemble lepidopteran caterpillars. I propose that such visual resemblance may reduce herbivory of galls and surrounding plant tissues, resulting in an increase in galler survival due to reduced gall damage and in enhanced galler growth due to improved nutrient inflow to the galls, when herbivores avoid colonizing or consuming plant parts that look as if they have been occupied by other herbivores. Potential predators and parasitoids of caterpillars may be attracted to the caterpillar-like galls and then attack real caterpillars and other invertebrate herbivores, which would also be beneficial for both gallers and their hosts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Parvovirus Minute Virus of Mice Induces a DNA Damage Response That Facilitates Viral Replication

PubMed Central

Adeyemi, Richard O.; Landry, Sebastien; Davis, Meredith E.; Weitzman, Matthew D.; Pintel, David J.

2010-01-01

Infection by DNA viruses can elicit DNA damage responses (DDRs) in host cells. In some cases the DDR presents a block to viral replication that must be overcome, and in other cases the infecting agent exploits the DDR to facilitate replication. We find that low multiplicity infection with the autonomous parvovirus minute virus of mice (MVM) results in the activation of a DDR, characterized by the phosphorylation of H2AX, Nbs1, RPA32, Chk2 and p53. These proteins are recruited to MVM replication centers, where they co-localize with the main viral replication protein, NS1. The response is seen in both human and murine cell lines following infection with either the MVMp or MVMi strains. Replication of the virus is required for DNA damage signaling. Damage response proteins, including the ATM kinase, accumulate in viral-induced replication centers. Using mutant cell lines and specific kinase inhibitors, we show that ATM is the main transducer of the signaling events in the normal murine host. ATM inhibitors restrict MVM replication and ameliorate virus-induced cell cycle arrest, suggesting that DNA damage signaling facilitates virus replication, perhaps in part by promoting cell cycle arrest. Thus it appears that MVM exploits the cellular DNA damage response machinery early in infection to enhance its replication in host cells. PMID:20949077

In situ hybridization for the detection of rust fungi in paraffin embedded plant tissue sections.

PubMed

Ellison, Mitchell A; McMahon, Michael B; Bonde, Morris R; Palmer, Cristi L; Luster, Douglas G

2016-01-01

Rust fungi are obligate pathogens with multiple life stages often including different spore types and multiple plant hosts. While individual rust pathogens are often associated with specific plants, a wide range of plant species are infected with rust fungi. To study the interactions between these important pathogenic fungi and their host plants, one must be able to differentiate fungal tissue from plant tissue. This can be accomplished using the In situ hybridization (ISH) protocol described here. To validate reproducibility using the ISH protocol, samples of Chrysanthemum × morifolium infected with Puccinia horiana, Gladiolus × hortulanus infected with Uromyces transversalis and Glycine max infected with Phakopsora pachyrhizi were tested alongside uninfected leaf tissue samples. The results of these tests show that this technique clearly distinguishes between rust pathogens and their respective host plant tissues. This ISH protocol is applicable to rust fungi and potentially other plant pathogenic fungi as well. It has been shown here that this protocol can be applied to pathogens from different genera of rust fungi with no background staining of plant tissue. We encourage the use of this protocol for the study of plant pathogenic fungi in paraffin embedded sections of host plant tissue.

Biomechanics Analysis of Pressure Ulcer Using Damaged Interface Model between Bone and Muscle in the Human Buttock

NASA Astrophysics Data System (ADS)

Slamet, Samuel Susanto; Takano, Naoki; Tanabe, Yoshiyuki; Hatano, Asako; Nagasao, Tomohisa

This paper aims at building up a computational procedure to study the bio-mechanism of pressure ulcer using the finite element method. Pressure ulcer is a disease that occurs in the human body after 2 hours of continuous external force. In the very early stage of pressure ulcer, it is found that the tissues inside the body are damaged, even though skin surface looks normal. This study assumes that tension and/or shear strain will cause damage to loose fibril tissue between the bone and muscle and that propagation of damaged area will lead to fatal stage. Analysis was performed using the finite element method by modeling the damaged fibril tissue as a cutout. By varying the loading directions and watching both tensile and shear strains, the risk of fibril tissue damage and propagation of the damaged area is discussed, which may give new insight for the careful nursing for patients, particularly after surgical treatment. It was found that the pressure ulcer could reoccur for a surgical flap treatment. The bone cut and surgical flap surgery is not perfect to prevent the bone-muscle interfacial damage.

Implanted Cell-Dense Prevascularized Tissues Develop Functional Vasculature That Supports Reoxygenation After Thrombosis

PubMed Central

White, Sean M.; Pittman, Chelsea R.; Hingorani, Ryan; Arora, Rajan; Esipova, Tatiana V.; Vinogradov, Sergei A.; Hughes, Christopher C.W.; Choi, Bernard

2014-01-01

Achieving adequate vascularization within implanted engineered tissues is a significant obstacle to maintaining viability and functionality. In vitro prevascularization of engineered tissues has been explored as a potential solution to this challenge. The traditional paradigm of in vitro prevascularization is to implant an engineered tissue with a preformed vascular network that is perfused after anastomosis with the host circulation. We investigated the efficacy of this strategy by implanting cell-dense prevascularized tissues created via cell-mediated contraction and composed of collagen and a collagen-fibrin mixture into dorsal window chambers surgically prepared on immunocompromised mice. We found that host-implant anastomosis takes place in 2–6 days and that perfusion of vessels within the implants is subsequently restricted by thrombosis. However, by day 7, a functional vascular network composed of host and implant vessels developed. Prevascularization enhanced intra-implant pO2 significantly as early as 2 days postimplantation, reaching a maximum of 55 mmHg by day 8, which was significantly greater than the maximum within cellularized control tissues (18 mmHg). By day 14, collagen tissues supported ∼0.51×109 implanted and host-derived cells per mL. Our findings elucidate key features of in vitro prevascularization that can be used toward the design of larger and more functionally complex engineered tissues. PMID:24593148

Oxidative stress response of the black tiger shrimp Penaeus monodon to Vibrio parahaemolyticus challenge.

PubMed

Duan, Yafei; Zhang, Jiasong; Dong, Hongbiao; Wang, Yun; Liu, Qingsong; Li, Hua

2015-10-01

Vibrio parahaemolyticus is a virulent pathogen that affects shrimp aquaculture. Reactive oxygen species are produced by the immune system that defends the host against foreign microorganisms. In the present study, the oxidative stress response in hepatopancreas and gills of Penaeus monodon to V. parahaemolyticus challenge were studied, such as respiratory burst, ROS production (·O2(-) and ·OH), activities of antioxidant enzymes (CAT, GPx, SOD, POD and GST) and oxidative damage to lipid and protein (indexed by contents of MDA). Compared with the control group, after V. parahaemolyticus challenge, respiratory burst and ROS production were up-regulated significantly. GPx and POD activity increased significantly in hepatopancreas and gills of the shrimps at 12 h, but CAT activity decreased markedly at 12 h and 24 h. SOD and GST activity in hepatopancreas of the shrimps increased significantly at 1.5 h, but decreased markedly at 12 h-48 h. MDA content increased significantly after 6 h-24 h challenge. HE staining showed that V. parahaemolyticus challenge induced damage symptoms in hepatopancreas of P. monodon. Our study revealed that V. parahaemolyticus influenced the antioxidative status and caused oxidative stress and tissue damage via confusion of antioxidant enzymes in P. monodon. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perturbation of bacterial ice nucleation activity by a grass antifreeze protein.

PubMed

Tomalty, Heather E; Walker, Virginia K

2014-09-26

Certain plant-associating bacteria produce ice nucleation proteins (INPs) which allow the crystallization of water at high subzero temperatures. Many of these microbes are considered plant pathogens since the formed ice can damage tissues, allowing access to nutrients. Intriguingly, certain plants that host these bacteria synthesize antifreeze proteins (AFPs). Once freezing has occurred, plant AFPs likely function to inhibit the growth of large damaging ice crystals. However, we postulated that such AFPs might also serve as defensive mechanisms against bacterial-mediated ice nucleation. Recombinant AFP derived from the perennial ryegrass Lolium perenne (LpAFP) was combined with INP preparations originating from the grass epiphyte, Pseudomonas syringae. The presence of INPs had no effect on AFP activity, including thermal hysteresis and ice recrystallization inhibition. Strikingly, the ice nucleation point of the INP was depressed up to 1.9°C in the presence of LpAFP, but a recombinant fish AFP did not lower the INP-imposed freezing point. Assays with mutant LpAFPs and the visualization of bacterially-displayed fluorescent plant AFP suggest that INP and LpAFP can interact. Thus, we postulate that in addition to controlling ice growth, plant AFPs may also function as a defensive strategy against the damaging effects of ice-nucleating bacteria. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Effects of soft X-ray radiation damage on paraffin-embedded rat tissues supported on ultralene: a chemical perspective.

PubMed

Bedolla, Diana E; Mantuano, Andrea; Pickler, Arissa; Mota, Carla Lemos; Braz, Delson; Salata, Camila; Almeida, Carlos Eduardo; Birarda, Giovanni; Vaccari, Lisa; Barroso, Regina Cély; Gianoncelli, Alessandra

2018-05-01

Radiation damage is an important aspect to be considered when analysing biological samples with X-ray techniques as it can induce chemical and structural changes in the specimens. This work aims to provide new insights into the soft X-ray induced radiation damage of the complete sample, including not only the biological tissue itself but also the substrate and embedding medium, and the tissue fixation procedure. Sample preparation and handling involves an unavoidable interaction with the sample matrix and could play an important role in the radiation-damage mechanism. To understand the influence of sample preparation and handling on radiation damage, the effects of soft X-ray exposure at different doses on ultralene, paraffin and on paraffin-embedded rat tissues were studied using Fourier-transform infrared (FTIR) microspectroscopy and X-ray microscopy. Tissues were preserved with three different commonly used fixatives: formalin, glutaraldehyde and Karnovsky. FTIR results showed that ultralene and paraffin undergo a dose-dependent degradation of their vibrational profiles, consistent with radiation-induced oxidative damage. In addition, formalin fixative has been shown to improve the preservation of the secondary structure of proteins in tissues compared with both glutaraldehyde and Karnovsky fixation. However, conclusive considerations cannot be drawn on the optimal fixation protocol because of the interference introduced by both substrate and embedding medium in the spectral regions specific to tissue lipids, nucleic acids and carbohydrates. Notably, despite the detected alterations affecting the chemical architecture of the sample as a whole, composed of tissue, substrate and embedding medium, the structural morphology of the tissues at the micrometre scale is essentially preserved even at the highest exposure dose.

Development of novel force-limiting grasping forceps with a simple mechanism.

PubMed

Sakaguchi, Yasuto; Sato, Toshihiko; Yutaka, Yojiro; Muranishi, Yusuke; Komatsu, Teruya; Yoshizawa, Akihiko; Nakajima, Naoki; Nakamura, Tatsuo; Date, Hiroshi

2018-06-06

In endoscopic surgery, fragile tissues may be damaged by the application of excessive force. Thus, we developed novel endoscopic forceps with a simple force-limiting mechanism. The novel forceps were constructed with a leaf spring, and the spring thickness determines grasping pressure. We established an evaluation system (maximum score is 11 points) for lung tissue damage leading to complications. We tested the conventional forceps (186.8 kPa) and 3 novel spring forceps with the following thicknesses: 1.3 mm (53.0 kPa), 2.2 mm (187.7 kPa) and 2.8 mm (369.2 kPa). After grasping, peripheral canine lung tissues were microscopically examined for acute- and late-phase damages. In the acute phase (20 sites), the novel forceps caused capillary congestion and haemorrhage in the subpleural tissue, whereas the conventional forceps caused deep tissue and pleural damages. In the late phase (30 sites), both forceps caused fibroblast formation and interstitial thickening, which progressed to the deeper tissues as grasping pressure increased. In the acute phase, the median scores were 2.0 and 6.0 for the novel and conventional forceps, respectively (P = 0.003). In the late phase, the median scores were 2.0, 2.5 and 5.0 for 1.3-, 2.2- and 2.8-mm thick forceps, respectively, and 5.0 for the conventional forceps (P < 0.001). In both phases, the novel forceps with grasping pressure set below 187.7 kPa (2.2 mm) caused significantly less lung tissue damage than the conventional forceps. The novel endoscopic forceps are able to regulate the tissue-grasping pressure and induce less damage in lung tissues than conventional forceps.

Effects of deoxynivalenol on content of chloroplast pigments in barley leaf tissues.

PubMed

Bushnell, W R; Perkins-Veazie, P; Russo, V M; Collins, J; Seeland, T M

2010-01-01

To understand further the role of deoxynivalenol (DON) in development of Fusarium head blight (FHB), we investigated effects of the toxin on uninfected barley tissues. Leaf segments, 1 to 1.2 cm long, partially stripped of epidermis were floated with exposed mesophyll in contact with DON solutions. In initial experiments with the leaf segments incubated in light, DON at 30 to 90 ppm turned portions of stripped tissues white after 48 to 96 h. The bleaching effect was greatly enhanced by addition of 1 to 10 mM Ca(2+), so that DON at 10 to 30 ppm turned virtually all stripped tissues white within 48 h. Content of chlorophylls a and b and of total carotenoid pigment was reduced. Loss of electrolytes and uptake of Evans blue indicated that DON had a toxic effect, damaging plasmalemmas in treated tissues before chloroplasts began to lose pigment. When incubated in the dark, leaf segments also lost electrolytes, indicating DON was toxic although the tissues remained green. Thus, loss of chlorophyll in light was due to photobleaching and was a secondary effect of DON, not required for toxicity. In contrast to bleaching effects, some DON treatments that were not toxic kept tissues green without bleaching or other signs of injury, indicating senescence was delayed compared with slow yellowing of untreated leaf segments. Cycloheximide, which like DON, inhibits protein synthesis, also bleached some tissues and delayed senescence of others. Thus, the effects of DON probably relate to its ability to inhibit protein synthesis. With respect to FHB, the results suggest DON may have multiple roles in host cells of infected head tissues, including delayed senescence in early stages of infection and contributing to bleaching and death of cells in later stages.

Non-contact hematoma damage and healing assessment using reflectance photoplethysmographic imaging

NASA Astrophysics Data System (ADS)

Amelard, Robert; Pfisterer, Kaylen J.; Clausi, David A.; Wong, Alexander

2016-03-01

Impact trauma may cause a hematoma, which is the leakage of venous blood into surrounding tissues. Large hematomas can be dangerous as they may inhibit local blood ow. Hematomas are often diagnosed visually, which may be problematic if the hematoma leaks deeper than the visible penetration depth. Furthermore, vascular wound healing is often monitored at home without the aid of a clinician. We therefore investigated the use of near infrared (NIR) re ectance photoplethysmographic imaging (PPGI) to assess vascular damage resulting from a hematoma, and monitor the healing process. In this case study, the participant experienced internal vascular damage in the form of a hematoma. Using a PPGI system with dual-mode temporally coded illumination for ambient-agnostic data acquisition and mounted optical elements, the tissue was illuminated with a spatially uniform irradiance pattern of 850 nm wavelength light for increased tissue penetration and high oxy-to-deoxyhemoglobin absorption ratio. Initial and follow-up PPGI data collection was performed to assess vascular damage and healing. The tissue PPGI sequences were spectrally analyzed, producing spectral maps of the tissue area. Experimental results show that spatial differences in spectral information can be observed around the damaged area. In particular, the damaged site exhibited lower pulsatility than the surrounding healthy tissue. This pulsatility was largely restored in the follow-up data, suggesting that the tissue had undergone vascular healing. These results indicate that hematomas can be assessed and monitored in a non-contact visual manner, and suggests that PPGI can be used for tissue health assessment, with potential extensions to peripheral vascular disease.

Characterizing the proteome and oxi-proteome of apple in response to a host (Penicillium expansum) and a non-host (Penicillium digitatum) pathogen.

PubMed

Buron-Moles, Gemma; Wisniewski, Michael; Viñas, Inmaculada; Teixidó, Neus; Usall, Josep; Droby, Samir; Torres, Rosario

2015-01-30

Apples are subjected to both abiotic and biotic stresses during the postharvest period, which lead to large economic losses worldwide. To obtain biochemical insights into apple defense response, we monitored the protein abundance changes (proteome), as well as the protein carbonyls (oxi-proteome) formed by reactive oxygen species (ROS) in 'Golden Smoothee' apple in response to wounding, Penicillium expansum (host) and Penicillium digitatum (non-host) pathogens with select transcriptional studies. To examine the biological relevance of the results, we described quantitative and oxidative protein changes into the gene ontology functional categories, as well as into de KEGG pathways. We identified 26 proteins that differentially changed in abundance in response to wounding, P. expansum or P. digitatum infection. While these changes showed some similarities between the apple responses and abiotic and biotic stresses, Mal d 1.03A case, other proteins as Mal d 1.03E and EF-Tu were specifically induced in response to P. digitatum infection. Using a protein carbonyl detection method based on fluorescent Bodipy, we detected and identified 27 oxidized proteins as sensitive ROS targets. These ROS target proteins were related to metabolism processes, suggesting that this process plays a leading role in apple fruit defense response against abiotic and biotic stresses. ACC oxidase and two glutamine synthetases showed the highest protein oxidation level in response to P. digitatum infection. Documenting changes in the proteome and, specifically in oxi-proteome of apple can provide information that can be used to better understand how impaired protein functions may affect apple defense mechanisms. Possible mechanisms by which these modified proteins are involved in fruit defense response are discussed. Mechanical damage in apple fruits is linked annually to large economic losses due to opportunistic infection by postharvest pathogens, such as P. expansum. Despite the current use of chemical fungicides and the implementation of new alternative strategies, blue mold remains a critical disease of these stored fruits worldwide. Actual trends are focused on acquiring the knowledge of the host-pathogen interactions because it may help on finding new rational and environmentally friendly control alternatives. Despite the economic importance of some postharvest diseases, proteomics has only been applied in a few cases to study fruit-pathogen interactions. On the one hand, this is the first study that monitored changes at the proteome and oxi-proteome level in 'Golden Smoothee' apple fruits in response to P. expansum (compatible) and P. digitatum (non-host) pathogens. On the other hand, the main technological innovation of the reported research is the detection and quantification of oxidized (carbonylated) proteins to assess protein oxidative damage, avoiding the immunoblotting technique. The importance of the biological process investigated lies in the different mechanisms induced in fruit in response to P. expansum and P. digitatum. Results revealed that fruit recognizes and reacts to P. expansum in a similar manner to wounding, while its response to P. digitatum exhibits few differences in the protein profile. Documenting changes in the proteome and, specifically in oxi-proteome of apple can provide information that can be used to better understand how impaired protein functions may affect apple defense mechanisms. It also provides new biomarkers for oxidative damage mainly caused by the oxidative response occurring in fruit tissue in response to a host and a non-host pathogen. Copyright © 2014 Elsevier B.V. All rights reserved.

Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo

PubMed Central

Brönnimann, Daniel; Bouchet, Audrey; Schneider, Christoph; Potez, Marine; Serduc, Raphaël; Bräuer-Krisch, Elke; Graber, Werner; von Gunten, Stephan; Laissue, Jean Albert; Djonov, Valentin

2016-01-01

Our goal was the visualizing the vascular damage and acute inflammatory response to micro- and minibeam irradiation in vivo. Microbeam (MRT) and minibeam radiation therapies (MBRT) are tumor treatment approaches of potential clinical relevance, both consisting of parallel X-ray beams and allowing the delivery of thousands of Grays within tumors. We compared the effects of microbeams (25–100 μm wide) and minibeams (200–800 μm wide) on vasculature, inflammation and surrounding tissue changes during zebrafish caudal fin regeneration in vivo. Microbeam irradiation triggered an acute inflammatory response restricted to the regenerating tissue. Six hours post irradiation (6 hpi), it was infiltrated by neutrophils and fli1a+ thrombocytes adhered to the cell wall locally in the beam path. The mature tissue was not affected by microbeam irradiation. In contrast, minibeam irradiation efficiently damaged the immature tissue at 6 hpi and damaged both the mature and immature tissue at 48 hpi. We demonstrate that vascular damage, inflammatory processes and cellular toxicity depend on the beam width and the stage of tissue maturation. Minibeam irradiation did not differentiate between mature and immature tissue. In contrast, all irradiation-induced effects of the microbeams were restricted to the rapidly growing immature tissue, indicating that microbeam irradiation could be a promising tumor treatment tool. PMID:27640676

Pushing the envelope: microinjection of Minute virus of mice into Xenopus oocytes causes damage to the nuclear envelope.

PubMed

Cohen, Sarah; Panté, Nelly

2005-12-01

Parvoviruses are small DNA viruses that replicate in the nucleus of their host cells. It has been largely assumed that parvoviruses enter the nucleus through the nuclear pore complex (NPC). However, the details of this mechanism remain undefined. To study this problem, the parvovirus Minute virus of mice (MVM) was microinjected into the cytoplasm of Xenopus oocytes and a transmission electron microscope was used to visualize the effect of the virus on the host cell. It was found that MVM caused damage to the nuclear envelope (NE) in a time- and concentration-dependent manner. Damage was predominantly to the outer nuclear membrane and was often near the NPCs. However, microinjection experiments in which the NPCs were blocked showed that NE damage induced by MVM was independent of the NPC. To address the question of whether this effect of MVM is specific to the NE, purified organelles were incubated with MVM. Visualization by electron microscopy revealed that MVM did not affect all intracellular membranes. These data represent a novel form of virus-induced damage to host cell nuclear structure and suggest that MVM is imported into the nucleus using a unique mechanism that is independent of the NPC, and involves disruption of the NE and import through the resulting breaks.

Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides.

PubMed

Zitnay, Jared L; Li, Yang; Qin, Zhao; San, Boi Hoa; Depalle, Baptiste; Reese, Shawn P; Buehler, Markus J; Yu, S Michael; Weiss, Jeffrey A

2017-03-22

Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and potentiates in pathological processes. Here, we utilize collagen hybridizing peptide (CHP), which binds unfolded collagen by triple helix formation, to detect molecular level subfailure damage to collagen in mechanically stretched rat tail tendon fascicle. Our results directly reveal that collagen triple helix unfolding occurs during tensile loading of collagenous tissues and thus is an important damage mechanism. Steered molecular dynamics simulations suggest that a likely mechanism for triple helix unfolding is intermolecular shearing of collagen α-chains. Our results elucidate a probable molecular failure mechanism associated with subfailure injuries, and demonstrate the potential of CHP targeting for diagnosis, treatment and monitoring of tissue disease and injury.

Differential attractiveness of potato tuber volatiles to Phthorimaea operculella (Gelechiidae) and the predator Orius insidiosus (Anthocoridae).

PubMed

Arab, Alberto; Trigo, José Roberto; Lourenção, André Luiz; Peixoto, Aiane Michele; Ramos, Fernanda; Bento, José Mauricio Simões

2007-10-01

The behavioral responses of the potato tuberworm moth Phthorimaea operculella and the polyphagous predator Orius insidiosus to volatiles emanating from exposed tubers were studied by four-arm olfactometer bioassays. Mated females of P. operculella distinguished volatiles released by intact potato tubers from volatiles damaged mechanically or by conspecific larvae. Volatiles from intact potato tubers were attractive to them. On the other hand, unmated females of P. operculella did not respond to tuber volatiles. Adults of O. insidiosus were attracted to volatiles from tubers damaged by P. operculella larvae, but did not respond to intact or mechanically damaged tubers. Methyl jasmonate (MeJA) was the only compound identified from the headspace of potato tubers (GC-MS of direct headspace sampling). The amount varied with the type of induction, being 0.001 +/- 0.0003 ng g(-1) in tissues of intact fresh tubers, 0.002 +/- 0.0007 ng g(-1) in mechanically damaged tubers, and showing a six- to tenfold increase in P. operculella damaged tubers (0.090 +/- 0.006 ng g(-1)). Behavioral bioassays with synthetic MeJA confirmed that the response of the insects is dependent on MeJA concentration. Mated females of P. operculella showed the highest response at 0.001 ng g(-1) (concentration released by intact tubers), whereas O. insidiosus showed the highest response, between 0.01 and 0.05 ng g(-1), which is close to the concentration released by P. operculella damaged tubers. Based on these results, we postulate that P. operculella and O. insidiosus have adapted their responses to plant volatiles differently, enabling them to locate suitable hosts or prey.

A 3D intestinal tissue model supports Clostridioides difficile germination, colonization, toxin production and epithelial damage.

PubMed

Shaban, Lamyaa; Chen, Ying; Fasciano, Alyssa C; Lin, Yinan; Kaplan, David L; Kumamoto, Carol A; Mecsas, Joan

2018-04-01

Endospore-forming Clostridioides difficile is a causative agent of antibiotic-induced diarrhea, a major nosocomial infection. Studies of its interactions with mammalian tissues have been hampered by the fact that C. difficile requires anaerobic conditions to survive after spore germination. We recently developed a bioengineered 3D human intestinal tissue model and found that low O 2 conditions are produced in the lumen of these tissues. Here, we compared the ability of C. difficile spores to germinate, produce toxin and cause tissue damage in our bioengineered 3D tissue model versus in a 2D transwell model in which human cells form a polarized monolayer. 3D tissue models or 2D polarized monolayers on transwell filters were challenged with the non-toxin producing C. difficile CCUG 37787 serotype X (ATCC 43603) and the toxin producing UK1 C. difficile spores in the presence of the germinant, taurocholate. Spores germinated in both the 3D tissue model as well as the 2D transwell system, however toxin activity was significantly higher in the 3D tissue models compared to the 2D transwells. Moreover, the epithelium damage in the 3D tissue model was significantly more severe than in 2D transwells and damage correlated significantly with the level of toxin activity detected but not with the amount of germinated spores. Combined, these results show that the bioengineered 3D tissue model provides a powerful system with which to study early events leading to toxin production and tissue damage of C. difficile with mammalian cells under anaerobic conditions. Furthermore, these systems may be useful for examining the effects of microbiota, novel drugs and other potential therapeutics directed towards C. difficile infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

A polarization sensitive hyperspectral imaging system for detection of differences in tissue properties

NASA Astrophysics Data System (ADS)

Peller, Joseph A.; Ceja, Nancy K.; Wawak, Amanda J.; Trammell, Susan R.

2018-02-01

Polarized light imaging and optical spectroscopy can be used to distinguish between healthy and diseased tissue. In this study, the design and testing of a single-pixel hyperspectral imaging system that uses differences in the polarization of light reflected from tissue to differentiate between healthy and thermally damaged tissue is discussed. Thermal lesions were created in porcine skin (n = 8) samples using an IR laser. The damaged regions were clearly visible in the polarized light hyperspectral images. Reflectance hyperspectral and white light imaging was also obtained for all tissue samples. Sizes of the thermally damaged regions as measured via polarized light hyperspectral imaging are compared to sizes of these regions as measured in the reflectance hyperspectral images and white light images. Good agreement between the sizes measured by all three imaging modalities was found. Hyperspectral polarized light imaging can differentiate between healthy and damaged tissue. Possible applications of this imaging system include determination of tumor margins during cancer surgery or pre-surgical biopsy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haque, Rizwanul; Umstead, Todd M.; Ponnuru, Padmavathi

Millions are exposed to ozone levels above recommended limits, impairing lung function, causing epithelial damage and inflammation, and predisposing some individuals to pneumonia, asthma, and other lung conditions. Surfactant protein-A (SP-A) plays a role in host defense, the regulation of inflammation, and repair of tissue damage. We tested the hypothesis that the lungs of SP-A(-/-) (KO) mice are more susceptible to ozone-induced damage. We compared the effects of ozone on KO and wild type (WT) mice on the C57BL/6 genetic background by exposing them to 2 parts/million of ozone for 3 or 6 h and sacrificing them 0, 4, andmore » 24 h later. Lungs were subject to bronchoalveolar lavage (BAL) or used to measure endpoints of oxidative stress and inflammation. Despite more total protein in BAL of KO mice after a 3 h ozone exposure, WT mice had increased oxidation of protein and had oxidized SP-A dimers. In KO mice there was epithelial damage as assessed by increased LDH activity and there was increased phospholipid content. In WT mice there were more BAL PMNs and elevated macrophage inflammatory protein (MIP)-2 and monocyte chemoattractant protein (MCP)-1. Changes in MIP-2 and MCP-1 were observed in both KO and WT, however mRNA levels differed. In KO mice MIP-2 mRNA levels changed little with ozone, but in WT levels they were significantly increased. In summary, several aspects of the inflammatory response differ between WT and KO mice. These in vivo findings appear to implicate SP-A in regulating inflammation and limiting epithelial damage in response to ozone exposure.« less

Regulations and guidelines governing stem cell based products: Clinical considerations

PubMed Central

George, Bobby

2011-01-01

The use of stem cells as medicines is a promising and upcoming area of research as they may be able to help the body to regenerate damaged or lost tissue in a host of diseases like Parkinson′s, multiple sclerosis, heart disease, liver disease, spinal cord damage, cancer and many more. Translating basic stem cell research into routine therapies is a complex multi-step process which entails the challenge related to managing the expected therapeutic benefits with the potential risks while complying with the existing regulations and guidelines. While in the United States (US) and European Union (EU) regulations are in place, in India, we do not have a well-defined regulatory framework for “stem cell based products (SCBP)”. There are several areas that need to be addressed as it is quite different from that of pharmaceuticals. These range from establishing batch consistency, product stability to product safety and efficacy through pre-clinical, clinical studies and marketing authorization. This review summarizes the existing regulations/guidelines in US, EU, India, and the associated challenges in developing SCBP with emphasis on clinical aspects. PMID:21897884

Transmission of Helminths between Species of Ruminants in Austria Appears More Likely to Occur than Generally Assumed

PubMed Central

Winter, Jakob; Rehbein, Steffen; Joachim, Anja

2018-01-01

Helminth infections of the gastrointestinal tract and lungs can lead to devastating economical losses to the pastoral based animal production. Farm animals can suffer from malnutrition, tissue damage, and blood loss resulting in impaired production traits and reproduction parameters. In Austria, pastures grazed by sheep, goats, and cattle overlap with the habitats of several species of wild cervids (roe deer, red deer, sika deer, and fallow deer) and bovids (mouflon, chamois, and ibex), and transmission of parasites between different ruminant species seems likely. A complete and updated overview on the occurrence of helminths of domestic and wild ruminants in Austria is presented. Based on these data, intersections of the host spectrum of the determined parasites were depicted. The “liability index” was applied to identify the ruminant species, which most likely transmit parasites between each other. A degree for host specificity was calculated for each parasite species based on the average taxonomic distance of their host species. Of the 73 identified helminth species 42 were identified as generalists, and 14 transmission experiments supported the assumed broad host specificity for 14 generalists and 1 specialist helminth species. Overall, 61 helminths were found to infect more than one host species, and 4 were found in all 10 ruminant species investigated. From these analyses, it can be concluded that a number of helminth parasites of the gastrointestinal tract and the lungs are potentially transmitted between domestic and wild ruminants in Austria. For some parasites and host species, experimental evidence is in support for possible transmission, while for other such studies are lacking. Host preference of different genotypes of the same parasite species may have a confounding effect on the evaluation of cross-transmission, but so far this has not been evaluated systematically in helminths in Austria. Further studies focusing on experimental cross-transmission and genetic characterization are needed to define the potential consequences for the epidemiology of those parasites, animal welfare, and economic impact. PMID:29662884

A tissue phantom for visualization and measurement of ultrasound-induced cavitation damage.

PubMed

Maxwell, Adam D; Wang, Tzu-Yin; Yuan, Lingqian; Duryea, Alexander P; Xu, Zhen; Cain, Charles A

2010-12-01

Many ultrasound studies involve the use of tissue-mimicking materials to research phenomena in vitro and predict in vivo bioeffects. We have developed a tissue phantom to study cavitation-induced damage to tissue. The phantom consists of red blood cells suspended in an agarose hydrogel. The acoustic and mechanical properties of the gel phantom were found to be similar to soft tissue properties. The phantom's response to cavitation was evaluated using histotripsy. Histotripsy causes breakdown of tissue structures by the generation of controlled cavitation using short, focused, high-intensity ultrasound pulses. Histotripsy lesions were generated in the phantom and kidney tissue using a spherically focused 1-MHz transducer generating 15 cycle pulses, at a pulse repetition frequency of 100 Hz with a peak negative pressure of 14 MPa. Damage appeared clearly as increased optical transparency of the phantom due to rupture of individual red blood cells. The morphology of lesions generated in the phantom was very similar to that generated in kidney tissue at both macroscopic and cellular levels. Additionally, lesions in the phantom could be visualized as hypoechoic regions on a B-mode ultrasound image, similar to histotripsy lesions in tissue. High-speed imaging of the optically transparent phantom was used to show that damage coincides with the presence of cavitation. These results indicate that the phantom can accurately mimic the response of soft tissue to cavitation and provide a useful tool for studying damage induced by acoustic cavitation. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Glycerophospholipid Profiles of Bats with White-Nose Syndrome.

PubMed

Pannkuk, Evan L; McGuire, Liam P; Warnecke, Lisa; Turner, James M; Willis, Craig K R; Risch, Thomas S

2015-01-01

Pseudogymnoascus destructans is an ascomycetous fungus responsible for the disease dubbed white-nose syndrome (WNS) and massive mortalities of cave-dwelling bats. The fungus infects bat epidermal tissue, causing damage to integumentary cells and pilosebaceous units. Differences in epidermal lipid composition caused by P. destructans infection could have drastic consequences for a variety of physiological functions, including innate immune efficiency and water retention. While bat surface lipid and stratum corneum lipid composition have been described, the differences in epidermal lipid content between healthy tissue and P. destructans-infected tissue have not been documented. In this study, we analyzed the effect of wing damage from P. destructans infection on the epidermal polar lipid composition (glycerophospholipids [GPs] and sphingomyelin) of little brown bats (Myotis lucifugus). We hypothesized that infection would lead to lower levels of total lipid or higher oxidized lipid product proportions. Polar lipids from three damaged and three healthy wing samples were profiled by electrospray ionization tandem mass spectrometry. We found lower total broad lipid levels in damaged tissue, specifically ether-linked phospholipids, lysophospholipids, phosphatidylcholine, and phosphatidylethanolamine. Thirteen individual GP species from four broad GP classes were present in higher amounts in healthy tissue. Six unsaturated GP species were absent in damaged tissue. Our results confirm that P. destructans infection leads to altered lipid profiles. Clinical signs of WNS may include lower lipid levels and lower proportions of unsaturated lipids due to cellular and glandular damage.

Ranking Quantitative Resistance to Septoria tritici Blotch in Elite Wheat Cultivars Using Automated Image Analysis.

PubMed

Karisto, Petteri; Hund, Andreas; Yu, Kang; Anderegg, Jonas; Walter, Achim; Mascher, Fabio; McDonald, Bruce A; Mikaberidze, Alexey

2018-05-01

Quantitative resistance is likely to be more durable than major gene resistance for controlling Septoria tritici blotch (STB) on wheat. Earlier studies hypothesized that resistance affecting the degree of host damage, as measured by the percentage of leaf area covered by STB lesions, is distinct from resistance that affects pathogen reproduction, as measured by the density of pycnidia produced within lesions. We tested this hypothesis using a collection of 335 elite European winter wheat cultivars that was naturally infected by a diverse population of Zymoseptoria tritici in a replicated field experiment. We used automated image analysis of 21,420 scanned wheat leaves to obtain quantitative measures of conditional STB intensity that were precise, objective, and reproducible. These measures allowed us to explicitly separate resistance affecting host damage from resistance affecting pathogen reproduction, enabling us to confirm that these resistance traits are largely independent. The cultivar rankings based on host damage were different from the rankings based on pathogen reproduction, indicating that the two forms of resistance should be considered separately in breeding programs aiming to increase STB resistance. We hypothesize that these different forms of resistance are under separate genetic control, enabling them to be recombined to form new cultivars that are highly resistant to STB. We found a significant correlation between rankings based on automated image analysis and rankings based on traditional visual scoring, suggesting that image analysis can complement conventional measurements of STB resistance, based largely on host damage, while enabling a much more precise measure of pathogen reproduction. We showed that measures of pathogen reproduction early in the growing season were the best predictors of host damage late in the growing season, illustrating the importance of breeding for resistance that reduces pathogen reproduction in order to minimize yield losses caused by STB. These data can already be used by breeding programs to choose wheat cultivars that are broadly resistant to naturally diverse Z. tritici populations according to the different classes of resistance.

Thermal damage control of dye-assisted laser tissue welding: effect of dye concentration

NASA Astrophysics Data System (ADS)

Xie, Hua; Buckley, Lisa A.; Prahl, Scott A.; Shaffer, Brian S.; Gregory, Kenton W.

2001-05-01

Successful laser-assisted tissue welding was implemented to provide proper weld strength with minimized tissue thermal injury. We investigated and compared the weld strengths and morphologic changes in porcine small intestinal submucose (SIS) and porcine ureteral tissues with various concentration of indocyanine green (ICG) and with a solid albumin sheet. The study showed that the tissues were welded at lower ICG concentration (0.05 mM) with minimized tissue thermal damage using an 800-nm wavelength diode laser.

Herbivores and pathogens on Alnus viridis subsp. fruticosa in interior Alaska: effects of leaf, tree, and neighbour characteristics on damage levels

Treesearch

Christa P.H. Mulder; Bitty A. Roy; Sabine Gusewell

2008-01-01

Parasite damage strongly affects dynamics of boreal forests. Damage levels may be affected by climate change, either directly or indirectly through changes in properties of host trees. We examined how herbivore and pathogen damage in Alnus viridis subsp. fruticosa (Rupr.) Nym. depend on leaf morphology and chemistry, tree size...

Application of immunohistochemical staining to detect antigen destruction as a measure of tissue damage.

PubMed

Onul, Abdullah; Colvard, Michael D; Paradise, William A; Elseth, Kim M; Vesper, Benjamin J; Gouvas, Eftychia; Deliu, Zane; Garcia, Kelly D; Pestle, William J; Radosevich, James A

2012-09-01

Electrocautery and directed energy devices (DEDs) such as lasers, which are used in surgery, result in tissue damage that cannot be readily detected by traditional histological methods, such as hematoxylin and eosin staining. Alternative staining methods, including 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to stain live tissue, have been reported. Despite providing superior detection of damaged tissue relative to the hematoxylin and eosin (H&E) method, the MTT method possesses a number of drawbacks, most notably that it must be carried out on live tissue samples. Herein, we report the development of a novel staining method, "antigen destruction immunohistochemistry" (ADI), which can be carried out on paraffin-embedded tissue. The ADI method takes advantage of epitope loss to define the area of tissue damage and provides many of the benefits of live tissue MTT staining without the drawbacks inherent to that method. In addition, the authors provide data to support the use of antibodies directed at a number of gene products for use in animal tissue for which there are no species-specific antibodies commercially available, as well as an example of a species-specific direct antibody. Data are provided that support the use of this method in many tissue models, as well as evidence that ADI is comparable to the live tissue MTT method.

Application of Immunohistochemical Staining to Detect Antigen Destruction as a Measure of Tissue Damage

PubMed Central

Onul, Abdullah; Colvard, Michael D.; Paradise, William A.; Elseth, Kim M.; Vesper, Benjamin J.; Gouvas, Eftychia; Deliu, Zane; Garcia, Kelly D.; Pestle, William J.

2012-01-01

Electrocautery and directed energy devices (DEDs) such as lasers, which are used in surgery, result in tissue damage that cannot be readily detected by traditional histological methods, such as hematoxylin and eosin staining. Alternative staining methods, including 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to stain live tissue, have been reported. Despite providing superior detection of damaged tissue relative to the hematoxylin and eosin (H&E) method, the MTT method possesses a number of drawbacks, most notably that it must be carried out on live tissue samples. Herein, we report the development of a novel staining method, “antigen destruction immunohistochemistry” (ADI), which can be carried out on paraffin-embedded tissue. The ADI method takes advantage of epitope loss to define the area of tissue damage and provides many of the benefits of live tissue MTT staining without the drawbacks inherent to that method. In addition, the authors provide data to support the use of antibodies directed at a number of gene products for use in animal tissue for which there are no species-specific antibodies commercially available, as well as an example of a species-specific direct antibody. Data are provided that support the use of this method in many tissue models, as well as evidence that ADI is comparable to the live tissue MTT method. PMID:22723525

Analysis of plastic deformation in cortical bone after insertion of coated and non-coated self-tapping orthopaedic screws.

PubMed

Koistinen, A P; Korhonen, H; Kiviranta, I; Kröger, H; Lappalainen, R

2011-07-01

Insertion of internal fracture fixation devices, such as screws, mechanically weakens the bone. Diamond-like carbon has outstanding tribology properties which may decrease the amount of damage in tissue. The purpose of this study was to investigate methods for quantification of cortical bone damage after orthopaedic bone screw insertion and to evaluate the effect of surface modification on tissue damage. In total, 48 stainless steel screws were inserted into cadaver bones. Half of the screws were coated with a smooth amorphous diamond coating. Geometrical data of the bones was determined by peripheral quantitative computed tomography. Thin sections of the bone samples were prepared after screw insertion, and histomorphometric evaluation of damage was performed on images obtained using light microscopy. Micro-computed tomography and scanning electron microscopy were also used to examine tissue damage. A positive correlation was found between tissue damage and the geometric properties of the bone. The age of the cadaver significantly affected the bone mineral density, as well as the damage perimeter and diameter of the screw hole. However, the expected positive effect of surface modification was probably obscured by large variations in the results and, thus, statistically significant differences were not found in this study. This can be explained by natural variability in bone tissue, which also made automated image analysis difficult.

Arterial embolism

MedlinePlus

... This can result in damage or tissue death ( necrosis ). Arterial emboli often occur in the legs and ... sloughing) of skin Skin erosion ( ulcer ) Tissue death (necrosis; skin is dark and damaged) Symptoms of a ...

Dual RNA-Sequencing of Eucalyptus nitens during Phytophthora cinnamomi Challenge Reveals Pathogen and Host Factors Influencing Compatibility

PubMed Central

Meyer, Febé E.; Shuey, Louise S.; Naidoo, Sitha; Mamni, Thandekile; Berger, Dave K.; Myburg, Alexander A.; van den Berg, Noëlani; Naidoo, Sanushka

2016-01-01

Damage caused by Phytophthora cinnamomi Rands remains an important concern on forest tree species. The pathogen causes root and collar rot, stem cankers, and dieback of various economically important Eucalyptus spp. In South Africa, susceptible cold tolerant Eucalyptus plantations have been affected by various Phytophthora spp. with P. cinnamomi considered one of the most virulent. The molecular basis of this compatible interaction is poorly understood. In this study, susceptible Eucalyptus nitens plants were stem inoculated with P. cinnamomi and tissue was harvested five days post inoculation. Dual RNA-sequencing, a technique which allows the concurrent detection of both pathogen and host transcripts during infection, was performed. Approximately 1% of the reads mapped to the draft genome of P. cinnamomi while 78% of the reads mapped to the Eucalyptus grandis genome. The highest expressed P. cinnamomi gene in planta was a putative crinkler effector (CRN1). Phylogenetic analysis indicated the high similarity of this P. cinnamomi CRN1 to that of Phytophthora infestans. Some CRN effectors are known to target host nuclei to suppress defense. In the host, over 1400 genes were significantly differentially expressed in comparison to mock inoculated trees, including suites of pathogenesis related (PR) genes. In particular, a PR-9 peroxidase gene with a high similarity to a Carica papaya PR-9 ortholog previously shown to be suppressed upon infection by Phytophthora palmivora was down-regulated two-fold. This PR-9 gene may represent a cross-species effector target during P. cinnamomi infection. This study identified pathogenicity factors, potential manipulation targets, and attempted host defense mechanisms activated by E. nitens that contributed to the susceptible outcome of the interaction. PMID:26973660

Foxp3+ regulatory T cells, immune stimulation and host defence against infection

PubMed Central

Rowe, Jared H; Ertelt, James M; Way, Sing Sing

2012-01-01

The immune system is intricately regulated allowing potent effectors to expand and become rapidly mobilized after infection, while simultaneously silencing potentially detrimental responses that averts immune-mediated damage to host tissues. This relies in large part on the delicate interplay between immune suppressive regulatory CD4+ T (Treg) cells and immune effectors that without active suppression by Treg cells cause systemic and organ-specific autoimmunity. Although these beneficial roles have been classically described as counterbalanced by impaired host defence against infection, newfound protective roles for Treg cells against specific viral pathogens (e.g. herpes simplex virus 2, lymphocytic choriomeningitis virus, West Nile virus) have been uncovered using transgenic mice that allow in vivo Treg-cell ablation based on Foxp3 expression. In turn, Foxp3+ Treg cells also provide protection against some parasitic (Plasmodium sp., Toxoplasma gondii) and fungal (Candida albicans) pathogens. By contrast, for bacterial and mycobacterial infections (e.g. Listeria monocytogenes, Salmonella enterica, Mycobacterium tuberculosis), experimental manipulation of Foxp3+ cells continues to indicate detrimental roles for Treg cells in host defence. This variance is probably related to functional plasticity in Treg cell suppression that shifts discordantly following infection with different types of pathogens. Furthermore, the efficiency whereby Treg cells silence immune activation coupled with the plasticity in Foxp3+ cell activity suggest that overriding Treg-mediated suppression represents a prerequisite ‘signal zero’ that together with other stimulation signals [T-cell receptor (signal 1), co-stimulation (signal 2), inflammatory cytokines (signal 3)] are essential for T-cell activation in vivo. Herein, the importance of Foxp3+ Treg cells in host defence against infection, and the significance of infection-induced shifts in Treg-cell suppression are summarized. PMID:22211994

Host pathogen interactions in Helicobacter pylori related gastric cancer

PubMed Central

Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

2017-01-01

Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154

Host pathogen interactions in Helicobacter pylori related gastric cancer.

PubMed

Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

2017-03-07

Helicobacter pylori ( H. pylori ), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori -related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori -driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor.

Global Reprogramming of Host SUMOylation during Influenza Virus Infection

PubMed Central

Domingues, Patricia; Golebiowski, Filip; Tatham, Michael H.; Lopes, Antonio M.; Taggart, Aislynn; Hay, Ronald T.; Hale, Benjamin G.

2015-01-01

Summary Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here, we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome remodeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection. PMID:26549460

Histopathological changes caused by the metacestodes of Neogryporhynchus cheilancristrotus (Wedl, 1855) in the gut of the gibel carp, Carassius gibelio.

PubMed

Molnár, K

2005-01-01

Metacestodes of Neogryporhynchus cheilancristrotus (Wedl, 1855) were found in the gut of some gibel carp (Carassius gibelio) specimens from a Hungarian water reservoir. Location of metacestodes in the freshly opened gut was marked with disseminated, red-coloured, pinhead-sized nodules in the anterior part of the intestine. In histological sections, metacestodes were found in a hole inside the propria layer of the intestinal folds. The worms were in direct contact with the host tissue without being encapsulated as a result of host reaction. In some specimens with extruded rostellum the rostellar hooks were bored into the host tissue and suckers grabbed pieces of the surrounding connective tissue. Around the worms, congested capillaries and formation of macrophages were seen in the lysed connective tissue.

Histopathology of a mesoparasitic hatschekiid copepod in hospite: does Mihbaicola sakamakii (Copepoda: Siphonostomatoida: Hatschekiidae) fast within the host fish tissue?

PubMed

Hirose, Euichi; Uyeno, Daisuke

2014-08-01

Mihbaicola sakamakii is a mesoparasitic copepod that infests the branchiostegal membranes of groupers (Perciformes: Serranidae). In this study, we observed M. sakamakii within host tissue. Histologically, copepods were found enclosed inside a pouch composed of the thickened epidermis of the host, tightly encased on all sides by the host epidermal pouch wall. There were no host blood cells or other food resources in the pouch lumen. Since the host epidermis was intact and continuous, even in the vicinity of the oral region of the parasite, the copepod would not have access to the host blood in this state. However, the stomach (ampullary part of the mid gut) was filled with granular components, the majority of which were crystalloids that likely originated from fish erythrocyte hemoglobin. We supposed that the parasite drinks blood exuded from the lesion in the fish caused by copepod entry into the host tissue. Invasion of the parasite may elicit immune responses in the host, but there were no traces on the copepod of any cellular immune reactions, such as encapsulation. The array of minute protuberances on the copepod cuticle surface may be involved in avoidance of cell adhesion. After the lesion has healed, the copepod is enclosed in a tough epidermal pouch, in which it gradually digests the contents of its stomach and continues egg production.

Cytonuclear Epistasis Controls the Density of Symbiont Wolbachia pipientis in Nongonadal Tissues of Mosquito Culex quinquefasciatus.

PubMed

Emerson, Kevin J; Glaser, Robert L

2017-08-07

Wolbachia pipientis , a bacterial symbiont infecting arthropods and nematodes, is vertically transmitted through the female germline and manipulates its host's reproduction to favor infected females. Wolbachia also infects somatic tissues where it can cause nonreproductive phenotypes in its host, including resistance to viral pathogens. Wolbachia -mediated phenotypes are strongly associated with the density of Wolbachia in host tissues. Little is known, however, about how Wolbachia density is regulated in native or heterologous hosts. Here, we measure the broad-sense heritability of Wolbachia density among families in field populations of the mosquito Culex pipiens , and show that densities in ovary and nongonadal tissues of females in the same family are not correlated, suggesting that Wolbachia density is determined by distinct mechanisms in the two tissues. Using introgression analysis between two different strains of the closely related species C. quinquefasciatus , we show that Wolbachia densities in ovary tissues are determined primarily by cytoplasmic genotype, while densities in nongonadal tissues are determined by both cytoplasmic and nuclear genotypes and their epistatic interactions. Quantitative-trait-locus mapping identified two major-effect quantitative-trait loci in the C. quinquefasciatus genome explaining a combined 23% of variance in Wolbachia density, specifically in nongonadal tissues. A better understanding of how Wolbachia density is regulated will provide insights into how Wolbachia density can vary spatiotemporally in insect populations, leading to changes in Wolbachia -mediated phenotypes such as viral pathogen resistance. Copyright © 2017 Emerson, Glaser.

Tumor proliferation and diffusion on percolation clusters.

PubMed

Jiang, Chongming; Cui, Chunyan; Zhong, Weirong; Li, Gang; Li, Li; Shao, Yuanzhi

2016-10-01

We study in silico the influence of host tissue inhomogeneity on tumor cell proliferation and diffusion by simulating the mobility of a tumor on percolation clusters with different homogeneities of surrounding tissues. The proliferation and diffusion of a tumor in an inhomogeneous tissue could be characterized in the framework of the percolation theory, which displays similar thresholds (0.54, 0.44, and 0.37, respectively) for tumor proliferation and diffusion in three kinds of lattices with 4, 6, and 8 connecting near neighbors. Our study reveals the existence of a critical transition concerning the survival and diffusion of tumor cells with leaping metastatic diffusion movement in the host tissues. Tumor cells usually flow in the direction of greater pressure variation during their diffusing and infiltrating to a further location in the host tissue. Some specific sites suitable for tumor invasion were observed on the percolation cluster and around these specific sites a tumor can develop into scattered tumors linked by some advantage tunnels that facilitate tumor invasion. We also investigate the manner that tissue inhomogeneity surrounding a tumor may influence the velocity of tumor diffusion and invasion. Our simulation suggested that invasion of a tumor is controlled by the homogeneity of the tumor microenvironment, which is basically consistent with the experimental report by Riching et al. as well as our clinical observation of medical imaging. Both simulation and clinical observation proved that tumor diffusion and invasion into the surrounding host tissue is positively correlated with the homogeneity of the tissue.

A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue

NASA Astrophysics Data System (ADS)

Yang, Seung Yun; O'Cearbhaill, Eoin D.; Sisk, Geoffroy C.; Park, Kyeng Min; Cho, Woo Kyung; Villiger, Martin; Bouma, Brett E.; Pomahac, Bohdan; Karp, Jeffrey M.

2013-04-01

Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here inspired by the endoparasite Pomphorhynchus laevis, which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~3.5-fold increase in adhesion strength compared with staples in skin graft fixation, and removal force of ~4.5 N cm-2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics.

A Bio-Inspired Swellable Microneedle Adhesive for Mechanical Interlocking with Tissue

PubMed Central

Yang, Seung Yun; O'Cearbhaill, Eoin D.; Sisk, Geoffroy C.; Park, Kyeng Min; Cho, Woo Kyung; Villiger, Martin; Bouma, Brett E.; Pomahac, Bohdan; Karp, Jeffrey M.

2013-01-01

Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here, inspired by the endoparasite Pomphorhynchus laevis which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~ 3.5 fold increase in adhesion strength compared to staples in skin graft fixation, and removal force of ~ 4.5 N/cm2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics. PMID:23591869

Toll-like receptors in the pathogenesis of chemotherapy-induced gastrointestinal toxicity.

PubMed

Cario, Elke

2016-06-01

Intestinal mucositis represents a common complication and dose-limiting toxicity of cancer chemotherapy. So far chemotherapy-induced intestinal mucositis remains poorly treatable resulting in significant morbidity and reduced quality of life in cancer patients. This review discusses recent insights into the pathophysiology of chemotherapy-induced intestinal mucositis. Novel mechanisms linking gut microbiota, host innate immunity and anticancer drug metabolism are highlighted. Gut microbiota may affect xenobiotic metabolism by direct and indirect mechanisms, critically modulating gut toxicity of chemotherapy drugs. Composition and metabolic function of the gut microbiome as well as innate immune responses of the intestinal mucosa are severely altered during chemotherapy. Commensal-mediated innate immune signaling via Toll-like receptors (TLRs) ambiguously shapes chemotherapy-induced genotoxic damage in the gastrointestinal tract. TLR2 may accelerate host detoxification by activating the multidrug transporter ATP-binding cassette 1 (ABCB1)/MDR1 P-glycoprotein to efflux harmful drugs, thus controlling the severity of cancer therapy-induced mucosal damage in the gastrointestinal tract. In contrast, selective chemotherapy drugs may drive LPS hyperresponsiveness via TLR4, which exacerbates mucosal injury through aberrant cytokine storms. Broad-spectrum antibiotic treatment does not seem to represent a valid therapeutic option, as drastic reduction in global gut microbiota may enhance risk of gastrointestinal toxicity and reduce efficacy of some chemotherapy drugs, at least in murine models. Several variables (environment, metabolism, dysbiosis, infections and/or genetics) influence the outcome of mucosal TLR signaling during cancer treatment. Differences in innate immune responses also reflect chemotherapy drug-specific effects. Future studies must investigate in more detail whether manipulating the delicate balance between gut microbiota and host immune responses by either monotherapy or combinations of different TLR agonists and antagonists may be indeed useful to limit the toxic side-effects of complex chemotherapy regimens, accelerate mucosal tissue regeneration and improve the anticancer treatment response.

Enhanced expressions of neurodegeneration-associated factors, UPS impairment, and excess Aβ accumulation in the hippocampus of mice with persistent cerebral toxocariasis.

PubMed

Chou, Chia-Mei; Lee, Yueh-Lun; Liao, Chien-Wei; Huang, Ying-Chieh; Fan, Chia-Kwung

2017-12-22

Toxocariasis is a worldwide zoonotic parasitic disease mainly caused by Toxocara canis. Humans can be infected by accidental ingestion of T. canis embryonated ovum-contaminated food, water, or encapsulated larvae in paratenic hosts' viscera or meat. Since humans and mice are paratenic hosts of T. canis, the wandering larvae might cause mechanical tissue damage and excretory-secretory antigens may trigger inflammatory injuries to local organs. Long-term residence of T. canis larvae in a paratenic host's brain may cause cerebral toxocariasis (CT) that contributes to cerebral damage, neuroinflammation and neuropsychiatric disorders in mice and clinical patients. Since the hippocampus has been long recognized as being responsible for learning and memory functions, parasitic invasion of this site may cause neuroinflammatory and neurodegenerative disorders. The present study intended to assess pathological changes, expressions of neurodegeneration-associated factors (NDAFs), including transforming growth factor (TGF)-β1, S100B, glial fibrillary acidic protein (GFAP), transglutaminase type 2 (TG2), claudin-5, substance P (SP) and interleukin (IL)-1β, and the ubiquitin-proteasome system (UPS) function in the hippocampus and associated cognitive behavior in ICR mice orally inoculated with a high, medium or low-dose of T. canis embryonated ova during a 20-week investigation. Results indicated although there were insignificant differences in learning and memory function between the experimental mice and uninfected control mice, possibly because the site where T. canis larvae invaded was the surrounding area but not the hippocampus per se. Nevertheless, enhanced expressions of NDAF, persistent UPS impairment and excess amyloid β (Aβ) accumulation concomitantly emerged in the experimental mice hippocampus at 8, 16 and 20 weeks post-infection. We thus postulate that progressive CT may still progress to neurodegeneration due to enhanced NDAF expressions, persistent UPS impairment and excess Aβ accumulation in the hippocampus.

RIG-I-like receptor regulation in virus infection and immunity

PubMed Central

Chan, Ying Kai; Gack, Michaela U

2016-01-01

Mammalian cells have the intrinsic capacity to detect viral pathogens and to initiate an antiviral response that is characterized by the induction of interferons (IFNs) and proinflammatory cytokines. A delicate regulation of the signaling pathways that lead to cytokine production is needed to ensure effective clearance of the virus, while preventing tissue damage caused by excessive cytokine release. Here, we focus on the mechanisms that modulate the signal transduction triggered by RIG-I-like receptors (RLRs) and their adaptor protein MAVS, key components of the host machinery for sensing foreign RNA. Specifically, we summarize recent advances in understanding how RLR signaling is regulated by posttranslational and posttranscriptional mechanisms, microRNAs (miRNAs) and autophagy. We further discuss how viruses target these regulatory mechanisms for immune evasion. PMID:25644461

Pathogenesis of African swine fever in domestic pigs and European wild boar.

PubMed

Blome, Sandra; Gabriel, Claudia; Beer, Martin

2013-04-01

African swine fever (ASF) is among the most important viral diseases that can affect domestic and feral pigs. Both clinical signs and pathomorphological changes vary considerably depending on strain virulence and host factors. Acute infections with highly virulent virus strains lead to a clinical course that resembles a viral haemorrhagic fever that is characterized by pronounced depletion of lymphoid tissues, apoptosis of lymphocyte subsets, and impairment of haemostasis and immune functions. It is generally accepted that most lesions can be attributed to cytokine-mediated interactions triggered by infected and activated monocytes and macrophages, rather than by virus-induced direct cell damage. Nevertheless, most pathogenetic mechanisms are far from being understood. This review summarizes the current knowledge and discusses implications and research gaps. Copyright © 2012 Elsevier B.V. All rights reserved.

Dissecting the Molecular Mechanism of Ionizing Radiation-Induced Tissue Damage in the Feather Follicle

PubMed Central

Chen, Xi; Liao, Chunyan; Chu, Qiqi; Zhou, Guixuan; Lin, Xiang; Li, Xiaobo; Lu, Haijie; Xu, Benhua; Yue, Zhicao

2014-01-01

Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It damages normal tissue and causes side effects including dermatitis and mucositis. Here we use the feather follicle as a model to investigate the mechanism of IR-induced tissue damage, because any perturbation of feather growth will be clearly recorded in its regular yet complex morphology. We find that IR induces defects in feather formation in a dose-dependent manner. No abnormality was observed at 5 Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy, leading to defects in the feather structure. This perturbation became irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation, DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR also induces patterning defects in feather formation, with disrupted branching morphogenesis. This perturbation is mediated by cytokine production and Stat1 activation, as manipulation of cytokine levels or ectopic Stat1 over-expression also led to irregular feather branching. Furthermore, AG-490, a chemical inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our results suggest that the feather follicle could serve as a useful model to address the in vivo impact of the many mechanisms of IR-induced tissue damage. PMID:24586618

Stromal regulation of vessel stability by MMP14 and TGFβ

PubMed Central

Sounni, Nor E.; Dehne, Kerstin; van Kempen, Leon; Egeblad, Mikala; Affara, Nesrine I.; Cuevas, Ileana; Wiesen, Jane; Junankar, Simon; Korets, Lidiya; Lee, Jake; Shen, Jennifer; Morrison, Charlotte J.; Overall, Christopher M.; Krane, Stephen M.; Werb, Zena; Boudreau, Nancy; Coussens, Lisa M.

2010-01-01

Innate regulatory networks within organs maintain tissue homeostasis and facilitate rapid responses to damage. We identified a novel pathway regulating vessel stability in tissues that involves matrix metalloproteinase 14 (MMP14) and transforming growth factor beta 1 (TGFβ1). Whereas plasma proteins rapidly extravasate out of vasculature in wild-type mice following acute damage, short-term treatment of mice in vivo with a broad-spectrum metalloproteinase inhibitor, neutralizing antibodies to TGFβ1, or an activin-like kinase 5 (ALK5) inhibitor significantly enhanced vessel leakage. By contrast, in a mouse model of age-related dermal fibrosis, where MMP14 activity and TGFβ bioavailability are chronically elevated, or in mice that ectopically express TGFβ in the epidermis, cutaneous vessels are resistant to acute leakage. Characteristic responses to tissue damage are reinstated if the fibrotic mice are pretreated with metalloproteinase inhibitors or TGFβ signaling antagonists. Neoplastic tissues, however, are in a constant state of tissue damage and exhibit altered hemodynamics owing to hyperleaky angiogenic vasculature. In two distinct transgenic mouse tumor models, inhibition of ALK5 further enhanced vascular leakage into the interstitium and facilitated increased delivery of high molecular weight compounds into premalignant tissue and tumors. Taken together, these data define a central pathway involving MMP14 and TGFβ that mediates vessel stability and vascular response to tissue injury. Antagonists of this pathway could be therapeutically exploited to improve the delivery of therapeutics or molecular contrast agents into tissues where chronic damage or neoplastic disease limits their efficient delivery. PMID:20223936

Does prolonged radiofrequency radiation emitted from Wi-Fi devices induce DNA damage in various tissues of rats?

PubMed

Akdag, Mehmet Zulkuf; Dasdag, Suleyman; Canturk, Fazile; Karabulut, Derya; Caner, Yusuf; Adalier, Nur

2016-09-01

Wireless internet (Wi-Fi) providers have become essential in our daily lives, as wireless technology is evolving at a dizzying pace. Although there are different frequency generators, one of the most commonly used Wi-Fi devices are 2.4GHz frequency generators. These devices are heavily used in all areas of life but the effect of radiofrequency (RF) radiation emission on users is generally ignored. Yet, an increasing share of the public expresses concern on this issue. Therefore, this study intends to respond to the growing public concern. The purpose of this study is to reveal whether long term exposure of 2.4GHz frequency RF radiation will cause DNA damage of different tissues such as brain, kidney, liver, and skin tissue and testicular tissues of rats. The study was conducted on 16 adult male Wistar-Albino rats. The rats in the experimental group (n=8) were exposed to 2.4GHz frequency radiation for over a year. The rats in the sham control group (n=8) were subjected to the same experimental conditions except the Wi-Fi generator was turned off. After the exposure period was complete the possible DNA damage on the rat's brain, liver, kidney, skin, and testicular tissues was detected through the single cell gel electrophoresis assay (comet) method. The amount of DNA damage was measured as percentage tail DNA value. Based on the DNA damage results determined by the single cell gel electrophoresis (Comet) method, it was found that the% tail DNA values of the brain, kidney, liver, and skin tissues of the rats in the experimental group increased more than those in the control group. The increase of the DNA damage in all tissues was not significant (p>0.05). However the increase of the DNA damage in rat testes tissue was significant (p<0.01). In conclusion, long-term exposure to 2.4GHz RF radiation (Wi-Fi) does not cause DNA damage of the organs investigated in this study except testes. The results of this study indicated that testes are more sensitive organ to RF radiation. Copyright © 2016 Elsevier B.V. All rights reserved.

Loading and conjugating cavity biostructures

DOEpatents

Hainfeld, J.F.

1997-11-25

Methods for the preparation and use of a biological delivery system are disclosed. The method of preparation includes the loading of a non-biological material into a biostructure having a load-bearing structure. The method also includes the removal of some of the biostructure`s contents and the loading of a non-biological material into the biostructure. The biostructure is biologically compatible with the host, and preferably is derived from the host, the host`s species or a related species. The loaded biostructure is used directly, or it can be targeted to specific cells, tissues and/or organs within a host. The targeted biostructure can be used to deliver the non-biological material to a specified tissue, organ or cell within a host for diagnostic, therapeutic or other purposes. 11 figs.

Loading and conjugating cavity biostructures

DOEpatents

Hainfeld, J.F.

1995-08-22

Methods for the preparation and use of a biological delivery system are disclosed. The method of preparation includes the loading of a non-biological material into a biostructure having a load-bearing structure. The method also includes the removal of some of the biostructure`s contents and the loading of a non-biological material into the biostructure. The biostructure is biologically compatible with the host, and preferably is derived from the host, the host`s species or a related species. The loaded biostructure is used directly, or it can be targeted to specific cells, tissues and/or organs within a host. The targeted biostructure can be used to deliver the non-biological material to a specified tissue, organ or cell within a host for diagnostic, therapeutic or other purposes. 11 figs.

Targeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis.

PubMed

Kamaly, Nazila; Fredman, Gabrielle; Fojas, Jhalique Jane R; Subramanian, Manikandan; Choi, Won Ii; Zepeda, Katherine; Vilos, Cristian; Yu, Mikyung; Gadde, Suresh; Wu, Jun; Milton, Jaclyn; Carvalho Leitao, Renata; Rosa Fernandes, Livia; Hasan, Moaraj; Gao, Huayi; Nguyen, Vance; Harris, Jordan; Tabas, Ira; Farokhzad, Omid C

2016-05-24

Inflammation is an essential protective biological response involving a coordinated cascade of signals between cytokines and immune signaling molecules that facilitate return to tissue homeostasis after acute injury or infection. However, inflammation is not effectively resolved in chronic inflammatory diseases such as atherosclerosis and can lead to tissue damage and exacerbation of the underlying condition. Therapeutics that dampen inflammation and enhance resolution are currently of considerable interest, in particular those that temper inflammation with minimal host collateral damage. Here we present the development and efficacy investigations of controlled-release polymeric nanoparticles incorporating the anti-inflammatory cytokine interleukin 10 (IL-10) for targeted delivery to atherosclerotic plaques. Nanoparticles were nanoengineered via self-assembly of biodegradable polyester polymers by nanoprecipitation using a rapid micromixer chip capable of producing nanoparticles with retained IL-10 bioactivity post-exposure to organic solvent. A systematic combinatorial approach was taken to screen nanoparticles, resulting in an optimal bioactive formulation from in vitro and ex vivo studies. The most potent nanoparticle termed Col-IV IL-10 NP22 significantly tempered acute inflammation in a self-limited peritonitis model and was shown to be more potent than native IL-10. Furthermore, the Col-IV IL-10 nanoparticles prevented vulnerable plaque formation by increasing fibrous cap thickness and decreasing necrotic cores in advanced lesions of high fat-fed LDLr(-/-) mice. These results demonstrate the efficacy and pro-resolving potential of this engineered nanoparticle for controlled delivery of the potent IL-10 cytokine for the treatment of atherosclerosis.

Transgenic tomato expressing interleukin-12 has a therapeutic effect in a murine model of progressive pulmonary tuberculosis

PubMed Central

Elías-López, A L; Marquina, B; Gutiérrez-Ortega, A; Aguilar, D; Gomez-Lim, M; Hernández-Pando, R

2008-01-01

Host control of mycobacterial infection, in both human and mouse models, has been shown to be associated with the production of interferon (IFN)-γ by CD4+ T cells. Interleukin (IL)-12 is known to be a crucial cytokine in the differentiation of IFN-γ-producing T helper 1 (Th1) cells. To determine whether continuous administration of IL-12 expressed in transgenic tomato (TT–IL-12) has therapeutic efficacy in a murine model of pulmonary tuberculosis, BALB/c mice were infected with either Mycobacterium tuberculosis H37Rv strain or a multi-drug-resistant clinical isolate (MDR) and treated with a daily oral dose of TT-IL12 crude fruit extracts. For the early H37Rv infection, TT–IL-12 administration was started 1 day before infection and continued for 60 days. In the H37Rv or MDR late infection, treatment was started 60 days after infection and continued for another 60 days. In both phases of infection, TT–IL-12 administration resulted in a reduction of bacterial loads and tissue damage compared with wild-type tomato (non-TT). The Th1 response was increased and the Th2 response was reduced. In the late infection, a long-term treatment with TT–IL-12 was necessary. We demonstrate that TT–IL-12 increases resistance to infection and reduces lung tissue damage during early and late drug-sensitive and drug-resistant mycobacterial infection. PMID:18727633

Sea lamprey (Petromyzon marinus) parasite-host interactions in the Great Lakes

USGS Publications Warehouse

Bence, James R.; Bergstedt, Roger A.; Christie, Gavin C.; Cochran, Phillip A.; Ebener, Mark P.; Koonce, Joseph F.; Rutter, Michael A.; Swink, William D.

2003-01-01

Prediction of how host mortality responds to efforts to control sea lampreys (Petromyzon marinus) is central to the integrated management strategy for sea lamprey (IMSL) in the Great Lakes. A parasite-host submodel is used as part of this strategy, and this includes a type-2 multi-species functional response, a developmental response, but no numerical response. General patterns of host species and size selection are consistent with the model assumptions, but some observations appear to diverge. For example, some patterns in sea lamprey marking on hosts suggest increases in selectivity for less preferred hosts and lower host survival when preferred hosts are scarce. Nevertheless, many of the IMSL assumptions may be adequate under conditions targeted by fish community objectives. Of great concern is the possibility that the survival of young parasites (parasitic-phase sea lampreys) varies substantially among lakes or over time. Joint analysis of abundance estimates for parasites being produced in streams and returning spawners could address this. Data on sea lamprey marks is a critical source of information on sea lamprey activity and potential effects. Theory connecting observed marks to sea lamprey feeding activity and host mortality is reviewed. Uncertainties regarding healing and attachment times, the probability of hosts surviving attacks, and problems in consistent classification of marks have led to widely divergent estimates of damages caused by sea lamprey. Laboratory and field studies are recommended to provide a firmer linkage between host blood loss, host mortality, and observed marks on surviving hosts, so as to improve estimates of damage.

The Circadian Clock in Cancer Development and Therapy

PubMed Central

Fu, Loning; Kettner, Nicole M.

2014-01-01

Most aspects of mammalian function display circadian rhythms driven by an endogenous clock. The circadian clock is operated by genes and comprises a central clock in the brain that responds to environmental cues and controls subordinate clocks in peripheral tissues via circadian output pathways. The central and peripheral clocks coordinately generate rhythmic gene expression in a tissue-specific manner in vivo to couple diverse physiological and behavioral processes to periodic changes in the environment. However, as the world industrialized, activities that disrupt endogenous homeostasis with external circadian cues have increased. This change in lifestyle has been linked to increased risk of diseases in all aspects of human health, including cancer. Studies in humans and animal models have revealed that cancer development in vivo is closely associated with the loss of circadian homeostasis in energy balance, immune function and aging that are supported by cellular functions important for tumor suppression including cell proliferation, senescence, metabolism and DNA damage response. The clock controls these cellular functions both locally in cells of peripheral tissues and at the organismal level via extracellular signaling. Thus, the hierarchical mammalian circadian clock provides a unique system to study carcinogenesis as a deregulated physiological process in vivo. The asynchrony between host and malignant tissues in cell proliferation and metabolism also provides new and exciting options for novel anti-cancer therapies. PMID:23899600

Repair of Osteochondral Defects Using Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells in a Rabbit Model

PubMed Central

Jia, Yanhui; Yuan, Mei; Guo, Weimin; Huang, Jingxiang; Zhao, Bin; Xu, Wenjing; Lu, Shibi

2017-01-01

Umbilical cord Wharton's jelly-derived mesenchymal stem cell (WJMSC) is a new-found mesenchymal stem cell in recent years with multiple lineage potential. Due to its abundant resources, no damage procurement, and lower immunogenicity than other adult MSCs, WJMSC promises to be a good xenogenous cell candidate for tissue engineering. This in vivo pilot study explored the use of human umbilical cord Wharton's jelly mesenchymal stem cells (hWJMSCs) containing a tissue engineering construct xenotransplant in rabbits to repair full-thickness cartilage defects in the femoral patellar groove. We observed orderly spatial-temporal remodeling of hWJMSCs into cartilage tissues during repair over 16 months, with characteristic architectural features, including a hyaline-like neocartilage layer with good surface regularity, complete integration with adjacent host cartilage, and regenerated subchondral bone. No immune rejection was detected when xenograft hWJMSCs were implanted into rabbit cartilage defects. The repair results using hWJMSCs were superior to those of chondrogenically induced hWJMSCs after assessing gross appearance and histological grading scores. These preliminary results suggest that using novel undifferentiated hWJMSCs as seed cells might be a better approach than using transforming growth factor-β-induced differentiated hWJMSCs for in vivo tissue engineering treatment of cartilage defects. hWJMSC allografts may be promising for clinical applications. PMID:28261617

On the use of 31P NMR for the quantification of hydrosoluble phosphorus-containing compounds in coral host tissues and cultured zooxanthellae.

PubMed

Godinot, Claire; Gaysinski, Marc; Thomas, Olivier P; Ferrier-Pagès, Christine; Grover, Renaud

2016-02-23

(31)P Nuclear Magnetic Resonance (NMR) was assessed to investigate the phosphorus-containing compounds present in the tissues of the scleractinian coral Stylophora pistillata as well as of cultured zooxanthellae (CZ). Results showed that phosphorus-containing compounds observed in CZ were mainly phosphate and phosphate esters. Phosphate accounted for 19 ± 2% of the total phosphorus compounds observed in CZ maintained under low P-levels (0.02 μM). Adding 5 mM of dissolved inorganic phosphorus (KH2PO4) to the CZ culture medium led to a 3.1-fold increase in intracellular phosphate, while adding 5 mM of dissolved organic phosphorus led to a reduction in the concentration of phosphorus compounds, including a 2.5-fold intracellular phosphate decrease. In sharp contrast to zooxanthellae, the host mainly contained phosphonates, and to a lesser extent, phosphate esters and phosphate. Two-months of host starvation decreased the phosphate content by 2.4 fold, while bleaching of fed corals did not modify this content. Based on (31)P NMR analyses, this study highlights the importance of phosphonates in the composition of coral host tissues, and illustrates the impact of phosphorus availability on the phosphorus composition of host tissues and CZ, both through feeding of the host and inorganic phosphorus enrichment of the CZ.

On the use of 31P NMR for the quantification of hydrosoluble phosphorus-containing compounds in coral host tissues and cultured zooxanthellae

NASA Astrophysics Data System (ADS)

Godinot, Claire; Gaysinski, Marc; Thomas, Olivier P.; Ferrier-Pagès, Christine; Grover, Renaud

2016-02-01

31P Nuclear Magnetic Resonance (NMR) was assessed to investigate the phosphorus-containing compounds present in the tissues of the scleractinian coral Stylophora pistillata as well as of cultured zooxanthellae (CZ). Results showed that phosphorus-containing compounds observed in CZ were mainly phosphate and phosphate esters. Phosphate accounted for 19 ± 2% of the total phosphorus compounds observed in CZ maintained under low P-levels (0.02 μM). Adding 5 mM of dissolved inorganic phosphorus (KH2PO4) to the CZ culture medium led to a 3.1-fold increase in intracellular phosphate, while adding 5 mM of dissolved organic phosphorus led to a reduction in the concentration of phosphorus compounds, including a 2.5-fold intracellular phosphate decrease. In sharp contrast to zooxanthellae, the host mainly contained phosphonates, and to a lesser extent, phosphate esters and phosphate. Two-months of host starvation decreased the phosphate content by 2.4 fold, while bleaching of fed corals did not modify this content. Based on 31P NMR analyses, this study highlights the importance of phosphonates in the composition of coral host tissues, and illustrates the impact of phosphorus availability on the phosphorus composition of host tissues and CZ, both through feeding of the host and inorganic phosphorus enrichment of the CZ.

On the use of 31P NMR for the quantification of hydrosoluble phosphorus-containing compounds in coral host tissues and cultured zooxanthellae

PubMed Central

Godinot, Claire; Gaysinski, Marc; Thomas, Olivier P.; Ferrier-Pagès, Christine; Grover, Renaud

2016-01-01

31P Nuclear Magnetic Resonance (NMR) was assessed to investigate the phosphorus-containing compounds present in the tissues of the scleractinian coral Stylophora pistillata as well as of cultured zooxanthellae (CZ). Results showed that phosphorus-containing compounds observed in CZ were mainly phosphate and phosphate esters. Phosphate accounted for 19 ± 2% of the total phosphorus compounds observed in CZ maintained under low P-levels (0.02 μM). Adding 5 mM of dissolved inorganic phosphorus (KH2PO4) to the CZ culture medium led to a 3.1-fold increase in intracellular phosphate, while adding 5 mM of dissolved organic phosphorus led to a reduction in the concentration of phosphorus compounds, including a 2.5-fold intracellular phosphate decrease. In sharp contrast to zooxanthellae, the host mainly contained phosphonates, and to a lesser extent, phosphate esters and phosphate. Two-months of host starvation decreased the phosphate content by 2.4 fold, while bleaching of fed corals did not modify this content. Based on 31P NMR analyses, this study highlights the importance of phosphonates in the composition of coral host tissues, and illustrates the impact of phosphorus availability on the phosphorus composition of host tissues and CZ, both through feeding of the host and inorganic phosphorus enrichment of the CZ. PMID:26902733

Biology and control of Varroa destructor.

PubMed

Rosenkranz, Peter; Aumeier, Pia; Ziegelmann, Bettina

2010-01-01

The ectoparasitic honey bee mite Varroa destructor was originally confined to the Eastern honey bee Apis cerana. After a shift to the new host Apis mellifera during the first half of the last century, the parasite dispersed world wide and is currently considered the major threat for apiculture. The damage caused by Varroosis is thought to be a crucial driver for the periodical colony losses in Europe and the USA and regular Varroa treatments are essential in these countries. Therefore, Varroa research not only deals with a fascinating host-parasite relationship but also has a responsibility to find sustainable solutions for the beekeeping. This review provides a survey of the current knowledge in the main fields of Varroa research including the biology of the mite, damage to the host, host tolerance, tolerance breeding and Varroa treatment. We first present a general view on the functional morphology and on the biology of the Varroa mite with special emphasis on host-parasite interactions during reproduction of the female mite. The pathology section describes host damage at the individual and colony level including the problem of transmission of secondary infections by the mite. Knowledge of both the biology and the pathology of Varroa mites is essential for understanding possible tolerance mechanisms in the honey bee host. We comment on the few examples of natural tolerance in A. mellifera and evaluate recent approaches to the selection of Varroa tolerant honey bees. Finally, an extensive listing and critical evaluation of chemical and biological methods of Varroa treatments is given. This compilation of present-day knowledge on Varroa honey bee interactions emphasizes that we are still far from a solution for Varroa infestation and that, therefore, further research on mite biology, tolerance breeding, and Varroa treatment is urgently needed. Copyright 2009 Elsevier Inc. All rights reserved.

Microbial and human heat shock proteins as 'danger signals' in sarcoidosis.

PubMed

Dubaniewicz, Anna

2013-12-01

In the light of the Matzinger's model of immune response, human heat shock proteins (HSPs) as main 'danger signals' (tissue damage-associated molecular patterns-DAMPs) or/and microbial HSPs as pathogen-associated molecular patterns (PAMPs) recognized by pattern recognition receptors (PRR), may induce sarcoid granuloma by both infectious and non-infectious factors in genetically different predisposed host. Regarding infectious causes of sarcoid models, low-virulence strains of, e.g. mycobacteria and propionibacteria recognized through changed PRR and persisting in altered host phagocytes, generate increased release of both human and microbial HSPs with their molecular and functional homology. High chronic spread of human and microbial HSPs altering cytokines, co-stimulatory molecules, and Tregs expression, apoptosis, oxidative stress, induces the autoimmunity, considered in sarcoidosis. Regarding non-infectious causes of sarcoidosis, human HSPs may be released at high levels during chronic low-grade exposure to misfolding amyloid precursor protein in stressed cells, phagocyted metal fumes, pigments with/without aluminum in tattoos, and due to heat shock in firefighters. Therefore, human HSPs as DAMPs and/or microbial HSPs as PAMPs produced as a result of non-infectious and infectious factors may induce different models of sarcoidosis, depending on the genetic background of the host. The number/expression of PRRs/ligands may influence the occurrence of sarcoidosis in particular organs. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

The multifunctional LigB adhesin binds homeostatic proteins with potential roles in cutaneous infection by pathogenic Leptospira interrogans.

PubMed

Choy, Henry A; Kelley, Melissa M; Croda, Julio; Matsunaga, James; Babbitt, Jane T; Ko, Albert I; Picardeau, Mathieu; Haake, David A

2011-02-09

Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9-11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats.

The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans

PubMed Central

Choy, Henry A.; Kelley, Melissa M.; Croda, Julio; Matsunaga, James; Babbitt, Jane T.; Ko, Albert I.; Picardeau, Mathieu; Haake, David A.

2011-01-01

Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9–11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats. PMID:21347378

Experimental Hyalohyphomycosis by Purpureocillium lilacinum: Outcome of the Infection in C57BL/6 Murine Models.

PubMed

de Sequeira, Danielly C M; Menezes, Rodrigo C; Oliveira, Manoel M E; Antas, Paulo R Z; De Luca, Paula M; de Oliveira-Ferreira, Joseli; Borba, Cintia de Moraes

2017-01-01

Purpureocillium lilacinum is a filamentous, hyaline fungus considered an emerging pathogen in humans. The aim of our study was to evaluate the outcome of hyalohyphomycosis in C57BL/6 murine models inoculated with two clinical P. lilacinum isolates (S1 and S2). Each isolate was inoculated in mice randomly distributed in immunocompetent (CPT) and immunosuppressed (SPS) groups. Mice were evaluated at day 7, 21, and 45 after inoculation for histopathological analysis, recovery of fungal cells, and immunological studies. Histological analysis showed scarce conidia-like structures in lung tissue from CPT mice and a lot of fungal cells in SPS mice inoculated with S2 compared to mice inoculated with S1. The maximum recovery of fungal cells was seen in CPT mice inoculated with both isolates at day 7, but with mean significantly higher in those inoculated with S2 isolate. Phenotypical characterization of T cells showed TCD8 + lymphocytes predominance over TCD4 + in immunosuppressed mice infected and control groups. We also observed higher percentages of the central and effector memory/effector phenotype in CPT mice infected with S2 strain, especially in TCD8 + in the initial period of infection. Regulatory T cells showed higher percentages in immunosuppressed, predominantly after the acute phase. Our results showed that the P. lilacinum is a fungus capable to cause damages in competent and immunosuppressed experimental hosts. Furthermore, S2 isolate seems to cause more damage to the experimental host and it was possible to identify different cellular subsets involved in the mice immune response.

Experimental Hyalohyphomycosis by Purpureocillium lilacinum: Outcome of the Infection in C57BL/6 Murine Models

PubMed Central

de Sequeira, Danielly C. M.; Menezes, Rodrigo C.; Oliveira, Manoel M. E.; Antas, Paulo R. Z.; De Luca, Paula M.; de Oliveira-Ferreira, Joseli; Borba, Cintia de Moraes

2017-01-01

Purpureocillium lilacinum is a filamentous, hyaline fungus considered an emerging pathogen in humans. The aim of our study was to evaluate the outcome of hyalohyphomycosis in C57BL/6 murine models inoculated with two clinical P. lilacinum isolates (S1 and S2). Each isolate was inoculated in mice randomly distributed in immunocompetent (CPT) and immunosuppressed (SPS) groups. Mice were evaluated at day 7, 21, and 45 after inoculation for histopathological analysis, recovery of fungal cells, and immunological studies. Histological analysis showed scarce conidia-like structures in lung tissue from CPT mice and a lot of fungal cells in SPS mice inoculated with S2 compared to mice inoculated with S1. The maximum recovery of fungal cells was seen in CPT mice inoculated with both isolates at day 7, but with mean significantly higher in those inoculated with S2 isolate. Phenotypical characterization of T cells showed TCD8+ lymphocytes predominance over TCD4+ in immunosuppressed mice infected and control groups. We also observed higher percentages of the central and effector memory/effector phenotype in CPT mice infected with S2 strain, especially in TCD8+ in the initial period of infection. Regulatory T cells showed higher percentages in immunosuppressed, predominantly after the acute phase. Our results showed that the P. lilacinum is a fungus capable to cause damages in competent and immunosuppressed experimental hosts. Furthermore, S2 isolate seems to cause more damage to the experimental host and it was possible to identify different cellular subsets involved in the mice immune response. PMID:28878763

The Effect of Intra-articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis

PubMed Central

Borić, Igor; Rod, Eduard; Jeleč, Željko; Radić, Andrej; Vrdoljak, Trpimir; Skelin, Andrea; Trbojević-Akmačić, Irena; Plečko, Mihovil; Primorac, Dragan

2017-01-01

Osteoarthritis (OA) is one of the leading musculoskeletal disorders in the adult population. It is associated with cartilage damage triggered by the deterioration of the extracellular matrix tissue. The present study explores the effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non-randomized, interventional, single-center, open-label clinical trial was conducted from January 2016 to April 2017. A total of 17 patients were enrolled in the study, and 32 knees with osteoarthritis were assessed. Surgical intervention (lipoaspiration) followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s) was performed in all patients. Patients were assessed for visual analogue scale (VAS), delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and immunoglobulin G (IgG) glycans at the baseline, three, six and 12 months after the treatment. Magnetic resonance sequence in dGEMRIC due to infiltration of the anionic, negatively charged contrast gadopentetate dimeglumine (Gd-DTPA2−) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. In addition, dGEMRIC consequently reflected subsequent changes in the mechanical axis of the lower extremities. The results of our study indicate that the use of autologous and microfragmented adipose tissue in patients with knee OA (measured by dGEMRIC MRI) increased glycosaminoglycan (GAG) content in hyaline cartilage, which is in line with observed VAS and clinical results. PMID:29027984

Angle-ply biomaterial scaffold for annulus fibrosus repair replicates native tissue mechanical properties, restores spinal kinematics, and supports cell viability.

PubMed

Borem, Ryan; Madeline, Allison; Walters, Joshua; Mayo, Henry; Gill, Sanjitpal; Mercuri, Jeremy

2017-08-01

Annulus fibrosus (AF) damage commonly occurs due to intervertebral disc (IVD) degeneration/herniation. The dynamic mechanical role of the AF is essential for proper IVD function and thus it is imperative that biomaterials developed to repair the AF withstand the mechanical rigors of the native tissue. Furthermore, these biomaterials must resist accelerated degradation within the proteolytic environment of degenerate IVDs while supporting integration with host tissue. We have previously reported a novel approach for developing collagen-based, multi-laminate AF repair patches (AFRPs) that mimic the angle-ply architecture and basic tensile properties of the human AF. Herein, we further evaluate AFRPs for their: tensile fatigue and impact burst strength, IVD attachment strength, and contribution to functional spinal unit (FSU) kinematics following IVD repair. Additionally, AFRP resistance to collagenase degradation and cytocompatibility were assessed following chemical crosslinking. In summary, AFRPs demonstrated enhanced durability at high applied stress amplitudes compared to human AF and withstood radially-directed biaxial stresses commonly borne by the native tissue prior to failure/detachment from IVDs. Moreover, FSUs repaired with AFRPs and nucleus pulposus (NP) surrogates had their axial kinematic parameters restored to intact levels. Finally, carbodiimide crosslinked AFRPs resisted accelerated collagenase digestion without detrimentally effecting AFRP tensile properties or cytocompatibility. Taken together, AFRPs demonstrate the mechanical robustness and enzymatic stability required for implantation into the damaged/degenerate IVD while supporting AF cell infiltration and viability. The quality of life for millions of individuals globally is detrimentally impacted by IVD degeneration and herniation. These pathologies often result in the structural demise of IVD tissue, particularly the annulus fibrosus (AF). Biomaterials developed for AF repair have yet to demonstrate the mechanical strength and durability required for utilization in the spine. Herein, we demonstrate the development of an angle-ply AF repair patch (AFRP) that can resist the application of physiologically relevant stresses without failure and which contributes to the restoration of functional spinal unit axial kinematics following repair. Furthermore, we show that this biomaterial can resist accelerated degradation in a simulated degenerate environment and supports AF cell viability. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Spatial and Temporal Variations in Stable Carbon (δ13C) and Nitrogen (δ15N) Isotopic Composition of Symbiotic Scleractinian Corals

PubMed Central

Nahon, Sarah; Richoux, Nicole B.; Kolasinski, Joanna; Desmalades, Martin; Ferrier Pages, Christine; Lecellier, Gael; Planes, Serge; Berteaux Lecellier, Véronique

2013-01-01

Tropical scleractinian corals are considered autotrophic as they rely mainly on photosynthesis-derived nutrients transferred from their photosymbionts. Corals are also able to capture and ingest suspended particulate organic matter, so heterotrophy can be an important supplementary trophic pathway to optimize coral fitness. The aim of this in situ study was to elucidate the trophic status of 10 coral species under contrasted environmental conditions in a French Polynesian lagoon. Carbon (δ13C) and nitrogen (δ15N) isotopic compositions of coral host tissues and photosymbionts were determined at 3 different fringing reefs during wet and dry seasons. Our results highlighted spatial variability in stable isotopic compositions of both coral host tissues and photosymbionts. Samples from the site with higher level of suspended particulate matter were 13C-depleted and 15N-enriched relative to corals and photosymbionts from less turbid sites. However, differences in both δ13C and δ15N between coral host tissues and their photosymbionts (Δhost-photosymbionts 13C and Δhost-photosymbionts 15N) were small (0.27 ± 0.76‰ and 1.40 ± 0.90‰, respectively) and similar at all sites, thus indicating no general increases in the heterotrophic pathway. Depleted δ13C and enriched δ15N values of coral host tissues measured at the most turbid site were explained by changes in isotopic composition of the inorganic nutrients taken up by photosymbionts and also by changes in rate of isotopic fractionation with environmental conditions. Our results also highlighted a lack of significant temporal variations in δ13C and δ15N values of coral host and photosymbiont tissues and in Δhost-photosymbionts 13C and Δhost-photosymbionts 15N values. This temporal stability indicated that corals remained principally autotrophic even during the wet season when photosymbiont densities were lower and the concentrations of phytoplankton were higher. Increased coral heterotrophy with higher food availability thus appears to be species-specific. PMID:24312542

Duration of emission of volatile organic compounds from mechanically damaged plant leaves.

PubMed

Smith, Lincoln; Beck, John J

2015-09-01

Classical biological control of invasive alien weeds depends on the use of arthropod herbivores that are sufficiently host specific to avoid risk of injuring nontarget plants. Host plant specificity is usually evaluated by using a combination of behavioral and developmental experiments under choice, no-choice and field conditions. Secondary plant compounds are likely to have an important influence on host plant specificity. However, relatively little is known about the volatile organic compounds (VOCs) that are emitted by target and nontarget plants, and how environmental conditions may affect their emission. Previous studies have shown that mechanical damage of leaves increases the composition and content of VOCs emitted. In this study we measured the VOC emissions of five species of plants in the subtribe Centaureinae (Asteraceae)--Carthamus tinctorius, Centaurea cineraria, Centaurea melitensis, Centaurea rothrockii, and Centaurea solstitialis--that have previously been used in host specificity experiments for a prospective biological control agent of yellow starthistle (C. solstitialis). Leaves of each plant were punctured with a needle and the VOCs were collected by solid-phase microextraction (SPME) periodically over 48 h and analyzed by GC-MS. A total of 49 compounds were detected. Damage caused an immediate increase of 200-600% in the composition of VOCs emitted from each plant species, and the amounts generally remained high for at least 48 h. The results indicate that a very unspecific mechanical damage can cause a prolonged change in the VOC profile of plants. Published by Elsevier GmbH.

Damage-plasticity model of the host rock in a nuclear waste repository

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koudelka, Tomáš; Kruis, Jaroslav, E-mail: kruis@fsv.cvut.cz

The paper describes damage-plasticity model for the modelling of the host rock environment of a nuclear waste repository. Radioactive Waste Repository Authority in Czech Republic assumes the repository to be in a granite rock mass which exhibit anisotropic behaviour where the strength in tension is lower than in compression. In order to describe this phenomenon, the damage-plasticity model is formulated with the help of the Drucker-Prager yield criterion which can be set to capture the compression behaviour while the tensile stress states is described with the help of scalar isotropic damage model. The concept of damage-plasticity model was implemented inmore » the SIFEL finite element code and consequently, the code was used for the simulation of the Äspö Pillar Stability Experiment (APSE) which was performed in order to determine yielding strength under various conditions in similar granite rocks as in Czech Republic. The results from the performed analysis are presented and discussed in the paper.« less

Host plant invests in growth rather than chemical defense when attacked by a specialist herbivore.

PubMed

Arab, Alberto; Trigo, José Roberto

2011-05-01

Plant defensive compounds may be a cost rather than a benefit when plants are attacked by specialist insects that may overcome chemical barriers by strategies such as sequestering plant compounds. Plants may respond to specialist herbivores by compensatory growth rather than chemical defense. To explore the use of defensive chemistry vs. compensatory growth we studied Brugmansia suaveolens (Solanaceae) and the specialist larvae of the ithomiine butterfly Placidina euryanassa, which sequester defensive tropane alkaloids (TAs) from this host plant. We investigated whether the concentration of TAs in B. suaveolens was changed by P. euryanassa damage, and whether plants invest in growth, when damaged by the specialist. Larvae feeding during 24 hr significantly decreased TAs in damaged plants, but they returned to control levels after 15 days without damage. Damaged and undamaged plants did not differ significantly in leaf area after 15 days, indicating compensatory growth. Our results suggest that B. suaveolens responds to herbivory by the specialist P. euryanassa by investing in growth rather than chemical defense.

Comprehensive Genetic Analysis of Early Host Body Reactions to the Bioactive and Bio-Inert Porous Scaffolds

PubMed Central

Ehashi, Tomo; Takemura, Taro; Hanagata, Nobutaka; Minowa, Takashi; Kobayashi, Hisatoshi; Ishihara, Kazuhiko; Yamaoka, Tetsuji

2014-01-01

To design scaffolds for tissue regeneration, details of the host body reaction to the scaffolds must be studied. Host body reactions have been investigated mainly by immunohistological observations for a long time. Despite of recent dramatic development in genetic analysis technologies, genetically comprehensive changes in host body reactions are hardly studied. There is no information about host body reactions that can predict successful tissue regeneration in the future. In the present study, porous polyethylene scaffolds were coated with bioactive collagen or bio-inert poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) and were implanted subcutaneously and compared the host body reaction to those substrates by normalizing the result using control non-coat polyethylene scaffold. The comprehensive analyses of early host body reactions to the scaffolds were carried out using a DNA microarray assay. Within numerous genes which were expressed differently among these scaffolds, particular genes related to inflammation, wound healing, and angiogenesis were focused upon. Interleukin (IL)-1β and IL-10 are important cytokines in tissue responses to biomaterials because IL-1β promotes both inflammation and wound healing and IL-10 suppresses both of them. IL-1β was up-regulated in the collagen-coated scaffold. Collagen-specifically up-regulated genes contained both M1- and M2-macrophage-related genes. Marked vessel formation in the collagen-coated scaffold was occurred in accordance with the up-regulation of many angiogenesis-inducible factors. The DNA microarray assay provided global information regarding the host body reaction. Interestingly, several up-regulated genes were detected even on the very bio-inert PMB-coated surfaces and those genes include inflammation-suppressive and wound healing-suppressive IL-10, suggesting that not only active tissue response but also the inert response may relates to these genetic regulations. PMID:24454803

Djhsp90s are crucial regulators during planarian regeneration and tissue homeostasis.

PubMed

Dong, Zimei; Chu, Gengbo; Sima, Yingxu; Chen, Guangwen

2018-04-15

Heat shock protein 90 family members (HSP90s), as molecular chaperones, have conserved roles in the physiological processes of eukaryotes regulating cytoprotection, increasing host resistance and so on. However, whether HSP90s affect regeneration in animals is unclear. Planarians are emerging models for studying regeneration in vivo. Here, the roles of three hsp90 genes from planarian Dugesia japonica are investigated by WISH and RNAi. The results show that: (1) Djhsp90s expressions are induced by heat and cold shock, tissue damage and ionic liquid; (2) Djhsp90s mRNA are mainly distributed each side of the body in intact worms as well as blastemas in regenerative worms; (3) the worms show head regression, lysis, the body curling and the regeneration arrest or even failure after Djhsp90s RNAi; (4) Djhsp90s are involved in autophagy and locomotion of the body. The research results suggest that Djhsp90s are not only conserved in cytoprotection, but also involved in homeostasis maintenance and regeneration process by regulating different pathways in planarians. Copyright © 2018 Elsevier Inc. All rights reserved.

The potential use of mesenchymal stem cells in hematopoietic stem cell transplantation

PubMed Central

Kim, Eun-Jung; Kim, Nayoun; Cho, Seok-Goo

2013-01-01

In the last 10 years, mesenchymal stem cells (MSCs) have emerged as a therapeutic approach to regenerative medicine, cancer, autoimmune diseases, and many more due to their potential to differentiate into various tissues, to repair damaged tissues and organs, and also for their immunomodulatory properties. Findings in vitro and in vivo have demonstrated immune regulatory function of MSCs and have facilitated their application in clinical trials, such as those of autoimmune diseases and chronic inflammatory diseases. There has been an increasing interest in the role of MSCs in allogeneic hematopoietic stem cell transplantation (HSCT), including hematopoietic stem cell engraftment and the prevention and treatment of graft-versus-host disease (GVHD), and their therapeutic potential has been reported in numerous clinical trials. Although the safety of clinical application of MSCs is established, further modifications to improve their efficacy are required. In this review, we summarize advances in the potential use of MSCs in HSCT. In addition, we discuss their use in clinical trials of the treatment of GVHD following HSCT, the immunomodulatory capacity of MSCs, and their regenerative and therapeutic potential in the field of HSCT. PMID:23306700

Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to-transplantation time

PubMed Central

Taeger, Christian D.; Friedrich, Oliver; Dragu, Adrian; Weigand, Annika; Hobe, Frieder; Drechsler, Caroline; Geppert, Carol I.; Arkudas, Andreas; Münch, Frank; Buchholz, Rainer; Pollmann, Charlotte; Schramm, Axel; Birkholz, Torsten; Horch, Raymund E.; Präbst, Konstantin

2015-01-01

Preventing ischemia-related cell damage is a priority when preserving tissue for transplantation. Perfusion protocols have been established for a variety of applications and proven to be superior to procedures used in clinical routine. Extracorporeal perfusion of muscle tissue though cumbersome is highly desirable since it is highly susceptible to ischemia-related damage. To show the efficacy of different perfusion protocols external field stimulation can be used to immediately visualize improvement or deterioration of the tissue during active and running perfusion protocols. This method has been used to show the superiority of extracorporeal perfusion using porcine rectus abdominis muscles perfused with heparinized saline solution. Perfused muscles showed statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. The combination of extracorporeal perfusion and external field stimulation may improve organ conservation research. PMID:26145230

Wound ballistics of firearm-related injuries--part 1: missile characteristics and mechanisms of soft tissue wounding.

PubMed

Stefanopoulos, P K; Filippakis, K; Soupiou, O T; Pazarakiotis, V C

2014-12-01

Firearm-related injuries are caused by a wide variety of weapons and projectiles. The kinetic energy of the penetrating projectile defines its ability to disrupt and displace tissue, whereas the actual tissue damage is determined by the mode of energy release during the projectile-tissue interaction and the particular characteristics of the tissues and organs involved. Certain projectile factors, namely shape, construction, and stability, greatly influence the rate of energy transfer to the tissues along the wound track. Two zones of tissue damage can be identified, the permanent cavity created by the passage of the bullet and a potential area of contused tissue surrounding it, produced mainly by temporary cavitation which is a manifestation of effective high-energy transfer to tissue. Due to the complex nature of these injuries, wound assessment and the type and extent of treatment required should be based on an understanding of the various mechanisms contributing to tissue damage. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Life cycle specialization of filamentous pathogens - colonization and reproduction in plant tissues.

PubMed

Haueisen, Janine; Stukenbrock, Eva H

2016-08-01

Filamentous plant pathogens explore host tissues to obtain nutrients for growth and reproduction. Diverse strategies for tissue invasion, defense manipulation, and colonization of inter and intra-cellular spaces have evolved. Most research has focused on effector molecules, which are secreted to manipulate plant immunity and facilitate infection. Effector genes are often found to evolve rapidly in response to the antagonistic host-pathogen co-evolution but other traits are also subject to adaptive evolution during specialization to the anatomy, biochemistry and ecology of different plant hosts. Although not directly related to virulence, these traits are important components of specialization but little is known about them. We present and discuss specific life cycle traits that facilitate exploration of plant tissues and underline the importance of increasing our insight into the biology of plant pathogens. Copyright © 2016. Published by Elsevier Ltd.

Pre-clinical characterization of tissue engineering constructs for bone and cartilage regeneration

PubMed Central

Trachtenberg, Jordan E.; Vo, Tiffany N.; Mikos, Antonios G.

2014-01-01

Pre-clinical animal models play a crucial role in the translation of biomedical technologies from the bench top to the bedside. However, there is a need for improved techniques to evaluate implanted biomaterials within the host, including consideration of the care and ethics associated with animal studies, as well as the evaluation of host tissue repair in a clinically relevant manner. This review discusses non-invasive, quantitative, and real-time techniques for evaluating host-materials interactions, quality and rate of neotissue formation, and functional outcomes of implanted biomaterials for bone and cartilage tissue engineering. Specifically, a comparison will be presented for pre-clinical animal models, histological scoring systems, and non-invasive imaging modalities. Additionally, novel technologies to track delivered cells and growth factors will be discussed, including methods to directly correlate their release with tissue growth. PMID:25319726

Pre-clinical characterization of tissue engineering constructs for bone and cartilage regeneration.

PubMed

Trachtenberg, Jordan E; Vo, Tiffany N; Mikos, Antonios G

2015-03-01

Pre-clinical animal models play a crucial role in the translation of biomedical technologies from the bench top to the bedside. However, there is a need for improved techniques to evaluate implanted biomaterials within the host, including consideration of the care and ethics associated with animal studies, as well as the evaluation of host tissue repair in a clinically relevant manner. This review discusses non-invasive, quantitative, and real-time techniques for evaluating host-materials interactions, quality and rate of neotissue formation, and functional outcomes of implanted biomaterials for bone and cartilage tissue engineering. Specifically, a comparison will be presented for pre-clinical animal models, histological scoring systems, and non-invasive imaging modalities. Additionally, novel technologies to track delivered cells and growth factors will be discussed, including methods to directly correlate their release with tissue growth.

Triboluminescent Materials for Smart Optical Damage Sensors for Space Applications

NASA Technical Reports Server (NTRS)

Aggarwal, M. D.; Penn, B. G.; Miller, J.; Sadate, S.; Batra, A. K.

2008-01-01

There is a need to develop a new technique of damage detection for composites, which could detect cracking or delamination from any desired location within a material structure in real time. Recently, triboluminescent materials have been proposed as smart sensors of structural damage. To sense the damage, these materials can be epoxy bonded, coated in a polymer matrix, or embedded in a composite host structure. When the damage or fracture takes place in the host structure, the resultant fracture of triboluminescent crystals creates a light emission. This will warn in real time that structural damage has occurred. The triboluminescent emission of the candidate phosphor has to be bright enough that the light reaching from the point of fracture to the detector through a fiber optic cable is detectable. There are a large number of triboluminescent materials, but few satisfy the above criterion. The authors have synthesized an organic material known as Europium tetrakis (dibenzoylmethide) triethylammonium (EuD4TEA), which is a potential candidate for application as a damage sensor and could be made into a wireless sensor with the addition of microchip, antenna, and electronics. Preliminary results on the synthesis and characterization of this material are presented.

Biomaterials and host versus graft response: A short review

PubMed Central

Velnar, Tomaz; Bunc, Gorazd; Klobucar, Robert; Gradisnik, Lidija

2016-01-01

Biomaterials and biotechnology are increasing becoming an important area in modern medicine. The main aim in this area is the development of materials, which are biocompatible to normal tissue. Tissue-implant interactions with molecular, biological and cellular characteristics at the implant-tissue interface are important for the use and development of implants. Implantation may cause an inflammatory and immune response in tissue, foreign body reaction, systemic toxicity and imminent infection. Tissue-implant interactions determine the implant life-period. The aims of the study are to consider the biological response to implants. Biomaterials and host reactions to implants and their mechanisms are also briefly discussed. PMID:26894284

Effects of tissue mechanical properties on susceptibility to histotripsy-induced tissue damage

NASA Astrophysics Data System (ADS)

Vlaisavljevich, Eli; Kim, Yohan; Owens, Gabe; Roberts, William; Cain, Charles; Xu, Zhen

2014-01-01

Histotripsy is a non-invasive tissue ablation method capable of fractionating tissue by controlling acoustic cavitation. To determine the fractionation susceptibility of various tissues, we investigated histotripsy-induced damage on tissue phantoms and ex vivo tissues with different mechanical strengths. A histotripsy bubble cloud was formed at tissue phantom surfaces using 5-cycle long ultrasound pulses with peak negative pressure of 18 MPa and PRFs of 10, 100, and 1000 Hz. Results showed significantly smaller lesions were generated in tissue phantoms of higher mechanical strength. Histotripsy was also applied to 43 different ex vivo porcine tissues with a wide range of mechanical properties. Gross morphology demonstrated stronger tissues with higher ultimate stress, higher density, and lower water content were more resistant to histotripsy damage in comparison to weaker tissues. Based on these results, a self-limiting vessel-sparing treatment strategy was developed in an attempt to preserve major vessels while fractionating the surrounding target tissue. This strategy was tested in porcine liver in vivo. After treatment, major hepatic blood vessels and bile ducts remained intact within a completely fractionated liver volume. These results identify varying susceptibilities of tissues to histotripsy therapy and provide a rational basis to optimize histotripsy parameters for treatment of specific tissues.

Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis

PubMed Central

Rohmer, Laurence; Hocquet, Didier; Miller, Samuel I.

2011-01-01

It is interesting to speculate that the evolutionary drive of microbes to develop pathogenic characteristics was to access the nutrient resources that animals provided. Environments in animals that pathogens colonize have also driven the evolution of new bacterial characteristics to maximize these new nutritional opportunities. This review focuses on genomic and functional aspects of pathogen metabolism that allow efficient utilization of nutrient resources provided by animals. Similar to genes encoding specific virulence traits, some genes encoding metabolic functions have been horizontally acquired by pathogens to provide a selective advantage in host tissues. Selective advantage in host tissues can also be gained in some circumstances by loss of function due to mutations that alter metabolic capabilities. Greater understanding of bacterial metabolism within host tissues should be important for increased understanding of host-pathogen interactions and the development of future therapeutic strategies. PMID:21600774

Histologic analysis of fetal bovine derived acellular dermal matrix in tissue expander breast reconstruction.

PubMed

Gaster, Richard S; Berger, Aaron J; Monica, Stefanie D; Sweeney, Robert T; Endress, Ryan; Lee, Gordon K

2013-04-01

This study seeks to determine human host response to fetal bovine acellular dermal matrix (ADM) in staged implant-based breast reconstruction. A prospective study was performed for patients undergoing immediate breast reconstruction with tissue expander placement and SurgiMend acellular fetal bovine dermis. At the time of exchange for permanent implant, we obtained tissue specimens of SurgiMend and native capsule. Histological and immunohistochemical assays were performed to characterize the extent of ADM incorporation/degradation, host cell infiltration, neovascularization, inflammation, and host replacement of acellular fetal bovine collagen. Seventeen capsules from 12 patients were included in our study. The average "implantation" time of SurgiMend was 7.8 months (range, 2-23 months). Histological analysis of the biopsy of tissue revealed rare infiltration of host inflammatory cells, even at 23 months. One patient had an infection requiring removal of the tissue expander at 2 months. Contracture, inflammatory changes, edema, and polymorphonuclear leukocyte infiltration were rare in the ADM. An acellular capsule was seen in many cases, at the interface of SurgiMend with the tissue expander. SurgiMend demonstrated a very infrequent inflammatory response. An antibody specific to bovine collagen allowed for direct identification of bovine collagen separate from human collagen. Cellular infiltration and neovascularization of SurgiMend correlated with the quality of the mastectomy skin flap rather than the duration of implantation. Future studies are needed to further characterize the molecular mechanisms underlying tissue incorporation of this product.

Ecotoxicoparasitology of the gastrointestinal tracts of pinnipeds: the effect of parasites on the potential bioavailability of total mercury (THg).

PubMed

McGrew, Ashley K; O'Hara, Todd M; Stricker, Craig A; Salman, Mo D; Van Bonn, William; Gulland, Frances M D; Whiting, Alex; Ballweber, Lora R

2018-08-01

Acanthocephalans, cestodes, and some species of nematodes acquire nutrients from the lumen contents in the gastrointestinal (GI) tract of their definitive host. These parasites are exposed to toxicants, such as mercury (Hg), through passive or active feeding mechanisms; therefore, the focus of this study was to determine if there is an effect of parasites on the dietary availability of total mercury (THg) within piscivorous pinniped hosts. THg concentrations ([THg]) in selected host tissues, parasites, and GI lumen contents from 22 California sea lions (Zalophus californianus), 15 ringed seals (Phoca hispida), and 4 spotted seals (Phoca largha) were determined. Among all pinnipeds, [THg] in acanthocephalans of the large intestine were significantly higher than concentrations in other samples (host lumen contents, other parasites and host intestinal wall), irrespective of location within the host GI tract. δ 15 N values of parasites depended both on parasite group and location within the GI tract. δ 15 N values were consistently higher in parasites inhabiting the large intestine, compared to elsewhere in the GI tract, for both sea lions and seals. δ 13 C values in parasites did not differ significantly from host GI tissues. Based on both [THg] and stable isotope values, parasites are likely affecting the Hg bioavailability within the GI lumen contents and host tissues, and toxicant-parasite interactions appear to depend on both parasitic taxon as well as their location within the host intestine. Copyright © 2018. Published by Elsevier B.V.

Influence of the Host Contact Sequence on the Outcome of Competition among Aspergillus flavus Isolates during Host Tissue Invasion▿

PubMed Central

Mehl, H. L.; Cotty, P. J.

2011-01-01

Biological control of aflatoxin contamination by Aspergillus flavus is achieved through competitive exclusion of aflatoxin producers by atoxigenic strains. Factors dictating the extent to which competitive displacement occurs during host infection are unknown. The role of initial host contact in competition between pairs of A. flavus isolates coinfecting maize kernels was examined. Isolate success during tissue invasion and reproduction was assessed by quantification of isolate-specific single nucleotide polymorphisms using pyrosequencing. Isolates were inoculated either simultaneously or 1 h apart. Increased success during competition was conferred to the first isolate to contact the host independent of that isolate's innate competitive ability. The first-isolate advantage decreased with the conidial concentration, suggesting capture of limited resources on kernel surfaces contributes to competitive exclusion. Attempts to modify access to putative attachment sites by either coating kernels with dead conidia or washing kernels with solvents did not influence the success of the first isolate, suggesting competition for limited attachment sites on kernel surfaces does not mediate first-isolate advantage. The current study is the first to demonstrate an immediate competitive advantage conferred to A. flavus isolates upon host contact and prior to either germ tube emergence or host colonization. This suggests the timing of host contact is as important to competition during disease cycles as innate competitive ability. Early dispersal to susceptible crop components may allow maintenance within A. flavus populations of genetic types with low competitive ability during host tissue invasion. PMID:21216896

[Scanning electron microscopy of heat-damaged bone tissue].

PubMed

Harsanyl, L

1977-02-01

Parts of diaphyses of bones were exposed to high temperature of 200-1300 degrees C. Damage to the bone tissue caused by the heat was investigated. The scanning electron microscopic picture seems to be characteristic of the temperature applied. When the bones heated to the high temperature of 700 degrees C characteristic changes appear on the periostal surface, higher temperatura on the other hand causes damage to the compact bone tissue and can be observed on the fracture-surface. Author stresses the importance of this technique in the legal medicine and anthropology.

S1P dependent inter organ trafficking of group 2 innate lymphoid cells suppots host defense

USDA-ARS?s Scientific Manuscript database

Innate lymphoid cells (ILCs) are considered to be the innate counterparts of adaptive T lymphocytes and play important roles in host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs are generally thought of as tissue-resident cells, but whether ILCs strictly behave in a...

Association of 5-hydroxymethylation and 5-methylation of DNA cytosine with tissue-specific gene expression

PubMed Central

Ponnaluri, V. K. Chaithanya; Ehrlich, Kenneth C.; Zhang, Guoqiang; Lacey, Michelle; Johnston, Douglas; Pradhan, Sriharsa; Ehrlich, Melanie

2017-01-01

ABSTRACT Differentially methylated or hydroxymethylated regions (DMRs) in mammalian DNA are often associated with tissue-specific gene expression but the functional relationships are still being unraveled. To elucidate these relationships, we studied 16 human genes containing myogenic DMRs by analyzing profiles of their epigenetics and transcription and quantitatively assaying 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) at specific sites in these genes in skeletal muscle (SkM), myoblasts, heart, brain, and diverse other samples. Although most human promoters have little or no methylation regardless of expression, more than half of the genes that we chose to study—owing to their myogenic DMRs—overlapped tissue-specific alternative or cryptic promoters displaying corresponding tissue-specific differences in histone modifications. The 5mC levels in myoblast DMRs were significantly associated with 5hmC levels in SkM at the same site. Hypermethylated myogenic DMRs within CDH15, a muscle- and cerebellum-specific cell adhesion gene, and PITX3, a homeobox gene, were used for transfection in reporter gene constructs. These intragenic DMRs had bidirectional tissue-specific promoter activity that was silenced by in vivo-like methylation. The CDH15 DMR, which was previously associated with an imprinted maternal germline DMR in mice, had especially strong promoter activity in myogenic host cells. These findings are consistent with the controversial hypothesis that intragenic DNA methylation can facilitate transcription and is not just a passive consequence of it. Our results support varied roles for tissue-specific 5mC- or 5hmC-enrichment in suppressing inappropriate gene expression from cryptic or alternative promoters and in increasing the plasticity of gene expression required for development and rapid responses to tissue stress or damage. PMID:27911668

Effect of tcdR Mutation on Sporulation in the Epidemic Clostridium difficile Strain R20291.

PubMed

Girinathan, Brintha P; Monot, Marc; Boyle, Daniel; McAllister, Kathleen N; Sorg, Joseph A; Dupuy, Bruno; Govind, Revathi

2017-01-01

Clostridium difficile is an important nosocomial pathogen and the leading cause of hospital-acquired diarrhea. Antibiotic use is the primary risk factor for the development of C. difficile -associated disease because it disrupts normally protective gut flora and enables C. difficile to colonize the colon. C. difficile damages host tissue by secreting toxins and disseminates by forming spores. The toxin-encoding genes, tcdA and tcdB , are part of a pathogenicity locus, which also includes the tcdR gene that codes for TcdR, an alternate sigma factor that initiates transcription of tcdA and tcdB genes. We created a tcdR mutant in epidemic-type C. difficile strain R20291 in an attempt to identify the global role of tcdR . A site-directed mutation in tcdR affected both toxin production and sporulation in C. difficile R20291. Spores of the tcdR mutant were more heat sensitive than the wild type (WT). Nearly 3-fold more taurocholate was needed to germinate spores from the tcdR mutant than to germinate the spores prepared from the WT strain. Transmission electron microscopic analysis of the spores also revealed a weakly assembled exosporium on the tcdR mutant spores. Accordingly, comparative transcriptome analysis showed many differentially expressed sporulation genes in the tcdR mutant compared to the WT strain. These data suggest that regulatory networks of toxin production and sporulation in C. difficile strain R20291 a re linked with each other. IMPORTANCE C. difficile infects thousands of hospitalized patients every year, causing significant morbidity and mortality. C. difficile spores play a pivotal role in the transmission of the pathogen in the hospital environment. During infection, the spores germinate, and the vegetative bacterial cells produce toxins that damage host tissue. Thus, sporulation and toxin production are two important traits of C. difficile . In this study, we showed that a mutation in tcdR , the toxin gene regulator, affects both toxin production and sporulation in epidemic-type C. difficile strain R20291.

Effect of tcdR Mutation on Sporulation in the Epidemic Clostridium difficile Strain R20291

PubMed Central

Girinathan, Brintha P.; Monot, Marc; Boyle, Daniel; McAllister, Kathleen N.; Dupuy, Bruno

2017-01-01

ABSTRACT Clostridium difficile is an important nosocomial pathogen and the leading cause of hospital-acquired diarrhea. Antibiotic use is the primary risk factor for the development of C. difficile-associated disease because it disrupts normally protective gut flora and enables C. difficile to colonize the colon. C. difficile damages host tissue by secreting toxins and disseminates by forming spores. The toxin-encoding genes, tcdA and tcdB, are part of a pathogenicity locus, which also includes the tcdR gene that codes for TcdR, an alternate sigma factor that initiates transcription of tcdA and tcdB genes. We created a tcdR mutant in epidemic-type C. difficile strain R20291 in an attempt to identify the global role of tcdR. A site-directed mutation in tcdR affected both toxin production and sporulation in C. difficile R20291. Spores of the tcdR mutant were more heat sensitive than the wild type (WT). Nearly 3-fold more taurocholate was needed to germinate spores from the tcdR mutant than to germinate the spores prepared from the WT strain. Transmission electron microscopic analysis of the spores also revealed a weakly assembled exosporium on the tcdR mutant spores. Accordingly, comparative transcriptome analysis showed many differentially expressed sporulation genes in the tcdR mutant compared to the WT strain. These data suggest that regulatory networks of toxin production and sporulation in C. difficile strain R20291 are linked with each other. IMPORTANCE C. difficile infects thousands of hospitalized patients every year, causing significant morbidity and mortality. C. difficile spores play a pivotal role in the transmission of the pathogen in the hospital environment. During infection, the spores germinate, and the vegetative bacterial cells produce toxins that damage host tissue. Thus, sporulation and toxin production are two important traits of C. difficile. In this study, we showed that a mutation in tcdR, the toxin gene regulator, affects both toxin production and sporulation in epidemic-type C. difficile strain R20291. PMID:28217744

Biotechnology

NASA Image and Video Library

2002-07-02

Diagram depicts the importance of cell-cell communication as central to the understanding of cancer growth and progression, the focus of the NASA bioreactor demonstration system (BDS-05) investigation. Microgravity studies will allow us to unravel the signaling and communication between these cells with the host and potential development of therapies for the treatment of cancer metastasis. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: Emory University.

Innate lymphoid cells in tissue homeostasis and diseases.

PubMed

Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva

2017-08-18

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

Micro-anatomical changes in major blood vessel caused by dengue virus (serotype 2) infection.

PubMed

Priya, Sivan Padma; Sakinah, S; Ling, Mok Pooi; Chee, Hui-Yee; Higuchi, Akon; Hamat, Rukman Awang; Neela, Vasantha Kumari; Alarfaj, Abdullah A; Munusamy, Murugan A; Hatamleh, Ashraf A; Al-Sabri, Ahmed E; Abdulaziz Al-Suwailem, Ibrahim Ahmad; Rajan, Mariappan; Benelli, Giovanni; Marlina; Kumar, S Suresh

2017-07-01

Dengue virus (DENV) has emerged as a major economic concern in developing countries, with 2.5 billion people believed to be at risk. Vascular endothelial cells (ECs) lining the circulatory system from heart to end vessels perform crucial functions in the human body, by aiding gas exchange in lungs, gaseous, nutritional and its waste exchange in all tissues, including the blood brain barrier, filtration of fluid in the glomeruli, neutrophil recruitment, hormone trafficking, as well as maintenance of blood vessel tone and hemostasis. These functions can be deregulated during DENV infection. In this study, BALB/c mice infected with DENV serotype 2 were analyzed histologically for changes in major blood vessels in response to DENV infection. In the uninfected mouse model, blood vessels showed normal architecture with intact endothelial monolayer, tunica media, and tunica adventitia. In the infected mouse model, DENV distorted the endothelium lining and disturbed the smooth muscle, elastic laminae and their supporting tissues causing vascular structural disarrangement. This may explain the severe pathological illness in DENV-infected individuals. The overall DENV-induced damages on the endothelial and it's supporting tissues and the dysregulated immune reactions initiated by the host were discussed. Copyright © 2017. Published by Elsevier B.V.

Neurosurgical patties: adhesion and damage mitigation.

PubMed

Stratton-Powell, Ashley A; Anderson, Ian A; Timothy, Jake; Kapur, Nikil; Culmer, Peter

2015-07-01

Neurosurgical patties are textile pads used during most neurosurgical operations to protect tissues, manage the fluid environment, control hemostasis, and aid tissue manipulation. Recent research has suggested that, contrary to their aim, patties adhere to brain tissue and cause damage during removal. This study aimed to characterize and quantify the degree of and consequences resulting from adhesion between neurosurgical patties and brain tissue. Using a customized peel apparatus, the authors performed 90° peel tests on 5 patty products: Policot, Telfa, Americot, Delicot, and Ray-Cot (n = 247) from American Surgical Company. They tested 4 conditions: wet patty on glass (control), wet patty on wet brain peeled at 5 mm/sec (wet), dry patty on wet brain peeled at 5 mm/sec (dry), and wet patty on wet brain peeled at 20 mm/sec (speed). The interaction between patty and tissue was analyzed using peel-force traces and pre-peel histological analysis. Adhesion strength differed between patty products (p < 0.001) and conditions (p < 0.001). Adhesion strength was greatest for Delicot patties under wet (2.22 mN/mm) and dry (9.88 mN/mm) conditions. For all patties, damage at the patty-tissue interface was proportional to the degree of fiber contact. When patties were irrigated, mechanical adhesion was reduced by up to 550% compared with dry usage. For all patty products, mechanical (destructive) and liquid-mediated (nondestructive) adhesion caused damage to neural tissue. The greatest adhesion occurred with Delicot patties. To mitigate patty adhesion and neural tissue damage, surgeons should consider regular irrigation to be essential during neurosurgical procedures.

[Helminth migration in the host].

PubMed

Horák, Petr

2006-08-01

Helminths belong to important human pathogens in tropical and subtropical countries. They have simple one-host life cycles or they use several hosts for their development. There are two main entry points for human helminths: the skin and the oral cavity. Skin penetration is followed by tissue migration of helminth stages towards target organs. Also some perorally acquired helminths migrate throughout the human body and then (a) they return to and mature in the intestine or (b) they search for specific final location in other (extraintestinal) tissues/organs. Particular developmental stages having different migration routes, and different roles of human beings as final, intermediate and paratenic hosts are briefly mentioned.

Optical monitoring of spinal cord subcellular damage after acute spinal cord injury

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Manouchehri, Neda; So, Kitty; Shortt, Katelyn; Fong, Allan; Streijger, Femke; Macnab, Andrew; Kwon, Brian K.

2018-02-01

Introduction: Sudden physical trauma to the spinal cord results in acute spinal cord injury (SCI), leading to spinal cord (SC) tissue destruction, acute inflammation, increased SC intraparenchymal pressure, and tissue ischemia, hypoxia, and cellular necrosis. The ability to monitor SC tissue viability at subcellular level, using a real-time noninvasive method, would be extremely valuable to clinicians for estimating acute SCI damage, and adjusting and monitoring treatment in the intensive care setting. This study examined the feasibility and sensitivity of a custommade near infrared spectroscopy (NIRS) sensor to monitor the oxidation state of SC mitochondrial cytochrome aa3 (CCO), which reflects the subcellular damage of SC tissue in an animal model of SCI. Methods: Six anesthetized Yorkshire pigs were studied using a custom-made multi-wavelength NIRS system with a miniaturized optical sensor applied directly on the surgically exposed SC at T9. The oxidation states of SC tissue hemoglobin and CCO were monitored before, during and after acute SCI, and during mean arterial pressure alterations. Results: Non-invasive NIRS monitoring reflected changes in SC tissue CCO, simultaneous but independent of changes in hemoglobin saturation following acute SCI. A consistent decrease in SC tissue CCO chromophore concentration (-1.98 +/- 2.1 ab, p<0.05) was observed following SCI, indicating progressive SC cellular damage at the injury site. Elevation of mean arterial pressure can reduce SC tissue damage as suggested by different researchers and observed by significant increase in SC tissue CCO concentration (1.51 +/- 1.7 ab, p<0.05) in this study. Conclusions: This pilot study indicates that a novel miniaturized multi-wave NIRS sensor has the potential to monitor post-SCI changes of SC cytochrome aa3 oxygenation state in real time. Further development of this method may offer new options for improved SCI care.

In vivo evaluation of needle force and friction stress during insertion at varying insertion speed into the brain.

PubMed

Casanova, Fernando; Carney, Paul R; Sarntinoranont, Malisa

2014-11-30

Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in tissue damage which can promote flowback along the needle track and improper targeting. The goal of this study was to evaluate friction stress (calculated from needle insertion force) as a measure of tissue contact and damage during needle insertion for varying insertion speeds. Forces and surface dimpling during needle insertion were measured in rat brain in vivo. Needle retraction forces were used to calculate friction stresses. These measures were compared to track damage from a previous study. Differences between brain tissues and soft hydrogels were evaluated for varying insertion speeds: 0.2, 2, and 10mm/s. In brain tissue, average insertion force and surface dimpling increased with increasing insertion speed. Average friction stress along the needle-tissue interface decreased with insertion speed (from 0.58 ± 0.27 to 0.16 ± 0.08 kPa). Friction stress varied between brain regions: cortex (0.227 ± 0.27 kPa), external capsule (0.222 ± 0.19 kPa), and CPu (0.383 ± 0.30 kPa). Hydrogels exhibited opposite trends for dimpling and friction stress with insertion speed. Previously, increasing needle damage with insertion speed has been measured with histological methods. Friction stress appears to decrease with increasing tissue damage and decreasing tissue contact, providing the potential for in vivo and real time evaluation along the needle track. Force derived friction stress decreased with increasing insertion speed and was smaller within white matter regions. Hydrogels exhibited opposite trends to brain tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

[Diversity and tissue distribution of fungal endophytes in Alpinia officinarum: an important south-China medicinal plant].

PubMed

Zhou, Ren-Chao; Huang, Juan; Li, Ze-En; Li, Shu-Bin

2014-08-01

In the present study, terminal-restriction fragment length polymorphism (T-RFLP) technique was applied to assess the diversity and tissue distribution of the fungal endophyte communities of Alpinia officinarum collected from Longtang town in Xuwen county, Guangdong province, China, at which the pharmacological effect of the medicine plant is traditional considered to be the significantly higher than that in any other growth areas in China. A total of 28 distinct Terminal-Restriction Fragment (T-RFs) were detected with HhaI Mono-digestion targeted amplified fungal nuclear ribosomal internal transcribed spacer region sequences (rDNA ITS) from the root, rhizome, stem, and leaf internal tissues of A. officinarum plant, indicating that at least 28 distinct fungal species were able to colonize the internal tissue of the host plant. The rDNA ITS-T-RFLP profiles obtained from different tissues of the host plant were obvious distinct. And the numbers of total T-RFs, and the dominant T-RFs detected from various tissues were significantly different. Based on the obtained T-RFLP profiles, Shannon's diversity index and the Shannon's evenness index were calculated, which were significantly different among tissues (P < 0.05). Furthermore, two types of active chemicals, total volatile oils by water vapor distillation method and galangin by methanol extraction-HPLC method, were examined in the each tissue of the tested plant. Both of tested components were detected in all of the four tissues of the medicine plant with varying contents. And the highest was in rhizome tissue. Correlation analysis revealed there were significant negative correlations between both of the tested active components contents and calculated Shannon's diversity index, as well as the Shannon's evenness index of the fungal endophyte communities of the host plant (P = 0, Pearson correlation coefficient ≤ -0.962), and significant positive correlations between both of the tested active components contents and 325 bp dominant T-RF linkage to Pestalotiopsis (P = 0, Pearson correlation coefficient ≥ 0.975). In conclusion, A. officinarum is colonized by diverse fungal endophytes communities. The diversity of the fungal endophytes was found in the A. officinarum varied with differences of the tissue types of the host plants and was closely correlated with the accumulation of main active components, total volatile oils and galangin contents in the host plant tissue.

Controlled-Release Personal Use Arthropod Repellent Formulation. Phase 2

DTIC Science & Technology

1986-09-15

damage, pitting M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to visualize due to severe opacity S - Granulation scar tissue POS...M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to visualize due to severe opacity S - Granulation scar tissue POS -Positive...Corneal epithelial damage, piling L - Corneal epithelial damage, pitting M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to

Effects of chytridiomycosis on hematopoietic tissue in the spleen, kidney and bone marrow in three diverse amphibian species.

PubMed

Brannelly, Laura A; Webb, Rebecca J; Skerratt, Lee F; Berger, Lee

2016-10-01

One of the major causes of amphibian population decline is the deadly fungal pathogen Batrachochytrium dendrobatidis, Bd Research on pathogenesis and host immunity aims to inform development of targeted conservation interventions. Studies examining global host immune responses as well as effects on lymphocytes in vitro suggest that Bd infection causes immunosuppression. However, it is unknown which hematopoietic tissues are affected and if these effects differ among host species. We investigated the effect of experimental Bd infection on three diverse amphibian species by quantifying the amount of hematopoietic tissue in the spleen, bone marrow and kidney. Upon Bd infection, hematopoietic tissue in the kidney tended to be depleted, while the spleen appeared unaffected. The bone marrow in highly susceptible species was depleted, whereas an increase in hematopoietic tissue was observed in the more resistant species. Our study demonstrates that species and hematopoietic tissues behave differently in response to Bd infection, and may be related to the species' susceptibility to infection. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Proton irradiation impacts age-driven modulations of cancer progression influenced by immune system transcriptome modifications from splenic tissue.

PubMed

Wage, Justin; Ma, Lili; Peluso, Michael; Lamont, Clare; Evens, Andrew M; Hahnfeldt, Philip; Hlatky, Lynn; Beheshti, Afshin

2015-09-01

Age plays a crucial role in the interplay between tumor and host, with additional impact due to irradiation. Proton irradiation of tumors induces biological modulations including inhibition of angiogenic and immune factors critical to 'hallmark' processes impacting tumor development. Proton irradiation has also provided promising results for proton therapy in cancer due to targeting advantages. Additionally, protons may contribute to the carcinogenesis risk from space travel (due to the high proportion of high-energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice was altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68-day) versus old (736-day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5 Gy (1-GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared with older subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74 and RUVBL2 indicated these were the key genes involved in the regulatory changes in the host environment response (i.e. the spleen). Collectively, these results suggest that a significant biological component of proton irradiation is modulated by host age through promotion of carcinogenesis in adolescence and resistance to immunosuppression, carcinogenesis and genetic perturbation associated with advancing age. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Validity of reciprocity rule on mouse skin thermal damage due to CO2 laser irradiation

NASA Astrophysics Data System (ADS)

Parvin, P.; Dehghanpour, H. R.; Moghadam, M. S.; Daneshafrooz, V.

2013-07-01

CO2 laser (10.6 μm) is a well-known infrared coherent light source as a tool in surgery. At this wavelength there is a high absorbance coefficient (860 cm-1), because of vibration mode resonance of H2O molecules. Therefore, the majority of the irradiation energy is absorbed in the tissue and the temperature of the tissue rises as a function of power density and laser exposure duration. In this work, the tissue damage caused by CO2 laser (1-10 W, ˜40-400 W cm-2, 0.1-6 s) was measured using 30 mouse skin samples. Skin damage assessment was based on measurements of the depth of cut, mean diameter of the crater and the carbonized layer. The results show that tissue damage as assessed above parameters increased with laser fluence and saturated at 1000 J cm-2. Moreover, the damage effect due to high power density at short duration was not equivalent to that with low power density at longer irradiation time even though the energy delivered was identical. These results indicate the lack of validity of reciprocity (Bunsen-Roscoe) rule for the thermal damage.

Tissue damage negatively regulates LPS-induced macrophage necroptosis.

PubMed

Li, Z; Scott, M J; Fan, E K; Li, Y; Liu, J; Xiao, G; Li, S; Billiar, T R; Wilson, M A; Jiang, Y; Fan, J

2016-09-01

Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mφ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mφ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mφ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules.

Tissue damage negatively regulates LPS-induced macrophage necroptosis

PubMed Central

Li, Z; Scott, M J; Fan, E K; Li, Y; Liu, J; Xiao, G; Li, S; Billiar, T R; Wilson, M A; Jiang, Y; Fan, J

2016-01-01

Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mφ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mφ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mφ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules. PMID:26943325

Tissue damage-induced intestinal stem cell division in Drosophila

PubMed Central

Amcheslavsky, Alla; Jiang, Jin; Ip, Y. Tony

2009-01-01

SUMMARY Stem cell division is essential for tissue integrity during growth, aging, and pathogenic assaults. Adult gastrointestinal tract encounters numerous stimulations and impaired tissue regeneration may lead to inflammatory diseases and cancer. Intestinal stem cells in adult Drosophila have recently been identified and shown to replenish the various cell types within the midgut. However, it is not known whether these intestinal stem cells can respond to environmental challenges. By feeding dextran sulfate sodium and bleomycin to flies and by expressing apoptotic proteins, we show that Drosophila intestinal stem cells can increase the rate of division in response to tissue damage. Moreover, if tissue damage results in epithelial cell loss, the newly formed enteroblasts can differentiate into mature epithelial cells. By using this newly established system of intestinal stem cell proliferation and tissue regeneration, we find that the insulin receptor signaling pathway is required for intestinal stem cell division. PMID:19128792

Biochemical and pharmacological characterization of Trimersurus malabaricus snake venom.

PubMed

Gowda, Raghavendra; Rajaiah, Rajesh; Angaswamy, Nataraj; Krishna, Sharath; Bannikuppe Sannanayak, Vishwanath

2018-07-01

Trimeresurus malabaricus is a venomous pit viper species endemic to southwestern part of India. In earlier reports, we have shown that envenomation by T. malabaricus venom leading to strong local tissue damage but the mechanism of action is not clearly revealed. Local tissue damage affected by T. malabaricus venom is of great importance since the poison has serious systemic effects including death in the case of multiple attacks. The present study details the major manifestations of T. malabaricus venom and the induction of local tissue damage, which suggests that most toxins are present in the form of hydrolytic enzymes. Hydrolytic activity of the enzymes was measured and the data indicated that protease and phospholipase A 2 activity was high which is responsible for local tissue damage. Furthermore, the role of hydrolytic enzymes in the induction of pathological events such as hemorrhage, edema, myotoxicity, and blood coagulation examination were assessed through animal models. © 2018 Wiley Periodicals, Inc.

Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.

This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in themore » low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.« less

Mapping host-species abundance of three major exotic forest pests

Treesearch

Randall S. Morin; Andrew M. Liebhold; Eugene R. Luzader; Andrew J. Lister; Kurt W. Gottschalk; Daniel B. Twardus

2005-01-01

Periodically over the last century, forests of the Eastern United States devastated by invasive pests. We used existing data to predict the geographical extent of future damage from beech bark disease (BBD), hemlock woolly adelgid (HWA), and gypsy moth. The distributions of host species of these alien pests were mapped in 1-km2 cells by interpolating host basal area/ha...

Fulfillment of Koch’s postulates and partial host range of Septoria lepidii Desm., a fungal pathogen for potential biological control of hoary cress (Lepidium spp.)

USDA-ARS?s Scientific Manuscript database

We have fulfilled Koch’s postulates and conducted host range tests with Septoria lepidii Desm. on five geographical accessions of hoary cress. Host range results showed the fungus specific to Lepidium spp. and damaging to hoary cress. This fungus is potentially an important biological control agent ...

Pickle Flavors Relish in Drosophila Immunity.

PubMed

Salminen, Tiina Susanna; Rämet, Mika

2016-09-14

Immune responses must be tightly controlled to avoid host damage. In Drosophila, two NF-κB signaling pathways, Toll and Imd, mediate host immune responses. In this issue of Cell Host & Microbe, Morris et al. (2016) introduce Pickle, a nuclear IκB that inhibits Drosophila immune signaling by modulating the NF-κB Relish. Copyright © 2016 Elsevier Inc. All rights reserved.

The relation of microdamage to fracture and material property degradation in human cortical bone tissue

NASA Astrophysics Data System (ADS)

Akkus, Ozan

This dissertation investigates the relation of microdamage to fracture and material property degradation of human cortical bone tissue. Fracture resistance and fatigue crack growth of microcracks were examined experimentally and material property degradation was examined through theoretical modeling. To investigate the contribution of microdamage to static fracture resistance, fracture toughness tests were conducted in the transverse and longitudinal directions to the osteonal orientation of normal bone tissue. Damage accumulation was monitored by acoustic emission during testing and was spatially observed by histological observation following testing. The results suggested that the propagation of the main crack involved weakening of the tissue by diffuse damage at the fracture plane and by formation of linear microcracks away from the fracture plane for the transverse specimens. For the longitudinal specimens, growth of the main crack occurred in the form of separations at lamellar interfaces. Acoustic emission results supported the histological observations. To investigate the contribution of ultrastructure to static fracture resistance, fracture toughness tests were conducted after altering the collagen phase of the bone tissue by gamma radiation. A significant decrease in the fracture toughness, Work-to-Fracture and the amount damage was observed due to irradiation in both crack growth directions. For cortical bone irradiated at 27.5kGy, fracture toughness is reduced due to the inhibition of damage formation at and near the crack tip. Microcrack fatigue crack growth and arrest were investigated through observations of surface cracks during cyclic loading. At the applied cyclic stresses, the microcracks propagated and arrested in less than 10,000 cycles. In addition, the microcracks were observed not to grow beyond a length of 150mum and a DeltaK of 0.5MNm-3/2, supporting a microstructural barrier concept. Finally, the contribution of linear microcracks to material property degradation was examined by developing a theoretical micromechanical damage model. The model was compared to experimentally induced damage in bone tissue. The percent contribution of linear microcracks to the total degradation was predicted to be less than 5%, indicating that diffuse damage or an unidentified form of damage is primarily responsible for material property degradation in human cortical bone tissue.

Damage threshold in adult rabbit eyes after scleral cross-linking by riboflavin/blue light application.

PubMed

Iseli, Hans Peter; Körber, Nicole; Karl, Anett; Koch, Christian; Schuldt, Carsten; Penk, Anja; Liu, Qing; Huster, Daniel; Käs, Josef; Reichenbach, Andreas; Wiedemann, Peter; Francke, Mike

2015-10-01

Several scleral cross-linking (SXL) methods were suggested to increase the biomechanical stiffness of scleral tissue and therefore, to inhibit axial eye elongation in progressive myopia. In addition to scleral cross-linking and biomechanical effects caused by riboflavin and light irradiation such a treatment might induce tissue damage, dependent on the light intensity used. Therefore, we characterized the damage threshold and mechanical stiffening effect in rabbit eyes after application of riboflavin combined with various blue light intensities. Adult pigmented and albino rabbits were treated with riboflavin (0.5 %) and varying blue light (450 ± 50 nm) dosages from 18 to 780 J/cm(2) (15 to 650 mW/cm(2) for 20 min). Scleral, choroidal and retinal tissue alterations were detected by means of light microscopy, electron microscopy and immunohistochemistry. Biomechanical changes were measured by shear rheology. Blue light dosages of 480 J/cm(2) (400 mW/cm(2)) and beyond induced pathological changes in ocular tissues; the damage threshold was defined by the light intensities which induced cellular degeneration and/or massive collagen structure changes. At such high dosages, we observed alterations of the collagen structure in scleral tissue, as well as pigment aggregation, internal hemorrhages, and collapsed blood vessels. Additionally, photoreceptor degenerations associated with microglia activation and macroglia cell reactivity in the retina were detected. These pathological alterations were locally restricted to the treated areas. Pigmentation of rabbit eyes did not change the damage threshold after a treatment with riboflavin and blue light but seems to influence the vulnerability for blue light irradiations. Increased biomechanical stiffness of scleral tissue could be achieved with blue light intensities below the characterized damage threshold. We conclude that riboflavin and blue light application increased the biomechanical stiffness of scleral tissue at blue light energy levels below the damage threshold. Therefore, applied blue light intensities below the characterized damage threshold might define a therapeutic blue light tolerance range. Copyright © 2015 Elsevier Ltd. All rights reserved.

Granulocyte colony-stimulating factor improves host defense to resuscitated shock and polymicrobial sepsis without provoking generalized neutrophil-mediated damage.

PubMed

Patton, J H; Lyden, S P; Ragsdale, D N; Croce, M A; Fabian, T C; Proctor, K G

1998-05-01

Granulocyte colony-stimulating factor (G-CSF) increases production and release of neutrophil precursors and activates multiple functions of circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects in many experimental models of sepsis; its actions with superimposed reperfusion insults are unknown. In traumatic conditions, G-CSF could exacerbate unregulated, PMN-dependent injury to otherwise normal host tissue or, it could partially reverse trauma-induced immune suppression, which may improve long-term outcome. This study tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. Anesthetized swine were subjected to cecal ligation and incision, 35% hemorrhage, and 1 hr of hypotension. Resuscitation consisted of intravenous G-CSF (5 microg/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observers, blind to the protocol, graded autopsy samples for localization of infection and quality of abscess wall formation. Data included complete blood count, granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein, lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in vitro (lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase (MPO). Neutrophilia and localization of infection, were significantly improved by G-CSF. Variables altered by G-CSF, though not significantly, showed GO2B potential increased by 50%, lipopolysaccharide-tumor necrosis factor decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF did not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous O2 saturations were unaltered. Our data show that G-CSF initiated at the time of resuscitation reduced the sequelae of posttrauma sepsis by increasing PMN proliferation and function without potentiating PMN-mediated lung reperfusion injury.

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

PubMed Central

Coats, Stephen R.; Hashim, Ahmed; Paramonov, Nikolay A.; Curtis, Michael A.

2016-01-01

ABSTRACT Intestinal homeostasis mechanisms must protect the host intestinal tissue from endogenous lipopolysaccharides (LPSs) produced by the intestinal microbiota. In this report, we demonstrate that murine intestinal fecal lipids effectively block Toll-like receptor 4 (TLR4) responses to naturally occurring Bacteroidetes sp. LPS. Cardiolipin (CL) represents a significant proportion of the total intestinal and fecal lipids and, furthermore, potently antagonizes TLR4 activation by reducing LPS binding at the lipopolysaccharide binding protein (LBP), CD14, and MD-2 steps of the TLR4 signaling pathway. It is further demonstrated that intestinal lipids and CL are less effective at neutralizing more potent Enterobacteriaceae-type LPS, which is enriched in feces obtained from mice with dextran sodium sulfate (DSS)-treated inflammatory bowel disease. The selective inhibition of naturally occurring LPS structures by intestinal lipids may represent a novel homeostasis mechanism that blocks LPS activation in response to symbiotic but not dysbiotic microbial communities. IMPORTANCE The guts of animals harbor a variety of Gram-negative bacteria associated with both states of intestinal health and states of disease. Environmental factors, such as dietary habits, can drive the microbial composition of the host animal's intestinal bacterial community toward a more pathogenic state. Both beneficial and harmful Gram-negative bacteria are capable of eliciting potentially damaging inflammatory responses from the host intestinal tissues via a lipopolysaccharide (LPS)-dependent pathway. Physical mucosal barriers and antibodies produced by the intestinal immune system protect against the undesired inflammatory effects of LPS, although it is unknown why some bacteria are more effective at overcoming the protective barriers than others. This report describes the discovery of a lipid-type protective barrier in the intestine that reduces the deleterious effects of LPSs from beneficial bacteria but is less effective in dampening the inflammatory effects of LPSs from harmful bacteria, providing a novel mechanistic insight into inflammatory intestinal disorders. PMID:27208127

Confocal Fluorescence Imaging Enables Noninvasive Quantitative Assessment of Host Cell Populations In Vivo Following Photodynamic Therapy

PubMed Central

Mitra, Soumya; Mironov, Oleg; Foster, Thomas H.

2012-01-01

We report the use of optical imaging strategies to noninvasively examine photosensitizer distribution and physiological and host responses to 2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) of EMT6 tumors established in the ears of BALB/c mice. 24 h following intravenous (IV) administration of 1 μmol kg-1 HPPH, wide-field fluorescence imaging reveals tumor selectivity with an approximately 2-3-fold differential between tumor and adjacent normal tissue. Confocal microscopy demonstrates a relatively homogeneous intratumor HPPH distribution. Labeling of host cells using fluorophore-conjugated antibodies allowed the visualization of Gr1+/CD11b+ leukocytes and major histocompatibility complex class II (MHC-II)+ cells in vivo. Imaging of the treated site at different time-points following irradiation shows significant and rapid increases in Gr1+ cells in response to therapy. The maximum accumulation of Gr1+ cells is found at 24 h post-irradiation, followed by a decrease at the 48 h time-point. Using IV-injected FITC-conjugated dextran as a fluorescent perfusion marker, we imaged tissue perfusion at different times post-irradiation and found that the reduced Gr1+ cell density at 48 h correlated strongly with functional damage to the vasculature as reported via decreased perfusion status. Dual color confocal imaging experiments demonstrates that about 90% of the anti-Gr1 cell population co-localized with anti-CD11b labeling, thus indicating that majority of the Gr1-labeled cells were neutrophils. At 24 h post-PDT, an approximately 2-fold increase in MHC-II+ cells relative to untreated control is also observed. Co-localization analysis reveals an increase in the fraction of Gr1+ cells expressing MHC-II, suggesting that HPPH-PDT is stimulating neutrophils to express an antigen-presenting phenotype. PMID:23082097

Integrated genomic and immunophenotypic classification of pancreatic cancer reveals three distinct subtypes with prognostic/predictive significance.

PubMed

Wartenberg, Martin; Cibin, Silvia; Zlobec, Inti; Vassella, Erik; Eppenberger-Castori, Serenella M M; Terracciano, Luigi; Eichmann, Micha; Worni, Mathias; Gloor, Beat; Perren, Aurel; Karamitopoulou, Eva

2018-04-16

Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins. Previous data on FOXP3 were integrated. Immune-cell counts and protein expression were correlated with tumor-derived driver mutations, clinicopathologic features (TNM 8. 2017), survival and epithelial-mesenchymal-transition (EMT)-like tumor budding.  Results: Three PDAC-subtypes were identified: the "immune-escape" (54%), poor in T- and B-cells and enriched in FOXP3+Tregs, with high-grade budding, frequent CDKN2A- , SMAD4- and PIK3CA-mutations and poor outcome; the "immune-rich" (35%), rich in T- and B-cells and poorer in FOXP3+Tregs, with infrequent budding, lower CDKN2A- and PIK3CA-mutation rate and better outcome and a subpopulation with tertiary lymphoid tissue (TLT), mutations in DNA damage response genes (STK11, ATM) and the best outcome; and the "immune-exhausted" (11%) with immunogenic microenvironment and two subpopulations: one with PD-L1-expression and high PIK3CA-mutation rate and a microsatellite-unstable subpopulation with high prevalence of JAK3-mutations. The combination of low budding, low stromal FOXP3-counts, presence of TLTs and absence of CDKN2A-mutations confers significant survival advantage in PDAC-patients. Immune host responses correlate with tumor characteristics leading to morphologically recognizable PDAC-subtypes with prognostic/predictive significance. Copyright ©2018, American Association for Cancer Research.

Reverse-Phase Microarray Analysis Reveals Novel Targets in Lymph Nodes of Bacillus anthracis Spore-Challenged Mice

PubMed Central

Popova, Taissia G.; Espina, Virginia; Liotta, Lance A.; Popov, Serguei G.

2015-01-01

Anthrax is a frequently fatal infection of many animal species and men. The causative agent Bacillus anthracis propagates through the lymphatic system of the infected host; however, the specific interactions of the host and microbe within the lymphatics are incompletely understood. We report the first description of the phosphoprotein signaling in the lymph nodes of DBA/2 mice using a novel technique combining the reverse-phase microarray with the laser capture microdissesction. Mice were challenged into foot pads with spores of toxinogenic, unencapsulated Sterne strain. The spores quickly migrated to the regional popliteal lymph nodes and spread to the bloodstream as early as 3 h post challenge. All mice died before 72 h post challenge from the systemic disease accompanied by a widespread LN tissue damage by bacteria, including the hemorrhagic necrotizing lymphadenitis, infiltration of CD11b+ and CD3+ cells, and massive proliferation of bacteria in lymph nodes. A macrophage scavenger receptor CD68/macrosialin was upregulated and found in association with vegetative bacteria likely as a marker of their prior interaction with macrophages. The major signaling findings among the 65 tested proteins included the reduced MAPK signaling, upregulation of STAT transcriptional factors, and altered abundance of a number of pro- and anti-apoptotic proteins with signaling properties opposing each other. Downregulation of ERK1/2 was associated with the response of CD11b+ macrophages/dendritic cells, while upregulation of the pro-apoptotic Puma indicated a targeting of CD3+ T-cells. A robust upregulation of the anti-apoptotic survivin was unexpected because generally it is not observed in adult tissues. Taken together with the activation of STATs it may reflect a new pathogenic mechanism aimed to delay the onset of apoptosis. Our data emphasize a notion that the net biological outcome of disease is determined by a cumulative impact of factors representing the microbial insult and the protective capacity of the host. PMID:26091359

Charting the Isophasic Endophyte of Dwarf Mistletoe Arceuthobium douglasii (Viscaceae) in Host Apical Buds

PubMed Central

LYE, DAVID

2006-01-01

• Background and Aims Dwarf mistletoes (Arceuthobium; Viscaceae) are highly specialized dioecious angiosperms parasitic on many gymnosperm hosts in the northern hemisphere. Several dwarf mistletoe species are capable of inducing an unusual form of isophasic infection in which the internal (endophytic) system proliferates even into the apical buds of its hosts. Studies of the internal endophytic system have, for the most part, focused on the parasite within secondary host tissues. The present anatomical and ultrastructural study characterizes the growth pattern of the isophasic endophytic system of Arceuthobium douglasii within the dormant apical buds of Pseudotsuga menziesii. • Methods Semi-thin serial sections from dwarf mistletoe-infected host apical buds were mounted, stained and micrographed. Graphic files were created from the serial micrographs and these files were stacked. These stacked files were utilized to describe the pattern of growth of the endophyte within the host tissue. The interface between cells of the mistletoe and host was also examined at the ultrastructural level by transmission electron microscopy. • Key Results By utilizing a novel technique of superimposed graphics, the current study reveals an organized pattern of mistletoe distribution that penetrates further into host tissues than previously known. A consistent pattern of growth occurring even into the preformed leaves of the host is documented. • Conclusions The apparently non-intrusive growth of the parasite appears to be developmentally synchronized with that of the host. No symplastic connections were observed in the ultrastructural examination of the parasite/host interface within the apical buds of Pseudotsuga menziesii parasitized by A. douglasii or of Pinus contorta parasitized by A. americanum. PMID:16613903

Infrared laser damage thresholds in corneal tissue phantoms using femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Boretsky, Adam R.; Clary, Joseph E.; Noojin, Gary D.; Rockwell, Benjamin A.

2018-02-01

Ultrafast lasers have become a fixture in many biomedical, industrial, telecommunications, and defense applications in recent years. These sources are capable of generating extremely high peak power that can cause laser-induced tissue breakdown through the formation of a plasma upon exposure. Despite the increasing prevalence of such lasers, current safety standards (ANSI Z136.1-2014) do not include maximum permissible exposure (MPE) values for the cornea with pulse durations less than one nanosecond. This study was designed to measure damage thresholds in corneal tissue phantoms in the near-infrared and mid-infrared to identify the wavelength dependence of laser damage thresholds from 1200-2500 nm. A high-energy regenerative amplifier and optical parametric amplifier outputting 100 femtosecond pulses with pulse energies up to 2 mJ were used to perform exposures and determine damage thresholds in transparent collagen gel tissue phantoms. Three-dimensional imaging, primarily optical coherence tomography, was used to evaluate tissue phantoms following exposure to determine ablation characteristics at the surface and within the bulk material. The determination of laser damage thresholds in the near-IR and mid-IR for ultrafast lasers will help to guide safety standards and establish the appropriate MPE levels for exposure sensitive ocular tissue such as the cornea. These data will help promote the safe use of ultrafast lasers for a wide range of applications.

Toxoplasma gondii and Epilepsy.

PubMed

Ayaz, Erol; Türkoğlu, Şule Aydın; Orallar, Hayriye

2016-06-01

Toxoplasma gondii is a zoonotic parasite can be seen in all the vital organ; in the acute phase, it can be found in the blood, cerebrospinal fluid, semen, tears, saliva, urine, and in almost all body fluids. Transplasental infection can lead to fetal damage and miscarriage. Its last hosts are felines and intermediate hosts are all mammals, including humans. People infected by the ingestion of meat containing cysts in undercooked or raw, are thrown oocysts with cat felines By taking in water and food, from mother to fetus transplacental way, the infected organ transplantation, blood transfusion, laboratory accidents and kaprofaj transmitted by mechanical vectors of the invertebrates. Suppression of the immune system is being transformed to the shape and texture of the cysts with bradyzoite. The parasite settles in the cells of the tissue cysts and causes change in the cellular mechanisms, such as cytokinin task. Depending on changes and type of neurotransmitter (GABA, glutamate, serotonin, dopamine) levels in CSF in ions (Ca, K, Cl, Mg), it is believed that there is a change in their concentration. In this review, literature about the relationship between T. gondii and epilepsy and epileptiform activity the importance of parasites, which settle in the brain, will be highlighted.

Transplantation of polarized type 2 donor T cells reduces mortality caused by experimental graft-versus-host disease.

PubMed

Krenger, W; Cooke, K R; Crawford, J M; Sonis, S T; Simmons, R; Pan, L; Delmonte, J; Karandikar, M; Ferrara, J L

1996-11-15

Acute graft-versus-host disease (GVHD) is thought to be initiated by alloreactive type 1 T cells that secrete gamma-interferon (IFN-gamma). IFN-gamma induces the production of inflammatory cytokines, e.g., tumor necrosis factor-alpha and interleukin (IL)-1, which are the distal mediators of GVHD. We demonstrate that the transplantation of polarized type 2 murine T cells (i.e., cells secreting IL-4 but not IFN-gamma) together with T-cell-depleted bone marrow results in a significant increase in survival (P<0.001) after bone marrow transplantation across minor histocompatibility barriers (B10.BR-->CBA/J). Further analysis demonstrated that increased survival in recipients of polarized type 2 T cells correlated with diminished production of both IFN-gamma and tumor necrosis factor-alpha but with increases in IL-4 2 weeks after transplantation. Despite improved survival, histologic changes of GVHD were evident in oral mucosal and hepatic tissues at 7 weeks after bone marrow transplantation. These data provide further evidence that inflammatory cytokines in the immediate posttransplant period are pivotal to the development of mortality but that they do not correlate with individual target organ damage.

Therapeutics for Graft-versus-Host Disease: From Conventional Therapies to Novel Virotherapeutic Strategies.

PubMed

Villa, Nancy Y; Rahman, Masmudur M; McFadden, Grant; Cogle, Christopher R

2016-03-22

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a curative potential for many hematologic malignancies and blood diseases. However, the success of allo-HSCT is limited by graft-versus-host disease (GVHD), an immunological syndrome that involves inflammation and tissue damage mediated by donor lymphocytes. Despite immune suppression, GVHD is highly incident even after allo-HSCT using human leukocyte antigen (HLA)-matched donors. Therefore, alternative and more effective therapies are needed to prevent or control GVHD while preserving the beneficial graft-versus-cancer (GVC) effects against residual disease. Among novel therapeutics for GVHD, oncolytic viruses such as myxoma virus (MYXV) are receiving increased attention due to their dual role in controlling GVHD while preserving or augmenting GVC. This review focuses on the molecular basis of GVHD, as well as state-of-the-art advances in developing novel therapies to prevent or control GVHD while minimizing impact on GVC. Recent literature regarding conventional and the emerging therapies are summarized, with special emphasis on virotherapy to prevent GVHD. Recent advances using preclinical models with oncolytic viruses such as MYXV to ameliorate the deleterious consequences of GVHD, while maintaining or improving the anti-cancer benefits of GVC will be reviewed.

CFTR expression and organ damage in cystic fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tizzano, E.; Chitayat, D.; Buchwald, M.

1994-09-01

To assist our understanding of the origin of organ damage caused by cystic fibrosis (CF) disease, we have analyzed the pattern of expression of the CF gene (CFTR). mRNA in situ hybridization analysis was carried out in human fetal, newborn, infant and adult tissues and the abundance of the mRNA was correlated with the known pathology at the various stages of human development. Analysis of the pattern of expression indicates a constitutive level of mRNA in gastrointestinal tissues starting during early development and maintained throughout life. Prenatal respiratory tissues show qualitative and quantitative major differences in comparison to postnatal lungmore » samples. Male reproductive tissues show high levels of expression in the head of the epididymis compared with the rest of the male ducts. Female reproductive tissues show a variable pattern of expression at different stages during fetal development and during puberty probably due to changes in hormonal levels. Gastrointestinal and male reproductive tissues have a consistent pathology at birth, whereas no lung abnormalities have been described in newborns affected by CF. Our results show that there is no exact correlations between organ damage present at birth and the degree of CFTR expression. To explain these observations, we hypothesize that the pathogenesis of organ damage in CF depend on at least three factors: the rate of CFTR-mediated fluid secretion, differences in genotype and environmental factors, such as the amount of macromolecules in the lumen of the ducts. This last element predicts that damage will occur in tissues with high protein loads and low flow rates (e.g. pancreas, epididymis), where the absence of CFTR function leads to obstruction and pathology. Organs that express CFTR but with no significant damage (e.g. prenatal lung, female reproductive tissues), will have a low protein load and a high flow rates.« less

Host conservatism or host specialization? Patterns of fungal diversification are influenced by host specificity in Ophiognomonia (Gnomoniaceae, Diaporthales)

USDA-ARS?s Scientific Manuscript database

Species of Ophiognomonia (Gnomoniaceae) are perithecial fungi that occur as endophytes, pathogens, and latent saprobes on leaf and stem tissue of plants in the Betulaceae, Fagaceae, Juglandaceae, Lauraceae, Malvaceae, Platanaceae, Rosaceae, Salicaceae, and Sapindaceae. In this study host plant patte...

Mathematical modelling of blood-brain barrier failure and edema

NASA Astrophysics Data System (ADS)

Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

2015-11-01

Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

Unresolved issues in the understanding of the pathogenesis of local tissue damage induced by snake venoms.

PubMed

Gutiérrez, José María; Rucavado, Alexandra; Escalante, Teresa; Herrera, Cristina; Fernández, Julián; Lomonte, Bruno; Fox, Jay W

2018-06-15

Snakebite envenoming by viperid species, and by some elapids, is characterized by a complex pattern of tissue damage at the anatomical site of venom injection. In severe cases, tissue destruction may be so extensive as to lead to permanent sequelae, with serious pathophysiological, social and psychological consequences. Significant advances have been performed in the study of venom-induced tissue damage, including identification and characterization of the toxins involved, insights into the mechanisms of action of venoms and toxins, and study of tissue responses to venom-induced injury. Nevertheless, much remains to be known and understood on the pathogenesis of these alterations. This review focuses on some of the pending issues in the topic of snake venom-induced local tissue damage. The traditional 'reductionist' approach, which has predominated in the study of snake venoms and their actions, needs to be complemented by more integrative and holistic perspectives aimed at capturing the complexity of these pathological alterations. Future advances in the study of these topics will certainly pave the way for innovative therapeutic interventions, with the goal of reducing the impact of this aspect of snakebite envenoming. Copyright © 2018 Elsevier Ltd. All rights reserved.

Parasitoids select plants more heavily infested with their caterpillar hosts: a new approach to aid interpretation of plant headspace volatiles

PubMed Central

Girling, Robbie D.; Stewart-Jones, Alex; Dherbecourt, Julie; Staley, Joanna T.; Wright, Denis J.; Poppy, Guy M.

2011-01-01

Plants produce volatile organic compounds (VOCs) in response to herbivore attack, and these VOCs can be used by parasitoids of the herbivore as host location cues. We investigated the behavioural responses of the parasitoid Cotesia vestalis to VOCs from a plant–herbivore complex consisting of cabbage plants (Brassica oleracea) and the parasitoids host caterpillar, Plutella xylostella. A Y-tube olfactometer was used to compare the parasitoids' responses to VOCs produced as a result of different levels of attack by the caterpillar and equivalent levels of mechanical damage. Headspace VOC production by these plant treatments was examined using gas chromatography–mass spectrometry. Cotesia vestalis were able to exploit quantitative and qualitative differences in volatile emissions, from the plant–herbivore complex, produced as a result of different numbers of herbivores feeding. Cotesia vestalis showed a preference for plants with more herbivores and herbivore damage, but did not distinguish between different levels of mechanical damage. Volatile profiles of plants with different levels of herbivores/herbivore damage could also be separated by canonical discriminant analyses. Analyses revealed a number of compounds whose emission increased significantly with herbivore load, and these VOCs may be particularly good indicators of herbivore number, as the parasitoid processes cues from its external environment. PMID:21270031

Detection of theileria parva in tissues of cattle undergoing severe east coast fever disease show significant parasite accumulation in the spleen

USDA-ARS?s Scientific Manuscript database

Infiltration and proliferation of Theileria parva infected lymphocytes in bovine host lymphoid organs is one of the hallmarks of T. parva infection. The relative abundance of parasites within infected host tissues, both lymphoid and non-lymphoid is however unknown. Using quantitative PCR, we have sh...

Using electrolyte leakage tests to determine lifting windows and detect tissue damage

Treesearch

Richard W. Tinus

2002-01-01

Physiological testing is rapidly coming into use as a means to determine the condition of nursery stock and predict how it will respond to treatment or use. One such test, the electrolyte leakage test, can be used to measure cold hardiness and detect tissue damage. The principle of this test is that when cell membranes are damaged, electrolytes leak out into the water...

Systemic acquired tolerance to virulent bacterial pathogens in tomato.

PubMed

Block, Anna; Schmelz, Eric; O'Donnell, Phillip J; Jones, Jeffrey B; Klee, Harry J

2005-07-01

Recent studies on the interactions between plants and pathogenic microorganisms indicate that the processes of disease symptom development and pathogen growth can be uncoupled. Thus, in many instances, the symptoms associated with disease represent an active host response to the presence of a pathogen. These host responses are frequently mediated by phytohormones. For example, ethylene and salicylic acid (SA) mediate symptom development but do not influence bacterial growth in the interaction between tomato (Lycopersicon esculentum) and virulent Xanthomonas campestris pv vesicatoria (Xcv). It is not apparent why extensive tissue death is integral to a defense response if it does not have the effect of limiting pathogen proliferation. One possible function for this hormone-mediated response is to induce a systemic defense response. We therefore assessed the systemic responses of tomato to Xcv. SA- and ethylene-deficient transgenic lines were used to investigate the roles of these phytohormones in systemic signaling. Virulent and avirulent Xcv did induce a systemic response as evidenced by expression of defense-associated pathogenesis-related genes in an ethylene- and SA-dependent manner. This systemic response reduced cell death but not bacterial growth during subsequent challenge with virulent Xcv. This systemic acquired tolerance (SAT) consists of reduced tissue damage in response to secondary challenge with a virulent pathogen with no effect upon pathogen growth. SAT was associated with a rapid ethylene and pathogenesis-related gene induction upon challenge. SAT was also induced by infection with Pseudomonas syringae pv tomato. These data show that SAT resembles systemic acquired resistance without inhibition of pathogen growth.

There Is a Method to the Madness: Strategies to Study Host Complement Evasion by Lyme Disease and Relapsing Fever Spirochetes.

PubMed

Marcinkiewicz, Ashley L; Kraiczy, Peter; Lin, Yi-Pin

2017-01-01

Lyme disease and relapsing fever are caused by various Borrelia species. Lyme disease borreliae , the most common vector-borne pathogens in both the U.S. and Europe, are transmitted by Ixodes ticks and disseminate from the site of tick bites to tissues leading to erythema migrans skin rash, arthritis, carditis, and neuroborreliosis. Relapsing fever borreliae , carried by ticks and lice, trigger reoccurring fever episodes. Following transmission, spirochetes survive in the blood to induce bacteremia at the early stages of infection, which is thought to promote evasion of the host complement system. The complement system acts as an important innate immune defense mechanism in humans and vertebrates. Upon activation, the cleaved complement components form complexes on the pathogen surface to eventually promote bacteriolysis. The complement system is negatively modulated by a number of functionally diverse regulators to avoid tissue damage. To evade and inhibit the complement system, spirochetes are capable of binding complement components and regulators. Complement inhibition results in bacterial survival in serum (serum resistance) and is thought to promote bloodstream survival, which facilitates spirochete dissemination and disease manifestations. In this review, we discuss current methodologies to elucidate the mechanisms of Borrelia spp. that promote serum resistance and bloodstream survival, as well as novel methods to study factors responsible for bloodstream survival of Lyme disease borreliae that can be applied to relapsing fever borreliae . Understanding the mechanisms these pathogens utilize to evade the complement system will ultimately aid in the development of novel therapeutic strategies and disease prevention to improve human health.

Pseudomonas aeruginosa proteolytically alters the interleukin 22-dependent lung mucosal defense.

PubMed

Guillon, Antoine; Brea, Deborah; Morello, Eric; Tang, Aihua; Jouan, Youenn; Ramphal, Reuben; Korkmaz, Brice; Perez-Cruz, Magdiel; Trottein, Francois; O'Callaghan, Richard J; Gosset, Philippe; Si-Tahar, Mustapha

2017-08-18

The IL-22 signaling pathway is critical for regulating mucosal defense and limiting bacterial dissemination. IL-22 is unusual among interleukins because it does not directly regulate the function of conventional immune cells, but instead targets cells at outer body barriers, such as respiratory epithelial cells. Consequently, IL-22 signaling participates in the maintenance of the lung mucosal barrier by controlling cell proliferation and tissue repair, and enhancing the production of specific chemokines and anti-microbial peptides. Pseudomonas aeruginosa is a major pathogen of ventilator-associated pneumonia and causes considerable lung tissue damage. A feature underlying the pathogenicity of this bacterium is its capacity to persist and develop in the host, particularly in the clinical context of nosocomial lung infections. We aimed to investigate the ability of P. auruginosa to disrupt immune-epithelial cells cross-talk. We found that P. aeruginosa escapes the host mucosal defenses by degrading IL-22, leading to severe inhibition of IL-22-mediated immune responses. We demonstrated in vitro that, protease IV, a type 2 secretion system-dependent serine protease, is responsible for the degradation of IL-22 by P. aeruginosa. Moreover, the major anti-proteases molecules present in the lungs were unable to inhibit protease IV enzymatic activity. In addition, tracheal aspirates of patients infected by P. aeruginosa contain protease IV activity which further results in IL-22 degradation. This so far undescribed cleavage of IL-22 by a bacterial protease is likely to be an immune-evasion strategy that contributes to P. aeruginosa-triggered respiratory infections.

Current Perspectives on Ophthalmic Mycoses

PubMed Central

Thomas, Philip A.

2003-01-01

Fungi may infect the cornea, orbit and other ocular structures. Species of Fusarium, Aspergillus, Candida, dematiaceous fungi, and Scedosporium predominate. Diagnosis is aided by recognition of typical clinical features and by direct microscopic detection of fungi in scrapes, biopsy specimens, and other samples. Culture confirms the diagnosis. Histopathological, immunohistochemical, or DNA-based tests may also be needed. Pathogenesis involves agent (invasiveness, toxigenicity) and host factors. Specific antifungal therapy is instituted as soon as the diagnosis is made. Amphotericin B by various routes is the mainstay of treatment for life-threatening and severe ophthalmic mycoses. Topical natamycin is usually the first choice for filamentous fungal keratitis, and topical amphotericin B is the first choice for yeast keratitis. Increasingly, the triazoles itraconazole and fluconazole are being evaluated as therapeutic options in ophthalmic mycoses. Medical therapy alone does not usually suffice for invasive fungal orbital infections, scleritis, and keratitis due to Fusarium spp., Lasiodiplodia theobromae, and Pythium insidiosum. Surgical debridement is essential in orbital infections, while various surgical procedures may be required for other infections not responding to medical therapy. Corticosteroids are contraindicated in most ophthalmic mycoses; therefore, other methods are being sought to control inflammatory tissue damage. Fungal infections following ophthalmic surgical procedures, in patients with AIDS, and due to use of various ocular biomaterials are unique subsets of ophthalmic mycoses. Future research needs to focus on the development of rapid, species-specific diagnostic aids, broad-spectrum fungicidal compounds that are active by various routes, and therapeutic modalities which curtail the harmful effects of fungus- and host tissue-derived factors. PMID:14557297

RIG-I-like receptor regulation in virus infection and immunity.

PubMed

Chan, Ying Kai; Gack, Michaela U

2015-06-01

Mammalian cells have the intrinsic capacity to detect viral pathogens and to initiate an antiviral response that is characterized by the induction of interferons (IFNs) and proinflammatory cytokines. A delicate regulation of the signaling pathways that lead to cytokine production is needed to ensure effective clearance of the virus, while preventing tissue damage caused by excessive cytokine release. Here, we focus on the mechanisms that modulate the signal transduction triggered by RIG-I-like receptors (RLRs) and their adaptor protein MAVS, key components of the host machinery for sensing foreign RNA. Specifically, we summarize recent advances in understanding how RLR signaling is regulated by posttranslational and posttranscriptional mechanisms, microRNAs (miRNAs) and autophagy. We further discuss how viruses target these regulatory mechanisms for immune evasion. Copyright © 2015 Elsevier B.V. All rights reserved.

[Physical and chemical emergencies in dermatology].

PubMed

Malisiewicz, B; Meissner, M; Kaufmann, R; Valesky, E

2018-05-01

Physical and chemical emergencies are often caused by household or work accidents. Regardless of the medical field and outside specialized clinics, the physician may be confronted with the situation for first or secondary care. The identification of the causing agent and a rapid assessment of the extent and severity of the tissue damage are essential to initiate early transfer to a specialized burn clinic. Grade 2b tissue damage is usually surgically treated. Smaller and superficial injuries can often be conservatively treated. Even supposedly safe and over-the-counter medicines can also lead to serious tissue damage.

A quantitative and non-contact technique to characterise microstructural variations of skin tissues during photo-damaging process based on Mueller matrix polarimetry.

PubMed

Dong, Yang; He, Honghui; Sheng, Wei; Wu, Jian; Ma, Hui

2017-10-31

Skin tissue consists of collagen and elastic fibres, which are highly susceptible to damage when exposed to ultraviolet radiation (UVR), leading to skin aging and cancer. However, a lack of non-invasive detection methods makes determining the degree of UVR damage to skin in real time difficult. As one of the fundamental features of light, polarization can be used to develop imaging techniques capable of providing structural information about tissues. In particular, Mueller matrix polarimetry is suitable for detecting changes in collagen and elastic fibres. Here, we demonstrate a novel, quantitative, non-contact and in situ technique based on Mueller matrix polarimetry for monitoring the microstructural changes of skin tissues during UVR-induced photo-damaging. We measured the Mueller matrices of nude mouse skin samples, then analysed the transformed parameters to characterise microstructural changes during the skin photo-damaging and self-repairing processes. Comparisons between samples with and without the application of a sunscreen showed that the Mueller matrix-derived parameters are potential indicators for fibrous microstructure in skin tissues. Histological examination and Monte Carlo simulations confirmed the relationship between the Mueller matrix parameters and changes to fibrous structures. This technique paves the way for non-contact evaluation of skin structure in cosmetics and dermatological health.

The comparison of thermal tissue injuries caused by ultrasonic scalpel and electrocautery use in rabbit tongue tissue

PubMed Central

Beriat, Guclu Kaan; Akmansu, Sefik Halit; Ezerarslan, Hande; Dogan, Cem; Han, Unsal; Saglam, Mehmet; Senel, Oytun Okan; Kocaturk, Sinan

2012-01-01

The aim of this study compares to the increase in tissue temperature and the thermal histological effects of ultrasonic scalpel, bipolar and unipolar electrosurgery incisions in the tongue tissue of rabbits. This study evaluates the histopathological changes related to thermal change and the maximum temperature values in the peripheral tissue brought about by the incisions carried out by the three methods in a comparative way. To assess thermal tissue damage induced by the three instruments, maximum tissue temperatures were measured during the surgical procedure and tongue tissue samples were examined histopathologically following the surgery. The mean maximum temperature values of the groups were 93.93±2.76 C° for the unipolar electrocautery group, whereas 85.07±5.95 C° for the bipolar electrocautery group, and 108.23±7.64 C° for the ultrasonic scalpel group. There was a statistically significant relationship between the increase in maximum temperature values and the separation among tissue layers, edema, congestion, necrosis, hemorrhage, destruction in blood vessel walls and fibrin accumulation, and between the existence of fibrin thrombus and tissue damage depth (p<0.05). It was concluded that the bipolar electrocautery use gives way to less temperature increase in the tissues and less thermal tissue damage in comparison to the other methods. PMID:22938541

The Role of Direct and Visual Force Feedback in Suturing Using a 7-DOF Dual-Arm Teleoperated System.

PubMed

Talasaz, Ali; Trejos, Ana Luisa; Patel, Rajni V

2017-01-01

The lack of haptic feedback in robotics-assisted surgery can result in tissue damage or accidental tool-tissue hits. This paper focuses on exploring the effect of haptic feedback via direct force reflection and visual presentation of force magnitudes on performance during suturing in robotics-assisted minimally invasive surgery (RAMIS). For this purpose, a haptics-enabled dual-arm master-slave teleoperation system capable of measuring tool-tissue interaction forces in all seven Degrees-of-Freedom (DOFs) was used. Two suturing tasks, tissue puncturing and knot-tightening, were chosen to assess user skills when suturing on phantom tissue. Sixteen subjects participated in the trials and their performance was evaluated from various points of view: force consistency, number of accidental hits with tissue, amount of tissue damage, quality of the suture knot, and the time required to accomplish the task. According to the results, visual force feedback was not very useful during the tissue puncturing task as different users needed different amounts of force depending on the penetration of the needle into the tissue. Direct force feedback, however, was more useful for this task to apply less force and to minimize the amount of damage to the tissue. Statistical results also reveal that both visual and direct force feedback were required for effective knot tightening: direct force feedback could reduce the number of accidental hits with the tissue and also the amount of tissue damage, while visual force feedback could help to securely tighten the suture knots and maintain force consistency among different trials/users. These results provide evidence of the importance of 7-DOF force reflection when performing complex tasks in a RAMIS setting.

Halide peroxidase in tissues that interact with bacteria in the host squid Euprymna scolopes.

PubMed

Small, A L; McFall-Ngai, M J

1999-03-15

An enzyme with similarities to myeloperoxidase, the antimicrobial halide peroxidase in mammalian neutrophils, occurs abundantly in the light organ tissue of Euprymna scolopes, a squid that maintains a beneficial association with the luminous bacterium Vibrio fischeri. Using three independent assays typically applied to the analysis of halide peroxidase enzymes, we directly compared the activity of the squid enzyme with that of human myeloperoxidase. One of these methods, the diethanolamine assay, confirmed that the squid peroxidase requires halide ions for its activity. The identification of a halide peroxidase in a cooperative bacterial association suggested that this type of enzyme can function not only to control pathogens, but also to modulate the interactions of host animals with their beneficial partners. To determine whether the squid peroxidase functions under both circumstances, we examined its distribution in a variety of host tissues, including those that typically interact with bacteria and those that do not. Tissues interacting with bacteria included those that have specific cooperative associations with bacteria (i.e., the light organ and accessory nidamental gland) and those that have transient nonspecific interactions with bacteria (i.e., the gills, which clear the cephalopod circulatory system of invading microorganisms). These bacteria-associated tissues were compared with the eye, digestive gland, white body, and ink-producing tissues, which do not typically interact directly with bacteria. Peroxidase enzyme assays, immunocytochemical localization, and DNA-RNA hybridizations showed that the halide-dependent peroxidase is consistently expressed in high concentration in tissues that interact bacteria. Elevated levels of the peroxidase were also found in the ink-producing tissues, which are known to have enzymatic pathways associated with antimicrobial activity. Taken together, these data suggest that the host uses a common biochemical response to the variety of types of associations that it forms with microorganisms.

Assessing Oak Decline Incidence and Distribution in the Southern U.S. Using Forest Inventory and Analysis Data

Treesearch

Steven W. Oak; James R. Steinman; Dale A. Starkey; Edwin K. Yockey

2004-01-01

Forest Inventory and Analysis data for twelve southern states were used to evaluate regional oak decline status. Total host type, vulnerable host type, and affected areas were determined. The attributes used for classification were forest type, predominant stem size class, oak basal area percent, and dieback damage coding. Host type totaled 104.7 million acres in the...

A self-lysis pathway that enhances the virulence of a pathogenic bacterium.

PubMed

McFarland, Kirsty A; Dolben, Emily L; LeRoux, Michele; Kambara, Tracy K; Ramsey, Kathryn M; Kirkpatrick, Robin L; Mougous, Joseph D; Hogan, Deborah A; Dove, Simon L

2015-07-07

In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of the alpA gene, which encodes a positive regulator that activates expression of the alpBCDE lysis cassette. Although this is lethal to the individual cell in which it occurs, we find it benefits the population as a whole during infection of a mammalian host. Thus, host and pathogen each may use PCD as a survival-promoting strategy. We suggest that activation of the Alp cell lysis pathway is a disease-enhancing response to bacterial DNA damage inflicted by the host immune system.

Canine and feline host ranges of canine parvovirus and feline panleukopenia virus: distinct host cell tropisms of each virus in vitro and in vivo.

PubMed Central

Truyen, U; Parrish, C R

1992-01-01

Canine parvovirus (CPV) emerged as an apparently new virus during the mid-1970s. The origin of CPV is unknown, but a variation from feline panleukopenia virus (FPV) or another closely related parvovirus is suspected. Here we examine the in vitro and in vivo canine and feline host ranges of CPV and FPV. Examination of three canine and six feline cell lines and mitogen-stimulated canine and feline peripheral blood lymphocytes revealed that CPV replicates in both canine and feline cells, whereas FPV replicates efficiently only in feline cells. The in vivo host ranges were unexpectedly complex and distinct from the in vitro host ranges. Inoculation of dogs with FPV revealed efficient replication in the thymus and, to some degree, in the bone marrow, as shown by virus isolation, viral DNA recovery, and Southern blotting and by strand-specific in situ hybridization. FPV replication could not be demonstrated in mesenteric lymph nodes or in the small intestine, which are important target tissues in CPV infection. Although CPV replicated well in all the feline cells tested in vitro, it did not replicate in any tissue of cats after intramuscular or intravenous inoculation. These results indicate that these viruses have complex and overlapping host ranges and that distinct tissue tropisms exist in the homologous and heterologous hosts. Images PMID:1323703

Milk phospholipid's protective effects against UV damage in skin equivalent models

NASA Astrophysics Data System (ADS)

Dargitz, Carl; Russell, Ashley; Bingham, Michael; Achay, Zyra; Jimenez-Flores, Rafael; Laiho, Lily H.

2012-03-01

Exposure of skin tissue to UV radiation has been shown to cause DNA photodamage. If this damaged DNA is allowed to replicate, carcinogenesis may occur. DNA damage is prevented from being passed on to daughter cells by upregulation of the protein p21. p21 halts the cells cycle allowing the cell to undergo apoptosis, or repair its DNA before replication. Previous work suggested that milk phospholipids may possess protective properties against UV damage. In this study, we observed cell morphology, cell apoptosis, and p21 expression in tissue engineered epidermis through the use of Hematoxylin and Eosin staining, confocal microscopy, and western blot respectively. Tissues were divided into four treatment groups including: a control group with no UV and no milk phospholipid treatment, a group exposed to UV alone, a group incubated with milk phospholipids alone, and a group treated with milk phospholipids and UV. All groups were incubated for twenty-four hours after treatment. Tissues were then fixed, processed, and embedded in paraffin. Performing western blots resulted in visible p21 bands for the UV group only, implying that in every other group, p21 expression was lesser. Numbers of apoptotic cells were determined by observing the tissues treated with Hoechst dye under a confocal microscope, and counting the number of apoptotic and total cells to obtain a percentage of apoptotic cells. We found a decrease in apoptotic cells in tissues treated with milk phospholipids and UV compared to tissues exposed to UV alone. Collectively, these results suggest that milk phospholipids protect cell DNA from damage incurred from UV light.

Bacteria influence mountain pine beetle brood development through interactions with symbiotic and antagonistic fungi: implications for climate-driven host range expansion.

PubMed

Therrien, Janet; Mason, Charles J; Cale, Jonathan A; Adams, Aaron; Aukema, Brian H; Currie, Cameron R; Raffa, Kenneth F; Erbilgin, Nadir

2015-10-01

Bark beetles are associated with diverse communities of symbionts. Although fungi have received significant attention, we know little about how bacteria, and in particular their interactions with fungi, affect bark beetle reproduction. We tested how interactions between four bacterial associates, two symbiotic fungi, and two opportunistic fungi affect performance of mountain pine beetles (Dendroctonus ponderosae) in host tissue. We compared beetle performance in phloem of its historical host, lodgepole pine (Pinus contorta), and its novel host recently accessed through warming climate, jack pine (Pinus banksiana). Overall, beetles produced more larvae, and established longer ovipositional and larval galleries in host tissue predominantly colonized by the symbiotic fungi, Grosmannia clavigera, or Ophiostoma montium than by the opportunistic colonizer Aspergillus and to a lesser extent, Trichoderma. This occurred in both historical and naïve hosts. Impacts of bacteria on beetle reproduction depended on particular fungus-bacterium combinations and host species. Some bacteria, e.g., Pseudomonas sp. D4-22 and Hy4T4 in P. contorta and Pseudomonas sp. Hy4T4 and Stenotrophomonas in P. banksiana, reduced antagonistic effects by Aspergillus and Trichoderma resulting in more larvae and longer ovipositional and larval galleries. These effects were not selective, as bacteria also reduced beneficial effects by symbionts in both host species. Interestingly, Bacillus enhanced antagonistic effects by Aspergillus in both hosts. These results demonstrate that bacteria influence brood development of bark beetles in host tissue. They also suggest that climate-driven range expansion of D. ponderosae through the boreal forest will not be significantly constrained by requirements of, or interactions among, its microbial associates.

Increased frequency of micronuclei in peripheral blood lymphocytes of subjects infected with Helicobacter pylori.

PubMed

Suárez, Susanna; Sueiro, Rosa Ana; Araujo, Manuel; Pardo, Fernanda; Menéndez, M Dolores; Pardiñas, M Carmen; Alvarez, Angel

2007-01-10

Epidemiological studies have demonstrated a close association between infection with Helicobacter pylori and the development of gastric carcinoma and mucosa-associated lymphoid tissue lymphomas in humans. The cytokinesis-block micronucleus assay was performed on peripheral blood lymphocytes of H. pylori-infected patients in order to investigate the possible induction of genotoxic damage. The study group consisted of 70 infected subjects including 33 women and 37 men, and 66 healthy controls (37 females and 29 males). Our results indicate that in the infected group the overall frequency of binucleated micronucleated cells (BNMN) per 1000 cells was higher (17.65+/-1.55) than in the controls (7.39+/-0.66), this difference being statistically significant. No differences were found between the infected and control groups regarding the cytokinesis-block proliferation index (CBPI). When the effect of different counfounding factors was evaluated, mutivariate statistical analysis revealed that age and alcohol consumption modulated the frequency of BNMN in infected people, and the interaction between alcohol use-smoking-infection also affected the BNMN frequency in H. pylori patients. Our results indicate that infection by H. pylori is associated with an increased level of cytogenetic damage in the cells of the host.

Effects of long non-coding RNA HOST2 on cell migration and invasion by regulating MicroRNA let-7b in breast cancer.

PubMed

Lu, Peng-Wei; Li, Lin; Wang, Fang; Gu, Yuan-Ting

2018-06-01

The study intends to investigate the effects of long non-coding RNA HOST2 (lncRNA HOST2) on cell migration and invasion by regulating microRNA let-7b (let-7b) in breast cancer. Breast cancer and adjacent normal tissues were collected from 98 patients with breast cancer. Breast cancer MCF-7 cells were divided into the blank, negative control (NC), pcDNA3-Mock, siHOST2, let-7b inhibitor, pcDNA3-HOST2, let-7b mimic, pcDNA3-HOST2 + let-7b mimic, and siHOST2 + let-7b inhibitor groups. RT-qPCR was used to detect the mRNA expressions of HOST2, let-7b, and c-Myc. Western blotting was conducted to measure the c-Myc expression. Scratch test and Transwell assay were applied to detect the cell motility, migration, and invasion. Xenograft tumor in nude mice was performed to evaluate the effect of different transfection on the tumor growth. Compared with adjacent normal tissues, HOST2 expression was higher but let-7b expression lower in breast cancer tissues. HOST2 expression in breast cancer cells was remarkably increased compared with that in the normal breast epithelial MCF-10A cells. In MCF-7 cells, in comparison with the blank and NC groups, expressions of HOST2 and c-Myc were reduced, but let-7b expression was remarkably elevated in the siHOST2 and let-7b mimic groups; the let-7b inhibitor group exhibited higher expressions of HOST2 and c-Myc but lower let-7b expression. Overexpression of HOST2 could promote cell motility, migration and invasion, thus enhancing the growth of breast cancer tumor. By inhibiting HOST2, opposite trends were found. LncRNA HOST2 promotes cell migration and invasion by inhibiting let-7b in breast cancer patients. © 2017 Wiley Periodicals, Inc.

Comparison of porcine thorax to gelatine blocks for wound ballistics studies.

PubMed

Mabbott, A; Carr, D J; Champion, S; Malbon, C

2016-09-01

Tissue simulants are typically used in ballistic testing as substitutes for biological tissues. Many simulants have been used, with gelatine amongst the most common. While two concentrations of gelatine (10 and 20 %) have been used extensively, no agreed standard exists for the preparation of either. Comparison of ballistic damage produced in both concentrations is lacking. The damage produced in gelatine is also questioned, with regards to what it would mean for specific areas of living tissue. The aim of the work discussed in this paper was to consider how damage caused by selected pistol and rifle ammunition varied in different simulants. Damage to gelatine blocks 10 and 20 % in concentration were tested with 9 mm Luger (9 × 19 full metal jacket; FMJ) rounds, while damage produced by .223 Remington (5.56 × 45 Federal Premium® Tactical® Bonded®) rounds to porcine thorax sections (skin, underlying tissue, ribs, lungs, ribs, underlying tissue, skin; backed by a block of 10 % gelatine) were compared to 10 and 20 % gelatine blocks. Results from the .223 Remington rifle round, which is one that typically expands on impact, revealed depths of penetration in the thorax arrangement were significantly different to 20 % gelatine, but not 10 % gelatine. The level of damage produced in the simulated thoraxes was smaller in scale to that witnessed in both gelatine concentrations, though greater debris was produced in the thoraxes.

Harnessing the therapeutic potential of mesenchymal stem cells in multiple sclerosis

PubMed Central

Darlington, Peter J; Boivin, Marie-Noëlle; Bar-Or, Amit

2011-01-01

Phase I clinical trials exploring the use of autologous mesenchymal stem cell (MSC) therapy for the treatment of multiple sclerosis (MS) have begun in a number of centers across the world. MS is a complex and chronic immune-mediated and neurodegenerative disease influenced by genetic susceptibility and environmental risk factors. The ideal treatment for MS would involve both attenuation of detrimental inflammatory responses, and induction of a degree of tissue protection/regeneration within the CNS. Preclinical studies have demonstrated that both human-derived and murine-derived MSCs are able to improve outcomes in the animal model of MS, experimental autoimmune encephalomyelitis. How MSCs ameliorate experimental autoimmune encephalomyelitis is being intensely investigated. One of the major mechanisms of action of MSC therapy is to inhibit various components of the immune system that contribute to tissue destruction. Emerging evidence now supports the idea that MSCs can access the CNS where they can provide protection against tissue damage, and may facilitate tissue regeneration through the production of growth factors. The prospect of cell-based therapy using MSCs has several advantages, including the relative ease with which they can be extracted from autologous bone marrow or adipose tissue and expanded in vitro to reach the purity and numbers required for transplantation, and the fact that MSC therapy has already been used in other human disease settings, such as graft-versus-host and cardiac disease, with initial reports indicating a good safety profile. This article will focus on the theoretical and practical issues relevant to considerations of MSC therapy in the context of MS. PMID:21864075

Lyme Borreliosis: is there a preexisting (natural) variation in antimicrobial susceptibility among Borrelia burgdorferi strains?

PubMed Central

Hodzic, Emir

2015-01-01

The development of antibiotics changed the world of medicine and has saved countless human and animal lives. Bacterial resistance/tolerance to antibiotics have spread silently across the world and has emerged as a major public health concern. The recent emergence of pan-resistant bacteria can overcome virtually any antibiotic and poses a major problem for their successful control. Selection for antibiotic resistance may take place where an antibiotic is present in the skin, gut, and other tissues of humans and animals and in the environment. Borrelia burgdorferi, the etiological agents of Lyme borreliosis, evades host immunity and establishes persistent infections in its mammalian hosts. The persistent infection poses a challenge to the effective antibiotic treatment, as demonstrated in various animal models. An increasingly heterogeneous subpopulation of replicatively attenuated spirochetes arises following treatment, and these persistent antimicrobial tolerant/resistant spirochetes are non-cultivable. The non-cultivable spirochetes resurge in multiple tissues at 12 months after treatment, with B. burgdorferi-specific DNA copy levels nearly equivalent to those found in shame-treated experimental animals. These attenuated spirochetes remain viable, but divide slowly, thereby being tolerant to antibiotics. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, spirochetes were acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues. A number of host cytokines were up- or down-regulated in tissues of both shame- and antibiotic-treated mice in the absence of histopathology, indicating a lack of host response to the presence of antimicrobial tolerant/resistant spirochetes. PMID:26295288

Lyme Borreliosis: Is there a preexisting (natural) variation in antimicrobial susceptibility among Borrelia burgdorferi strains?

PubMed

Hodzic, Emir

2015-07-08

The development of antibiotics changed the world of medicine and has saved countless human and animal lives. Bacterial resistance/tolerance to antibiotics have spread silently across the world and has emerged as a major public health concern. The recent emergence of pan-resistant bacteria can overcome virtually any antibiotic and poses a major problem for their successful control. Selection for antibiotic resistance may take place where an antibiotic is present: in the skin, gut, and other tissues of humans and animals and in the environment. Borrelia burgdorferi, the etiological agents of Lyme borreliosis, evades host immunity and establishes persistent infections in its mammalian hosts. The persistent infection poses a challenge to the effective antibiotic treatment, as demonstrated in various animal models. An increasingly heterogeneous subpopulation of replicatively attenuated spirochetes arises following treatment, and these persistent antimicrobial tolerant/resistant spirochetes are non-cultivable. The non-cultivable spirochetes resurge in multiple tissues at 12 months after treatment, with B. burgdorferi-specific DNA copy levels nearly equivalent to those found in shame-treated experimental animals. These attenuated spirochetes remain viable, but divide slowly, thereby being tolerant to antibiotics. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, spirochetes were acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues. A number of host cytokines were up- or down-regulated in tissues of both shame- and antibiotic-treated mice in the absence of histopathology, indicating a lack of host response to the presence of antimicrobial tolerant/resistant spirochetes.

Ability of the gut microbiota to produce PUFA-derived bacterial metabolites: Proof of concept in germ-free versus conventionalized mice.

PubMed

Druart, Céline; Bindels, Laure B; Schmaltz, Robert; Neyrinck, Audrey M; Cani, Patrice D; Walter, Jens; Ramer-Tait, Amanda E; Delzenne, Nathalie M

2015-08-01

The gut microbiota is able to modulate host physiology through the production of bioactive metabolites. Our recent studies suggest that changes in gut microbiota composition upon prebiotics supplementation alter tissue levels of PUFA-derived metabolites in mice. However, in vivo evidence that gut microbes produces PUFA-derived metabolites is lacking. This study aimed to decipher the contribution of gut microbes versus that of the host in PUFA-derived metabolite production. To achieve this goal, we compared the proportion of PUFA-derived metabolites and the expression of fatty acid desaturases in germ-free (GF) and conventionalized (CONV) mice fed either a low fat or Western diet. Higher concentrations of PUFA-derived metabolites were found in the colonic contents of conventionalized mice (CONV) mice compared to GF mice. The abundance of these metabolites in host tissues was modulated by dietary treatments but not by microbial status. Although microbial status did significantly influence desaturase expression, no correlations between host enzymes and tissue PUFA-derived metabolite levels were observed. Together, these results highlight the ability of the gut microbiota to produce PUFA-derived metabolites from dietary PUFA. However, microbial production of these metabolites in colonic contents is not necessarily associated with modifications of their concentration in host tissues. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thresholds for thermal damage to normal tissues: an update.

PubMed

Yarmolenko, Pavel S; Moon, Eui Jung; Landon, Chelsea; Manzoor, Ashley; Hochman, Daryl W; Viglianti, Benjamin L; Dewhirst, Mark W

2011-01-01

The purpose of this review is to summarise a literature survey on thermal thresholds for tissue damage. This review covers published literature for the consecutive years from 2002-2009. The first review on this subject was published in 2003. It included an extensive discussion of how to use thermal dosimetric principles to normalise all time-temperature data histories to a common format. This review utilises those same principles to address sensitivity of a variety of tissues, but with particular emphasis on brain and testis. The review includes new data on tissues that were not included in the original review. Several important observations have come from this review. First, a large proportion of the papers examined for this review were discarded because time-temperature history at the site of thermal damage assessment was not recorded. It is strongly recommended that future research on this subject include such data. Second, very little data is available examining chronic consequences of thermal exposure. On a related point, the time of assessment of damage after exposure is critically important for assessing whether damage is transient or permanent. Additionally, virtually no data are available for repeated thermal exposures which may occur in certain recreational or occupational activities. For purposes of regulatory guidelines, both acute and lasting effects of thermal damage should be considered.

The sesquiterpene botrydial produced by Botrytis cinerea induces the hypersensitive response on plant tissues and its action is modulated by salicylic acid and jasmonic acid signaling.

PubMed

Rossi, Franco Rubén; Gárriz, Andrés; Marina, María; Romero, Fernando Matías; Gonzalez, María Elisa; Collado, Isidro González; Pieckenstain, Fernando Luis

2011-08-01

Botrytis cinerea, as a necrotrophic fungus, kills host tissues and feeds on the remains. This fungus is able to induce the hypersensitive response (HR) on its hosts, thus taking advantage on the host's defense machinery for generating necrotic tissues. However, the identity of HR effectors produced by B. cinerea is not clear. The aim of this work was to determine whether botrydial, a phytotoxic sesquiterpene produced by B. cinerea, is able to induce the HR on plant hosts, using Arabidopsis thaliana as a model. Botrydial induced the expression of the HR marker HSR3, callose deposition, and the accumulation of reactive oxygen species and phenolic compounds. Botrydial also induced the expression of PR1 and PDF1.2, two pathogenesis-related proteins involved in defense responses regulated by salicylic acid (SA) and jasmonic acid (JA), respectively. A. thaliana and tobacco plants defective in SA signaling were more resistant to botrydial than wild-type plants, as opposed to A. thaliana plants defective in JA signaling, which were more sensitive. It can be concluded that botrydial induces the HR on its hosts and its effects are modulated by host signaling pathways mediated by SA and JA.

Blood Flukes Exploit Peyer's Patch Lymphoid Tissue to Facilitate Transmission from the Mammalian Host

PubMed Central

Turner, Joseph D.; Narang, Priyanka; Coles, Mark C.; Mountford, Adrian P.

2012-01-01

Schistosomes are blood-dwelling parasitic helminths which produce eggs in order to facilitate transmission. Intestinal schistosomes lay eggs in the mesenteries, however, it is unclear how their eggs escape the vasculature to exit the host. Using a murine model of infection, we reveal that Schistosoma mansoni exploits Peyer's Patches (PP) gut lymphoid tissue as a preferential route of egress for their eggs. Egg deposition is favoured within PP as a result of their more abundant vasculature. Moreover, the presence of eggs causes significant vascular remodeling leading to an expanded venule network. Egg deposition results in a decrease in stromal integrity and lymphoid cellularity, including secretory IgA producing lymphocytes, and the focal recruitment of macrophages. In mice lacking PP, egg excretion is significantly impaired, leading to greater numbers of ova being entrapped in tissues and consequently, exacerbated morbidity. Thus, we demonstrate how schistosomes directly facilitate transmission from the host by targeting lymphoid tissue. For the host, PP-dependency of egg egress represents a trade-off, as limiting potentially life-threatening morbidity is balanced by loss of PP structure and perturbed PP IgA production. PMID:23308064

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

PubMed Central

Maisani, Mathieu; Pezzoli, Daniele; Chassande, Olivier; Mantovani, Diego

2017-01-01

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels. PMID:28634532

A quantitative multiplex nuclease protection assay reveals immunotoxicity gene expression profiles in the rabbit model for vaginal drug safety evaluation.

PubMed

Fichorova, Raina N; Mendonca, Kevin; Yamamoto, Hidemi S; Murray, Ryan; Chandra, Neelima; Doncel, Gustavo F

2015-06-15

Any vaginal product that alters the mucosal environment and impairs the immune barrier increases the risk of sexually transmitted infections, especially HIV infection, which thrives on mucosal damage and inflammation. The FDA-recommended rabbit vaginal irritation (RVI) model serves as a first line selection tool for vaginal products; however, for decades it has been limited to histopathology scoring, insufficient to select safe anti-HIV microbicides. In this study we incorporate to the RVI model a novel quantitative nuclease protection assay (qNPA) to quantify mRNA levels of 25 genes representing leukocyte differentiation markers, toll-like receptors (TLR), cytokines, chemokines, epithelial repair, microbicidal and vascular markers, by designing two multiplex arrays. Tissue sections were obtained from 36 rabbits (6 per treatment arm) after 14 daily applications of a placebo gel, saline, 4% nonoxynol-9 (N-9), and three combinations of the anti-HIV microbicides tenofovir (TFV) and UC781 in escalating concentrations (highest: 10% TFV+2.5%UC781). Results showed that increased expression levels of toll-like receptor (TLR)-4, interleukin (IL)-1β, CXCL8, epithelial membrane protein (EMP)-1 (P<0.05), and decreased levels of TLR2 (P<0.05), TLR3 and bactericidal permeability increasing protein (BPI) (P<0.001) were associated with cervicovaginal mucosal alteration (histopathology). Seven markers showed a significant linear trend predicting epithelial damage (up with CD4, IL-1β, CXCL8, CCL2, CCL21, EMP1 and down with BPI). Despite the low tissue damage RVI scores, the high-dose microbicide combination gel caused activation of HIV host cells (SLC and CD4) while N-9 caused proinflammatory gene upregulation (IL-8 and TLR4) suggesting a potential for increasing risk of HIV via different mechanisms depending on the chemical nature of the test product. Copyright © 2015 Elsevier Inc. All rights reserved.