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Sample records for human cardiovascular tissues

  1. Protein kinase C isoenzymes in rat and human cardiovascular tissues

    PubMed Central

    Erdbrügger, W; Keffel, J; Knocks, M; Otto, T; Philipp, T; Michel, M C

    1997-01-01

    We have compared the expression of protein kinase C (PKC) activity and immuno-detectable isoenzymes in cytosolic and membrane extracts of rat and human cardiovascular tissues (heart, kidney, aorta, saphenous vein). Experiments were performed in raw extracts and upon combined diethylaminoethylcellulose (DEAE) and phenylsepharose column chromatography. PKC activity that bound to DEAE mostly eluted with 200 mM NaCl. DEAE-purified PKC from all tissues except rat kidney bound almost quantitatively to phenylsepharose and eluted with 0.5–0 M NaCl. Immunoblots with an antibody against classical PKCs and the activator profile for phosphatidylserine, diolein and Ca2+ revealed that the PKC from rat kidney, which did not bind to phenylsepharose, was most probably due to a proteolytically-generated, constitutively active PKC which is not under the control of a regulatory subunit. Studies in the reference tissue, rat brain, demonstrated that all PKC isoenzymes investigated (classical PKCs α, β, γ, new PKCs δ, ε, ζ, θ, and atypial PKCs ζ, λ, ι) have similar DEAE and phenylsepharose chromatography elution profiles. In the functional assay an inhibitor of all known PKC isoenzymes, bisindolylmaleimide, and a specific inhibitor of classical PKCs, Gö 6976, both inhibited PKC from rat brain completely and with high potency indicating that the functional assay preferentially detects classical PKC isoenzymes. Each PKC isoenzyme had a tissue-specific expression profile which was similar in rat and man. The classical PKCα, the new PKCs δ and ε and all atypical PKCs were detectable in most tissues, whereas the PKCβ and PKCγ were not detected in any pheripheral tissue; PKCζ and PKCθ were found in some tissues. We conclude that combined DEAE and phenylsepharose chromatography is useful to enrich and detect PKC isoenzymes; no major species differences in tissues-specific expression patterns appear to exist between rat and man. PMID:9117107

  2. Advancing cardiovascular tissue engineering

    PubMed Central

    Truskey, George A.

    2016-01-01

    Cardiovascular tissue engineering offers the promise of biologically based repair of injured and damaged blood vessels, valves, and cardiac tissue. Major advances in cardiovascular tissue engineering over the past few years involve improved methods to promote the establishment and differentiation of induced pluripotent stem cells (iPSCs), scaffolds from decellularized tissue that may produce more highly differentiated tissues and advance clinical translation, improved methods to promote vascularization, and novel in vitro microphysiological systems to model normal and diseased tissue function. iPSC technology holds great promise, but robust methods are needed to further promote differentiation. Differentiation can be further enhanced with chemical, electrical, or mechanical stimuli. PMID:27303643

  3. Prospective isolation of human embryonic stem cell-derived cardiovascular progenitors that integrate into human fetal heart tissue.

    PubMed

    Ardehali, Reza; Ali, Shah R; Inlay, Matthew A; Abilez, Oscar J; Chen, Michael Q; Blauwkamp, Timothy A; Yazawa, Masayuki; Gong, Yongquan; Nusse, Roeland; Drukker, Micha; Weissman, Irving L

    2013-02-26

    A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the human heart. Previous studies to evaluate the developmental potential of candidate hESC-derived progenitors have delivered these cells into murine and porcine cardiac tissue, with inconclusive evidence regarding the capacity of these human cells to physiologically engraft in xenotransplantation assays. Further, the potential of hESC-derived cardiovascular lineage cells to functionally couple to human myocardium remains untested and unknown. Here, we have prospectively identified a population of hESC-derived ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells that give rise to cardiomyocytes, endothelial cells, and vascular smooth muscle cells in vitro at a clonal level. We observed rare clusters of ROR2(+) cells and diffuse expression of KDR and PDGFRα in first-trimester human fetal hearts. We then developed an in vivo transplantation model by transplanting second-trimester human fetal heart tissues s.c. into the ear pinna of a SCID mouse. ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells were delivered into these functioning fetal heart tissues: in contrast to traditional murine heart models for cell transplantation, we show structural and functional integration of hESC-derived cardiovascular progenitors into human heart.

  4. Fundamentals of laser light interaction with human tissue, especially in the cardiovascular system.

    PubMed

    Haina, D; Landthaler, M

    1988-06-01

    The absorption of single photons in the molecules of biological tissue can induce various reactions. For the most medical laser applications the transformation from radiation energy into heat is relevant. The laser beam is used for coagulation or vaporization of tissue. The changes in tissue, which are created by light of different wavelengths depends on the thermal and optical properties (absorption and scatting) of tissue but also on the parameters of irradiation. As an example measurements from human skin are discussed. In the cardiovascular system laser light must have a clearly defined effect. Atherosclerotic plaques of different consistence have to be vaporized without damage of the vessel walls. From different reasons the usual medical CW-lasers, Argon-laser, CO2-laser and Nd:YAG-laser, are not optimal for direct ablation of arterial occlusions. In order to mimize reocclusion the walls of the channels have to be completely smooth and free of coagulation necrosis. This can be obtained by short laser pulses. Selection of a light wavelength, which is stronger absorbed in atherosclerotic plaques than in vessel walls and additional selective staining are two ways to reduce the risk of damaging the vessel walls.

  5. Automatic recognition of fundamental tissues on histology images of the human cardiovascular system.

    PubMed

    Mazo, Claudia; Trujillo, Maria; Alegre, Enrique; Salazar, Liliana

    2016-10-01

    Cardiovascular disease is the leading cause of death worldwide. Therefore, techniques for improving diagnosis and treatment in this field have become key areas for research. In particular, approaches for tissue image processing may support education system and medical practice. In this paper, an approach to automatic recognition and classification of fundamental tissues, using morphological information is presented. Taking a 40× or 10× histological image as input, three clusters are created with the k-means algorithm using a structural tensor and the red and the green channels. Loose connective tissue, light regions and cell nuclei are recognised on 40× images. Then, the cell nuclei's features - shape and spatial projection - and light regions are used to recognise and classify epithelial cells and tissue into flat, cubic and cylindrical. In a similar way, light regions, loose connective and muscle tissues are recognised on 10× images. Finally, the tissue's function and composition are used to refine muscle tissue recognition. Experimental validation is then carried out by histologist following expert criteria, along with manually annotated images that are used as a ground-truth. The results revealed that the proposed approach classified the fundamental tissues in a similar way to the conventional method employed by histologists. The proposed automatic recognition approach provides for epithelial tissues a sensitivity of 0.79 for cubic, 0.85 for cylindrical and 0.91 for flat. Furthermore, the experts gave our method an average score of 4.85 out of 5 in the recognition of loose connective tissue and 4.82 out of 5 for muscle tissue recognition.

  6. Bioreactor Technology in Cardiovascular Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Mertsching, H.; Hansmann, J.

    Cardiovascular tissue engineering is a fast evolving field of biomedical science and technology to manufacture viable blood vessels, heart valves, myocar-dial substitutes and vascularised complex tissues. In consideration of the specific role of the haemodynamics of human circulation, bioreactors are a fundamental of this field. The development of perfusion bioreactor technology is a consequence of successes in extracorporeal circulation techniques, to provide an in vitro environment mimicking in vivo conditions. The bioreactor system should enable an automatic hydrodynamic regime control. Furthermore, the systematic studies regarding the cellular responses to various mechanical and biochemical cues guarantee the viability, bio-monitoring, testing, storage and transportation of the growing tissue.

  7. Large scale expansion of human umbilical cord cells in a rotating bed system bioreactor for cardiovascular tissue engineering applications.

    PubMed

    Reichardt, Anne; Polchow, Bianca; Shakibaei, Mehdi; Henrich, Wolfgang; Hetzer, Roland; Lueders, Cora

    2013-01-01

    Widespread use of human umbilical cord cells for cardiovascular tissue engineering requires production of large numbers of well-characterized cells under controlled conditions. In current research projects, the expansion of cells to be used to create a tissue construct is usually performed in static cell culture systems which are, however, often not satisfactory due to limitations in nutrient and oxygen supply. To overcome these limitations dynamic cell expansion in bioreactor systems under controllable conditions could be an important tool providing continuous perfusion for the generation of large numbers of viable pre-conditioned cells in a short time period. For this purpose cells derived from human umbilical cord arteries were expanded in a rotating bed system bioreactor for up to 9 days. For a comparative study, cells were cultivated under static conditions in standard culture devices. Our results demonstrated that the microenvironment in the perfusion bioreactor was more favorable than that of the standard cell culture flasks. Data suggested that cells in the bioreactor expanded 39 fold (38.7 ± 6.1 fold) in comparison to statically cultured cells (31.8 ± 3.0 fold). Large-scale production of cells in the bioreactor resulted in more than 3 x 10(8) cells from a single umbilical cord fragment within 9 days. Furthermore cell doubling time was lower in the bioreactor system and production of extracellular matrix components was higher. With this study, we present an appropriate method to expand human umbilical cord artery derived cells with high cellular proliferation rates in a well-defined bioreactor system under GMP conditions.

  8. Studies of nontarget-mediated distribution of human full-length IgG1 antibody and its FAb fragment in cardiovascular and metabolic-related tissues.

    PubMed

    Davidsson, Pia; Söderling, Ann-Sofi; Svensson, Lena; Ahnmark, Andrea; Flodin, Christine; Wanag, Ewa; Screpanti-Sundqvist, Valentina; Gennemark, Peter

    2015-05-01

    Tissue distribution and pharmacokinetics (PK) of full-length nontargeted antibody and its antigen-binding fragment (FAb) were evaluated for a range of tissues primarily of interest for cardiovascular and metabolic diseases. Mice were intravenously injected with a dose of 10 mg/kg of either human IgG1or its FAb fragment; perfused tissues were collected at a range of time points over 3 weeks for the human IgG1 antibody and 1 week for the human FAb antibody. Tissues were homogenized and antibody concentrations were measured by specific immunoassays on the Gyros system. Exposure in terms of maximum concentration (Cmax ) and area under the curve was assessed for all nine tissues. Tissue exposure of full-length antibody relative to plasma exposure was found to be between 1% and 10%, except for brain (0.2%). Relative concentrations of FAb antibody were the same, except for kidney tissue, where the antibody concentration was found to be ten times higher than in plasma. However, the absolute tissue uptake of full-length IgG was significantly higher than the absolute tissue uptake of the FAb antibody. This study provides a reference PK state for full-length whole and FAb antibodies in tissues related to cardiovascular and metabolic diseases that do not include antigen or antibody binding.

  9. Increased vascular selectivity and prolonged pharmacological efficacy of the L-type Ca2+ channel antagonist lercanidipine in human cardiovascular tissue.

    PubMed

    Brixius, Klara; Gross, Thomas; Tossios, Paschalios; Geissler, Hans-Joachim; Mehlhorn, Uwe; Schwinger, Robert H G; Hekmat, Khosro

    2005-09-01

    1. The present study investigates the vasoselectivity of lercanidipine (LER), a 1,4-dihydropyridine calcium channel blocker, compared with amlodipine (AML) and nifedipine (NIF) in human cardiovascular tissue. Experiments were performed either in human left ventricular failing myocardium (orthotopic heart transplants) or in isolated right atrial trabeculae and isolated vessel preparations of arteria mammaria obtained from patients undergoing aortocoronary bypass operation. 2. The obtained rank order for the L-type Ca2+ channel affinity in human tissue was LER > NIF >or= AML. Lercanidipine had the lowest negative inotropic efficacy (1 micromol/L LER: 60.3% basal < AML: 79.1% basal < NIF: 92.4 basal) and potency (IC50 NIF: 3.5 nmol/L < AML: 48 nmol/L < Ler: 127 nmol/L) in right atrial trabeculae. 3. The vasorelaxant potency of LER (IC50 0.5 nmol/L) and AML (IC50 0.8 nmol/L) was similar and significantly increased compared with that of NIF (IC50 5.9 nmol/L) in arteria mammaria preparations of the very same patients. 4. The following rank order was obtained for vasoselectivity: LER (260) < AML (60) < NIF (0.6). 5. The pharmacological effects of LER and AML were still present 2 h after drug washout. 3. Lercanidipine is characterized by a high vasoselectivity and a prolonged interaction with the L-type calcium channel in human cardiovascular tissue This may be advantageous, especially in the treatment of patients with arterial hypertension.

  10. Cardiovascular tissues contain independent circadian clocks

    NASA Technical Reports Server (NTRS)

    Davidson, A. J.; London, B.; Block, G. D.; Menaker, M.

    2005-01-01

    Acute cardiovascular events exhibit a circadian rhythm in the frequency of occurrence. The mechanisms underlying these phenomena are not yet fully understood, but they may be due to rhythmicity inherent in the cardiovascular system. We have begun to characterize rhythmicity of the clock gene mPer1 in the rat cardiovascular system. Luciferase activity driven by the mPer1 gene promoter is rhythmic in vitro in heart tissue explants and a wide variety of veins and arteries cultured from the transgenic Per1-luc rat. The tissues showed between 3 and 12 circadian cycles of gene expression in vitro before damping. Whereas peak per1-driven bioluminescence consistently occurred during the late night in the heart and all arteries sampled, the phases of the rhythms in veins varied significantly by anatomical location. Varying the time of the culture procedure relative to the donor animal's light:dark cycle revealed that, unlike some other rat tissues such as liver, the phases of in vitro rhythms of arteries, veins, and heart explants were affected by culture time. However, phase relationships among tissues were consistent across culture times; this suggests diversity in circadian regulation among components of the cardiovascular system.

  11. Drug releasing systems in cardiovascular tissue engineering.

    PubMed

    Spadaccio, Cristiano; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto; Toyoda, Yoshiya; Genovese, Jorge A

    2009-03-01

    Heart disease and atherosclerosis are the leading causes of morbidity and mortality worldwide. The lack of suitable autologous grafts has produced a need for artificial grafts; however, current artificial grafts carry significant limitations, including thrombosis, infection, limited durability and the inability to grow. Tissue engineering of blood vessels, cardiovascular structures and whole organs is a promising approach for creating replacement tissues to repair congenital defects and/or diseased tissues. In an attempt to surmount the shortcomings of artificial grafts, tissue-engineered cardiovascular graft (TECVG), constructs obtained using cultured autologous vascular cells seeded onto a synthetic biodegradable polymer scaffold, have been developed. Autologous TECVGs have the potential advantages of growth, durability, resistance to infection, and freedom from problems of rejection, thrombogenicity and donor scarcity. Moreover polymers engrafted with growth factors, cytokines, drugs have been developed allowing drug-releasing systems capable of focused and localized delivery of molecules depending on the environmental requirements and the milieu in which the scaffold is placed. A broad range of applications for compound-releasing, tissue-engineered grafts have been suggested ranging from drug delivery to gene therapy. This review will describe advances in the development of drug-delivery systems for cardiovascular applications focusing on the manufacturing techniques and on the compounds delivered by these systems to date.

  12. Drug releasing systems in cardiovascular tissue engineering

    PubMed Central

    Spadaccio, Cristiano; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto; Toyoda, Yoshiya; Genovese, Jorge A

    2009-01-01

    Abstract Heart disease and atherosclerosis are the leading causes of morbidity and mortality worldwide. The lack of suitable autologous grafts has produced a need for artificial grafts; however, current artificial grafts carry significant limitations, including thrombosis, infection, limited durability and the inability to grow. Tissue engineering of blood vessels, cardiovascular structures and whole organs is a promising approach for creating replacement tissues to repair congenital defects and/or diseased tissues. In an attempt to surmount the shortcomings of artificial grafts, tissue-engineered cardiovascular graft (TECVG), constructs obtained using cultured autologous vascular cells seeded onto a synthetic biodegradable polymer scaffold, have been developed. Autologous TECVGs have the potential advantages of growth, durability, resistance to infection, and freedom from problems of rejection, thrombogenicity and donor scarcity. Moreover polymers engrafted with growth factors, cytokines, drugs have been developed allowing drug-releasing systems capable of focused and localized delivery of molecules depending on the environmental requirements and the milieu in which the scaffold is placed. A broad range of applications for compound-releasing, tissue-engineered grafts have been suggested ranging from drug delivery to gene therapy. This review will describe advances in the development of drug-delivery systems for cardiovascular applications focusing on the manufacturing techniques and on the compounds delivered by these systems to date. PMID:19379142

  13. Human cardiovascular model and applications.

    PubMed

    Zhu, K Y; Ang, Alvin; Acharya U, Rajendra; Lim, C M

    2011-10-01

    Cardiovascular diseases (CVDs) can be known as a class of diseases which affect different parts of the cardiovascular system such as the heart or blood vessels. Hemodynamic signals are an important tool used by doctors to diagnose the type of CVD occurred in a patient. Diagnosing the correct type of CVD in a patient early will allow the patient to have the suitable medical treatment. Some examples of CVDs include coronary heart disease, cerebrovascular disease and peripheral arterial disease. A human cardiovascular model is developed in order to simulate different hemodynamic signals of the cardiovascular system. The hemodynamic signals include the blood pressures, flow rates and volumes in various part of the cardiovascular system. This paper presents a model which is able to simulate hemodynamic signals and they are able to represent the human arterial blood pressure accurately. Hence this model can also be used to simulate hypertensive patients in order to design control systems for regulation of blood pressure. Signal verification has been performed and the stability of the model is being investigated. Applications of the human cardiovascular model are also presented.

  14. [Cardiovascular manifestations of human toxocariasis].

    PubMed

    Bolívar-Mejía, Adrián; Rodríguez-Morales, Alfonso J; Paniz-Mondolfi, Alberto E; Delgado, Olinda

    2013-01-01

    Toxocariasis is a parasitic infection produced by helminths that cannot reach their adult stage in humans. For their etiological species (Toxocara canis and Toxocara cati), man is a paratenic host. Infection by such helminths can produce a variety of clinical manifestations, such as: visceral larvae migrans syndrome, ocular larvae migrans syndrome and covert toxocariasis. In the visceral larvae migrans syndrome, the organs that are mainly involved include liver, lungs, skin, nervous system, muscles, kidneys and the heart. Regarding the latter, the importance of cardiovascular manifestations in toxocariasis, as well as its clinical relevance, has increasingly begun to be recognized. The current article is based on a systematic information search, focused mainly on the clinical and pathological aspects of cardiovascular manifestations in toxocariasis, including its pathophysiology, laboratory findings, diagnosis and therapeutical options, with the objective of highlighting its importance as a zoonosis and its relevance to the fields of cardiovascular medicine in adults and children.

  15. The potential of GMP-compliant platelet lysate to induce a permissive state for cardiovascular transdifferentiation in human mediastinal adipose tissue-derived mesenchymal stem cells.

    PubMed

    Siciliano, Camilla; Chimenti, Isotta; Bordin, Antonella; Ponti, Donatella; Iudicone, Paola; Peruzzi, Mariangela; Rendina, Erino Angelo; Calogero, Antonella; Pierelli, Luca; Ibrahim, Mohsen; De Falco, Elena

    2015-01-01

    Human adipose tissue-derived mesenchymal stem cells (ADMSCs) are considered eligible candidates for cardiovascular stem cell therapy applications due to their cardiac transdifferentiation potential and immunotolerance. Over the years, the in vitro culture of ADMSCs by platelet lysate (PL), a hemoderivate containing numerous growth factors and cytokines derived from platelet pools, has allowed achieving a safe and reproducible methodology to obtain high cell yield prior to clinical administration. Nevertheless, the biological properties of PL are still to be fully elucidated. In this brief report we show the potential ability of PL to induce a permissive state of cardiac-like transdifferentiation and to cause epigenetic modifications. RTPCR results indicate an upregulation of Cx43, SMA, c-kit, and Thy-1 confirmed by immunofluorescence staining, compared to standard cultures with foetal bovine serum. Moreover, PL-cultured ADMSCs exhibit a remarkable increase of both acetylated histones 3 and 4, with a patient-dependent time trend, and methylation at lysine 9 on histone 3 preceding the acetylation. Expression levels of p300 and SIRT-1, two major regulators of histone 3, are also upregulated after treatment with PL. In conclusion, PL could unravel novel biological properties beyond its routine employment in noncardiac applications, providing new insights into the plasticity of human ADMSCs.

  16. Human Cardiovascular Responses to Passive Heat Stress

    PubMed Central

    Crandall, Craig G.; Wilson, Thad E.

    2016-01-01

    Heat stress increases human morbidity and mortality compared to normothermic conditions. Many occupations, disease states, as well as stages of life are especially vulnerable to the stress imposed on the cardiovascular system during exposure to hot ambient conditions. This review focuses on the cardiovascular responses to heat stress that are necessary for heat dissipation. To accomplish this regulatory feat requires complex autonomic nervous system control of the heart and various vascular beds. For example, during heat stress cardiac output increases up to twofold, by increases in heart rate and an active maintenance of stroke volume via increases in inotropy in the presence of decreases in cardiac preload. Baroreflexes retain the ability to regulate blood pressure in many, but not all, heat stress conditions. Central hypovolemia is another cardiovascular challenge brought about by heat stress, which if added to a subsequent central volumetric stress, such as hemorrhage, can be problematic and potentially dangerous, as syncope and cardiovascular collapse may ensue. These combined stresses can compromise blood flow and oxygenation to important tissues such as the brain. It is notable that this compromised condition can occur at cardiac outputs that are adequate during normothermic conditions but are inadequate in heat because of the increased systemic vascular conductance associated with cutaneous vasodilation. Understanding the mechanisms within this complex regulatory system will allow for the development of treatment recommendations and countermeasures to reduce risks during the ever-increasing frequency of severe heat events that are predicted to occur. PMID:25589263

  17. Cardiovascular Deconditioning in Humans: Human Studies Core

    NASA Technical Reports Server (NTRS)

    Williams, Gordon

    1999-01-01

    Major cardiovascular problems, secondary to cardiovascular deconditioning, may occur on extended space missions. While it is generally assumed that the microgravity state is the primary cause of cardiovascular deconditioning, sleep deprivation and disruption of diurnal rhythms may also play an important role. Factors that could be modified by either or both of these perturbations include: autonomic function and short-term cardiovascular reflexes, vasoreactivity, circadian rhythm of cardiovascular hormones (specifically the renin-angiotensin system) and renal sodium handling and hormonal influences on that process, venous compliance, cardiac mass, and cardiac conduction processes. The purpose of the Human Studies Core is to provide the infrastructure to conduct human experiments which will allow for the assessment of the likely role of such factors in the space travel associated cardiovascular deconditioning process and to develop appropriate countermeasures. The Core takes advantage of a newly-created Intensive Physiologic Monitoring (IPM) Unit at the Brigham and Women's Hospital, Boston, MA, to perform these studies. The Core includes two general experimental protocols. The first protocol involves a head down tilt bed-rest study to simulate microgravity. The second protocol includes the addition of a disruption of circadian rhythms to the simulated microgravity environment. Before and after each of these environmental manipulations, the subjects will undergo acute stressors simulating changes in volume and/or stress, which could occur in space and on return to Earth. The subjects are maintained in a rigidly controlled environment with fixed light/dark cycles, activity pattern, and dietary intake of nutrients, fluids, ions and calories.

  18. Decellularized matrices for cardiovascular tissue engineering

    PubMed Central

    Moroni, Francesco; Mirabella, Teodelinda

    2014-01-01

    Cardiovascular disease (CVD) is one of the leading causes of death in the Western world. The replacement of damaged vessels and valves has been practiced since the 1950’s. Synthetic grafts, usually made of bio-inert materials, are long-lasting and mechanically relevant, but fail when it comes to “biointegration”. Decellularized matrices, instead, can be considered biological grafts capable of stimulating in vivo migration and proliferation of endothelial cells (ECs), recruitment and differentiation of mural cells, finally, culminating in the formation of a biointegrated tissue. Decellularization protocols employ osmotic shock, ionic and non-ionic detergents, proteolitic digestions and DNase/RNase treatments; most of them effectively eliminate the cellular component, but show limitations in preserving the native structure of the extracellular matrix (ECM). In this review, we examine the current state of the art relative to decellularization techniques and biological performance of decellularized heart, valves and big vessels. Furthermore, we focus on the relevance of ECM components, native and resulting from decellularization, in mediating in vivo host response and determining repair and regeneration, as opposed to graft corruption. PMID:24660110

  19. Cardiovascular Tissue Engineering: Preclinical Validation to Bedside Application

    PubMed Central

    Best, Cameron; Onwuka, Ekene; Pepper, Victoria; Sams, Malik; Breuer, Jake

    2015-01-01

    Advancements in biomaterial science and available cell sources have spurred the translation of tissue-engineering technology to the bedside, addressing the pressing clinical demands for replacement cardiovascular tissues. Here, the in vivo status of tissue-engineered blood vessels, heart valves, and myocardium is briefly reviewed, illustrating progress toward a tissue-engineered heart for clinical use. PMID:26661524

  20. Cardiovascular tissue engineering I. Perfusion bioreactors: a review.

    PubMed

    Mironov, Vladimir; Kasyanov, Vladimir A; Yost, Michael J; Visconti, Richard; Twal, Waleed; Trusk, Thomas; Wen, Xuejun; Ozolanta, Iveta; Kadishs, Arnolds; Prestwich, Glenn D; Terracio, Louis; Markwald, Roger R

    2006-01-01

    Tissue engineering is a fast-evolving field of biomedical science and technology with future promise to manufacture living tissues and organs for replacement, repair, and regeneration of diseased organs. Owing to the specific role of hemodynamics in the development, maintenance, and functioning of the cardiovascular system, bioreactors are a fundamental of cardiovascular tissue engineering. The development of perfusion bioreactor technology for cardiovascular tissue engineering is a direct sequence of previous historic successes in extracorporeal circulation techniques. Bioreactors provide a fluidic environment for tissue engineered tissue and organs, and guarantee their viability, maturation, biomonitoring, testing, storage, and transportation. There are different types of bioreactors and they vary greatly in their size, complexity, and functional capabilities. Although progress in design and functional properties of perfusion bioreactors for tissue engineered blood vessels, heart valves, and myocardial patches is obvious, there are some challenges and insufficiently addressed issues, and room for bioreactor design improvement and performance optimization. These challenges include creating a triple perfusion bioreactor for vascularized tubular tissue engineered cardiac construct; designing and manufacturing fluidics-based perfused minibioreactors; incorporation of systematic mathematical modeling and computer simulation based on computational fluid dynamics into the bioreactor designing process; and development of automatic systems of hydrodynamic regime control. Designing and engineering of built-in noninvasive biomonitoring systems is another important challenge. The optimal and most efficient perfusion and conditioning regime, which accelerates tissue maturation of tissue-engineered constructs also remains to be determined. This is a first article in a series of reviews on critical elements of cardiovascular tissue engineering technology describing the current

  1. Resilin-Based Hybrid Hydrogels for Cardiovascular Tissue Engineering

    PubMed Central

    McGann, Christopher L.; Levenson, Eric A.

    2013-01-01

    The outstanding elastomeric properties of natural resilin, an insect protein, have motivated the engineering of resilin-like polypeptides (RLPs) as a potential material for cardiovascular tissue engineering. The RLPs, which incorporate biofunctional domains for cell-matrix interactions, are cross-linked into RLP–PEG hybrid hydrogels via a Michael-type addition of cysteine residues on the RLP with vinyl sulfones of an end-functionalized multi-arm star PEG. Oscillatory rheology indicated the useful mechanical properties of these materials. Assessments of cell viability via con-focal microscopy clearly show the successful encapsulation of human aortic adventitial fibroblasts in the three-dimensional matrices and the adoption of a spread morphology following 7 days of culture. PMID:23956463

  2. Fibroblast growth factor 16 and 18 are expressed in human cardiovascular tissues and induce on endothelial cells migration but not proliferation

    SciTech Connect

    Antoine, M.; Wirz, W.; Tag, C.G.; Gressner, A.M.; Wycislo, M.; Mueller, R.; Kiefer, P. . E-mail: pkiefer@ukaachen.de

    2006-07-21

    Endothelial cells line the blood vessel and precursor endothelial cells appear to have a pivotal effect on the organ formation of the heart, the embryonic development of the kidney, and the liver. Several growth factors including the fibroblast growth factors (FGF) seem to be involved in these processes. Ligands such as basic FGF produced and secreted by endothelial cells may also coordinate cellular migration, differentiation, and proliferation under pathological conditions including wound healing, tumorgenesis, and fibrogenesis in the adult. Recently we demonstrated the expression of two secreted FGFs, FGF16, and FGF18, in HUVEC and in rat aortic tissue. In the present report, we confirmed by RT-PCR analysis that FGF18 is wildly expressed in the cardiovascular tissue, while FGF16 showed a more restricted expression pattern. HUVEC clearly demonstrated chemotaxis towards FGF16 and FGF18. Both FGFs also enhanced cell migration in response to mechanical damage. However, recombinant FGF16 and FGF18 failed to induce endothelial cell proliferation or sprouting in a three-dimensional in vitro angiogenesis assay. Fgf18 expression was earlier reported in the liver, and we detected FGF18 expression in liver vascular and liver sinusoidal endothelial cells (LSECs), but not in hepatic parenchymal cells. Recombinant FGF18 stimulated DNA synthesis in primary hepatocytes, suggesting, that endothelial FGF18 might have a paracrine function in promoting growth of the parenchymal tissue. Interestingly, FGF2, which is mitogenic on endothelial cells and hepatocytes stimulates a sustained MAPK activation in both cell types, while FGF18 causes a short transient activation of the MAPK pathway in endothelial cells but a sustained activation in hepatocytes. Therefore, the difference in the time course of MAPK activation by the different FGFs appears to be the cause for the different cellular responses.

  3. Imidazoline binding sites and receptors in cardiovascular tissue.

    PubMed

    Molderings, G J; Göthert, M

    1999-01-01

    1. Imidazoline binding sites and receptors and their endogenous ligands have been identified in cardiovascular tissue of various species including human beings. 2. I2- (but only exceptionally I1-)imidazoline binding sites have been shown to exist on cardiac myocytes and vascular smooth muscle cells; at present, their functional role is unknown. 3. The sympathetic nerves supplying the cardiovascular system are endowed with presynaptic inhibitory imidazoline receptors that may become of therapeutic relevance as targets of drugs. 4. ATP-sensitive K+ channels present in heart and blood vessels can be blocked by several imidazolines and guanidines; hence, those drugs can interfere with the cardioprotective effects resulting from K(ATP) channel activation by a decrease in the endogenous ligand ATP or by drugs. 5. Imidazoline derivatives exhibit antiarrhythmic properties that are due to a reduction of sympathetic tone by central and peripheral mechanisms and to blockade of postsynaptic alpha2-adrenoceptors in the heart and coronary arteries. 6. Agmatine and clonidine-displacing substance, which are endogenous ligands at imidazoline and alpha2-receptors, are present in the blood serum and appear to participate in vascular smooth muscle proliferation and blood pressure regulation.

  4. Current progress in 3D printing for cardiovascular tissue engineering.

    PubMed

    Mosadegh, Bobak; Xiong, Guanglei; Dunham, Simon; Min, James K

    2015-03-16

    3D printing is a technology that allows the fabrication of structures with arbitrary geometries and heterogeneous material properties. The application of this technology to biological structures that match the complexity of native tissue is of great interest to researchers. This mini-review highlights the current progress of 3D printing for fabricating artificial tissues of the cardiovascular system, specifically the myocardium, heart valves, and coronary arteries. In addition, how 3D printed sensors and actuators can play a role in tissue engineering is discussed. To date, all the work with building 3D cardiac tissues have been proof-of-principle demonstrations, and in most cases, yielded products less effective than other traditional tissue engineering strategies. However, this technology is in its infancy and therefore there is much promise that through collaboration between biologists, engineers and material scientists, 3D bioprinting can make a significant impact on the field of cardiovascular tissue engineering.

  5. The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages

    PubMed Central

    Masumoto, Hidetoshi; Nakane, Takeichiro; Tinney, Joseph P.; Yuan, Fangping; Ye, Fei; Kowalski, William J.; Minakata, Kenji; Sakata, Ryuzo; Yamashita, Jun K.; Keller, Bradley B.

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) are a robust source for cardiac regenerative therapy due to their potential to support autologous and allogeneic transplant paradigms. The in vitro generation of three-dimensional myocardial tissue constructs using biomaterials as an implantable hiPSC-derived myocardium provides a path to realize sustainable myocardial regeneration. We generated engineered cardiac tissues (ECTs) from three cellular compositions of cardiomyocytes (CMs), endothelial cells (ECs), and vascular mural cells (MCs) differentiated from hiPSCs. We then determined the impact of cell composition on ECT structural and functional properties. In vitro force measurement showed that CM+EC+MC ECTs possessed preferential electromechanical properties versus ECTs without vascular cells indicating that incorporation of vascular cells augmented tissue maturation and function. The inclusion of MCs facilitated more mature CM sarcomeric structure, preferential alignment, and activated multiple tissue maturation pathways. The CM+EC+MC ECTs implanted onto infarcted, immune tolerant rat hearts engrafted, displayed both host and graft-derived vasculature, and ameliorated myocardial dysfunction. Thus, a composition of CMs and multiple vascular lineages derived from hiPSCs and incorporated into ECTs promotes functional maturation and demonstrates myocardial replacement and perfusion relevant for clinical translation. PMID:27435115

  6. Human Cardiovascular Adaptation to Weightlessness

    NASA Technical Reports Server (NTRS)

    Norsk, Peter

    2011-01-01

    Entering weightlessness (0 G) induces immediately a shift of blood and fluid from the lower to the upper parts of the body inducing expansion of the cardiac chambers (Bungo et al. 1986; Charles & Lathers 1991; Videbaek & Norsk 1997). For many years the effects of sudden 0 G on central venous pressure (CVP) was discussed, and it puzzled researchers that CVP compared to the 1-G supine position decreased during the initial hours of spaceflight, when at the same time left atrial diameter increased (Buckey et al. 1996). By measuring esophageal pressure as an estimate of inter-pleural pressure, it was later shown that this pressure decreases more than CVP does during 0 G induced by parabolic flights (Videbaek & Norsk 1997). Thus, transmural CVP is increased, which distends the cardiac chambers. This unique lung-heart interaction whereby 1) inter-pleural pressure decreases and 2) central blood volume is expanded is unique for 0 G. Because transmural CVP is increased, stroke volume increases according to the law of Frank-Starling leading to an increase in cardiac output, which is maintained increased during months of 0 G in space to levels of some 25% above that of the 1-G seated position (Norsk unpublished). Simultaneously, sympathetic nervous activity is at the level of the upright 1-G posture, which is difficult to explain based on the high stroke volume and decreased blood pressure and systemic vascular resistance. This paradox should be explored and the mechanisms revealed, because it might have implications for estimating the cardiovascular risk of travelling in space.

  7. From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues.

    PubMed

    Borovjagin, Anton V; Ogle, Brenda M; Berry, Joel L; Zhang, Jianyi

    2017-01-06

    Current strategies for engineering cardiovascular cells and tissues have yielded a variety of sophisticated tools for studying disease mechanisms, for development of drug therapies, and for fabrication of tissue equivalents that may have application in future clinical use. These efforts are motivated by the need to extend traditional 2-dimensional (2D) cell culture systems into 3D to more accurately replicate in vivo cell and tissue function of cardiovascular structures. Developments in microscale devices and bioprinted 3D tissues are beginning to supplant traditional 2D cell cultures and preclinical animal studies that have historically been the standard for drug and tissue development. These new approaches lend themselves to patient-specific diagnostics, therapeutics, and tissue regeneration. The emergence of these technologies also carries technical challenges to be met before traditional cell culture and animal testing become obsolete. Successful development and validation of 3D human tissue constructs will provide powerful new paradigms for more cost effective and timely translation of cardiovascular tissue equivalents.

  8. [Human brown adipose tissue].

    PubMed

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  9. Possible Muscle Repair in the Human Cardiovascular System.

    PubMed

    Sommese, Linda; Zullo, Alberto; Schiano, Concetta; Mancini, Francesco P; Napoli, Claudio

    2017-04-01

    The regenerative potential of tissues and organs could promote survival, extended lifespan and healthy life in multicellular organisms. Niches of adult stemness are widely distributed and lead to the anatomical and functional regeneration of the damaged organ. Conversely, muscular regeneration in mammals, and humans in particular, is very limited and not a single piece of muscle can fully regrow after a severe injury. Therefore, muscle repair after myocardial infarction is still a chimera. Recently, it has been recognized that epigenetics could play a role in tissue regrowth since it guarantees the maintenance of cellular identity in differentiated cells and, therefore, the stability of organs and tissues. The removal of these locks can shift a specific cell identity back to the stem-like one. Given the gradual loss of tissue renewal potential in the course of evolution, in the last few years many different attempts to retrieve such potential by means of cell therapy approaches have been performed in experimental models. Here we review pathways and mechanisms involved in the in vivo repair of cardiovascular muscle tissues in humans. Moreover, we address the ongoing research on mammalian cardiac muscle repair based on adult stem cell transplantation and pro-regenerative factor delivery. This latter issue, involving genetic manipulations of adult cells, paves the way for developing possible therapeutic strategies in the field of cardiovascular muscle repair.

  10. Adipose Tissue Oxygenation in Obesity: A Matter of Cardiovascular Risk?

    PubMed

    Landini, Linda; Honka, Miikka-Juhani; Ferrannini, Ele; Nuutila, Pirjo

    2016-01-01

    Obesity, a chronic low-grade inflammation disorder characterized by an expansion in adipose tissue mass, is rapidly expanding worldwide leading to an increase in the incidence of comorbidities such as insulin resistance, type 2 diabetes and cardiovascular diseases. This has led to a renewed interest in the adipose tissue function, historically considered as a passive fat storage. It is now well established that adipose tissue is an organ with an active role in production and release of a variety of molecules called adipocytokines. Dysregulated production of adipocytokines seems to be responsible for the pathogenesis of insulin resistance and type 2 diabetes; however, the mechanisms are still unclear. Hypoxia, that occurs when adipocytes expand in obesity, has been proposed as a possible cause of adipose tissue inflammation. On the other hand, recent studies have shown that adipose tissue oxygen tension was actually higher (hyperoxia) than normal and associated with insulin resistance in obesity, despite a reduction in blood flow. This might be explained by the role of mitochondrial oxygen consumption. Hence, further studies are needed to understand the role of adipose tissue oxygenation and perfusion in obesity to assess pathophysiology and novel opportunities for treating the diseases.

  11. Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice

    NASA Astrophysics Data System (ADS)

    Meneton, Pierre; Bloch-Faure, May; Hagege, Albert A.; Ruetten, Hartmut; Huang, Wei; Bergaya, Sonia; Ceiler, Debbie; Gehring, Doris; Martins, Isabelle; Salmon, Georges; Boulanger, Chantal M.; Nussberger, Jürg; Crozatier, Bertrand; Gasc, Jean-Marie; Heudes, Didier; Bruneval, Patrick; Doetschman, Tom; Ménard, Joël; Alhenc-Gelas, François

    2001-02-01

    Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins in many organs like the kidneys, colon, salivary glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans, but the exact role of the protease in cardiovascular function has not been established largely because of the lack of specific inhibitors. This study demonstrates that mice lacking tissue kallikrein are unable to generate significant levels of kinins in most tissues and develop cardiovascular abnormalities early in adulthood despite normal blood pressure. The heart exhibits septum and posterior wall thinning and a tendency to dilatation resulting in reduced left ventricular mass. Cardiac function estimated in vivo and in vitro is decreased both under basal conditions and in response to βadrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in isolated perfused carotid arteries, which express, like the heart, low levels of the protease. These data show that tissue kallikrein is the main kinin-generating enzyme in vivo and that a functional kallikrein-kinin system is necessary for normal cardiac and arterial function in the mouse. They suggest that the kallikrein-kinin system could be involved in the development or progression of cardiovascular diseases.

  12. Monocyte heterogeneity in human cardiovascular disease.

    PubMed

    Zawada, Adam M; Rogacev, Kyrill S; Schirmer, Stephan H; Sester, Martina; Böhm, Michael; Fliser, Danilo; Heine, Gunnar H

    2012-12-01

    Atherosclerosis has been characterized as an inflammatory process, in which monocytes and monocyte-derived macrophages are of paramount importance. Contrasting with their established role in atherosclerosis, monocytes have not unanimously been found to predict cardiovascular events in large epidemiological studies. However, in these studies human monocyte heterogeneity has been largely overlooked so far. Three human monocyte subsets can be distinguished: classical CD14(++)CD16(-), intermediate CD14(++)CD16(+) and nonclassical CD14(+)CD16(++) monocytes. Of note, correct enumeration of subset counts requires appropriate staining and gating strategies that encompass a pan-monocytic marker (e.g. HLA-DR or CD86). In experimental studies on murine atherogenesis a monocyte subset-specific contribution to atherosclerosis has been established. However, major interspecies differences in atherogenesis itself, as well as in the immune system (including monocyte subset phenotype and distribution) preclude a direct extrapolation to human pathology. Experimental and pilot clinical studies point to a prominent involvement of intermediate CD14(++)CD16(+) monocytes in human atherosclerosis. Future clinical studies should analyze monocyte heterogeneity in cardiovascular disease. If a specific contribution of intermediate monocytes should be confirmed, immunomodulation of this monocyte subset could represent a future therapeutic target in atherosclerosis.

  13. Human Tissue Stimulator

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Neurodyne Corporation Human Tissue Stimulator (HTS) is a totally implantable system used for treatment of chronic pain and involuntary motion disorders by electrical stimulation. It was developed by Pacesetter Systems, Inc. in cooperation with the Applied Physics Laboratory. HTS incorporates a nickel cadmium battery, telemetry and command systems technologies of the same type as those used in NASA's Small Astronomy Satellite-3 in microminiature proportions so that the implantable element is the size of a deck of cards. The stimulator includes a rechargeable battery, an antenna and electronics to receive and process commands and to report on its own condition via telemetry, a wireless process wherein instrument data is converted to electrical signals and sent to a receiver where signals are presented as usable information. The HTS is targeted to nerve centers or to particular areas of the brain to provide relief from intractable pain or arrest involuntary motion. The nickel cadmium battery can be recharged through the skin. The first two HTS units were implanted last year and have been successful. Extensive testing is required before HTS can be made available for general use.

  14. Lead Induces Apoptosis and Histone Hyperacetylation in Rat Cardiovascular Tissues.

    PubMed

    Xu, Li-Hui; Mu, Fang-Fang; Zhao, Jian-Hong; He, Qiang; Cao, Cui-Li; Yang, Hui; Liu, Qi; Liu, Xue-Hui; Sun, Su-Ju

    2015-01-01

    Acute and chronic lead (Pb) exposure might cause hypertension and cardiovascular diseases. The purpose of this study was to evaluate the effects of early acute exposure to Pb on the cellular morphology, apoptosis, and proliferation in rats and to elucidate the early mechanisms involved in the development of Pb-induced hypertension. Very young Sprague-Dawley rats were allowed to drink 1% Pb acetate for 12 and 40 days. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA) decreased in the tissues of the abdominal and thoracic aortas and increased in the cardiac tissue after 12 and 40 days of Pb exposure, respectively. Bax was upregulated and Bcl-2 was downregulated in vascular and cardiac tissues after 40 days of Pb exposure. In addition, an increase in caspase-3 activity was observed after 40 days of exposure to Pb. In terms of morphology, we found that the internal elastic lamina (IEL) of aorta lost the original curve and the diameter of cardiac cell was enlarged after 40 days. Furthermore, the exposure led to a marked increase in acetylated histone H3 levels in the aortas and cardiac tissue after 12 and 40 days, than that in the control group. These findings indicate that Pb might increase the level of histone acetylation and induce apoptosis in vascular and cardiac tissues. However, the mechanism involved need to be further investigated.

  15. The human cardiovascular system during space flight

    NASA Astrophysics Data System (ADS)

    Grigoriev, A. I.; Kotovskaya, A. R.; Fomina, G. A.

    2011-05-01

    Purpose of the work is to analyze and to summarize the data of investigations into human hemodynamics performed over 20 years aboard orbital stations Salyut-7 and Mir with participation of 26 cosmonauts on space flights (SF) from 8 to 438 days in duration. The ultrasonic techniques and occlusive plethysmography demonstrated dynamics of changes in the cardiovascular system during SF of various durations. The parameters of general hemodynamics, the pumping function of the heart and arterial circulation in the brain remained stable in all the space flights; however, there were alterations in peripheral circulation associated with blood redistribution and hypovolemie in microgravity. The anti-gravity distribution of the vascular tone decayed gradually as unneeded. The most considerable changes were observed in leg vessels, equally in arteries (decrease in resistance) and veins (increase in maximum capacity). The lower body negative pressure test (LBNP) revealed deterioration of the gravity-dependent reactions that changed for the worse as SF duration extended. The cardiovascular deconditioning showed itself as loss of descent acceleration tolerance and orthostatic instability in the postflight period.

  16. Potential cardiovascular implications of Sea Buckthorn berry consumption in humans.

    PubMed

    Sayegh, Marietta; Miglio, Cristiana; Ray, Sumantra

    2014-08-01

    Diets rich in fruits and vegetables have been correlated with decreased risks of cardiovascular disease. Particularly, berry consumption has been associated with reductions in cardiovascular risk. Despite the range of potentially beneficial phytochemical components (vitamins, polyphenols, carotenoids, and fatty acids), there is little evidence underpinning the cardiovascular effects of sea buckthorn (SB) berries. The purpose of this review is to evaluate the benefits of SB consumption on cardiovascular health in human trials. Only six human studies were found, which examine the effect of SB berries on cardiovascular outcomes (i.e., lipid metabolism, platelet aggregation, and inflammation). Although there appears to be an inverse association between SB consumption and cardiovascular risk factors, the evidence is still scarce and the results are inconsistent. In addition, limitations in study design made it difficult to form firm conclusions. More "high-quality" human clinical trials are needed in order to establish the cardio-protective benefits of SB berries.

  17. Analysis of Cardiovascular Tissue Components for the Diagnosis of Coronary Vulnerable Plaque from Intravascular Ultrasound Images

    PubMed Central

    Hwang, Yoo Na; Kim, Ga Young; Shin, Eun Seok

    2017-01-01

    The purpose of this study was to characterize cardiovascular tissue components and analyze the different tissue properties for predicting coronary vulnerable plaque from intravascular ultrasound (IVUS) images. For this purpose, sequential IVUS image frames were obtained from human coronary arteries using 20 MHz catheters. The plaque regions between the intima and media-adventitial borders were manually segmented in all IVUS images. Tissue components of the plaque regions were classified into having fibrous tissue (FT), fibrofatty tissue (FFT), necrotic core (NC), or dense calcium (DC). The media area and lumen diameter were also estimated simultaneously. In addition, the external elastic membrane (EEM) was computed to predict the vulnerable plaque after the tissue characterization. The reliability of manual segmentation was validated in terms of inter- and intraobserver agreements. The quantitative results found that the FT and the media as well as the NC would be good indicators for predicting vulnerable plaques in IVUS images. In addition, the lumen was not suitable for early diagnosis of vulnerable plaque because of the low significance compared to the other vessel parameters. To predict vulnerable plaque rupture, future study should have additional experiments using various tissue components, such as the EEM, FT, NC, and media.

  18. Characterization of human tissue carnosinase.

    PubMed Central

    Lenney, J F; Peppers, S C; Kucera-Orallo, C M; George, R P

    1985-01-01

    Human tissue carnosinase (EC 3.4.13.3) had optimum activity at pH9.5 and was a cysteine peptidase, being activated by dithiothreitol and inhibited by p-hydroxymercuribenzoate. By optimizing assay conditions, the activity per g of tissue was increased 10-fold compared with values in the literature. The enzyme was present in every human tissue assayed and was entirely different from serum carnosinase. Highly purified tissue carnosinase had a broader specificity than hog kidney carnosinase. Although tissue carnosinase was very strongly inhibited by bestatin, it did not hydrolyse tripeptides, and thus appears to be a dipeptidase rather than an aminopeptidase. It had a relative molecular mass of 90 000, an isoelectric point of 5.6, and a Km value of 10 mM-carnosine. Two forms of kidney and brain carnosinase were separated by high-resolution anion-exchange chromatography, although only one form was detected by various electrophoretic methods. Homocarnosinase and Mn2+-independent carnosinase were not detected in human tissues, although these enzymes are present in rat and hog kidney. PMID:4026801

  19. Physics of the human cardiovascular system

    NASA Astrophysics Data System (ADS)

    Stefanovska, Aneta

    1999-01-01

    Contemporary measurement techniques permit the non-invasive observation of several cardiovascular functions, both from the central and peripheral points of view. We show that, within one cycle of blood through the cardiovascular system, the same dynamics characterizes heart function as well as blood flow in the capillary bed where cells exchange energy and matter. Analyses of several quite different signals derived from respiration, cardiac function and blood flow, all reveal the existence of five almost periodic frequency components. This result is interpreted as evidence that cardiovascular dynamics is governed by five coupled oscillators. The couplings provide co-ordination among the physiological processes involved, and are essential for efficient cardiovascular function. Understanding the dynamics of a system of five coupled oscillators not only represents a theoretical challenge, but also carries practical implications for diagnosis and for predicting the future behaviour of this life giving system.

  20. Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Patel, Zarana; Huff, Janice; Saha, Janapriya; Wang, Minli; Blattnig, Steve; Wu, Honglu; Cucinotta, Francis

    2015-01-01

    Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray

  1. Connective Tissue Disorders and Cardiovascular Complications: The indomitable role of Transforming Growth Factor-beta signaling

    PubMed Central

    Wheeler, Jason B.; Ikonomidis, John S.; Jones, Jeffrey A.

    2015-01-01

    Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-β) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-β signaling pathway, heritable connective tissue syndromes related to TGF-β receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-β to these syndromes with a primary focus on the cardiovascular system. PMID:24443024

  2. Tissue engineering a human phalanx.

    PubMed

    Landis, W J; Chubinskaya, S; Tokui, T; Wada, Y; Isogai, N; Jacquet, R

    2016-03-21

    A principal purpose of tissue engineering is the augmentation, repair or replacement of diseased or injured human tissue. This study was undertaken to determine whether human biopsies as a cell source could be utilized for successful engineering of human phalanges consisting of both bone and cartilage. This paper reports the use of cadaveric human chondrocytes and periosteum as a model for the development of phalanx constructs. Two factors, osteogenic protein-1 [OP-1/bone morphogenetic protein-7 (BMP7)], alone or combined with insulin-like growth factor (IGF-1), were examined for their potential enhancement of chondrocytes and their secreted extracellular matrices. Design of the study included culture of chondrocytes and periosteum on biodegradable polyglycolic acid (PGA) and poly-l-lactic acid (PLLA)-poly-ε-caprolactone (PCL) scaffolds and subsequent implantation in athymic nu/nu (nude) mice for 5, 20, 40 and 60 weeks. Engineered constructs retrieved from mice were characterized with regard to genotype and phenotype as a function of developmental (implantation) time. Assessments included gross observation, X-ray radiography or microcomputed tomography, histology and gene expression. The resulting data showed that human cell-scaffold constructs could be successfully developed over 60 weeks, despite variability in donor age. Cartilage formation of the distal phalanx models enhanced with both OP-1 and IGF-1 yielded more cells and extracellular matrix (collagen and proteoglycans) than control chondrocytes without added factors. Summary data demonstrated that human distal phalanx models utilizing cadaveric chondrocytes and periosteum were successfully fabricated and OP-1 and OP-1/IGF-1 accelerated construct development and mineralization. The results suggest that similar engineering and transplantation of human autologous tissues in patients are clinically feasible. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Heat waves, aging, and human cardiovascular health.

    PubMed

    Kenney, W Larry; Craighead, Daniel H; Alexander, Lacy M

    2014-10-01

    This brief review is based on a President's Lecture presented at the Annual Meeting of the American College of Sports Medicine in 2013. The purpose of this review was to assess the effects of climate change and consequent increases in environmental heat stress on the aging cardiovascular system. The earth's average global temperature is slowly but consistently increasing, and along with mean temperature changes come increases in heat wave frequency and severity. Extreme passive thermal stress resulting from prolonged elevations in ambient temperature and prolonged physical activity in hot environments creates a high demand on the left ventricle to pump blood to the skin to dissipate heat. Even healthy aging is accompanied by altered cardiovascular function, which limits the extent to which older individuals can maintain stroke volume, increase cardiac output, and increase skin blood flow when exposed to environmental extremes. In the elderly, the increased cardiovascular demand during heat waves is often fatal because of increased strain on an already compromised left ventricle. Not surprisingly, excess deaths during heat waves 1) occur predominantly in older individuals and 2) are overwhelmingly cardiovascular in origin. Increasing frequency and severity of heat waves coupled with a rapidly growing at-risk population dramatically increase the extent of future untoward health outcomes.

  4. Bacteriology testing of cardiovascular tissues: comparison of transport solution versus tissue testing.

    PubMed

    Díaz Rodríguez, R; Van Hoeck, B; Mujaj, B; Ngakam, R; Fan, Y; Bogaerts, K; Jashari, R

    2016-06-01

    Bacteriology testing is mandatory for quality control of recovered cardiovascular allografts (CVA). In this paper, two different bacteriology examinations (A tests) performed before tissue antibiotic decontamination were compared: transport solution filtration analysis (A1) and tissue fragment direct incubation (A2). For this purpose, 521 CVA (326 heart and 195 artery tissues) from 280 donors were collected and analyzed by the European Homograft Bank (EHB). Transport solution (A1) tested positive in 43.25 % of hearts and in 48.21 % of arteries, whereas the tissue samples (A2) tested positive in 38.34 % of hearts and 33.85 % of arteries. The main species identified in both A1 and A2 were Staphylococcus spp. in 55 and 26 % of cases, and Propionibacterium spp. in 8 and 19 %, respectively. Mismatches in bacteriology results between both initial tests A1 and A2 were found. 18.40 % of the heart valves were identified as positive by A1 whilst 13.50 % were considered positive by A2. For arteries, 20.51 % of cases were positive in A1 and negative in A2, and just 6.15 % of artery allografts presented contamination in the A2 test but were considered negative for the A1 test. Comparison between each A test with the B and C tests after antibiotic treatment of the allograft was also performed. A total decontamination rate of 70.8 % of initial positive A tests was obtained. Due to the described mismatches and different bacteria identification percentage, utilization of both A tests should be implemented in tissue banks in order to avoid false negatives.

  5. Mental stress and human cardiovascular disease.

    PubMed

    Esler, Murray

    2017-03-01

    The London physician and neuroanatomist Thomas Willis in the 17th century correctly attributed the source of emotions to the brain, not the heart as believed in antiquity. Contemporary research documents the phenomenon of "triggered" heart disease, when the autonomic nervous system control of the heart by the brain goes awry, producing heart disease of sudden onset, precipitated by acute emotional upheaval. This can take the form of, variously, cardiac arrhythmias, myocardial infarction, Takotsubo cardiomyopathy and sudden death. Chronic psychological distress also can have adverse cardiovascular consequences, in the causal linkage of depressive illness to heart disease, and in the probable causation of atherosclerosis and hypertension by chronic mental stress. In patients with essential hypertension, stress biomarkers are present. The sympathetic nervous system is the usual mediator between these acute and chronic psychological substrates and cardiovascular disease.

  6. Micro- and nanotechnology in cardiovascular tissue engineering.

    PubMed

    Zhang, Boyang; Xiao, Yun; Hsieh, Anne; Thavandiran, Nimalan; Radisic, Milica

    2011-12-09

    While in nature the formation of complex tissues is gradually shaped by the long journey of development, in tissue engineering constructing complex tissues relies heavily on our ability to directly manipulate and control the micro-cellular environment in vitro. Not surprisingly, advancements in both microfabrication and nanofabrication have powered the field of tissue engineering in many aspects. Focusing on cardiac tissue engineering, this paper highlights the applications of fabrication techniques in various aspects of tissue engineering research: (1) cell responses to micro- and nanopatterned topographical cues, (2) cell responses to patterned biochemical cues, (3) controlled 3D scaffolds, (4) patterned tissue vascularization and (5) electromechanical regulation of tissue assembly and function.

  7. Cardiovascular disease associated with human immunodeficiency virus: a review.

    PubMed

    Costa, Luísa Amado; Almeida, Ana G

    2015-01-01

    The cardiovascular manifestations of human immunodeficiency virus (HIV) infection have changed significantly following the introduction of highly active antiretroviral therapy (HAART) regimens. On one hand, HAART has altered the course of HIV disease, with longer survival of HIV-infected patients, and cardiovascular complications of HIV infection such as myocarditis have been reduced. On the other hand, HAART is associated with an increase in the prevalence of both peripheral and coronary arterial disease. As longevity increases in HIV-infected individuals, long-term effects, such as cardiovascular disease, are emerging as leading health issues in this population. In the present review article, we discuss HIV-associated cardiovascular disease, focusing on epidemiology, etiopathogenesis, diagnosis, prognosis, management and therapy. Cardiovascular involvement in treatment-naive patients is still important in situations such as non-adherence to treatment, late initiation of treatment, and/or limited access to HAART in developing countries. We therefore describe the cardiovascular consequences in treatment-naive patients and the potential effect of antiretroviral treatment on their regression, as well as the metabolic and cardiovascular implications of HAART regimens in HIV-infected individuals.

  8. Radiation Effect on Human Tissue

    NASA Technical Reports Server (NTRS)

    Richmond, Robert C.; Cruz, Angela; Bors, Karen; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Predicting the occurrence of human cancer following exposure of an epidemiologic population to any agent causing genetic damage is a difficult task. To an approximation, this is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within clinically normal individuals. This situation begs the need for alternate controlled experimental models that are predictive for the development of human cancer following exposures to agents causing genetic damage. Such models historically have not been of substantial proven value. It is more recently encouraging, however, that developments in molecular and cell biology have led to an expanded knowledge of human carcinogenesis, and of molecular markers associated with that process. It is therefore appropriate to consider new laboratory models developed to accomodate that expanded knowledge in order to assess the cancer risks associated with exposures to genotoxic agents. When ionizing radiation of space is the genotoxic agent, then a series of additional considerations for human cancer risk assessment must also be applied. These include the dose of radiation absorbed by tissue at different locations in the body, the quality of the absorbed radiation, the rate at which absorbed dose accumulates in tissue, the way in which absorbed dose is measured and calculated, and the alterations in incident radiation caused by shielding materials. It is clear that human cancer risk assessment for damage caused by ionizing radiation is a multidisciplinary responsibility, and that within this responsibility no single discipline can hold disproportionate sway if a risk assessment model of radiation-induced human cancer is to be developed that has proven value. Biomolecular and cellular markers from the work reported here are considered

  9. Microbiota of Human Breast Tissue

    PubMed Central

    Urbaniak, Camilla; Cummins, Joanne; Brackstone, Muriel; Macklaim, Jean M.; Gloor, Gregory B.; Baban, Chwanrow K.; Scott, Leslie; O'Hanlon, Deidre M.; Burton, Jeremy P.; Francis, Kevin P.; Tangney, Mark

    2014-01-01

    In recent years, a greater appreciation for the microbes inhabiting human body sites has emerged. In the female mammary gland, milk has been shown to contain bacterial species, ostensibly reaching the ducts from the skin. We decided to investigate whether there is a microbiome within the mammary tissue. Using 16S rRNA sequencing and culture, we analyzed breast tissue from 81 women with and without cancer in Canada and Ireland. A diverse population of bacteria was detected within tissue collected from sites all around the breast in women aged 18 to 90, not all of whom had a history of lactation. The principal phylum was Proteobacteria. The most abundant taxa in the Canadian samples were Bacillus (11.4%), Acinetobacter (10.0%), Enterobacteriaceae (8.3%), Pseudomonas (6.5%), Staphylococcus (6.5%), Propionibacterium (5.8%), Comamonadaceae (5.7%), Gammaproteobacteria (5.0%), and Prevotella (5.0%). In the Irish samples the most abundant taxa were Enterobacteriaceae (30.8%), Staphylococcus (12.7%), Listeria welshimeri (12.1%), Propionibacterium (10.1%), and Pseudomonas (5.3%). None of the subjects had signs or symptoms of infection, but the presence of viable bacteria was confirmed in some samples by culture. The extent to which these organisms play a role in health or disease remains to be determined. PMID:24610844

  10. Psoriasis strikes back! Epicardial adipose tissue: another contributor to the higher cardiovascular risk in psoriasis.

    PubMed

    Raposo, Inês; Torres, Tiago

    2015-10-01

    For many years psoriasis was considered an inflammatory condition restricted to the skin. However, nowadays it is considered an immune-mediated, systemic inflammatory condition associated with numerous medical comorbidities, particularly cardiometabolic diseases, and overall cardiovascular mortality. Several studies have suggested that psoriasis may be an independent risk factor for atherosclerosis, indicating that psoriasis itself poses an intrinsic risk for cardiovascular disease, probably due to the disease's inflammatory burden. However, other causes beyond systemic inflammation and traditional cardiovascular risk factors may be implicated in cardiovascular disease in psoriasis. Recently, epicardial adipose tissue, an emerging cardiovascular risk factor, has been shown to be increased in psoriasis patients and to be associated with subclinical atherosclerosis, providing another possible link between psoriasis and atherosclerosis. The reason for the increase in epicardial adipose tissue in patients with psoriasis is unknown, but it is probably multifactorial, with genetic, immune-mediated and behavioral factors having a role. Thus, along with the increased prevalence of cardiometabolic risk factors and systemic inflammation in psoriasis, epicardial adipose tissue is probably another important contributor to the higher cardiovascular risk observed in psoriasis.

  11. Credit scores, cardiovascular disease risk, and human capital.

    PubMed

    Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E

    2014-12-02

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.

  12. Ultrasound strain imaging for quantification of tissue function: cardiovascular applications

    NASA Astrophysics Data System (ADS)

    de Korte, Chris L.; Lopata, Richard G. P.; Hansen, Hendrik H. G.

    2013-03-01

    With ultrasound imaging, the motion and deformation of tissue can be measured. Tissue can be deformed by applying a force on it and the resulting deformation is a function of its mechanical properties. Quantification of this resulting tissue deformation to assess the mechanical properties of tissue is called elastography. If the tissue under interrogation is actively deforming, the deformation is directly related to its function and quantification of this deformation is normally referred as `strain imaging'. Elastography can be used for atherosclerotic plaques characterization, while the contractility of the heart or skeletal muscles can be assessed with strain imaging. We developed radio frequency (RF) based ultrasound methods to assess the deformation at higher resolution and with higher accuracy than commercial methods using conventional image data (Tissue Doppler Imaging and 2D speckle tracking methods). However, the improvement in accuracy is mainly achieved when measuring strain along the ultrasound beam direction, so 1D. We further extended this method to multiple directions and further improved precision by using compounding of data acquired at multiple beam steered angles. In arteries, the presence of vulnerable plaques may lead to acute events like stroke and myocardial infarction. Consequently, timely detection of these plaques is of great diagnostic value. Non-invasive ultrasound strain compounding is currently being evaluated as a diagnostic tool to identify the vulnerability of plaques. In the heart, we determined the strain locally and at high resolution resulting in a local assessment in contrary to conventional global functional parameters like cardiac output or shortening fraction.

  13. Cardiac adipose tissue and its relationship to diabetes mellitus and cardiovascular disease

    PubMed Central

    Noyes, Adam M; Dua, Kirandeep; Devadoss, Ramprakash; Chhabra, Lovely

    2014-01-01

    Type-2 diabetes mellitus (T2DM) plays a central role in the development of cardiovascular disease (CVD). However, its relationship to epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) in particular is important in the pathophysiology of coronary artery disease. Owing to its close proximity to the heart and coronary vasculature, EAT exerts a direct metabolic impact by secreting proinflammatory adipokines and free fatty acids, which promote CVD locally. In this review, we have discussed the relationship between T2DM and cardiac fat deposits, particularly EAT and PAT, which together exert a big impact on the cardiovascular health. PMID:25512789

  14. Decadal Cycles in the Human Cardiovascular System

    PubMed Central

    Halberg, Franz; Cornelissen, Germaine; Sothern, Robert B.; Hillman, Dewayne; Watanabe, Yoshihiko; Haus, Erhard; Schwartzkopff, Othild; Best, William R.

    2013-01-01

    Seven of the eight authors of this report each performed physiologic self-surveillance, some around the clock for decades. We here document the presence of long cycles (decadals, including circaundecennians) in the time structure of systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR). Because of the non-stationary nature in time and space of these and other physiologic and environmental periodic components that, like the wind, can appear and disappear in a given or other geographic location at one or another time, they have been called “Aeolian”. The nonlinear estimation of the uncertainties of the periods (τs) of two or more variables being compared has been used to determine whether these components are congruent or not, depending on whether their CIs (95% confidence intervals) overlap or not. Among others, congruence has been found for components with τs clustering around 10 years in us and around us. There is a selective assortment among individuals, variables and cycle characteristics (mean and circadian amplitude and acrophase). Apart from basic interest, like other nonphotic solar signatures such as transyears with periods slightly longer than one year or about 33-year Brückner-Egeson-Lockyer (BEL) cycles, about 10-year and longer cycles present in 7 of 7 self-monitoring individuals are of interest in the diagnosis of Vascular Variability Anomalies (VVAs), including MESOR-hypertension, and others. Some of the other VVAs, such as a circadian overswing, i.e., CHAT (Circadian Hyper-Aplitude-Tension), or an excessive pulse pressure, based on repeated 7-day around-the-clock records, can represent a risk of severe cardiovascular events, greater than that of a high BP. The differential diagnosis of physiologic cycles, infradians (components with a τ longer than 28 hours) as well as circadians awaits the collection of reference values for the infradian parameters of the cycles described herein. Just as in stroke-prone spontaneously

  15. Cardiovascular

    NASA Video Gallery

    Overview of Cardiovascular research which addresses risks of space flight, including adaptive changes to the cephalad fluid shift (such as reduced circulating blood volume), potential for heart rhy...

  16. 'Browning' the cardiac and peri-vascular adipose tissues to modulate cardiovascular risk.

    PubMed

    Aldiss, Peter; Davies, Graeme; Woods, Rachel; Budge, Helen; Sacks, Harold S; Symonds, Michael E

    2017-02-01

    Excess visceral adiposity, in particular that located adjacent to the heart and coronary arteries is associated with increased cardiovascular risk. In the pathophysiological state, dysfunctional adipose tissue secretes an array of factors modulating vascular function and driving atherogenesis. Conversely, brown and beige adipose tissues utilise glucose and lipids to generate heat and are associated with improved cardiometabolic health. The cardiac and thoracic perivascular adipose tissues are now understood to be composed of brown adipose tissue in the healthy state and undergo a brown-to-white transition i.e. during obesity which may be a driving factor of cardiovascular disease. In this review we discuss the risks of excess cardiac and vascular adiposity and potential mechanisms by which restoring the brown phenotype i.e. "re-browning" could potentially be achieved in clinically relevant populations.

  17. Role of Extracellular Matrix Signaling Cues in Modulating Cell Fate Commitment for Cardiovascular Tissue Engineering

    PubMed Central

    Nakayama, Karina H.; Hou, Luqia; Huang, Ngan F.

    2014-01-01

    It is generally agreed that engineered cardiovascular tissues require cellular interactions with the local milieu. Within the microenvironment, the extracellular matrix (ECM) is an important support structure that provides dynamic signaling cues in part through its chemical, physical, and mechanical properties. In response to ECM factors, cells activate biochemical and mechanotransduction pathways that modulate their survival, growth, migration, differentiation, and function. This review describes the role of ECM chemical composition, spatial patterning, and mechanical stimulation in the specification of cardiovascular lineages, with a focus on stem cell differentiation, direct transdifferentiation, and endothelial-to-mesenchymal transition. The translational application of ECMs will be discussed in the context of cardiovascular tissue engineering and regenerative medicine. PMID:24443420

  18. Chronic intermittent hypoxia activates nuclear factor-{kappa}B in cardiovascular tissues in vivo

    SciTech Connect

    Greenberg, Harly; Ye Xiaobing; Wilson, David; Htoo, Aung K.; Hendersen, Todd; Liu Shufang . E-mail: sliu@lij.edu

    2006-05-05

    Obstructive sleep apnea (OSA) is an important risk factor for cardiovascular morbidity and mortality. The mechanisms through which OSA promotes the development of cardiovascular disease are poorly understood. In this study, we tested the hypotheses that chronic exposure to intermittent hypoxia and reoxygenation (CIH) is a major pathologic factor causing cardiovascular inflammation, and that CIH-induces cardiovascular inflammation and pathology by activating the NF-{kappa}B pathway. We demonstrated that exposure of mice to CIH activated NF-{kappa}B in cardiovascular tissues, and that OSA patients had markedly elevated monocyte NF-{kappa}B activity, which was significantly decreased when obstructive apneas and their resultant CIH were eliminated by nocturnal CPAP therapy. The elevated NF-{kappa}B activity induced by CIH is accompanied by and temporally correlated to the increased expression of iNOS protein, a putative and important NF-{kappa}B-dependent gene product. Thus, CIH-mediated NF-{kappa}B activation may be a molecular mechanism linking OSA and cardiovascular pathologies seen in OSA patients.

  19. Human dignity and human tissue: a meaningful ethical relationship?

    PubMed

    Kirchhoffer, David G; Dierickx, Kris

    2011-09-01

    Human dignity has long been used as a foundational principle in policy documents and ethical guidelines intended to govern various forms of biomedical research. Despite the vast amount of literature concerning human dignity and embryonic tissues, the majority of biomedical research uses non-embryonic human tissue. Therefore, this contribution addresses a notable lacuna in the literature: the relationship, if any, between human dignity and human tissue. This paper first elaborates a multidimensional understanding of human dignity that overcomes many of the shortcomings associated with the use of human dignity in other ethical debates. Second, it discusses the relationship between such an understanding of human dignity and 'non-embryonic' human tissue. Finally, it considers the implications of this relationship for biomedical research and practice involving human tissue. The contribution demonstrates that while human tissue cannot be said to have human dignity, human dignity is nevertheless implicated by human tissue, making what is done with human tissue and how it is done worthy of moral consideration.

  20. Recent genetic discoveries implicating ion channels in human cardiovascular diseases.

    PubMed

    George, Alfred L

    2014-04-01

    The term 'channelopathy' refers to human genetic disorders caused by mutations in genes encoding ion channels or their interacting proteins. Recent advances in this field have been enabled by next-generation DNA sequencing strategies such as whole exome sequencing with several intriguing and unexpected discoveries. This review highlights important discoveries implicating ion channels or ion channel modulators in cardiovascular disorders including cardiac arrhythmia susceptibility, cardiac conduction phenotypes, pulmonary and systemic hypertension. These recent discoveries further emphasize the importance of ion channels in the pathophysiology of human disease and as important druggable targets.

  1. Forebrain neurocircuitry associated with human reflex cardiovascular control

    PubMed Central

    Shoemaker, J. Kevin; Goswami, Ruma

    2015-01-01

    Physiological homeostasis depends upon adequate integration and responsiveness of sensory information with the autonomic nervous system to affect rapid and effective adjustments in end organ control. Dysregulation of the autonomic nervous system leads to cardiovascular disability with consequences as severe as sudden death. The neural pathways involved in reflexive autonomic control are dependent upon brainstem nuclei but these receive modulatory inputs from higher centers in the midbrain and cortex. Neuroimaging technologies have allowed closer study of the cortical circuitry related to autonomic cardiovascular adjustments to many stressors in awake humans and have exposed many forebrain sites that associate strongly with cardiovascular arousal during stress including the medial prefrontal cortex, insula cortex, anterior cingulate, amygdala and hippocampus. Using a comparative approach, this review will consider the cortical autonomic circuitry in rodents and primates with a major emphasis on more recent neuroimaging studies in awake humans. A challenge with neuroimaging studies is their interpretation in view of multiple sensory, perceptual, emotive and/or reflexive components of autonomic responses. This review will focus on those responses related to non-volitional baroreflex control of blood pressure and also on the coordinated responses to non-fatiguing, non-painful volitional exercise with particular emphasis on the medial prefrontal cortex and the insula cortex. PMID:26388780

  2. Cardiovascular and fluid volume control in humans in space.

    PubMed

    Norsk, Peter

    2005-08-01

    The human cardiovascular system and regulation of fluid volume are heavily influenced by gravity. When decreasing the effects of gravity in humans such as by anti-orthostatic posture changes or immersion into water, venous return is increased by some 25%. This leads to central blood volume expansion, which is accompanied by an increase in renal excretion rates of water and sodium. The mechanisms for the changes in renal excretory rates include a complex interaction of cardiovascular reflexes, neuroendocrine variables, and physical factors. Weightlessness is unique to obtain more information on this complex interaction, because it is the only way to completely abolish the effects of gravity over longer periods. Results from space have been unexpected, because astronauts exhibit a fluid and sodium retaining state with activation of the sympathetic nervous system, which subjects during simulations by head-down bed rest do not. Therefore, the concept as to how weightlessness affects the cardiovascular system and modulates regulation of body fluids should be revised and new simulation models developed. Knowledge as to how gravity and weightlessness modulate integrated fluid volume control is of importance for understanding pathophysiology of heart failure, where gravity plays a strong role in fluid and sodium retention.

  3. Cardiovascular Deconditioning in Humans: Alteration in Cardiovascular Regulation and Function During Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Cohen, Richard

    1999-01-01

    Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In this project we apply a powerful, new method - cardiovascular system identification (CSI) - for the study of the effects of space flight on the cardiovascular system so that effective countermeasures can be developed. CSI involves the mathematical analysis of second-to-second fluctuations in non-invasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV - respiratory activity) in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of all the physiologic mechanisms coupling these signals, CSI provides a model of the closed-loop cardiovascular regulatory state in an individual subject. The model includes quantitative descriptions of the heart rate baroreflex, autonomic function, as well as other important physiologic mechanisms. We are in the process of incorporating beat-to-beat fluctuations of stroke volume into the CSI technique in order to quantify additional physiologic mechanisms such as those involved in control of peripheral vascular resistance and alterations in cardiac contractility. We apply CSI in conjunction with the two general protocols of the Human Studies Core project. The first protocol involves ground-based, human head down tilt bed rest to simulate microgravity and acute stressors - upright tilt, standing and bicycle exercise - to provide orthostatic and exercise challenges. The second protocol is intended to be the same as the first but with the addition of sleep deprivation to determine whether

  4. Molecular mechanisms for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

    PubMed

    Watanabe, Hiroshi

    2013-01-01

    Chronic kidney disease (CKD), marked by a progressive loss in renal function, is a leading cause of hemodialysis initiation and cardiovascular disease (CVD). There are currently 13.3 million patients with CKD and 300 thousand patients are currently undergoing hemodialysis in Japan. Therefore, preventing the initiation of dialysis and reducing the risk of cardiovascular death are high-priority issues from the viewpoint of public health and economic implications. Understanding the molecular mechanism responsible for the progression of CKD and cardiovascular damage regarding crosstalk between the kidney and cardiovascular system is an important issue in controlling the pathogenesis of CKD-CVD. However, the mechanisms involved in CKD-CVD are not well understood. This hinders the development of new treatment strategies. We have been investigating the role of protein bound uremic toxins, that are difficult to remove by hemodialysis, on the onset and progression of CKD and CVD. The relationship between their redox properties and the pathogenesis of CKD-CVD was examined. In this review, we focus on two sulfate conjugated uremic toxins, namely, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and summarize recent studies that provide new insights on the molecular mechanisms responsible for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

  5. Cardiovascular Involvement in Connective Tissue Disease: The Role of Interstitial Lung Disease

    PubMed Central

    Wang, XiaoBing; Lou, MeiNa; Li, Yongji; Ye, WenJing; Zhang, ZhiYong; Jia, Xiufen; Shi, HongYing; Zhu, XiaoChun; Wang, LiangXing

    2015-01-01

    Objective The aim of this study was to assess cardiovascular involvement in patients with connective tissue disease (CTD), and determine whether interstitial lung disease (ILD) in these patients is associated with elevated cardiovascular risk. Methods This study evaluated a retrospective cohort of 436 CTD patients admitted to a large teaching hospital in Zhejiang province, China, along with an additional 436 participants of an annual community health screening conducted in the physical examination center who served as age- and gender-matched controls. Demographic, clinical, serologic and imaging characteristics, as well as medications used by each participant were recorded. Cardiovascular involvement was defined by uniform criteria. Correlations between clinical/serologic factors and cardiovascular involvement were determined by univariate and multivariate analyses. Results CTD patients had a significantly higher cardiovascular involvement rate than controls (64.7% vs 23.4%), with higher rates of diabetes, hypertension, and hyperlipidemia, elevated systolic and diastolic pressures, C-reactive protein, total cholesterol, and low-density lipoprotein cholesterol, and lower albumin and high-density lipoprotein cholesterol (all p < 0.05). Furthermore, CTP patients with cardiovascular involvement were significantly older, had higher systolic and diastolic pressures, C-reactive protein, glucose, and uric acid, higher rates of diabetes, hypertension, and use of moderate- to high-dose glucocorticoids, and longer disease duration compared to patients without involvement (all p < 0.05). Moreover, CTD in patients with cardiovascular involvement was more likely to be complicated by ILD (p < 0.01), which manifested as a higher alveolar inflammation score (p < 0.05). In the multivariate analysis, cardiovascular involvement in CTD patients was associated with age, systolic pressure, body mass index, uric acid, disease duration > 2 years, use of moderate- to high

  6. Assessment of permeation of lipoproteins in human carotid tissue

    NASA Astrophysics Data System (ADS)

    Ghosn, Mohamad G.; Syed, Saba H.; Leba, Michael; Morrisett, Joel D.; Tuchin, Valery V.; Larin, Kirill V.

    2010-02-01

    Cardiovascular disease is among the leading causes of death in the United States. Specifically, atherosclerosis is an increasingly devastating contributor to the tally and has been found to be a byproduct of arterial permeability irregularities in regards to lipoprotein penetration. To further explore arterial physiology and molecular transport, the imaging technique of Optical Coherence Tomography (OCT) was employed. With OCT, the permeation of glucose (MW = 180 Da), low density lipoprotein (LDL; MW = 2.1 × 106 Da), and high density lipoprotein (HDL; MW = 2.5 × 105 Da) in human carotid tissue was studied to determine the effect of different molecular characteristics on permeation in atherosclerotic tissues. The permeability rates calculated from the diffusion of the molecular agents into the abnormal carotid tissue samples is compared to those of normal, healthy tissue. The results show that in the abnormal tissue, the permeation of agents correlate to the size constraints. The larger molecules of LDL diffuse the slowest, while the smallest molecules of glucose diffuse the fastest. However, in normal tissue, LDL permeates at a faster rate than the other two agents, implying the existence of a transport mechanism that facilitates the passage of LDL molecules. These results highlight the capability of OCT as a sensitive and specific imaging technique as well as provide significant information to the understanding of atherosclerosis and its effect on tissue properties.

  7. Humanized mice and tissue transplantation

    PubMed Central

    Kenney, Laurie L; Shultz, Leonard D.; Greiner, Dale L; Brehm, Michael A.

    2017-01-01

    Our understanding of the molecular pathways that control immune responses, particularly immunomodulatory molecules that control the extent and duration of an immune response, have led to new approaches in the field of transplantation immunology to induce allograft survival. These molecular pathways are being defined precisely in murine models, and are now being translated into clinical practice. However, many of the newly available drugs are human-specific reagents and furthermore, there exist many species-specific differences between mouse and human immune systems. Recent advances in the development of humanized mice, i.e., immunodeficient mice engrafted with functional human immune systems, have led to the availability of a small animal model for the study of human immune responses. Humanized mice represent an important pre-clinical model system for evaluation of new drugs as well as identification of the mechanisms underlying human allograft rejection without putting patients at risk. This review highlights recent advances in the development of humanized mice and their use as pre-clinical models for the study of human allograft responses. PMID:26588186

  8. Tissue Specificity of Human Disease Module

    PubMed Central

    Kitsak, Maksim; Sharma, Amitabh; Menche, Jörg; Guney, Emre; Ghiassian, Susan Dina; Loscalzo, Joseph; Barabási, Albert-László

    2016-01-01

    Genes carrying mutations associated with genetic diseases are present in all human cells; yet, clinical manifestations of genetic diseases are usually highly tissue-specific. Although some disease genes are expressed only in selected tissues, the expression patterns of disease genes alone cannot explain the observed tissue specificity of human diseases. Here we hypothesize that for a disease to manifest itself in a particular tissue, a whole functional subnetwork of genes (disease module) needs to be expressed in that tissue. Driven by this hypothesis, we conducted a systematic study of the expression patterns of disease genes within the human interactome. We find that genes expressed in a specific tissue tend to be localized in the same neighborhood of the interactome. By contrast, genes expressed in different tissues are segregated in distinct network neighborhoods. Most important, we show that it is the integrity and the completeness of the expression of the disease module that determines disease manifestation in selected tissues. This approach allows us to construct a disease-tissue network that confirms known and predicts unexpected disease-tissue associations. PMID:27748412

  9. Coconut oil consumption and cardiovascular risk factors in humans

    PubMed Central

    Eyres, Michael F.; Chisholm, Alexandra; Brown, Rachel C.

    2016-01-01

    Coconut oil is being heavily promoted as a healthy oil, with benefits that include support of heart health. To assess the merits of this claim, the literature on the effect of coconut consumption on cardiovascular risk factors and outcomes in humans was reviewed. Twenty-one research papers were identified for inclusion in the review: 8 clinical trials and 13 observational studies. The majority examined the effect of coconut oil or coconut products on serum lipid profiles. Coconut oil generally raised total and low-density lipoprotein cholesterol to a greater extent than cis unsaturated plant oils, but to a lesser extent than butter. The effect of coconut consumption on the ratio of total cholesterol to high-density lipoprotein cholesterol was often not examined. Observational evidence suggests that consumption of coconut flesh or squeezed coconut in the context of traditional dietary patterns does not lead to adverse cardiovascular outcomes. However, due to large differences in dietary and lifestyle patterns, these findings cannot be applied to a typical Western diet. Overall, the weight of the evidence from intervention studies to date suggests that replacing coconut oil with cis unsaturated fats would alter blood lipid profiles in a manner consistent with a reduction in risk factors for cardiovascular disease. PMID:26946252

  10. Coconut oil consumption and cardiovascular risk factors in humans.

    PubMed

    Eyres, Laurence; Eyres, Michael F; Chisholm, Alexandra; Brown, Rachel C

    2016-04-01

    Coconut oil is being heavily promoted as a healthy oil, with benefits that include support of heart health. To assess the merits of this claim, the literature on the effect of coconut consumption on cardiovascular risk factors and outcomes in humans was reviewed. Twenty-one research papers were identified for inclusion in the review: 8 clinical trials and 13 observational studies. The majority examined the effect of coconut oil or coconut products on serum lipid profiles. Coconut oil generally raised total and low-density lipoprotein cholesterol to a greater extent than cis unsaturated plant oils, but to a lesser extent than butter. The effect of coconut consumption on the ratio of total cholesterol to high-density lipoprotein cholesterol was often not examined. Observational evidence suggests that consumption of coconut flesh or squeezed coconut in the context of traditional dietary patterns does not lead to adverse cardiovascular outcomes. However, due to large differences in dietary and lifestyle patterns, these findings cannot be applied to a typical Western diet. Overall, the weight of the evidence from intervention studies to date suggests that replacing coconut oil with cis unsaturated fats would alter blood lipid profiles in a manner consistent with a reduction in risk factors for cardiovascular disease.

  11. Grating-based tomography of human tissues

    NASA Astrophysics Data System (ADS)

    Müller, Bert; Schulz, Georg; Mehlin, Andrea; Herzen, Julia; Lang, Sabrina; Holme, Margaret; Zanette, Irene; Hieber, Simone; Deyhle, Hans; Beckmann, Felix; Pfeiffer, Franz; Weitkamp, Timm

    2012-07-01

    The development of therapies to improve our health requires a detailed knowledge on the anatomy of soft tissues from the human body down to the cellular level. Grating-based phase contrast micro computed tomography using synchrotron radiation provides a sensitivity, which allows visualizing micrometer size anatomical features in soft tissue without applying any contrast agent. We show phase contrast tomography data of human brain, tumor vessels and constricted arteries from the beamline ID 19 (ESRF) and urethral tissue from the beamline W2 (HASYLAB/DESY) with micrometer resolution. Here, we demonstrate that anatomical features can be identified within brain tissue as well known from histology. Using human urethral tissue, the application of two photon energies is compared. Tumor vessels thicker than 20 μm can be perfectly segmented. The morphology of coronary arteries can be better extracted in formalin than after paraffin embedding.

  12. State-of-the-Art Review of 3D Bioprinting for Cardiovascular Tissue Engineering.

    PubMed

    Duan, Bin

    2017-01-01

    3D bioprinting is a group of rapidly growing techniques that allows building engineered tissue constructs with complex and hierarchical structures, mechanical and biological heterogeneity. It enables implementation of various bioinks through different printing mechanisms and precise deposition of cell and/or biomolecule laden biomaterials in predefined locations. This review briefly summarizes applicable bioink materials and various bioprinting techniques, and presents the recent advances in bioprinting of cardiovascular tissues, with focusing on vascularized constructs, myocardium and heart valve conduits. Current challenges and further perspectives are also discussed to help guide the bioink and bioprinter development, improve bioprinting strategies and direct future organ bioprinting and translational applications.

  13. Circadian misalignment increases cardiovascular disease risk factors in humans

    PubMed Central

    Morris, Christopher J.; Purvis, Taylor E.; Hu, Kun; Scheer, Frank A. J. L.

    2016-01-01

    Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show—by using two 8-d laboratory protocols—that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8–15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3–29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk. PMID:26858430

  14. Circadian misalignment increases cardiovascular disease risk factors in humans.

    PubMed

    Morris, Christopher J; Purvis, Taylor E; Hu, Kun; Scheer, Frank A J L

    2016-03-08

    Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show-by using two 8-d laboratory protocols-that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8-15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3-29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.

  15. NCI’s Cooperative Human Tissue Network

    Cancer.gov

    Quality biospecimens are a foundational resource for cancer research. One of NCI’s longest running biospecimen programs is the Cooperative Human Tissue Network, a resource mainly for basic discovery and early translational research.

  16. Urgent need for human resources to promote global cardiovascular health.

    PubMed

    Vedanthan, Rajesh; Fuster, Valentin

    2011-02-01

    The World Health Organization estimates the existence of a global shortage of over 4 million health-care workers. Given the growing global burden of cardiovascular disease (CVD), the shortfall in global human resources for health (HRH) is probably even greater than predicted. A critical challenge going forward is to determine how to integrate CVD-related human resource needs into the overall global HRH agenda. We describe the CVD implications of core HRH objectives, including coverage, motivation, and competence, in addition to issues such as health-care worker migration and the need for input from multiple stakeholders to successfully address the current problems. We emphasize gaps in knowledge regarding HRH for global CVD-related care and research opportunities. In light of the current global epidemiologic transition from communicable to noncommunicable diseases, now is the time for the global health community to focus on CVD-related human resource needs.

  17. Melanin content of hamster tissues, human tissues, and various melanomas

    SciTech Connect

    Watts, K.P.; Fairchild, R.G.; Slatkin, D.N.; Greenberg, D.; Packer, S.; Atkins, H.L.; Hannon, S.J.

    1981-02-01

    Melanin content (percentage by weight) was determined in both pigmented and nonpigmented tissues of Syrian golden hamsters bearing Greene melanoma. Melanin content was also measured in various other melanoma models (B-16 in C57 mice, Harding-Passey in BALB/c mice, and KHDD in C3H mice) and in nine human melanomas, as well as in selected normal tissues. The purpose was to evaluate the possible efficacy of chlorpromazine, which is known to bind to melanin, as a vehicle for boron transport in neutron capture therapy. Successful therapy would depend upon selective uptake and absolute concentration of borated compounds in tumors; these parameters will in turn depend upon melanin concentration in melanomas and nonpigmented ''background'' tissues. Hamster whole eyes, hamster melanomas, and other well-pigmented animal melanomas were found to contain 0.3 to 0.8% melanin by weight, whereas human melanomas varied from 0.1 to 0.9% (average, 0.35%). Other tissues, with the exception of skin, were lower in content by a factor of greater than or equal to30. Melanin pigment was extracted from tissues, and the melanin content was determined spectrophotometrically. Measurements were found to be sensitive to the presence of other proteins. Previous procedures for isolating and quantifying melanin often neglected the importance of removing proteins and other interfering nonmelanic substances.

  18. Variation in alternative splicing across human tissues

    PubMed Central

    Yeo, Gene; Holste, Dirk; Kreiman, Gabriel; Burge, Christopher B

    2004-01-01

    Background Alternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues. Results Controlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most pronounced differences between tissues were seen for the frequencies of alternative 3' splice site and alternative 5' splice site usage, which were about 50 to 100% higher in the liver than in any other human tissue studied. Quantifying differences in splice junction usage, the brain, pancreas, liver and the peripheral nervous system had the most distinctive patterns of AS. Analysis of available microarray expression data showed that the liver had the most divergent pattern of expression of serine-arginine protein and heterogeneous ribonucleoprotein genes compared to the other human tissues studied, possibly contributing to the unusually high frequency of alternative splice site usage seen in liver. Sequence motifs enriched in alternative exons in genes expressed in the brain, testis and liver suggest specific splicing factors that may be important in AS regulation in these tissues. Conclusions This study distinguishes the human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis-regulatory elements and trans-acting factors likely to have important roles in tissue-specific AS in human cells. PMID:15461793

  19. Adipose tissue-derived stem cells as a therapeutic tool for cardiovascular disease

    PubMed Central

    Suzuki, Etsu; Fujita, Daishi; Takahashi, Masao; Oba, Shigeyoshi; Nishimatsu, Hiroaki

    2015-01-01

    Adipose tissue-derived stem cells (ADSCs) are adult stem cells that can be easily harvested from subcutaneous adipose tissue. Many studies have demonstrated that ADSCs differentiate into vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), and cardiomyocytes in vitro and in vivo. However, ADSCs may fuse with tissue-resident cells and obtain the corresponding characteristics of those cells. If fusion occurs, ADSCs may express markers of VECs, VSMCs, and cardiomyocytes without direct differentiation into these cell types. ADSCs also produce a variety of paracrine factors such as vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1 that have proangiogenic and/or antiapoptotic activities. Thus, ADSCs have the potential to regenerate the cardiovascular system via direct differentiation into VECs, VSMCs, and cardiomyocytes, fusion with tissue-resident cells, and the production of paracrine factors. Numerous animal studies have demonstrated the efficacy of ADSC implantation in the treatment of acute myocardial infarction (AMI), ischemic cardiomyopathy (ICM), dilated cardiomyopathy, hindlimb ischemia, and stroke. Clinical studies regarding the use of autologous ADSCs for treating patients with AMI and ICM have recently been initiated. ADSC implantation has been reported as safe and effective so far. Therefore, ADSCs appear to be useful for the treatment of cardiovascular disease. However, the tumorigenic potential of ADSCs requires careful evaluation before their safe clinical application. PMID:26322185

  20. Human histocultures (tissue explants) in retrovirology

    PubMed Central

    Arakelyan, Anush; Fitzgerald, Wendy; Grivel, Jean-Charles; Vanpouille, Christophe; Margolis, Leonid

    2014-01-01

    Summary Viral pathogenesis is studied predominantly in cultures of primary isolated cells or cell lines. Many retroviruses efficiently replicate only in activated cells. Therefore, in order to become efficient viral producers cells should be artificially activated, a procedure which significantly changes cell physiology. However, for many viral diseases, like HIV-1 and other retroviruses’ diseases, critical pathogenic events occur in tissues and cell isolation from their native microenvironment prevents single cell cultures from faithfully reflecting important aspects of cell-cell and cell-pathogen interactions that occur in the context of complex tissue cytoarchitecture. Tissue explants (histocultures) that retain tissue cytoarchitecture and many aspects of cell-cell interactions more faithfully represent in vivo tissue features. Human histocultures constitute an adequate model for studying viral pathogenesis under controlled laboratory conditions. Protocols for various human histocultures as applied to study retroviral pathogenesis, in particular of HIV-1, have been refined by our laboratory and are described in the present publication. Human histocultures of human tonsils and lymph nodes, as well as of recto-sigmoid and cervico-vaginal tissues can be used to study viral transmission, pathogenesis and as a pre-clinical platform for antivirals evaluation. PMID:24158827

  1. Accumulation of perfluoroalkyl substances in human tissues.

    PubMed

    Pérez, Francisca; Nadal, Martí; Navarro-Ortega, Alícia; Fàbrega, Francesc; Domingo, José L; Barceló, Damià; Farré, Marinella

    2013-09-01

    Perfluoroalkyl substances (PFASs) are environmental pollutants with an important bioaccumulation potential. However, their metabolism and distribution in humans are not well studied. In this study, the concentrations of 21 PFASs were analyzed in 99 samples of autopsy tissues (brain, liver, lung, bone, and kidney) from subjects who had been living in Tarragona (Catalonia, Spain). The samples were analyzed by solvent extraction and online purification by turbulent flow and liquid chromatography coupled to tandem mass spectrometry. The occurrence of PFASs was confirmed in all human tissues. Although PFASs accumulation followed particular trends depending on the specific tissue, some similarities were found. In kidney and lung, perfluorobutanoic acid was the most frequent compound, and at highest concentrations (median values: 263 and 807ng/g in kidney and lung, respectively). In liver and brain, perfluorohexanoic acid showed the maximum levels (median: 68.3 and 141ng/g, respectively), while perfluorooctanoic acid was the most contributively in bone (median: 20.9ng/g). Lung tissues accumulated the highest concentration of PFASs. However, perfluorooctane sulfonic acid and perfluorooctanoic acid were more prevalent in liver and bone, respectively. To the best of our knowledge, the accumulation of different PFASs in samples of various human tissues from the same subjects is here reported for the very first time. The current results may be of high importance for the validation of physiologically based pharmacokinetic models, which are being developed for humans. However, further studies on the distribution of the same compounds in the human body are still required.

  2. Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration

    PubMed Central

    Hu, Jiang; Wang, Yongyu; Jiao, Jiao; Liu, Zhongning; Zhao, Chao; Zhou, Zhou; Zhang, Zhanpeng; Forde, Kaitlynn; Wang, Lunchang; Wang, Jiangang; Baylink, David J.; Zhang, Xiao-Bing; Gao, Shaorong; Yang, Bo; Chen, Y. Eugene; Ma, Peter X.

    2015-01-01

    Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue. PMID:26398309

  3. Humanized mice with ectopic artificial liver tissues.

    PubMed

    Chen, Alice A; Thomas, David K; Ong, Luvena L; Schwartz, Robert E; Golub, Todd R; Bhatia, Sangeeta N

    2011-07-19

    "Humanized" mice offer a window into aspects of human physiology that are otherwise inaccessible. The best available methods for liver humanization rely on cell transplantation into immunodeficient mice with liver injury but these methods have not gained widespread use due to the duration and variability of hepatocyte repopulation. In light of the significant progress that has been achieved in clinical cell transplantation through tissue engineering, we sought to develop a humanized mouse model based on the facile and ectopic implantation of a tissue-engineered human liver. These human ectopic artificial livers (HEALs) stabilize the function of cryopreserved primary human hepatocytes through juxtacrine and paracrine signals in polymeric scaffolds. In contrast to current methods, HEALs can be efficiently established in immunocompetent mice with normal liver function. Mice transplanted with HEALs exhibit humanized liver functions persistent for weeks, including synthesis of human proteins, human drug metabolism, drug-drug interaction, and drug-induced liver injury. Here, mice with HEALs are used to predict the disproportionate metabolism and toxicity of "major" human metabolites using multiple routes of administration and monitoring. These advances may enable manufacturing of reproducible in vivo models for diverse drug development and research applications.

  4. ECG-gated, mechanical and electromechanical wave imaging of cardiovascular tissues in vivo.

    PubMed

    Pernot, Mathieu; Fujikura, Kana; Fung-Kee-Fung, Simon D; Konofagou, Elisa E

    2007-07-01

    In simplistic terms, the motion of the heart can be summarized as an active contraction and passive relaxation of the myocardium. However, the local motion of cardiovascular tissues over the course of an entire cardiac cycle results from various transient events such as the valves closing/opening, sudden changes in blood pressure and electrical conduction of the myocardium. The transient motion generated by most of these events occurs within a very short time (on the order of 1 ms) and cannot be imaged correctly with conventional imaging systems, due to their limited temporal resolution. In this paper, we propose a method for imaging this rapid transient motion of tissues in cardiovascular applications. Our method is based on imaging tissues with ultrasound at high frame rates (up to 8000 fps) by synchronizing the two-dimensional (2D) image acquisition on the electrocardiogram (ECG) signals. In vivo feasibility is demonstrated in anesthetized mice. The propagation of several transient mechanical waves was imaged in different regions of the myocardium and the wave phase velocities were found to be between 0.44 m/s and 5 m/s. These waves may be generated by either a purely mechanical effects or through electromechanical coupling in the myocardium depending on the phase of the cardiac cycle, in which they occur. The abdominal aorta was also imaged using the same technique and the propagation of a mechanical pulse wave was imaged. The pulse wave velocity was measured and the Young's modulus of the vessel wall was derived based on the Moens-Korteweg equation. This method could potentially be used for mapping the stiffness of the myocardium and the artery walls and may lead to the early diagnosis of cardiovascular diseases.

  5. Fabrication of polyurethane and polyurethane based composite fibres by the electrospinning technique for soft tissue engineering of cardiovascular system.

    PubMed

    Kucinska-Lipka, J; Gubanska, I; Janik, H; Sienkiewicz, M

    2015-01-01

    Electrospinning is a unique technique, which provides forming of polymeric scaffolds for soft tissue engineering, which include tissue scaffolds for soft tissues of the cardiovascular system. Such artificial soft tissues of the cardiovascular system may possess mechanical properties comparable to native vascular tissues. Electrospinning technique gives the opportunity to form fibres with nm- to μm-scale in diameter. The arrangement of obtained fibres and their surface determine the biocompatibility of the scaffolds. Polyurethanes (PUs) are being commonly used as a prosthesis of cardiovascular soft tissues due to their excellent biocompatibility, non-toxicity, elasticity and mechanical properties. PUs also possess fine spinning properties. The combination of a variety of PU properties with an electrospinning technique, conducted at the well tailored conditions, gives unlimited possibilities of forming novel polyurethane materials suitable for soft tissue scaffolds applied in cardiovascular tissue engineering. This paper can help researches to gain more widespread and deeper understanding of designing electrospinable PU materials, which may be used as cardiovascular soft tissue scaffolds. In this paper we focus on reagents used in PU synthesis designed to increase PU biocompatibility (polyols) and biodegradability (isocyanates). We also describe suggested surface modifications of electrospun PUs, and the direct influence of surface wettability on providing enhanced biocompatibility of scaffolds. We indicate a great influence of electrospinning parameters (voltage, flow rate, working distance) and used solvents (mostly DMF, THF and HFIP) on fibre alignment and diameter - what impacts the biocompatibility and hemocompatibility of such electrospun PU scaffolds. Moreover, we present PU modifications with natural polymers with novel approach applied in electrospinning of PU scaffolds. This work may contribute with further developing of novel electrospun PUs, which may be

  6. Mathematical modelling of flow distribution in the human cardiovascular system

    NASA Technical Reports Server (NTRS)

    Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.

    1992-01-01

    The paper presents a detailed model of the entire human cardiovascular system which aims to study the changes in flow distribution caused by external stimuli, changes in internal parameters, or other factors. The arterial-venous network is represented by 325 interconnected elastic segments. The mathematical description of each segment is based on equations of hydrodynamics and those of stress/strain relationships in elastic materials. Appropriate input functions provide for the pumping of blood by the heart through the system. The analysis employs the finite-element technique which can accommodate any prescribed boundary conditions. Values of model parameters are from available data on physical and rheological properties of blood and blood vessels. As a representative example, simulation results on changes in flow distribution with changes in the elastic properties of blood vessels are discussed. They indicate that the errors in the calculated overall flow rates are not significant even in the extreme case of arteries and veins behaving as rigid tubes.

  7. Automated classification of optical coherence tomography images of human atrial tissue

    NASA Astrophysics Data System (ADS)

    Gan, Yu; Tsay, David; Amir, Syed B.; Marboe, Charles C.; Hendon, Christine P.

    2016-10-01

    Tissue composition of the atria plays a critical role in the pathology of cardiovascular disease, tissue remodeling, and arrhythmogenic substrates. Optical coherence tomography (OCT) has the ability to capture the tissue composition information of the human atria. In this study, we developed a region-based automated method to classify tissue compositions within human atria samples within OCT images. We segmented regional information without prior information about the tissue architecture and subsequently extracted features within each segmented region. A relevance vector machine model was used to perform automated classification. Segmentation of human atrial ex vivo datasets was correlated with trichrome histology and our classification algorithm had an average accuracy of 80.41% for identifying adipose, myocardium, fibrotic myocardium, and collagen tissue compositions.

  8. The vestibulosympathetic reflex in humans: neural interactions between cardiovascular reflexes

    NASA Technical Reports Server (NTRS)

    Ray, Chester A.; Monahan, Kevin D.

    2002-01-01

    1. Over the past 5 years, there has been emerging evidence that the vestibular system regulates sympathetic nerve activity in humans. We have studied this issue in humans by using head-down rotation (HDR) in the prone position. 2. These studies have clearly demonstrated increases in muscle sympathetic nerve activity (MSNA) and calf vascular resistance during HDR. These responses are mediated by engagement of the otolith organs and not the semicircular canals. 3. However, differential activation of sympathetic nerve activity has been observed during HDR. Unlike MSNA, skin sympathetic nerve activity does not increase with HDR. 4. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes (i.e. barorereflexes and skeletal muscle reflexes) has shown an additive interaction for MSNA. 5. The additive interaction between the baroreflexes and vestibulosympathetic reflex suggests that the vestibular system may assist in defending against orthostatic challenges in humans by elevating MSNA beyond that of the baroreflexes. 6. In addition, the further increase in MSNA via otolith stimulation during isometric handgrip, when arterial pressure is elevated markedly, indicates that the vestibulosympathetic reflex is a powerful activator of MSNA and may contribute to blood pressure and flow regulation during dynamic exercise. 7. Future studies will help evaluate the importance of the vestibulosympathetic reflex in clinical conditions associated with orthostatic hypotension.

  9. Vestibular influences on autonomic cardiovascular control in humans

    NASA Technical Reports Server (NTRS)

    Biaggioni, I.; Costa, F.; Kaufmann, H.; Robertson, D. (Principal Investigator)

    1998-01-01

    There is substantial evidence that anatomical connections exist between vestibular and autonomic nuclei. Animal studies have shown functional interactions between the vestibular and autonomic systems. The nature of these interactions, however, is complex and has not been fully defined. Vestibular stimulation has been consistently found to reduce blood pressure in animals. Given the potential interaction between vestibular and autonomic pathways this finding could be explained by a reduction in sympathetic activity. However, rather than sympathetic inhibition, vestibular stimulation has consistently been shown to increase sympathetic outflow in cardiac and splanchnic vascular beds in most experimental models. Several clinical observations suggest that a link between vestibular and autonomic systems may also exist in humans. However, direct evidence for vestibular/autonomic interactions in humans is sparse. Motion sickness has been found to induce forearm vasodilation and reduce baroreflex gain, and head down neck flexion induces transient forearm and calf vasoconstriction. On the other hand, studies using optokinetic stimulation have found either very small, variable, or inconsistent changes in heart rate and blood pressure, despite substantial symptoms of motion sickness. Furthermore, caloric stimulation severe enough to produce nystagmus, dizziness, and nausea had no effect on sympathetic nerve activity measured directly with microneurography. No effect was observed on heart rate, blood pressure, or plasma norepinephrine. Several factors may explain the apparent discordance of these results, but more research is needed before we can define the potential importance of vestibular input to cardiovascular regulation and orthostatic tolerance in humans.

  10. High prevalence of cardiovascular disease in South Asians: Central role for brown adipose tissue?

    PubMed

    Boon, Mariëtte R; Bakker, Leontine E H; van der Linden, Rianne A D; van Ouwerkerk, Antoinette F; de Goeje, Pauline L; Counotte, Jacqueline; Jazet, Ingrid M; Rensen, Patrick C N

    2015-01-01

    Cardiovascular disease (CVD) is the leading cause of death in modern society. Interestingly, the risk of developing CVD varies between different ethnic groups. A particularly high risk is faced by South Asians, representing over one-fifth of the world's population. Here, we review potential factors contributing to the increased cardiovascular risk in the South Asian population and discuss novel therapeutic strategies based on recent insights. In South Asians, classical ('metabolic') risk factors associated with CVD are highly prevalent and include central obesity, insulin resistance, type 2 diabetes, and dyslipidemia. A contributing factor that may underlie the development of this disadvantageous metabolic phenotype is the presence of a lower amount of brown adipose tissue (BAT) in South Asian subjects, resulting in lower energy expenditure and lower lipid oxidation and glucose uptake. As it has been established that the increased prevalence of classical risk factors in South Asians cannot fully explain their increased risk for CVD, other non-classical risk factors must underlie this residual risk. In South Asians, the prevalence of "inflammatory" risk factors including visceral adipose tissue inflammation, endothelial dysfunction, and HDL dysfunction are higher compared with Caucasians. We conclude that a potential novel therapy to lower CVD risk in the South Asian population is to enhance BAT volume or its activity in order to diminish classical risk factors. Furthermore, anti-inflammatory therapy may lower non-classical risk factors in this population and the combination of both strategies may be especially effective.

  11. Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine

    PubMed Central

    Hinderer, Svenja; Brauchle, Eva

    2015-01-01

    Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug‐free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus‐free vascular substitutes that are smaller than 6 mm, and stem cell‐recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off‐the‐shelf biomaterials as well as automatable and up‐scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact‐ and marker‐free biomaterial and extracellular matrix assessment methods are highlighted. PMID:25778713

  12. Non-destructive analysis of extracellular matrix development in cardiovascular tissue-engineered constructs.

    PubMed

    Tuemen, M; Nguyen, D V A; Raffius, J; Flanagan, T C; Dietrich, M; Frese, J; Schmitz-Rode, T; Jockenhoevel, S

    2013-05-01

    In the field of tissue engineering, there is an increasing demand for non-destructive methods to quantify the synthesis of extracellular matrix (ECM) components such as collagens, elastin or sulphated glycosaminoglycans (sGAGs) in vitro as a quality control before clinical use. In this study, procollagen I carboxyterminal peptide (PICP), procollagen III aminoterminal peptide (PIIINP), tropoelastin and sGAGs are investigated for their potential use as non-destructive markers in culture medium of statically cultivated cell-seeded fibrin gels. Measurement of PICP as marker for type I collagen synthesis, and PIIINP as marker of type III collagen turnover, correlated well with the hydroxyproline content of the fibrin gels, with a Pearson correlation coefficient of 0.98 and 0.97, respectively. The measurement of tropoelastin as marker of elastin synthesis correlated with the amount of elastin retained in fibrin gels with a Pearson correlation coefficient of 0.99. sGAGs were retained in fibrin gels, but were not detectable in culture medium at any time of measurement. In conclusion, this study demonstrates the potential of PICP and tropoelastin as non-destructive culture medium markers for collagen and elastin synthesis. To our knowledge, this is the first study in cardiovascular tissue engineering investigating the whole of here proposed biomarkers of ECM synthesis to monitor the maturation process of developing tissue non-invasively, but for comprehensive assessment of ECM development, these biomarkers need to be investigated in further studies, employing dynamic cultivation conditions and more complex tissue constructs.

  13. Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine.

    PubMed

    Hinderer, Svenja; Brauchle, Eva; Schenke-Layland, Katja

    2015-11-18

    Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug-free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus-free vascular substitutes that are smaller than 6 mm, and stem cell-recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off-the-shelf biomaterials as well as automatable and up-scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact- and marker-free biomaterial and extracellular matrix assessment methods are highlighted.

  14. Frequency domain optical tomography in human tissue

    NASA Astrophysics Data System (ADS)

    Yao, Yuqi; Wang, Yao; Pei, Yaling; Zhu, Wenwu; Hu, Jenhun; Barbour, Randall L.

    1995-10-01

    In this paper, a reconstruction algorithm for frequency-domain optical tomography in human tissue is presented. A fast and efficient multigrid finite difference (MGFD) method is adopted as a forward solver to obtain the simulated detector responses and the required imaging operator. The solutions obtained form MGFD method for 3D problems with weakly discontinuous cocoefficients are compared with analyzed solutions to determine the accuracy of the numerical method. Simultaneous reconstruction of both absorption and scattering coefficients for tissue-like media is accomplished by solving a perturbation equation using the Born approximation. This solution is obtained by a conjugate gradient descent method with Tikhonov regularization. Two examples are given to show the quality of the reconstruction results. Both involve the examination of anatomically accurate optical models of tissue derived from segmented 3D magnetic resonance images to which have been assigned optical coefficients to the designated tissue types. One is a map of a female breast containing two small 'added pathologies', such as tumors. The other is a map of the brain containing a 'local bleeding' area, representing a hemorrhage. The reconstruction results show that the algorithm is computationally practical and can yield qualitatively correct geometry of the objects embedded in the simulated human tissue. Acceptable results are obtaiend even when 10% noise is present in the data.

  15. Promising Therapeutic Strategies for Mesenchymal Stem Cell-Based Cardiovascular Regeneration: From Cell Priming to Tissue Engineering

    PubMed Central

    Ji, Seung Taek; Yun, Jisoo

    2017-01-01

    The primary cause of death among chronic diseases worldwide is ischemic cardiovascular diseases, such as stroke and myocardial infarction. Recent evidence indicates that adult stem cell therapies involving cardiovascular regeneration represent promising strategies to treat cardiovascular diseases. Owing to their immunomodulatory properties and vascular repair capabilities, mesenchymal stem cells (MSCs) are strong candidate therapeutic stem cells for use in cardiovascular regeneration. However, major limitations must be overcome, including their very low survival rate in ischemic lesion. Various attempts have been made to improve the poor survival and longevity of engrafted MSCs. In order to develop novel therapeutic strategies, it is necessary to first identify stem cell modulators for intracellular signal triggering or niche activation. One promising therapeutic strategy is the priming of therapeutic MSCs with stem cell modulators before transplantation. Another is a tissue engineering-based therapeutic strategy involving a cell scaffold, a cell-protein-scaffold architecture made of biomaterials such as ECM or hydrogel, and cell patch- and 3D printing-based tissue engineering. This review focuses on the current clinical applications of MSCs for treating cardiovascular diseases and highlights several therapeutic strategies for promoting the therapeutic efficacy of MSCs in vitro or in vivo from cell priming to tissue engineering strategies, for use in cardiovascular regeneration. PMID:28303152

  16. Mammalian tissue extracts used to treat cardiovascular disease as exemplified by Recosen.

    PubMed

    Fitzgerald, Desmond

    2016-01-01

    This paper reviews the cardiovascular effects of an aqueous extract of animal heart, which was in clinical development in the early 1950s. The aqueous extract reversed the negative inotropic effects of hypoxia in the frog heart preparation. In extensive observational clinical trials between 1950 and 1975, beneficial effects were reported on reducing cardiac arrhythmias, improving effort in angina pectoris, as well as improving heart failure. The majority of clinical publications came from Germany, Switzerland and Austria. Jackson and Temple identified tyramine as the main constituent in the aqueous extract. While the hemodynamic effects of tyramine in humans are well characterized, the relationship to its clinical efficacy remains speculative.

  17. Echocardiographic epicardial adipose tissue measurements provide information about cardiovascular risk in hemodialysis patients.

    PubMed

    Ulusal Okyay, Gülay; Okyay, Kaan; Polattaş Solak, Evşen; Sahinarslan, Asife; Paşaoğlu, Özge; Ayerden Ebinç, Fatma; Paşaoğlu, Hatice; Boztepe Derici, Ülver; Sindel, Şükrü; Arınsoy, Turgay

    2015-07-01

    Epicardial adipose tissue (EAT) is a cardiovascular risk predictor in general population. However, its value has not been well validated in maintainance hemodialysis (MHD) patients. We aimed to assess associations of EAT with cardiovascular risk predictors in nondiabetic MHD patients. In this cross-sectional study, we measured EAT thickness by transthoracic echocardiography in 50 MHD patients (45.8 ± 14.6 years of age, 37 male). Antropometric measurements, bioimpedance analysis, left ventricular (LV) mass, carotis intima media thickness, blood tests, homeostasis model assessment for insulin resistance (HOMA-IR) and hemodialysis dose by single-pool urea clearence index (spKt/V) were determined. The mean EAT thickness was 3.28 ± 1.04 mm. There were significant associations of EAT with body mass index (β = 0.590, P < 0.001), waist circumference (β = 0.572, P < 0.001), body fat mass (β = 0.562, P < 0.001), percentage of body fat mass (β = 0.408, P = 0.003), percentage of lean tissue mass (β = -0.421, P = 0.002), LV mass (β = 0.426, P = 0.002), carotis intima media thickness (β = 0.289, P = 0.042), triglyceride/high-density lipoprotein cholesterol ratio (β = 0.529, P < 0.001), 1/HOMA-IR (β = -0.386, P = 0.006), and spKt/V (β = -0.311, P = 0.028). No association was exhibited with visfatin C, high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha (for all, P > 0.05). Body mass index, waist circumference, body fat mass, percentage of lean tissue mass, LV mass, triglyceride/high-density lipoprotein cholesterol ratio, HOMA-IR, and spKt/V appeared as independent predictors of EAT. EAT was significantly associated with body fat measures, cardiovascular risk predictors, and dialysis dose in MHD patients.

  18. PAI-1 and TNF-α profiles of adipose tissue in obese cardiovascular disease patients

    PubMed Central

    Bilgic Gazioglu, Sema; Akan, Gokce; Atalar, Fatma; Erten, Gaye

    2015-01-01

    Obesity as a leading preventable cause of death worldwide is closely linked to cardiovascular disease (CVD). Plasma plasminogen activator inhibitor (PAI)-1, a potent inhibitor of plasminogen activation and fibrinolysis, is increased in many clinical situations associated with high incidence of CVD. In the obesity-linked elevation of PAI-1, evidence points to TNF-α as an important regulator of PAI-1 expression in adipose tissue. Background: This study aims to evaluate mediastinal PAI-1 and TNF-α mRNA levels in adipose tissues (AT) and compare serum levels in obesity with and without coronary artery disease (CAD). Patients and methods: Obese patients with (n=37) and without CAD (n=20) were included in the study. Results: The serum levels of PAI-1 and TNF-α were significantly higher in obese patients with CAD compared to obese patients without CAD. PAI-1 mRNA expression was significantly increased in mediastinal adipose tissue (MAT) of obese patients with CAD compared to those without CAD, TNF-α mRNA expressions were found to be higher in EAT (epicardial AT), MAT and SAT (subcutaneous AT) of obese patients with CAD. Conclusions: The study demonstrated a close direct relationship between TNF-α and PAI-1. PAI-1 mRNA expression strongly correlated positively with serum TNF-α in MAT, and TNF-α expressions with PAI-1 serum levels. PMID:26884864

  19. Cardiovascular nursing on human genomics: what do cardiovascular nurses need to know about congestive heart failure?

    PubMed

    Frazier, Lorraine; Wung, Shu-Fen; Sparks, Elizabeth; Eastwood, Cathy

    2009-09-01

    This paper presents the main causes of heart failure (HF) and an update on the genetics studies on each cause. The review includes a delineation of the etiology and fundamental pathophysiology of HF and provides rational for treatment for the patient and family. Various cardiomyopathies are discussed, including primary cardiomyopathies, mixed cardiomyopathies, cardiomyopathies that involve altered cardiac muscle along with generalized multiorgan disorders, and various cardiovascular conditions, such as coronary artery disease (ischemic cardiomyopathy) and hypertension (hypertensive cardiomyopathy). A brief review of pharmacogenetics and HF is presented. The application of the genetic components of cardiomyopathy and pharmacogenetics is included to enhance cardiovascular nursing care.

  20. A mesofluidics-based test platform for systematic development of scaffolds for in situ cardiovascular tissue engineering.

    PubMed

    Smits, Anthal I P M; Driessen-Mol, Anita; Bouten, Carlijn V C; Baaijens, Frank P T

    2012-06-01

    Recently, in situ tissue engineering has emerged as a new approach to obtain autologous, living replacement tissues with off-the-shelf availability. The method is based on the use of an instructive biodegradable scaffold that is capable of repopulation with host cells in situ and subsequent tissue formation. This approach imposes high demands on scaffold properties. For cardiovascular grafts, the repopulation with endogenous cells from the circulation is further hypothesized to be influenced by the hemodynamic environment of the scaffold. To systematically study the effect of scaffold properties on the response of circulating cells, we aimed to develop a mesofluidics-based in vitro test platform that enables on-stage investigation of the interaction of circulating cells with three-dimensional (3D) synthetic scaffolds under physiologic hemodynamic conditions. The test platform consists of a custom-developed cross-flow chamber that houses small-scale 3D scaffolds. The cross-flow chamber is incorporated into a flow-loop to drive a cell suspension along the scaffold with physiological wall shear stress and perfusion pressure. The fluidics system is validated numerically and experimentally using a computational fluid dynamics model and real-time microbead tracing studies, demonstrating a fully developed flow profile with a homogeneous shear stress distribution over the scaffold. Wall shear stresses and pressure can be controlled independently, well within the target physiological range (0-8 Pa and 0-100 mmHg, respectively). Bench-top evaluation is performed using electrospun poly(ɛ-caprolactone) scaffolds with varying fiber diameter, exposed to a suspension of human peripheral blood mononuclear cells in pulsatile flow for 72 h. Cell adhesion and infiltration are monitored using time-lapsed confocal laser scanning microscopy. In conclusion, we have successfully developed a mesofluidics platform to study cell-scaffold interactions under hemodynamic conditions in vitro

  1. l-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats

    PubMed Central

    Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

    2015-01-01

    This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P < 0.05, for each tissue and enzyme) in hyper- and hypothyroid rats, respectively. Arginase I abundance in aorta, heart, and kidney was increased (P < 0.05, for each tissue) in hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P < 0.05, for each tissue). Arginase II was augmented in aorta and kidney (P < 0.05, for each tissue) of hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P < 0.05, for all tissues) in hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P < 0.05) in hyper- and hypothyroid rats, respectively, in all organs studied. OAT and proline levels were positively modulated by thyroid hormones in liver but not in the other tissues. ADC protein levels were positively modulated by thyroid hormones in all tissues. According to these findings, thyroid hormone treatment positively modulates different l-arginine metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might

  2. Vascular hyperpolarization in human physiology and cardiovascular risk conditions and disease.

    PubMed

    Schinzari, F; Tesauro, M; Cardillo, C

    2017-01-01

    Hyperpolarization causing smooth muscle relaxation contributes to the maintenance of vascular homeostasis, particularly in small-calibre arteries and arterioles. It may also become a compensatory vasodilator mechanism upregulated in states with impaired nitric oxide (NO) availability. Bioassay of vascular hyperpolarization in the human circulation has been hampered by the complexity of mechanisms involved and the limited availability of investigational tools. Firm evidence, however, supports the notion that hyperpolarization participates in the regulation of resting vasodilator tone and vascular reactivity in healthy subjects. In addition, an enhanced endothelium-derived hyperpolarization contributes to both resting and agonist-stimulated vasodilation in a variety of cardiovascular risk conditions and disease. Thus, hyperpolarization mediated by epoxyeicosatrienoic acids (EETs) and H2 O2 has been observed in coronary arterioles of patients with coronary artery disease. Similarly, ouabain-sensitive and EETs-mediated hyperpolarization has been observed to compensate for NO deficiency in patients with essential hypertension. Moreover, in non-hypertensive patients with multiple cardiovascular risk factors and in hypercholesterolaemia, KCa channel-mediated vasodilation appears to be activated. A novel paradigm establishes that perivascular adipose tissue (PVAT) is an additional regulator of vascular tone/function and endothelium is not the only agent in vascular hyperpolarization. Indeed, some PVAT-derived relaxing substances, such as adiponectin and angiotensin 1-7, may exert anticontractile and vasodilator actions by the opening of KCa channels in smooth muscle cells. Conversely, PVAT-derived factors impair coronary vasodilation via differential inhibition of some K(+) channels. In view of adipose tissue abnormalities occurring in human obesity, changes in PVAT-dependent hyperpolarization may be relevant for vascular dysfunction also in this condition.

  3. UWB pulse propagation into human tissues

    NASA Astrophysics Data System (ADS)

    Cavagnaro, Marta; Pittella, Erika; Pisa, Stefano

    2013-12-01

    In this paper the propagation of a UWB pulse into a layered model of the human body is studied to characterize absorption and reflection of the UWB signal due to the different body tissues. Several time behaviours for the incident UWB pulse are considered and compared with reference to the feasibility of breath and heartbeat activity monitoring. Results show that if the UWB source is placed far from the human body, the reflection coming from the interface between air and skin can be used to detect the respiratory activity. On the contrary, if the UWB source is placed close to the human body, a small reflection due to the interface between the posterior lung wall and the bone, which is well distanced in time from the reflections due to the first layers of the body model, can be used to detect lung and heart changes associated with the cardio-respiratory activity.

  4. Sorption studies of human keratinized tissues

    NASA Astrophysics Data System (ADS)

    Johnsen, G. K.; Martinsen, Ø. G.; Grimnes, Sverre

    2010-04-01

    Water content is known to be the most important single parameter for keratinized tissue to remain its vital functions. In that sense, a general knowledge of the water binding properties is of great interest, and a reliable measurement setup must be found. Also, revealing the sorption properties of human keratinized tissues is vital towards a calibration of susceptance based skin hydration measurements that already is an important diagnostic tool in clinical dermatology, and we will see that any hysteresis will complicate such a calibration further. In this study we investigated the sorption properties of keratinized tissues such as human epidermal stratum corneum (SC), hair and nail. The study was performed under controlled environmental conditions with a dynamic vapor sorption (DVS) instrument, and the water uptake of the keratinized test samples was measured as the relative humidity in the ambient air was altered step-wisely. In this study, vital and characteristic water sorption properties such as the isotherm, relative water uptake, and hysteresis were investigated and will be discussed.

  5. Effect of Tissue Specificity on the Performance of Extracellular Matrix in Improving Endothelialization of Cardiovascular Implants

    PubMed Central

    Tu, Qiufen; Yang, Zhilu; Zhu, Ying; Xiong, Kaiqin; Maitz, Manfred F.; Wang, Jin; Zhao, Yuancong; Jin, Jian; Lei, Yuechang

    2013-01-01

    Natural extracellular matrix (ECM) deposited in situ by cultured endothelial cells (ECs) has been proven effective in accelerating endothelialization of titanium (Ti) cardiovascular implants (CVIs) in our previous studies. In this study, the ECM deposited by smooth muscle cells (SMCs) was used in comparison to investigate the effects of tissue specificity of the ECM on the ability to accelerate endothelialization of CVIs. The results demonstrated that the ECM deposited by ECs and SMCs (EC-ECM, SMC-ECM, respectively) differed considerably in components and fibril morphology. Surface modification of Ti CVIs with both types of natural ECM was effective in improving their in vitro hemocompatibility and cytocompatibility simultaneously. However, the endothelialization of ECM-modified Ti CVIs in a canine model demonstrated a high tissue specificity of the ECM. Although the ECM deposited by SMCs (SMC-ECM) induced fewer platelet adhesion and sustained better growth and viability of ECs in vitro, its performance in accelerating in vivo endothelialization of Ti CVIs was extremely poor. In contrast, the ECM deposited by ECs (EC-ECM) led to complete endothelium formation in vivo. PMID:22924620

  6. Osseous differentiation of human fat tissue grafts: From tissue engineering to tissue differentiation

    PubMed Central

    Bondarava, Maryna; Cattaneo, Chiara; Ren, Bin; Thasler, Wolfgang E.; Jansson, Volkmar; Müller, Peter E.; Betz, Oliver B.

    2017-01-01

    Conventional bone tissue engineering approaches require isolation and in vitro propagation of autologous cells, followed by seeding on a variety of scaffolds. Those protracted procedures impede the clinical applications. Here we report the transdifferentiation of human fat tissue fragments retrieved from subcutaneous fat into tissue with bone characteristics in vitro without prior cell isolation and propagation. 3D collagen-I cultures of human fat tissue were cultivated either in growth medium or in osteogenic medium (OM) with or without addition of Bone Morphogenetic Proteins (BMPs) BMP-2, BMP-7 or BMP-9. Ca2+ depositions were observed after two weeks of osteogenic induction which visibly increased when either type of BMP was added. mRNA levels of alkaline phosphatase (ALP) and osteocalcin (OCN) increased when cultured in OM alone but addition of BMP-2, BMP-7 or BMP-9 caused significantly higher expression levels of ALP and OCN. Immunofluorescent staining for OCN, osteopontin and sclerostin supported the observed real-time-PCR data. BMP-9 was the most effective osteogenic inducer in this system. Our findings reveal that tissue regeneration can be remarkably simplified by omitting prior cell isolation and propagation, therefore removing significant obstacles on the way to clinical applications of much needed regeneration treatments. PMID:28054585

  7. Adipose tissue as an endocrine organ: role of leptin and adiponectin in the pathogenesis of cardiovascular diseases.

    PubMed

    Fortuño, A; Rodríguez, A; Gómez-Ambrosi, J; Frühbeck, G; Díez, J

    2003-03-01

    Obesity, the most common nutritional disorder in industrial countries, is associated with increased cardiovascular mortality and morbidity. Nevertheless, the molecular basis linking obesity with cardiovascular disturbances have not yet been fully clarified. Recent advances in the biology of adipose tissue indicate that it is not simply an energy storage organ, but also a secretory organ, producing a variety of bioactive substances, including leptin and adiponectin, that may influence the function as well as the structural integrity of the cardiovascular system. Leptin, besides being a satiety signal for the central nervous system and to be related to insulin and glucose metabolism, may also play an important role in regulating vascular tone because of the widespread distribution of functional receptors in the vascular cells. On the other hand, the more recently discovered protein, adiponectin, seems to play a protective role in experimental models of vascular injury, in probable relation to its ability to suppress the attachment of monocytes to endothelial cells, which is an early event in the atherosclerotic process. There is already considerable evidence linking altered production of some adipocyte hormones with the cardiovascular complications of obesity. Therefore, the knowledge of alterations in the endocrine function of adipose tissue may help to further understand the high cardiovascular risk associated with obesity.

  8. European homograft bank: twenty years of cardiovascular tissue banking and collaboration with transplant coordination in Europe.

    PubMed

    Jashari, R; Goffin, Y; Vanderkelen, A; Van Hoeck, B; du Verger, A; Fan, Y; Holovska, V; Brahy, O

    2010-01-01

    Established in 1989 in Brussels as an international nonprofit association, the European Homograft Bank (EHB) has been collaborating closely with the transplant coordination of the different centers in Belgium and other European countries. Donor selection is made after discussion of exclusion criteria with the transplant coordinator of the procurement center. EHB collaborates with 15 Belgian, 11 German, 10 French, 10 Swiss, 3 Italian, 3 Dutch, and some other procurement and/or implantation centers. Donor ages range from newborn to 65 years. Tissue preparation, morphologic evaluation, and functional testing are performed under Class A laminar flow. After decontamination in a cocktail of 3 antibiotics (lincomycin, vancomycin, and polymixin B) during 20-48 hours, the tissues cryopreserved with liquid nitrogen to -100 degrees C are stored in vapors of liquid nitrogen below -150 degrees C for a maximum of 5 years. Systematic virologic examination of donor blood is performed for HIV, HTLV, hepatitis B/C, and syphilis, as well as for enteroviruses, Q fever, malaria, and West Nile virus by indication. Bacteriologic examination for anaerobic and aerobic contamination is performed at the different steps of processing. Histologic examination for malignant disease and infection is performed systematically. Indications for implantation are discussed with the requesting surgeon. Transport to the implantation center is carried out safely in a dry shipper at -150 degrees C or in dry ice at -76 degrees C. The EHB received 4,511 hearts and 1,169 batches of arteries from January 1989 to December 2008. The 5,133 heart valves (1,974 aortic, 3,106 pulmonary, and 53 mitral) and 2,066 arterial segments have been prepared and stored; 4,600 cryopreserved valvular (2,717 pulmonary, 1,835 aortic, and 48 mitral) and 1,937 arterial allografts have been distributed for implantation in various European Cardiovascular Centers. EHB is not always able to meet the increased demand for heart valves and

  9. An experimental design for quantification of cardiovascular responses to music stimuli in humans.

    PubMed

    Chang, S-H; Luo, C-H; Yeh, T-L

    2004-01-01

    There have been several researches on the relationship between music and human physiological or psychological responses. However, there are cardiovascular index factors that have not been explored quantitatively due to the qualitative nature of acoustic stimuli. This study proposes and demonstrates an experimental design for quantification of cardiovascular responses to music stimuli in humans. The system comprises two components: a unit for generating and monitoring quantitative acoustic stimuli and a portable autonomic nervous system (ANS) analysis unit for quantitative recording and analysis of the cardiovascular responses. The experimental results indicate that the proposed system can exactly achieve the goal of full control and measurement for the music stimuli, and also effectively support many quantitative indices of cardiovascular response in humans. In addition, the analysis results are discussed and predicted in the future clinical research.

  10. Inotropic action of the puberty hormone kisspeptin in rat, mouse and human: cardiovascular distribution and characteristics of the kisspeptin receptor.

    PubMed

    Maguire, Janet J; Kirby, Helen R; Mead, Emma J; Kuc, Rhoda E; d'Anglemont de Tassigny, Xavier; Colledge, William H; Davenport, Anthony P

    2011-01-01

    Kisspeptins, the ligands of the kisspeptin receptor known for its roles in reproduction and cancer, are also vasoconstrictor peptides in atherosclerosis-prone human aorta and coronary artery. The aim of this study was to further investigate the cardiovascular localisation and function of the kisspeptins and their receptor in human compared to rat and mouse heart. Immunohistochemistry and radioligand binding techniques were employed to investigate kisspeptin receptor localisation, density and pharmacological characteristics in cardiac tissues from all three species. Radioimmunoassay was used to detect kisspeptin peptide levels in human normal heart and to identify any pathological changes in myocardium from patients transplanted for cardiomyopathy or ischaemic heart disease. The cardiac function of kisspeptin receptor was studied in isolated human, rat and mouse paced atria, with a role for the receptor confirmed using mice with targeted disruption of Kiss1r. The data demonstrated that kisspeptin receptor-like immunoreactivity localised to endothelial and smooth muscle cells of intramyocardial blood vessels and to myocytes in human and rodent tissue. [(125)I]KP-14 bound saturably, with subnanomolar affinity to human and rodent myocardium (K(D) = 0.12 nM, human; K(D) = 0.44 nM, rat). Positive inotropic effects of kisspeptin were observed in rat, human and mouse. No response was observed in mice with targeted disruption of Kiss1r. In human heart a decrease in cardiac kisspeptin level was detected in ischaemic heart disease. Kisspeptin and its receptor are expressed in the human, rat and mouse heart and kisspeptins possess potent positive inotropic activity. The cardiovascular actions of the kisspeptins may contribute to the role of these peptides in pregnancy but the consequences of receptor activation must be considered if kisspeptin receptor agonists are developed for use in the treatment of reproductive disorders or cancer.

  11. Hippocampus and epilepsy: findings from human tissues

    PubMed Central

    Huberfeld, Gilles; Blauwblomme, Thomas; Miles, Richard

    2015-01-01

    Surgical removal of the epileptogenic zone provides an effective therapy for several epileptic syndromes. This surgery offers the opportunity to study pathological activity in living human tissue for pharmacoresistant partial epilepsy syndromes including (1) temporal lobe epilepsies with hippocampal sclerosis, (2) cortical dysplasias, (3) epilepsies associated with tumors and (4) developmental malformations. Slices of tissue from patient with these syndromes retain functional neuronal networks and may generate epileptic activities. The properties of cells in this tissue may not be greatly changed, but excitatory synaptic transmission is often enhanced and GABAergic inhibition is preserved. Typically epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated, not in the hippocampus but in the subiculum an output region which projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells which paradoxically excite about 20% of subicular pyramidal cells while simultaneously inhibiting the majority. Interictal discharges thus depend on both GABAergic and glutamatergic signaling. The depolarizing effects of GABA depend on a pathological elevation in levels of chloride in some subicular cells, similar to those of developmentally immature cells. Such defect is caused by a perturbed expression of the cotransporters regulating intracellular chloride concentration, the importer NKCC1 and the extruder KCC2. Blockade of NKCC1 actions by the diuretic bumetanide, restores intracellular chloride and thus hyperpolarizing GABAergic actions so suppressing interictal activity. PMID

  12. Numerical simulation of global hydro-dynamics in a pulsatile bioreactor for cardiovascular tissue engineering.

    PubMed

    Shi, Yubing

    2008-01-01

    Previous numerical simulations of the hydro-dynamic response in the various bioreactor designs were mostly concentrated on the local flow field analysis using computational fluid dynamics, which cannot provide the global hydro-dynamics information to assist the bioreactor design. In this research, a mathematical model is developed to simulate the global hydro-dynamic changes in a pulsatile bioreactor design by considering the flow resistance, the elasticity of the vessel and the inertial effect of the media fluid in different parts of the system. The developed model is used to study the system dynamic response in a typical pulsatile bioreactor design for the culturing of cardiovascular tissues. Simulation results reveal the detailed pressure and flow-rate changes in the different positions of the bioreactor, which are very useful for the evaluation of hydro-dynamic performance in the bioreactor designed. Typical pressure and flow-rate changes simulated agree well with the published experimental data, thus validates the mathematical model developed. The proposed mathematical model can be used for design optimization of other pulsatile bioreactors that work under different experimental conditions and have different system configurations.

  13. The reconstruction and analysis of tissue specific human metabolic networks.

    PubMed

    Hao, Tong; Ma, Hong-Wu; Zhao, Xue-Ming; Goryanin, Igor

    2012-02-01

    Human tissues have distinct biological functions. Many proteins/enzymes are known to be expressed only in specific tissues and therefore the metabolic networks in various tissues are different. Though high quality global human metabolic networks and metabolic networks for certain tissues such as liver have already been studied, a systematic study of tissue specific metabolic networks for all main tissues is still missing. In this work, we reconstruct the tissue specific metabolic networks for 15 main tissues in human based on the previously reconstructed Edinburgh Human Metabolic Network (EHMN). The tissue information is firstly obtained for enzymes from Human Protein Reference Database (HPRD) and UniprotKB databases and transfers to reactions through the enzyme-reaction relationships in EHMN. As our knowledge of tissue distribution of proteins is still very limited, we replenish the tissue information of the metabolic network based on network connectivity analysis and thorough examination of the literature. Finally, about 80% of proteins and reactions in EHMN are determined to be in at least one of the 15 tissues. To validate the quality of the tissue specific network, the brain specific metabolic network is taken as an example for functional module analysis and the results reveal that the function of the brain metabolic network is closely related with its function as the centre of the human nervous system. The tissue specific human metabolic networks are available at .

  14. Influence of immune activation and inflammatory response on cardiovascular risk associated with the human immunodeficiency virus.

    PubMed

    Beltrán, Luis M; Rubio-Navarro, Alfonso; Amaro-Villalobos, Juan Manuel; Egido, Jesús; García-Puig, Juan; Moreno, Juan Antonio

    2015-01-01

    Patients infected with the human immunodeficiency virus (HIV) have an increased cardiovascular risk. Although initially this increased risk was attributed to metabolic alterations associated with antiretroviral treatment, in recent years, the attention has been focused on the HIV disease itself. Inflammation, immune system activation, and endothelial dysfunction facilitated by HIV infection have been identified as key factors in the development and progression of atherosclerosis. In this review, we describe the epidemiology and pathogenesis of cardiovascular disease in patients with HIV infection and summarize the latest knowledge on the relationship between traditional and novel inflammatory, immune activation, and endothelial dysfunction biomarkers on the cardiovascular risk associated with HIV infection.

  15. The human cardiovascular system in the absence of gravity

    NASA Technical Reports Server (NTRS)

    Bungo, M. W.; Charles, J. B.

    1985-01-01

    The data collected from a Space Shuttle crew to investigate cardiovascular changes due to microgravity are presented. The experimental procedures which involved preflight, immediate postflight, and one week following postflight echocardiograms of 13 individuals are described. The immediate postflight results reveal a 20 percent decrease in stroke volume, a 16 percent decrease in left ventricular diastolic volume index (LVDVI), no change in systolic volume, blood pressure, or cardiac index, and a 24 percent increase in heart rate. One week later a 17 percent stroke volume increase, a 29 percent increase in cardiac index, and normal blood pressure, and LVDVI were observed. It is concluded that upon reexposure to gravity a readaptation process for the cardiovascular system occurs.

  16. Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells.

    PubMed

    Soh, Boon-Seng; Ng, Shi-Yan; Wu, Hao; Buac, Kristina; Park, Joo-Hye C; Lian, Xiaojun; Xu, Jiejia; Foo, Kylie S; Felldin, Ulrika; He, Xiaobing; Nichane, Massimo; Yang, Henry; Bu, Lei; Li, Ronald A; Lim, Bing; Chien, Kenneth R

    2016-03-08

    Coronary arteriogenesis is a central step in cardiogenesis, requiring coordinated generation and integration of endothelial cell and vascular smooth muscle cells. At present, it is unclear whether the cell fate programme of cardiac progenitors to generate complex muscular or vascular structures is entirely cell autonomous. Here we demonstrate the intrinsic ability of vascular progenitors to develop and self-organize into cardiac tissues by clonally isolating and expanding second heart field cardiovascular progenitors using WNT3A and endothelin-1 (EDN1) human recombinant proteins. Progenitor clones undergo long-term expansion and differentiate primarily into endothelial and smooth muscle cell lineages in vitro, and contribute extensively to coronary-like vessels in vivo, forming a functional human-mouse chimeric circulatory system. Our study identifies EDN1 as a key factor towards the generation and clonal derivation of ISL1(+) vascular intermediates, and demonstrates the intrinsic cell-autonomous nature of these progenitors to differentiate and self-organize into functional vasculatures in vivo.

  17. 2010 Great Lakes Human Health Fish Tissue Study Fish Tissue Data Dictionary

    EPA Pesticide Factsheets

    The Office of Science and Technology (OST) is providing the fish tissue results from the 2010 Great Lakes Human Health Fish Tissue Study (GLHHFTS). This document includes the “data dictionary” for Mercury, PFC, PBDE and PCBs.

  18. Differential Distribution of Bradykinin B(2) Receptors in the Rat and Human Cardiovascular System.

    PubMed

    Figueroa, Carlos D.; Marchant, Alejandra; Novoa, Ulises; Förstermann, Ulrich; Jarnagin, Kurt; Schölkens, Bernward; Müller-Esterl, Werner

    2001-01-01

    -Bradykinin, a major vasodilator peptide, plays an important role in the local regulation of blood pressure, blood flow, and vascular permeability; however, the cellular distribution of the major bradykinin B(2) receptor in the cardiovascular system is not precisely known. Immunoblot analysis with an anti-peptide antibody to the bradykinin B(2) receptor or chemical cross-linkage with [(125)I]Tyr(0)-bradykinin revealed a band of 69+/-3 kDa at varying intensity in the homogenates of the endothelium and tunica media of the rat aorta and endocardium. Immunostaining showed that the B(2) receptor is abundant in the endothelial linings of the aorta, other elastic arteries, muscular arteries, capillaries, venules, and large veins, where it localizes preferentially to the luminal face of the endothelial cells. In marked contrast, small arterioles (ie, the principal blood-pressure regulating vessels) of the mesenterium, heart, urinary bladder, brain, salivary gland, and kidney had a different staining pattern in which B(2) receptor was prominent in the perivascular smooth muscle cells of the tunica media. A similar distribution pattern was found in mouse as well as in human tissues, indicating that the particular distribution pattern of the B(2) receptor in arterioles is not a species-specific phenomenon. During development, the distribution of B(2) receptor in the heart changes; for example, in the heart of newborn rats, the B(2) receptor was abundant in the myocardium, whereas in the adult heart, the receptor was present in the endocardium of atria, atrioventricular valves, and ventricles but not in the myocardium. Thus, B(2) receptors are localized differentially in different parts of the cardiovascular system: the arterioles have smooth muscle-localized B(2) receptors, and large elastic vessels have endothelium-localized receptors.

  19. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  20. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  1. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  2. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  3. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  4. An optimized index of human cardiovascular adaptation to simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Wang, M.; Hassebrook, L.; Evans, J.; Varghese, T.; Knapp, C.

    1996-01-01

    Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.

  5. Patient-specific modeling of human cardiovascular system elements

    NASA Astrophysics Data System (ADS)

    Kossovich, Leonid Yu.; Kirillova, Irina V.; Golyadkina, Anastasiya A.; Polienko, Asel V.; Chelnokova, Natalia O.; Ivanov, Dmitriy V.; Murylev, Vladimir V.

    2016-03-01

    Object of study: The research is aimed at development of personalized medical treatment. Algorithm was developed for patient-specific surgical interventions of the cardiovascular system pathologies. Methods: Geometrical models of the biological objects and initial and boundary conditions were realized by medical diagnostic data of the specific patient. Mechanical and histomorphological parameters were obtained with the help mechanical experiments on universal testing machine. Computer modeling of the studied processes was conducted with the help of the finite element method. Results: Results of the numerical simulation allowed evaluating the physiological processes in the studied object in normal state, in presence of different pathologies and after different types of surgical procedures.

  6. Comparison of Biomarkers of Oxidative Stress and Cardiovascular Disease in Humans and Chimpanzees (Pan troglodytes)

    PubMed Central

    Videan, Elaine N; Heward, Christopher B; Chowdhury, Kajal; Plummer, John; Su, Yali; Cutler, Richard G

    2009-01-01

    In the oxidative stress hypothesis of aging, the aging process is the result of cumulative damage by reactive oxygen species. Humans and chimpanzees are remarkably similar; but humans live twice as long as chimpanzees and therefore are believed to age at a slower rate. The purpose of this study was to compare biomarkers for cardiovascular disease, oxidative stress, and aging between male chimpanzees and humans. Compared with men, male chimpanzees were at increased risk for cardiovascular disease because of their significantly higher levels of fibrinogen, IGF1, insulin, lipoprotein a, and large high-density lipoproteins. Chimpanzees showed increased oxidative stress, measured as significantly higher levels of 5-hydroxymethyl-2-deoxyuridine and 8-iso-prostaglandin F2α, a higher peroxidizability index, and higher levels of the prooxidants ceruloplasmin and copper. In addition, chimpanzees had decreased levels of antioxidants, including α- and β-carotene, β-cryptoxanthin, lycopene, and tocopherols, as well as decreased levels of the cardiovascular protection factors albumin and bilirubin. As predicted by the oxidative stress hypothesis of aging, male chimpanzees exhibit higher levels of oxidative stress and a much higher risk for cardiovascular disease, particularly cardiomyopathy, compared with men of equivalent age. Given these results, we hypothesize that the longer lifespan of humans is at least in part the result of greater antioxidant capacity and lower risk of cardiovascular disease associated with lower oxidative stress. PMID:19619420

  7. Mathematical modeling of human cardiovascular system for simulation of orthostatic response

    NASA Technical Reports Server (NTRS)

    Melchior, F. M.; Srinivasan, R. S.; Charles, J. B.

    1992-01-01

    This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.

  8. Gravitational effects on human cardiovascular responses to isometric muscle contractions

    NASA Astrophysics Data System (ADS)

    Bonde-Petersen, Flemmig; Suzuki, Yoji; Sadamoto, Tomoko

    Isometric exercise induces profound cardiovascular adaptations increasing mean arterial pressure and heart rate. We investigated effects of simulated +Gz and -Gz respectively on the central and peripheral cardiovascular system. Sustained handgrip exercise was performed at 40% of maximum for 2 minutes in five subjects. This maneuver increased mean arterial pressure by 40-45 mm Hg both during head out water immersion which simulates weightlessness, as well as bedrest during -25, 0, and +25 degrees tilt from the horizontal. Lower body negative pressure (-60 mm Hg for 10 min) attenuated the response to handgrip exercise to 30 mm Hg. It also increased the heart rate minimally by about 20 beats per minute while the water immersion, as well as head up, head down and horizontal bedrest showed increments of about 50 beats per min. It was concluded that the response to isometric contraction is mediated through the high pressure baroreceptors, because similar responses were seen during stresses producing a wide variation in central venous pressure. During lower body negative pressure the increased sympathetic nervous activity itself increased resting heart rate and mean arterial pressure. The responses to static exercise were, therefore, weaker.

  9. Hormone Receptor Expression in Human Fascial Tissue

    PubMed Central

    Fede, C.; Albertin, G.; Petrelli, L.; Sfriso, M.M.; Biz, C.; De Caro, R.

    2016-01-01

    Many epidemiologic, clinical, and experimental findings point to sex differences in myofascial pain in view of the fact that adult women tend to have more myofascial problems with respect to men. It is possible that one of the stimuli to sensitization of fascial nociceptors could come from hormonal factors such as estrogen and relaxin, that are involved in extracellular matrix and collagen remodeling and thus contribute to functions of myofascial tissue. Immunohistochemical and molecular investigations (real-time PCR analysis) of relaxin receptor 1 (RXFP1) and estrogen receptor-alpha (ERα) localization were carried out on samples of human fascia collected from 8 volunteers patients during orthopedic surgery (all females, between 42 and 70 yrs, divided into pre- and post-menopausal groups), and in fibroblasts isolated from deep fascia, to examine both protein and RNA expression levels. We can assume that the two sex hormone receptors analyzed are expressed in all the human fascial districts examined and in fascial fibroblasts culture cells, to a lesser degree in the post-menopausal with respect to the pre-menopausal women. Hormone receptor expression was concentrated in the fibroblasts, and RXFP1 was also evident in blood vessels and nerves. Our results are the first demonstrating that the fibroblasts located within different districts of the muscular fasciae express sex hormone receptors and can help to explain the link between hormonal factors and myofascial pain. It is known, in fact, that estrogen and relaxin play a key role in extracellular matrix remodeling by inhibiting fibrosis and inflammatory activities, both important factors affecting fascial stiffness and sensitization of fascial nociceptors. PMID:28076930

  10. Effects of Caloric Restriction on Cardiovascular Aging in Non-human Primates and Humans

    PubMed Central

    Cruzen, Christina; Colman, Ricki J.

    2009-01-01

    Synopsis Approximately one in three Americans has some form of cardiovascular disease (CVD), accounting for one of every 2.8 deaths in the United States in 2004. Two of the major risk factors for CVD are advancing age and obesity. An intervention able to positively impact both aging and obesity, such as caloric restriction (CR), may prove extremely useful in the fight against CVD. CR is the only environmental or lifestyle intervention that has repeatedly been shown to increase maximum life span and to retard aging in laboratory rodents. In this article, we review evidence that CR in nonhuman primates and humans has a positive effect on risk factors for CVD. PMID:19944270

  11. The use of animal tissues alongside human tissue: Cultural and ethical considerations.

    PubMed

    Kaw, Anu; Jones, D Gareth; Zhang, Ming

    2016-01-01

    Teaching and research facilities often use cadaveric material alongside animal tissues, although there appear to be differences in the way we handle, treat, and dispose of human cadaveric material compared to animal tissue. This study sought to analyze cultural and ethical considerations and provides policy recommendations on the use of animal tissues alongside human tissue. The status of human and animal remains and the respect because of human and animal tissues were compared and analyzed from ethical, legal, and cultural perspectives. The use of animal organs and tissues is carried out within the context of understanding human anatomy and function. Consequently, the interests of human donors are to be pre-eminent in any policies that are enunciated, so that if any donors find the presence of animal remains unacceptable, the latter should not be employed. The major differences appear to lie in differences in our perceptions of their respective intrinsic and instrumental values. Animals are considered to have lesser intrinsic value and greater instrumental value than humans. These differences stem from the role played by culture and ethical considerations, and are manifested in the resulting legal frameworks. In light of this discussion, six policy recommendations are proposed, encompassing the nature of consent, respect for animal tissues as well as human remains, and appropriate separation of both sets of tissues in preparation and display.

  12. Successful cryopreservation of human ovarian cortex tissues using supercooling.

    PubMed

    Moriguchi, Hisashi; Zhang, Yue; Mihara, Makoto; Sato, Chifumi

    2012-01-01

    The development of new method to cryopreserve human ovarian cortex tissues without damage is needed for the improvement of quality of life (QOL) of female cancer patients. Here we show novel cryopreservation method of human ovarian cortex tissues by using supercooling (S.C.) procedure. Our method will be helpful in order to preserve fertility of female cancer patients.

  13. Fundamentals of gas phase plasmas for treatment of human tissue.

    PubMed

    Kushner, Mark J; Babaeva, Natalia Yu

    2011-01-01

    The use of gas phase plasmas for treating human tissue is at the intersection of two disciplines - plasma physics and engineering, and medicine. In this paper, a primer will be provided for the medical practitioner on the fundamentals of generating gas phase plasmas at atmospheric pressure in air for the treatment of human tissue. The mechanisms for gas phase plasmas interacting with tissue and biological fluids will also be discussed using results from computer modeling.

  14. Role of tissue kallikrein-kininogen-kinin pathways in the cardiovascular system.

    PubMed

    Sharma, Jagdish N

    2006-04-01

    All the components of the kallikrein-kinin system are located in the cardiac muscle, and its deficiency may lead to cardiac dysfunction. In recent years, numerous observations obtained from clinical and experimental models of diabetes, hypertension, cardiac failure, ischemia, myocardial infarction and left ventricular hypertrophy have suggested that the reduced activity of the local kallikrein-kinin system may be instrumental for the induction of cardiovascular-related diseases. The cardioprotective property of the angiotensin converting enzyme inhibitors is primarily mediated via kinin-releasing pathway, which may cause regression of the left ventricular hypertrophy in hypertensive situations. The ability of kallikrein gene delivery to produce a wide spectrum of beneficial effects makes it an excellent candidate in treating hypertension, cardiovascular and renal diseases. In addition, stable kinin agonists may also be available in the future as therapeutic agents for cardiovascular and renal disorders.

  15. Nine months in space: effects on human autonomic cardiovascular regulation.

    PubMed

    Cooke, W H; Ames JE, I V; Crossman, A A; Cox, J F; Kuusela, T A; Tahvanainen, K U; Moon, L B; Drescher, J; Baisch, F J; Mano, T; Levine, B D; Blomqvist, C G; Eckberg, D L

    2000-09-01

    We studied three Russian cosmonauts to better understand how long-term exposure to microgravity affects autonomic cardiovascular control. We recorded the electrocardiogram, finger photoplethysmographic pressure, and respiratory flow before, during, and after two 9-mo missions to the Russian space station Mir. Measurements were made during four modes of breathing: 1) uncontrolled spontaneous breathing; 2) stepwise breathing at six different frequencies; 3) fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R-R) interval standard deviations decreased in all and respiratory frequency R-R interval spectral power decreased in two cosmonauts in space. Two weeks after the cosmonauts returned to Earth, R-R interval spectral power was decreased, and systolic pressure spectral power was increased in all. The transfer function between systolic pressures and R-R intervals was reduced in-flight, was reduced further the day after landing, and had not returned to preflight levels by 14 days after landing. Our results suggest that long-duration spaceflight reduces vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these changes may persist as long as 2 wk after return to Earth.

  16. Sodium, potassium, blood pressure, and cardiovascular disease in humans.

    PubMed

    Whelton, Paul K

    2014-08-01

    The scientific underpinning for recommended levels of dietary sodium and potassium intake is of great importance to healthcare providers and policy decision-makers. Recent clinical trials and meta-analyses confirm the capacity of dietary sodium reduction and potassium supplementation to reduce blood pressure with no harmful effects on blood lipid levels in customary clinical settings. Blood pressure is thought to be a good surrogate for cardiovascular disease events and the most important preventable risk factor for mortality and disability-adjusted life years. Cohort analyses and related pooling studies that have been used to explore the relationship between dietary Na and CVD were all based on secondary analyses of datasets that were not designed for this purpose. Most are of insufficient quality to provide dependable information. The limited information available from clinical trial experience and cohort studies of higher quality suggests a reduction in dietary Na decreases CVD morbidity and mortality. Modeling studies suggest that a small reduction in dietary sodium would result in a sizable general population health benefit. Some countries have experienced a progressive decline in average dietary sodium consumption. However, there is no evidence of a corresponding trend in the United States, and almost the entire population is failing to meet dietary sodium and potassium guideline recommendations.

  17. Brown adipose tissue as an anti-obesity tissue in humans.

    PubMed

    Chechi, K; Nedergaard, J; Richard, D

    2014-02-01

    During the 11th Stock Conference held in Montreal, Quebec, Canada, world-leading experts came together to present and discuss recent developments made in the field of brown adipose tissue biology. Owing to the vast capacity of brown adipose tissue for burning food energy in the process of thermogenesis, and due to demonstrations of its presence in adult humans, there is tremendous interest in targeting brown adipose tissue as an anti-obesity tissue in humans. However, the future of such therapeutic approaches relies on our understanding of the origin, development, recruitment, activation and regulation of brown adipose tissue in humans. As reviewed here, the 11th Stock Conference was organized around these themes to discuss the recent progress made in each aspect, to identify gaps in our current understanding and to further provide a common groundwork that could support collaborative efforts aimed at a future therapy for obesity, based on brown adipose tissue thermogenesis.

  18. Decellularized extracellular matrix derived from human adipose tissue as a potential scaffold for allograft tissue engineering.

    PubMed

    Choi, Ji Suk; Kim, Beob Soo; Kim, Jun Young; Kim, Jae Dong; Choi, Young Chan; Yang, Hyun-Jin; Park, Kinam; Lee, Hee Young; Cho, Yong Woo

    2011-06-01

    Decellularized tissues composed of extracellular matrix (ECM) have been clinically used to support the regeneration of various human tissues and organs. Most decellularized tissues so far have been derived from animals or cadavers. Therefore, despite the many advantages of decellularized tissue, there are concerns about the potential for immunogenicity and the possible presence of infectious agents. Herein, we present a biomaterial composed of ECM derived from human adipose tissue, the most prevalent, expendable, and safely harvested tissue in the human body. The ECM was extracted by successive physical, chemical, and enzymatic treatments of human adipose tissue isolated by liposuction. Cellular components including nucleic acids were effectively removed without significant disruption of the morphology or structure of the ECM. Major ECM components were quantified, including acid/pepsin-soluble collagen, sulfated glycosaminoglycan (GAG), and soluble elastin. In an in vivo experiment using mice, the decellularized ECM graft exhibited good compatibility to surrounding tissues. Overall results suggest that the decellularized ECM containing biological and chemical cues of native human ECM could be an ideal scaffold material not only for autologous but also for allograft tissue engineering.

  19. Controlled breathing protocols probe human autonomic cardiovascular rhythms

    NASA Technical Reports Server (NTRS)

    Cooke, W. H.; Cox, J. F.; Diedrich, A. M.; Taylor, J. A.; Beightol, L. A.; Ames, J. E. 4th; Hoag, J. B.; Seidel, H.; Eckberg, D. L.

    1998-01-01

    The purpose of this study was to determine how breathing protocols requiring varying degrees of control affect cardiovascular dynamics. We measured inspiratory volume, end-tidal CO2, R-R interval, and arterial pressure spectral power in 10 volunteers who followed the following 5 breathing protocols: 1) uncontrolled breathing for 5 min; 2) stepwise frequency breathing (at 0.3, 0.25, 0.2, 0.15, 0.1, and 0.05 Hz for 2 min each); 3) stepwise frequency breathing as above, but with prescribed tidal volumes; 4) random-frequency breathing (approximately 0.5-0.05 Hz) for 6 min; and 5) fixed-frequency breathing (0.25 Hz) for 5 min. During stepwise breathing, R-R interval and arterial pressure spectral power increased as breathing frequency decreased. Control of inspired volume reduced R-R interval spectral power during 0.1 Hz breathing (P < 0.05). Stepwise and random-breathing protocols yielded comparable coherence and transfer functions between respiration and R-R intervals and systolic pressure and R-R intervals. Random- and fixed-frequency breathing reduced end-tidal CO2 modestly (P < 0.05). Our data suggest that stringent tidal volume control attenuates low-frequency R-R interval oscillations and that fixed- and random-rate breathing may decrease CO2 chemoreceptor stimulation. We conclude that autonomic rhythms measured during different breathing protocols have much in common but that a stepwise protocol without stringent control of inspired volume may allow for the most efficient assessment of short-term respiratory-mediated autonomic oscillations.

  20. Characterization and analysis of human arterial tissue secretome by 2-DE and nLC-MS/MS.

    PubMed

    de la Cuesta, Fernando; Barderas, Maria G; Calvo, Enrique; Zubiri, Irene; Maroto, Aroa S; Lopez, Juan Antonio; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2013-01-01

    Early detection of cardiovascular diseases and knowledge of underlying mechanisms is essential. Tissue secretome studies resemble more closely to the in vivo situation, showing a much narrower protein concentrations dynamic range than plasma. In the present chapter, we detail the characterization and analysis of human arterial tissue secretome by two-dimensional electrophoresis (2-DE) and nano-liquid chromatography on-line coupled to mass spectrometry (nLC-MS/MS). General strategies shown here can be extended to other tissue secretome studies.

  1. Macrophages modulate engineered human tissues for enhanced vascularization and healing

    PubMed Central

    Spiller, Kara L.; Freytes, Donald O.; Vunjak-Novakovic, Gordana

    2014-01-01

    Tissue engineering is increasingly based on recapitulating human physiology, through integration of biological principles into engineering designs. In spite of all progress in engineering functional human tissues, we are just beginning to develop effective methods for establishing blood perfusion and controlling the inflammatory factors following implantation into the host. Functional vasculature largely determines tissue survival and function in vivo. The inflammatory response is a major regulator of vascularization and overall functionality of engineered tissues, through the activity of different types of macrophages and the cytokines they secrete. We discuss cell-scaffold-bioreactor systems for harnessing the inflammatory response for enhanced tissue vascularization and healing. To this end, inert scaffolds that have been considered for many decades a “gold standard” in regenerative medicine are beginning to be replaced by a new generation of “smart” tissue engineering systems designed to actively mediate tissue survival and function. PMID:25331098

  2. Diagnose human colonic tissues by terahertz near-field imaging

    NASA Astrophysics Data System (ADS)

    Chen, Hua; Ma, Shihua; Wu, Xiumei; Yang, Wenxing; Zhao, Tian

    2015-03-01

    Based on a terahertz (THz) pipe-based near-field imaging system, we demonstrate the capability of THz imaging to diagnose freshly surgically excised human colonic tissues. Through THz near-field scanning the absorbance of the colonic tissues, the acquired images can clearly distinguish cancerous tissues from healthy tissues fast and automatically without pathological hematoxylin and eosin stain diagnosis. A statistical study on 58 specimens (20 healthy tissues and 38 tissues with tumor) from 31 patients (mean age: 59 years; range: 46 to 79 years) shows that the corresponding diagnostic sensitivity and specificity on colonic tissues are both 100%. Due to its capability to perform quantitative analysis, our study indicates the potential of the THz pipe-based near-field imaging for future automation on human tumor pathological examinations.

  3. Mathematical modelling of the human cardiovascular system in the presence of stenosis

    NASA Technical Reports Server (NTRS)

    Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.

    1993-01-01

    This paper reports a theoretical study on the distribution of blood flow in the human cardiovascular system when one or more blood vessels are affected by stenosis. The analysis employs a mathematical model of the entire system based on the finite element method. The arterial-venous network is represented by a large number of interconnected segments in the model. Values for the model parameters are based upon the published data on the physiological and rheological properties of blood. Computational results show how blood flow through various parts of the cardiovascular system is affected by stenosis in different blood vessels. No significant changes in the flow parameters of the cardiovascular system were found to occur when the reduction in the lumen diameter of the stenosed vessels was less than 65%.

  4. Mathematical modelling of the human cardiovascular system in the presence of stenosis.

    PubMed

    Sud, V K; Srinivasan, R S; Charles, J B; Bungo, M W

    1993-03-01

    This paper reports a theoretical study on the distribution of blood flow in the human cardiovascular system when one or more blood vessels are affected by stenosis. The analysis employs a mathematical model of the entire system based on the finite element method. The arterial-venous network is represented by a large number of interconnected segments in the model. Values for the model parameters are based upon the published data on the physiological and rheological properties of blood. Computational results show how blood flow through various parts of the cardiovascular system is affected by stenosis in different blood vessels. No significant changes in the flow parameters of the cardiovascular system were found to occur when the reduction in the lumen diameter of the stenosed vessels was less than 65%.

  5. Depth-resolved fluorescence of human ectocervical tissue

    NASA Astrophysics Data System (ADS)

    Wu, Yicong; Xi, Peng; Cheung, Tak-Hong; Yim, So Fan; Yu, Mei-Yung; Qu, Jianan Y.

    2005-04-01

    The depth-resolved autofluorescence of normal and dysplastic human ectocervical tissue within 120um depth were investigated utilizing a portable confocal fluorescence spectroscopy with the excitations at 355nm and 457nm. From the topmost keratinizing layer of all ectocervical tissue samples, strong keratin fluorescence with the spectral characteristics similar to collagen was observed, which created serious interference in seeking the correlation between tissue fluorescence and tissue pathology. While from the underlying non-keratinizing epithelial layer, the measured NADH fluorescence induced by 355nm excitation and FAD fluorescence induced by 457nm excitation were strongly correlated to the tissue pathology. The ratios between NADH over FAD fluorescence increased statistically in the CIN epithelial relative to the normal and HPV epithelia, which indicated increased metabolic activity in precancerous tissue. This study demonstrates that the depth-resolved fluorescence spectroscopy can reveal fine structural information on epithelial tissue and potentially provide more accurate diagnostic information for determining tissue pathology.

  6. Transcriptomics resources of human tissues and organs.

    PubMed

    Uhlén, Mathias; Hallström, Björn M; Lindskog, Cecilia; Mardinoglu, Adil; Pontén, Fredrik; Nielsen, Jens

    2016-04-04

    Quantifying the differential expression of genes in various human organs, tissues, and cell types is vital to understand human physiology and disease. Recently, several large-scale transcriptomics studies have analyzed the expression of protein-coding genes across tissues. These datasets provide a framework for defining the molecular constituents of the human body as well as for generating comprehensive lists of proteins expressed across tissues or in a tissue-restricted manner. Here, we review publicly available human transcriptome resources and discuss body-wide data from independent genome-wide transcriptome analyses of different tissues. Gene expression measurements from these independent datasets, generated using samples from fresh frozen surgical specimens and postmortem tissues, are consistent. Overall, the different genome-wide analyses support a distribution in which many proteins are found in all tissues and relatively few in a tissue-restricted manner. Moreover, we discuss the applications of publicly available omics data for building genome-scale metabolic models, used for analyzing cell and tissue functions both in physiological and in disease contexts.

  7. Matricryptic sites control tissue injury responses in the cardiovascular system: relationships to pattern recognition receptor regulated events.

    PubMed

    Davis, George E

    2010-03-01

    This review addresses new concepts related to the importance of how cells within the cardiovascular system respond to matricryptic sites generated from the extracellular matrix (ECM) following tissue injury. A model is presented whereby matricryptic sites exposed from the ECM result in activation of multiple cell surface receptors including integrins, scavenger receptors, and toll-like receptors which together are hypothesized to coactivate downstream signaling pathways which alter cell behaviors following tissue injury. Of great interest are the relationships between matricryptic fragments of ECM called matricryptins and other stimuli that activate cells during injury states such as released components from cells (DNA, RNA, cytoskeletal components such as actin) or products from infectious agents in innate immunity responses. These types of cell activating molecules, which are composed of repeating molecular elements, are known to interact with pattern recognition receptors that (i) are expressed from cell surfaces, (ii) are released from cells following tissue injury, or (iii) circulate as components of plasma. Thus, cell recognition of matricryptic sites from the ECM appears to be an important component of a broad cell and tissue sensory system to detect and respond to environmental cues generated following varied types of tissue injury.

  8. Distribution of miRNA expression across human tissues.

    PubMed

    Ludwig, Nicole; Leidinger, Petra; Becker, Kurt; Backes, Christina; Fehlmann, Tobias; Pallasch, Christian; Rheinheimer, Steffi; Meder, Benjamin; Stähler, Cord; Meese, Eckart; Keller, Andreas

    2016-05-05

    We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10(-8)) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas).

  9. Carbon nanotubes reinforced chitosan films: mechanical properties and cell response of a novel biomaterial for cardiovascular tissue engineering.

    PubMed

    Kroustalli, A; Zisimopoulou, A E; Koch, S; Rongen, L; Deligianni, D; Diamantouros, S; Athanassiou, G; Kokozidou, M; Mavrilas, D; Jockenhoevel, S

    2013-12-01

    Carbon nanotubes have been proposed as fillers to reinforce polymeric biomaterials for the strengthening of their structural integrity to achieve better biomechanical properties. In this study, a new polymeric composite material was introduced by incorporating various low concentrations of multiwalled carbon nanotubes (MWCNTs) into chitosan (CS), aiming at achieving a novel composite biomaterial with superior mechanical and biological properties compared to neat CS, in order to be used in cardiovascular tissue engineering applications. Both mechanical and biological characteristics in contact with the two relevant cell types (endothelial cells and vascular myofibroblasts) were studied. Regarding the mechanical behavior of MWCNT reinforced CS (MWCNT/CS), 5 and 10 % concentrations of MWCNTs enhanced the mechanical behavior of CS, with that of 5 % exhibiting a superior mechanical strength compared to 10 % concentration and neat CS. Regarding biological properties, MWCNT/CS best supported proliferation of endothelial and myofibroblast cells, MWCNTs and MWCNT/CS caused no apoptosis and were not toxic of the examined cell types. Conclusively, the new material could be suitable for tissue engineering (TE) and particularly for cardiovascular TE applications.

  10. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  11. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

  12. MicroRNA-21 coordinates human multipotent cardiovascular progenitors therapeutic potential.

    PubMed

    Richart, Adèle; Loyer, Xavier; Néri, Tui; Howangyin, Kiave; Guérin, Coralie L; Ngkelo, Anta; Bakker, Wineke; Zlatanova, Ivana; Rouanet, Marie; Vilar, José; Lévy, Bernard; Rothenberg, Marc; Mallat, Ziad; Pucéat, Michel; Silvestre, Jean-Sébastien

    2014-11-01

    Published clinical trials in patients with ischemic diseases show limited benefit of adult stem cell-based therapy, likely due to their restricted plasticity and commitment toward vascular cell lineage. We aim to uncover the potent regenerative ability of MesP1/stage-specific embryonic antigen 1 (SSEA-1)-expressing cardiovascular progenitors enriched from human embryonic stem cells (hESCs). Injection of only 10(4) hESC-derived SSEA-1(+) /MesP1(+) cells, or their progeny obtained after treatment with VEGF-A or PDGF-BB, was effective enough to enhance postischemic revascularization in immunodeficient mice with critical limb ischemia (CLI). However, the rate of incorporation of hESC-derived SSEA-1(+) /MesP1(+) cells and their derivatives in ischemic tissues was modest. Alternatively, these cells possessed a unique miR-21 signature that inhibited phosphotase and tensin homolog (PTEN) thereby activating HIF-1α and the systemic release of VEGF-A. Targeting miR-21 limited cell survival and inhibited their proangiogenic capacities both in the Matrigel model and in mice with CLI. We next assessed the impact of mR-21 in adult angiogenesis-promoting cells. We observed an impaired postischemic angiogenesis in miR-21-deficient mice. Notably, miR-21 was highly expressed in circulating and infiltrated monocytes where it targeted PTEN/HIF-1α/VEGF-A signaling and cell survival. As a result, miR-21-deficient mice displayed an impaired number of infiltrated monocytes and a defective angiogenic phenotype that could be partially restored by retransplantation of bone marrow-derived cells from wild-type littermates. hESC-derived SSEA-1(+) /MesP1(+) cells progenitor cells are powerful key integrators of therapeutic angiogenesis in ischemic milieu and miR-21 is instrumental in this process as well as in the orchestration of the biological activity of adult angiogenesis-promoting cells.

  13. Altered autophagy in human adipose tissues in obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat d...

  14. Tissue-Based Imaging Model of Human Trabecular Meshwork

    PubMed Central

    Chu, Edward R.; Gonzalez, Jose M.

    2014-01-01

    Abstract We have developed a tissue-based model of the human trabecular meshwork (TM) using viable postmortem corneoscleral donor tissue. Two-photon microscopy is used to optically section and image deep in the tissue to analyze cells and extracellular matrix (ECM) within the original three-dimensional (3D) environment of the TM. Multimodal techniques, including autofluorescence (AF), second harmonic generation (SHG), intravital dye fluorescence, and epifluorescence, are combined to provide unique views of the tissue at the cellular and subcellular level. SHG and AF imaging are non-invasive tissue imaging techniques with potential for clinical application, which can be modeled in the system. We describe the following in the tissue-based model: analysis of live cellularity to determine tissue viability; characteristics of live cells based on intravital labeling; features and composition of the TM's structural ECM; localization of specific ECM proteins to regions such as basement membrane; in situ induction and expression of tissue markers characteristic of cultured TM cells relevant to glaucoma; analysis of TM actin and pharmacological effects; in situ visualization of TM, inner wall endothelium, and Schlemm's canal; and application of 3D reconstruction, modeling, and quantitative analysis to the TM. The human model represents a cost-effective use of valuable and scarce yet available human tissue that allows unique cell biology, pharmacology, and translational studies of the TM. PMID:24517246

  15. Microwave non-contact imaging of subcutaneous human body tissues

    PubMed Central

    Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

    2015-01-01

    A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated. PMID:26609415

  16. Microwave non-contact imaging of subcutaneous human body tissues.

    PubMed

    Kletsov, Andrey; Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

    2015-10-01

    A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated.

  17. Clocks and cardiovascular function

    PubMed Central

    McLoughlin, Sarah C.; Haines, Philip; FitzGerald, Garret A.

    2016-01-01

    Circadian clocks in central and peripheral tissues enable the temporal synchronization and organization of molecular and physiological processes of rhythmic animals, allowing optimum functioning of cells and organisms at the most appropriate time of day. Disruption of circadian rhythms, from external or internal forces, leads to widespread biological disruption and is postulated to underlie many human conditions, such as the incidence and timing of cardiovascular disease. Here, we describe in vivo and in vitro methodology relevant to studying the role of circadian rhythms in cardiovascular function and dysfunction PMID:25707279

  18. Dynamics of extracellular matrix production and turnover in tissue engineered cardiovascular structures.

    PubMed

    Stock, U A; Wiederschain, D; Kilroy, S M; Shum-Tim, D; Khalil, P N; Vacanti, J P; Mayer, J E; Moses, M A

    2001-03-26

    Appropriate matrix formation, turnover and remodeling in tissue-engineered small diameter vascular conduits are crucial requirements for their long-term patency and function. This complex process requires the deposition and accumulation of extracellular matrix molecules as well as the remodeling of this extracellular matrix (ECM) by matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs). In this study, we have investigated the dynamics of ECM production and the activity of MMPs and TIMPs in long-term tissue-engineered vascular conduits using quantitative ECM analysis, substrate gel electrophoresis, radiometric enzyme assays and Western blot analyses. Over a time period of 169 days in vivo, levels of elastin and proteoglycans/glycosaminoglycans in tissue-engineered constructs came to approximate those of their native tissue counter parts. The kinetics of collagen deposition and remodeling, however, apparently require a much longer time period. Through the use of substrate gel electrophoresis, proteolytic bands whose molecular weight was consistent with their identification as the active form of MMP-2 (approximately 64--66 kDa) were detected in all native and tissue-engineered samples. Additional proteolytic bands migrating at approximately 72 kDa representing the latent form of MMP-2 were detected in tissue-engineered samples at time points from 5 throughout 55 days. Radiometric assays of MMP-1 activity demonstrated no significant differences between the native and tissue-engineered samples. This study determines the dynamics of ECM production and turnover in a long-term tissue-engineered vascular tissue and highlights the importance of ECM remodeling in the development of successful tissue-engineered vascular structures.

  19. Human endothelial cell responses to cardiovascular inspired pulsatile shear stress

    NASA Astrophysics Data System (ADS)

    Watson, Matthew; Baugh, Lauren; Black, Lauren, III; Kemmerling, Erica

    2016-11-01

    It is well established that hemodynamic shear stress regulates blood vessel structure and the development of vascular pathology. This process can be studied via in vitro models of endothelial cell responses to pulsatile shear stress. In this study, a macro-scale cone and plate viscometer was designed to mimic various shear stress waveforms found in the body and apply these stresses to human endothelial cells. The device was actuated by a PID-controlled DC gear-motor. Cells were exposed to 24 hours of pulsatile shear and then imaged and stained to track their morphology and secretions. These measurements were compared with control groups of cells exposed to constant shear and no shear. The results showed that flow pulsatility influenced levels of secreted proteins such as VE-cadherin and neuroregulin IHC. Cell morphology was also influenced by flow pulsatility; in general cells exposed to pulsatile shear stress developed a higher aspect ratio than cells exposed to no flow but a lower aspect ratio than cells exposed to steady flow.

  20. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

    PubMed Central

    Bayzigitov, Daniel R.; Medvedev, Sergey P.; Dementyeva, Elena V.; Bayramova, Sevda A.; Pokushalov, Evgeny A.; Karaskov, Alexander M.; Zakian, Suren M.

    2016-01-01

    Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes. PMID:27110425

  1. Physics of the cardiovascular system: An intrinsic control mechanism of the human heart

    NASA Astrophysics Data System (ADS)

    Uehara, Mituo; Sakane, Kumiko K.

    2003-04-01

    Differential equations for the cardiovascular system are derived by applying the continuity equation of fluid mechanics to the rate of blood flow and variation of blood volume in different parts of the system. The equations are used to explain the Frank-Starling mechanism, which plays an important role in the maintenance of the stability of the distribution of blood in the system. This treatment can be easily understood by undergraduate physics students with no previous knowledge of human physiology.

  2. Total DDT and dieldrin content of human adipose tissue

    SciTech Connect

    Ahmad, N.; Harsas, W.; Marolt, R.S.; Morton, M.; Pollack, J.K.

    1988-12-01

    As far as the authors could ascertain only 4 well-documented analytical studies have been carried out in Australia determining the total DDT and dieldrin content of human adipose tissue. The latest of these studies was published over 16 years ago. Therefore it is timely and important to re-examine the total DDT and dieldrin concentration within the adipose tissue of the Australian population. The present investigation has analyzed 290 samples of human adipose tissue obtained from Westmead Hospital situated in an outer suburb of Sydney, New South Wales for their content of total DDT and dieldrin.

  3. Characterization of a simplified method of cryopreserving human parathyroid tissue.

    PubMed

    Saxe, A W; Gibson, G W; Kay, S

    1990-12-01

    Cryopreservation of human parathyroid tissue plays an important role in managing difficult parathyroid disease. It also can permit investigators to conduct experiments without dependence on the operating room schedule. Availability of cryopreservation has been limited by the perceived need for expensive, complex equipment. We adapted a simple method of freezing cell suspensions to freezing human parathyroid tissue. Vials containing human parathyroid in culture media, dimethylsulfoxide, and patient serum were placed in a plastic rack in a metal pan containing prechilled (4 degrees C) ethanol and placed in a -70 degrees C freezer. We compared viability (trypan blue dye exclusion by collagenase dispersed cells) of tissue frozen in this manner to that of tissue frozen in a programmable liquid nitrogen freezer at 1 degrees C per minute, a cooling rate recommended for human parathyroid tissue. The viability of 30 patients' samples cooled in liquid nitrogen (average length of storage 5 months) was 74% +/- 15% and that of 64 patients' samples cooled in ethanol (average length of storage 26 months) was 71% +/- 15%. Viability of 19 samples of fresh tissue was 79% +/- 10%. Neither method had a statistically significant correlation between length of storage and viability. Successful cryopreservation with simplified technology may expand the availability of parathyroid tissue to meet both clinical and investigative requirements.

  4. Efficient In Vitro Electropermeabilization of Reconstructed Human Dermal Tissue.

    PubMed

    Madi, Moinecha; Rols, Marie-Pierre; Gibot, Laure

    2015-10-01

    DNA electrotransfer is a successful technic for gene delivery. However, its use in clinical applications is limited since little is known about the mechanisms governing DNA electrotransfer in the complex environment occurring in a tissue. The objectives of this work were to investigate the role of the extracellular matrix (ECM) in that process. Tumor ECM composition was shown to modulate in vivo gene electrotransfer efficiency. In order to assess the effects of ECM composition and organization, as well as intercellular junctions and communication, in normal tissue response to electric pulses, we developed an innovative three-dimensional (3D) reconstructed human connective tissue model. 3D human dermal tissue was reconstructed in vitro by a tissue engineering approach and was representative of in vivo cell organization since cell-cell contacts were present as well as complex ECM. This human cell model presented multiple layers of primary dermal fibroblasts embedded in a native, collagen-rich ECM. This dermal tissue could become a useful tool to study skin DNA electrotransfer mechanisms. As proof of the concept, we show here that the cells within this standardized 3D tissue can be efficiently electropermeabilized by milliseconds electric pulses. We believe that a better comprehension of gene electrotransfer in such a model tissue would help improve electrogene therapy approaches such as the systemic delivery of therapeutic proteins and DNA vaccination.

  5. Nutritional regulation of lipid metabolism in human adipose tissue.

    PubMed

    Coppack, S W; Patel, J N; Lawrence, V J

    2001-01-01

    Pfeiffer and colleagues years ago pointed out that different distributions and amounts of adipose tissue are associated with abnormalities of lipolysis and lipoprotein metabolism. Adipose tissue has several crucial roles including (i) mobilization from stores of fatty acids as an energy source, (ii) catabolism of lipoproteins such as very-low-density lipoprotein and (iii) synthesis and release of hormonal signals such as leptin and interleukin-6. These adipose tissue actions are crucially regulated by nutrition. The review considers the existence of metabolic pathways and modes of regulation within adipose tissue, and how such metabolic activity can be quantitated in humans. Nutrition can influence adipose tissue at several 'levels'. Firstly the level of obesity or malnutrition has important effects on many aspects of adipose tissue metabolism. Secondly short-term overfeeding, underfeeding and exercise have major impacts on adipose tissue behaviour. Lastly, specific nutrients are capable of regulating adipose tissue metabolism. Recently there have been considerable advances in understanding adipose tissue metabolism and in particular its regulation. This review discusses the behaviour of adipose tissue under various nutritional conditions. There is then a review of recent work examining the ways in which nutritional influences act via intra-cellular mechanisms, insulin and the sympathetic innervation of adipose tissue.

  6. Meeting report: human fetal tissue transplantation research panel.

    PubMed

    Barnes, D W; Stevenson, R E

    1989-01-01

    On September 14 through 16, 1988, a meeting on the use of human fetal tissue in transplantation was held at the National Institutes of Health, Bethesda Maryland, USA. The meeting sponsored by NIH for the Human Fetal Tissue Transplantation Research Panel, a consultant group to the Advisory Committee to the Director. The consultant group was convened to deal with the scientific, judicial and moral questions associated with research involving transplantation of human fetal tissue obtained after induced abortions. The first day of the meeting was devoted to presentations addressing scientific issues. Included among the speakers was Dr. Lars Olson, Professor of Neurobiology, Karolinska Institute, Stockholm, who described the use of transplanted human fetal tissue in the treatment of patients with Parkinson's disease and Dr. Eugene Redmond, Professor of Psychiatry, Yale University School of Medicine, who showed results of work with transplantation of tissue to correct induced Parkinson-like disease in monkeys. Other speakers addressed the present, past or potential use of fetal tissue in the treatment of diabetes, immune disorders, and other diseases, as well as the use of fetal cells in the production of biologicals. At the conclusion of the meeting the panel did not recommend that research be halted on fetal tissue within the context discussed, although the recommendation of the committee is not binding, and an additional assembly of the panel will probably occur before the final recommendation to an NIH advisory committee is made in November. Other meetings on this subject include a meeting on the use of fetal tissue sponsored by the American Association of Tissue Banks, March 6-7, 1989, in Washington D. C. (Crystal City) and a meeting June 10, 1989, the day before the annual meeting of the Tissue Culture Association, USA, in Orlando, Florida, on fetal cells and ownership of cultured cells and products derived from clinical specimens. Following are statements to the

  7. Correlation of Endostatin and Tissue Inhibitor of Metalloproteinases 2 (TIMP2) Serum Levels With Cardiovascular Involvement in Systemic Sclerosis Patients

    PubMed Central

    Dziankowska-Bartkowiak, Bożena; Waszczykowska, Elżbieta; Zalewska, Anna; Sysa-Jędrzejowska, Anna

    2005-01-01

    Fibrosis of oesophagus, lungs, heart, and kidney in the course of systemic sclerosis (SSc) may lead to dysfunction of the above organs or even patients death. Recent studies point out the role of angiogenesis and fibrosis disturbances in the pathogenesis of SSc. Heart fibrosis is one of the most important prognostic factors in SSc patients. So, the aim of our study was to examine cardiovascular dysfunction in SSc patients and its correlation with serum levels of vascular endothelial growth factor (VEGF), endostatin, and tissue inhibitor of metalloproteinase 2 (TIMP2). The study group comprised 34 patients (19 with limited scleroderma (lSSc) and 15 with diffuse scleroderma (dSSc)). The control group consisted of 20 healthy persons, age and sex matched. Internal organ involvement was assessed on the basis of specialist procedures. Serum VEGF, endostatin, and TIMP2 levels were evaluated by ELISA. We found cardiovascular changes in 15 patients with SSc (8 with lSSc and 7 with dSSc). The observed symptoms were of different characters and also coexisted with each other. Higher endostatin serum levels in all systemic sclerosis patients in comparison to the control group were demonstrated (P < .05). Also higher serum levels of endostatin and TIMP2 were observed in patients with cardiovascular changes in comparison to the patients without such changes (P < .05). The obtained results support the notion that angiogenesis and fibrosis disturbances may play an important role in SSc. Evaluation of endostatin and TIMP2 serum levels seems to be one of the noninvasive, helpful examinations of heart involvement in the course of systemic sclerosis. PMID:16106100

  8. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tissue culture media for human ex vivo tissue and cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell...

  9. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tissue culture media for human ex vivo tissue and cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell...

  10. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tissue culture media for human ex vivo tissue and cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell...

  11. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tissue culture media for human ex vivo tissue and cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell...

  12. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tissue culture media for human ex vivo tissue and cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell...

  13. Cardiovascular function, compliance, and connective tissue remodeling in the turtle, Trachemys scripta, following thermal acclimation

    PubMed Central

    Keen, Adam N.; Crossley, Dane A.

    2016-01-01

    Low temperature directly alters cardiovascular physiology in freshwater turtles, causing bradycardia, arterial hypotension, and a reduction in systemic blood pressure. At the same time, blood viscosity and systemic resistance increase, as does sensitivity to cardiac preload (e.g., via the Frank-Starling response). However, the long-term effects of these seasonal responses on the cardiovascular system are unclear. We acclimated red-eared slider turtles to a control temperature (25°C) or to chronic cold (5°C). To differentiate the direct effects of temperature from a cold-induced remodeling response, all measurements were conducted at the control temperature (25°C). In anesthetized turtles, cold acclimation reduced systemic resistance by 1.8-fold and increased systemic blood flow by 1.4-fold, resulting in a 2.3-fold higher right to left (R-L; net systemic) cardiac shunt flow and a 1.8-fold greater shunt fraction. Following a volume load by bolus injection of saline (calculated to increase stroke volume by 5-fold, ∼2.2% of total blood volume), systemic resistance was reduced while pulmonary blood flow and systemic pressure increased. An increased systemic blood flow meant the R-L cardiac shunt was further pronounced. In the isolated ventricle, passive stiffness was increased following cold acclimation with 4.2-fold greater collagen deposition in the myocardium. Histological sections of the major outflow arteries revealed a 1.4-fold higher elastin content in cold-acclimated animals. These results suggest that cold acclimation alters cardiac shunting patterns with an increased R-L shunt flow, achieved through reducing systemic resistance and increasing systemic blood flow. Furthermore, our data suggests that cold-induced cardiac remodeling may reduce the stress of high cardiac preload by increasing compliance of the vasculature and decreasing compliance of the ventricle. Together, these responses could compensate for reduced systolic function at low temperatures in

  14. A New Antigen Retrieval Technique for Human Brain Tissue

    PubMed Central

    Byne, William; Haroutunian, Vahram; García-Villanueva, Mercedes; Rábano, Alberto; García-Amado, María; Prensa, Lucía; Giménez-Amaya, José Manuel

    2008-01-01

    Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times. PMID:18852880

  15. Mechanized syringe homogenization of human and animal tissues.

    PubMed

    Kurien, Biji T; Porter, Andrew C; Patel, Nisha C; Kurono, Sadamu; Matsumoto, Hiroyuki; Scofield, R Hal

    2004-06-01

    Tissue homogenization is a prerequisite to any fractionation schedule. A plethora of hands-on methods are available to homogenize tissues. Here we report a mechanized method for homogenizing animal and human tissues rapidly and easily. The Bio-Mixer 1200 (manufactured by Innovative Products, Inc., Oklahoma City, OK) utilizes the back-and-forth movement of two motor-driven disposable syringes, connected to each other through a three-way stopcock, to homogenize animal or human tissue. Using this method, we were able to homogenize human or mouse tissues (brain, liver, heart, and salivary glands) in 5 min. From sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and a matrix-assisted laser desorption/ionization time-of-flight mass spectrometric enzyme assay for prolidase, we have found that the homogenates obtained were as good or even better than that obtained used a manual glass-on-Teflon (DuPont, Wilmington, DE) homogenization protocol (all-glass tube and Teflon pestle). Use of the Bio-Mixer 1200 to homogenize animal or human tissue precludes the need to stay in the cold room as is the case with the other hands-on homogenization methods available, in addition to freeing up time for other experiments.

  16. Human natural killer cell development in secondary lymphoid tissues

    PubMed Central

    Freud, Aharon G.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34+CD45RA+ hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field. PMID:24661538

  17. Human natural killer cell development in secondary lymphoid tissues.

    PubMed

    Freud, Aharon G; Yu, Jianhua; Caligiuri, Michael A

    2014-04-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34(+)CD45RA(+) hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field.

  18. 78 FR 44134 - Submission for OMB Review; 30-day Comment Request: Financial Sustainability of Human Tissue...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ...: Financial Sustainability of Human Tissue Biobanking (NCI) SUMMARY: Under the provisions of Section 3507(a)(1... Collection: Financial Sustainability of Human Tissue Biobanking, 0925-NEW, National Cancer Institute...

  19. The TissueNet v.2 database: A quantitative view of protein-protein interactions across human tissues

    PubMed Central

    Basha, Omer; Barshir, Ruth; Sharon, Moran; Lerman, Eugene; Kirson, Binyamin F.; Hekselman, Idan; Yeger-Lotem, Esti

    2017-01-01

    Knowledge of the molecular interactions of human proteins within tissues is important for identifying their tissue-specific roles and for shedding light on tissue phenotypes. However, many protein–protein interactions (PPIs) have no tissue-contexts. The TissueNet database bridges this gap by associating experimentally-identified PPIs with human tissues that were shown to express both pair-mates. Users can select a protein and a tissue, and obtain a network view of the query protein and its tissue-associated PPIs. TissueNet v.2 is an updated version of the TissueNet database previously featured in NAR. It includes over 40 human tissues profiled via RNA-sequencing or protein-based assays. Users can select their preferred expression data source and interactively set the expression threshold for determining tissue-association. The output of TissueNet v.2 emphasizes qualitative and quantitative features of query proteins and their PPIs. The tissue-specificity view highlights tissue-specific and globally-expressed proteins, and the quantitative view highlights proteins that were differentially expressed in the selected tissue relative to all other tissues. Together, these views allow users to quickly assess the unique versus global functionality of query proteins. Thus, TissueNet v.2 offers an extensive, quantitative and user-friendly interface to study the roles of human proteins across tissues. TissueNet v.2 is available at http://netbio.bgu.ac.il/tissuenet. PMID:27899616

  20. Earthing (Grounding) the Human Body Reduces Blood Viscosity—a Major Factor in Cardiovascular Disease

    PubMed Central

    Chevalier, Gaétan; Sinatra, Stephen T.; Delany, Richard M.

    2013-01-01

    Abstract Objectives Emerging research is revealing that direct physical contact of the human body with the surface of the earth (grounding or earthing) has intriguing effects on human physiology and health, including beneficial effects on various cardiovascular risk factors. This study examined effects of 2 hours of grounding on the electrical charge (zeta potential) on red blood cells (RBCs) and the effects on the extent of RBC clumping. Design/interventions Subjects were grounded with conductive patches on the soles of their feet and palms of their hands. Wires connected the patches to a stainless-steel rod inserted in the earth outdoors. Small fingertip pinprick blood samples were placed on microscope slides and an electric field was applied to them. Electrophoretic mobility of the RBCs was determined by measuring terminal velocities of the cells in video recordings taken through a microscope. RBC aggregation was measured by counting the numbers of clustered cells in each sample. Settings/location Each subject sat in a comfortable reclining chair in a soundproof experiment room with the lights dimmed or off. Subjects Ten (10) healthy adult subjects were recruited by word-of-mouth. Results Earthing or grounding increased zeta potentials in all samples by an average of 2.70 and significantly reduced RBC aggregation. Conclusions Grounding increases the surface charge on RBCs and thereby reduces blood viscosity and clumping. Grounding appears to be one of the simplest and yet most profound interventions for helping reduce cardiovascular risk and cardiovascular events. PMID:22757749

  1. Short-term magnesium deficiency downregulates telomerase, upregulates neutral sphingomyelinase and induces oxidative DNA damage in cardiovascular tissues: relevance to atherogenesis, cardiovascular diseases and aging

    PubMed Central

    Shah, Nilank C; Shah, Gatha J; Li, Zhiqiang; Jiang, Xian-Cheng; Altura, Bella T; Altura, Burton M

    2014-01-01

    The present work tested the hypotheses that: 1) short-term dietary deficiency of magnesium (Mg; 21 days) in rats (MgD) would result in a downregulation of telomerase in cardiac and aortic smooth muscle cells, 2) low levels of Mg2+ added to drinking water (DW) would either prevent or greatly reduce the downregulation of telomerase in MgD, 3) MgD in rats would cause an upregulation of neutral-sphingomyelinase (N-SMAse) and p53, 4) short-term MgD would result in oxidation of DNA in diverse cardiac muscle and aortic smooth muscle cells as exemplified by measurement of 8-hydroxydeoxyguanosine (8-OH-dG), and 5) cross-talk between telomerase, N-SMase, p53, and 8-OH-dG would be evident in left ventricular (LV), right ventricular (RV), atrial and aortic smooth muscle obtained from rats subjected to short-term MgD. The data indicated that short-term MgD (10% normal dietary intake) resulted in downregulation of telomerase in LV, RV, atrial and aortic muscle cells; even very low levels of water-bourne Mg2+ (e.g., 15-40 mg/lday) either prevented or ameliorated the downregulation of telomerase. Our experiments also showed that MgD resulted in a 7-10 fold increased formation of 8-OH-dG in the cardiac and aortic muscle cells. The experiments also confirmed that short-term dietary deficiency of Mg resulted in greatly increased upregulation of N-SMAse and p53 in the cardiac and aortic muscle tissues. These new experiments point to a sizeable cross-talk among telomerase, N-SMAse, and p53 in rat cardiac and peripheral vascular muscle exposed to a short-term MgD. These studies would be compatible with the idea that even short-term MgD could cause alterations of the genome in diverse cell types leading to mutations of cardiac, vascular, and endothelial cells seen in aging and atherogenesis. Since we have shown, previously, that activation of N-SMAse in MgD leads to synthesis and release of ceramide in cardiovascular tissues and cells, we believe this pathway, most likely, helps to

  2. Predicting Tissue-Specific Enhancers in the Human Genome

    SciTech Connect

    Pennacchio, Len A.; Loots, Gabriela G.; Nobrega, Marcelo A.; Ovcharenko, Ivan

    2006-07-01

    Determining how transcriptional regulatory signals areencoded in vertebrate genomes is essential for understanding the originsof multi-cellular complexity; yet the genetic code of vertebrate generegulation remains poorly understood. In an attempt to elucidate thiscode, we synergistically combined genome-wide gene expression profiling,vertebrate genome comparisons, and transcription factor binding siteanalysis to define sequence signatures characteristic of candidatetissue-specific enhancers in the human genome. We applied this strategyto microarray-based gene expression profiles from 79 human tissues andidentified 7,187 candidate enhancers that defined their flanking geneexpression, the majority of which were located outside of knownpromoters. We cross-validated this method for its ability to de novopredict tissue-specific gene expression and confirmed its reliability in57 of the 79 available human tissues, with an average precision inenhancer recognition ranging from 32 percent to 63 percent, and asensitivity of 47 percent. We used the sequence signatures identified bythis approach to assign tissue-specific predictions to ~;328,000human-mouse conserved noncoding elements in the human genome. Byoverlapping these genome-wide predictions with a large in vivo dataset ofenhancers validated in transgenic mice, we confirmed our results with a28 percent sensitivity and 50 percent precision. These results indicatethe power of combining complementary genomic datasets as an initialcomputational foray into the global view of tissue-specific generegulation in vertebrates.

  3. Effect of Sustained Human Centrifugation on Autonomic Cardiovascular and Vestibular Function

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Wood, Scott J.; Brown, Troy E.; Benavides, Edgar W.; Harm, Deborah L.; Rupert, A. H.

    2002-01-01

    Repeated exposure to +Gz enhances human baroreflex responsiveness and improves tolerance to cardiovascular stress. However, both sustained exposure to +Gx and changes in otolith function resulting from the gravitational changes of space flight and parabolic flight may adversely affect autonomic cardiovascular function and orthostatic tolerance. HYPOTHESES: Baroreflex function and orthostatic tolerance are acutely improved by a single sustained (30 min) exposure to +3Gz but not +3Gx. Moreover, after 30 min of +3Gx, any changes that occur in autonomic cardiovascular function will relate commensurately to changes in otolith function. METHODS: Twenty-two healthy human subjects were first exposed to 5 min of +3 Gz centrifugation and then subsequently up to a total of30 min of either +3Gz (n = 15) or +3Gx (n = 7) centrifugation. Tests of autonomic cardiovascular function both before and after both types of centrifugation included: (a) power spectral determinations of beat-to-beat R-R intervals and arterial pressures; (b) carotid-cardiac baroreflex tests; ( c) Valsalva tests; and (d) 30-min head-up tilt (HUT) tests. Otolith function was assessed during centrifugation by the linear vestibulo-ocular reflex and both before and after centrifugation by measurements of ocular counter-rolling and dynamic posturography. RESULTS: All four +3Gz subjects who were intolerant to HUT before centrifugation became tolerant to HUT after centrifugation. The operational point of the carotid-cardiac baroreflex and the Valsalva-related baroreflex were also enhanced in the +3Gz group but not in the +3Gx group. No significant vestibular-autonomic relationships were detected, other than a significant vestibular-cerebrovascular interaction reported previously. CONCLUSIONS: A single, sustained exposure to +3 Gz centrifugation acutely improves baroreflex function and orthostatic tolerance whereas a similar exposure to +3 Gx centrifugation appears to have less effect.

  4. High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers.

    PubMed

    Chew, G L; Huang, D; Lin, S J; Huo, C; Blick, T; Henderson, M A; Hill, P; Cawson, J; Morrison, W A; Campbell, I G; Hopper, J L; Southey, M C; Haviv, I; Thompson, E W

    2012-08-01

    Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal (p = 0.0002) and lower adipose (p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area (p = 0.4) or count (p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer.

  5. Ethics, public policy, and human fetal tissue transplantation research.

    PubMed

    Childress, James F

    1991-06-01

    This article focuses on the deliberations of the National Institutes of Health Human Fetal Tissue Transplantation Research Panel in 1988. It explores various arguments for and against the use of fetal tissue for transplantation research, following elective abortion, and for and against the use of federal funds for such research. After examining the relevance of various positions on the moral status of the fetus and the morality of abortion, the article critically examines charges that such research, especially with federal funds, would involve complicity in the moral evil of abortion, would legitimate abortion practices, and would provide incentives for abortions. Finally, it considers whether the donation model is appropriate for the transfer of human fetal tissue and whether the woman who chooses to have an abortion is the apppropriate donor of the tissue.

  6. Characterization of muscarinic receptor subtypes in human tissues

    SciTech Connect

    Giraldo, E.; Martos, F.; Gomez, A.; Garcia, A.; Vigano, M.A.; Ladinsky, H.; Sanchez de La Cuesta, F.

    1988-01-01

    The affinities of selective, pirenzepine and AF-DX 116, and classical, N-methylscopolamine and atropine, muscarinic cholinergic receptor antagonists were investigated in displacement binding experiments with (/sup 3/H)Pirenzepine and (/sup 3/H)N-methylscopolamine in membranes from human autoptic tissues (forebrain, cerebellum, atria, ventricle and submaxillary salivary glands). Affinity estimates of N-methylscopolamine and atropine indicated a non-selective profile. Pirenzepine showed differentiation between the M/sub 1/ neuronal receptor of the forebrain and the receptors in other tissues while AF-DX 116 clearly discriminated between muscarinic receptors of heart and glands. The results in human tissues confirm the previously described selectivity profiles of pirenzepine and AF-DX 116 in rat tissues. These findings thus reveal the presence also in man of three distinct muscarinic receptor subtypes: the neuronal M/sub 1/, the cardiac M/sub 2/ and the glandular M/sub 3/.

  7. Large-scale discovery of enhancers from human heart tissue.

    PubMed

    May, Dalit; Blow, Matthew J; Kaplan, Tommy; McCulley, David J; Jensen, Brian C; Akiyama, Jennifer A; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Afzal, Veena; Simpson, Paul C; Rubin, Edward M; Black, Brian L; Bristow, James; Pennacchio, Len A; Visel, Axel

    2011-12-04

    Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified ∼6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their in vivo enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart.

  8. Effects of perinatal, late foetal, and early embryonic insults on the cardiovascular phenotype in experimental animal models and humans.

    PubMed

    Meister, Theo Arthur; Rexhaj, Emrush; Rimoldi, Stefano Flavio; Scherrer, Urs; Sartori, Claudio

    2016-11-01

    Cardiovascular diseases are the main cause of mortality and morbidity in Western countries, but the underlying mechanisms are still poorly understood. Genetic polymorphisms, once thought to represent a major determinant of cardiovascular risk, individually and collectively, only explain a tiny fraction of phenotypic variation and disease risk in humans. It is now clear that non-genetic factors, i.e., factors that modify gene activity without changing the DNA sequence and that are sensitive to the environment can cause important alterations of the cardiovascular phenotype in experimental animal models and humans. Here, we will review recent studies demonstrating that distinct pathological events during the perinatal (transient perinatal hypoxemia), late foetal (preeclampsia), and early embryonic (assisted reproductive technologies) periods induce profound alterations of the cardiovascular phenotype in humans and experimental animals. Moreover, we will provide evidence that epigenetic modifications are contributing importantly to this problem and are conferring the potential for its transmission to subsequent generations.

  9. Engineered human broncho-epithelial tissue-like assemblies

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J. (Inventor)

    2012-01-01

    Three-dimensional human broncho-epithelial tissue-like assemblies (TLAs) are produced in a rotating wall vessel (RWV) with microcarriers by coculturing mesenchymal bronchial-tracheal cells (BTC) and bronchial epithelium cells (BEC). These TLAs display structural characteristics and express markers of in vivo respiratory epithelia. TLAs are useful for screening compounds active in lung tissues such as antiviral compounds, cystic fibrosis treatments, allergens, and cytotoxic compounds.

  10. An improved cryopreservation procedure for human fetal pancreas tissues.

    PubMed

    Shiogama, T; Mullen, Y; Klandorf, H; Terada, M; Clark, W R

    1987-11-01

    Improved viability and function of insulin-producing beta (B) cells of frozen-stored human fetal pancreatic tissue was obtained by a two-step method utilizing high concentrations of dimethyl sulfoxide (DMSO). Human fetal pancreata (14-23-week gestation) obtained from pathologic abortions were teased and cultured overnight. Prior to freezing the tissues were immersed in 0.9% saline containing 0.5 M DMSO for 30 min (room temperature) and then placed in 2.1 M DMSO on ice for 5 min. The tissues were frozen by the method previously developed in our laboratory and stored at -196 degrees C. The frozen-stored tissues were subsequently thawed at 24 degrees C and cultured overnight before viability testing. Viability and function of the B cells were assessed by several specific assay methods; glucose plus theophylline-induced insulin release during static incubation and perifusion, 3H-leucine incorporation into insulin, and insulin content of the tissue grown in athymic mice for 7 days. The response to glucose plus theophylline stimulation, measured on the frozen-thawed tissue one day after thawing, was 80% of the level measured in control tissue maintained in organ culture. Frozen-thawed tissues maintained in organ culture for 1 week responded comparably in the in vitro assay systems. The insulin content of frozen-thawed pancreatic tissue removed from athymic mice 1 week after transplantation was approximately 60% of the amount measured in the control grafts. These results demonstrate the utility of our procedure in the maintenance of the viability and function of frozen-stored human B cells both in culture and after transplantation.

  11. Laser ablation of human atherosclerotic plaque without adjacent tissue injury

    NASA Technical Reports Server (NTRS)

    Grundfest, W. S.; Litvack, F.; Forrester, J. S.; Goldenberg, T.; Swan, H. J. C.

    1985-01-01

    Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

  12. Advancing biomaterials of human origin for tissue engineering

    PubMed Central

    Chen, Fa-Ming; Liu, Xiaohua

    2015-01-01

    Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for

  13. Glomus tissue in the vicinity of the human carotid sinus.

    PubMed Central

    Garfia, A

    1980-01-01

    Three of 60 cadavers have shown, in the adventitia or in the adipose tissue from the human carotid sinus region, small islands of tissue richly and typically vascularized and with nerve endings contacting cells like the tissue of the principal carotid body. In two of the cases such 'miniglomera' were single but in the third there were several all on the same side. A modified en bloc silver nitrate reduction stain was used to demonstrate the microvascular arrangements and the nerve endings by light microscopy of serial tangential sections of the carotid bifurcation. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:7364653

  14. Immunohistochemical characterization of FHIT expression in normal human tissues

    PubMed Central

    Kujan, Omar; Abuderman, Abdulwahab; Al-Shawaf, Ahmad Zahi

    2016-01-01

    Background Fragile histidine triad (FHIT) is a tumor suppressor gene that is commonly inactivated in human tumors. Interestingly, the normal pattern of FHIT expression is largely unknown. Aim This study is aimed to characterize the expression of FHIT protein in normal human tissues. Materials and methods A total of 119 normal human tissue specimens were analyzed for the FHIT expression using immunohistochemistry technique. The inclusion criteria included: normal/inflammatory tissue with no evidence of cellular atypia. Results All studied specimens were stained positively with FHIT and showed either nuclear or cytoplasmic expression. Interestingly, the pattern of FHIT staining was similar among different specimens from each organ. FHIT is located predominantly in the nucleus, although cytoplasmic staining is also present in some cell types. Oral squamous epithelium, breast ductal epithelium, squamous and tubal metaplastic epithelium of the uterine cervix, esophageal squamous epithelium, salivary glands, and bronchial epithelia all strongly expressed the nuclear protein. In connective tissue, FHIT has shown strong cytoplasmic expression in histocytes including macrophages and dendritic cells, fibroblasts, and myofibroblasts. Conclusion Documentation of the pattern of FHIT expression in normal tissues will contribute to our understanding of the normal function of this protein and to interpretation of potentially altered FHIT expression in human tumors. PMID:28250975

  15. Biomechanical behavior of pericardial human tissue: a constitutive formulation.

    PubMed

    Pavan, Piero G; Pachera, Paola; Tiengo, Cesare; Natali, Arturo N

    2014-09-01

    This work aims to present a constitutive model suitable to interpret the biomechanical response of human pericardial tissues. The model is consistent with the need of describing large strains, anisotropy, almost incompressibility, and time-dependent effects. Attention is given to human pericardial tissue because of the increased interest in its application as a substitute in reconstructive surgery. Specific, even limited, experimental investigation has been performed on human samples taken from surgical grafts in order to verify the capability of the constitutive model in supplying a correct description of tissue mechanical response. Experimental data include uni-axial tensile tests and stress relaxation tests up to 300 s, developed along different directions of the tissue. The grafts tested show different mechanical characteristics for what concern the level of anisotropy of the tissue. The constitutive model proposed shows to adapt to the different configurations of the human pericardium grafts, as emerged by experimental data considered, and it is capable to describe the variability of the mechanical characteristics.

  16. Near Infrared Spectral Determination of Human Tissue pH.

    DTIC Science & Technology

    1995-10-01

    Continuous Tissue pH Monitory in the Human Fetus During Labor", Obstet . Gynecol ., 55:523, 1980. 23. [Lemer 82] Lemer, H., et al., "Measurement of Glucose...Umbilical Blood pH", Am. J. Obstet . Gynecol ., 128: 901-903, 1977. 38. [Weyer 85] Weyer, L G., "Near Infrared Spectroscopy of Organic Substances," Applied...Patterns and Tissue pH in the Human Fetus", Am. J. Obstet . Gynecol ., 134:685-690, 1979. 24 Appendix I An Estimation Extension of the FKNN Algorithm In

  17. Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

    PubMed

    Hubbard, Dallin; Enda, Michael; Bond, Tanner; Moghaddam, Seyyed Pouya Hadipour; Conarton, Josh; Scaife, Courtney; Volckmann, Eric; Ghandehari, Hamidreza

    2015-11-02

    Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium. It was observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM concentration do not have a statistically higher permeability compared to free FITC controls in isolated human jejunum and colonic tissues. Mannitol permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2 dendrimers. Significant histological changes in human colonic and jejunal tissues were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose limiting toxicity may occur at similar concentrations in vivo. The permeability through human isolated intestinal tissue in this study was compared to previous rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral drug delivery may be feasible, but it may be limited to highly potent drugs.

  18. Infectious and Non-infectious Etiologies of Cardiovascular Disease in Human Immunodeficiency Virus Infection

    PubMed Central

    Chastain, Daniel B.; King, Travis S.; Stover, Kayla R.

    2016-01-01

    Background: Increasing rates of HIV have been observed in women, African Americans, and Hispanics, particularly those residing in rural areas of the United States. Although cardiovascular (CV) complications in patients infected with human immunodeficiency virus (HIV) have significantly decreased following the introduction of antiretroviral therapy on a global scale, in many rural areas, residents face geographic, social, and cultural barriers that result in decreased access to care. Despite the advancements to combat the disease, many patients in these medically underserved areas are not linked to care, and fewer than half achieve viral suppression. Methods: Databases were systematically searched for peer-reviewed publications reporting infectious and non-infectious etiologies of cardiovascular disease in HIV-infected patients. Relevant articles cited in the retrieved publications were also reviewed for inclusion. Results: A variety of outcomes studies and literature reviews were included in the analysis. Relevant literature discussed the manifestations, diagnosis, treatment, and outcomes of infectious and non-infectious etiologies of cardiovascular disease in HIV-infected patients. Conclusion: In these medically underserved areas, it is vital that clinicians are knowledgeable in the manifestations, diagnosis, and treatment of CV complications in patients with untreated HIV. This review summarizes the epidemiology and causes of CV complications associated with untreated HIV and provide recommendations for management of these complications. PMID:27583063

  19. Discordance of DNA Methylation Variance Between two Accessible Human Tissues

    PubMed Central

    Jiang, Ruiwei; Jones, Meaghan J.; Chen, Edith; Neumann, Sarah M.; Fraser, Hunter B.; Miller, Gregory E.; Kobor, Michael S.

    2015-01-01

    Population epigenetic studies have been seeking to identify differences in DNA methylation between specific exposures, demographic factors, or diseases in accessible tissues, but relatively little is known about how inter-individual variability differs between these tissues. This study presents an analysis of DNA methylation differences between matched peripheral blood mononuclear cells (PMBCs) and buccal epithelial cells (BECs), the two most accessible tissues for population studies, in 998 promoter-located CpG sites. Specifically we compared probe-wise DNA methylation variance, and how this variance related to demographic factors across the two tissues. PBMCs had overall higher DNA methylation than BECs, and the two tissues tended to differ most at genomic regions of low CpG density. Furthermore, although both tissues showed appreciable probe-wise variability, the specific regions and magnitude of variability differed strongly between tissues. Lastly, through exploratory association analysis, we found indication of differential association of BEC and PBMC with demographic variables. The work presented here offers insight into variability of DNA methylation between individuals and across tissues and helps guide decisions on the suitability of buccal epithelial or peripheral mononuclear cells for the biological questions explored by epigenetic studies in human populations. PMID:25660083

  20. Cortisol in human tissues at different stages of life.

    PubMed

    Costa, A; Benedetto, C; Fabris, C; Giraudi, G F; Testori, O; Bertino, E; Marozio, L; Varvello, G; Arisio, R; Ariano, M; Emanuel, A

    1996-01-01

    Aim of the work was to measure the cortisol level in human tissues at different stages of life, by means of radioimmunoassay and by chromatography. Viable samples of 13 different tissues were obtained during surgical intervention from 30 to 70 years old patients of either sex. Mean tissue cortisol concentration was 78 +/- 35 ng/g, ranging from 20 +/- 10 ng/g in the thyroid to 124 +/- 76 ng/g in the kidney. Similar values were measured in the corresponding tissues from not decayed corpses, so that paired values could be mediated. However the pancreas, and corrupted autopsy tissues, gave nil or exceedingly high cortisol concentration values; in some cases, opposite extreme values were measured in different organs of the same body. Cortisol concentration was also measured in 11 sound different tissues of spontaneously aborted or stillbirth fetuses, between 16 and 36 weeks of gestation. Mean value was 63 +/- 27 ng/g, ranging from 30 +/- 25 ng/g in the liver to 104 +/- 52 ng/g in the lungs. Also in fetuses nil or exceedingly high cortisol values occurred in altered tissues. One hundred and fourteen samples of limbs and carcasses of 7 to 12 gestational weeks embryos, obtained from voluntary abortions, were also examined: 20% gave nil result, in the remaining mean cortisol concentration was 32 ng/g. In 33 samples of embryos' mixed viscera, RIA and chromatography gave unreliable exceedingly high values. The nil and the exceedingly high values measured in the altered autoptic tissue specimens were inconsistent with the cortisol blood level measured in the patients, as were those measured in embryonic tissues with the acknowledged blood and adrenals cortisol levels at that stage of life. Thus cortisol may be measured by RIA and by chromatography in sound tissues, while the values obtained in the pancreas, in corrupted tissues, and in embryonal viscera do not represent the hormonal milieu, but are likely artifacts due to impeachment of the diagnostic system.

  1. Cardiovascular Deconditioning

    NASA Technical Reports Server (NTRS)

    Charles, John B.; Fritsch-Yelle, Janice M.; Whitson, Peggy A.; Wood, Margie L.; Brown, Troy E.; Fortner, G. William

    1999-01-01

    Spaceflight causes adaptive changes in cardiovascular function that may deleteriously affect crew health and safety. Over the last three decades, symptoms of cardiovascular changes have ranged from postflight orthostatic tachycardia and decreased exercise capacity to serious cardiac rhythm disturbances during extravehicular activities (EVA). The most documented symptom of cardiovascular dysfunction, postflight orthostatic intolerance, has affected a significant percentage of U.S. Space Shuttle astronauts. Problems of cardiovascular dysfunction associated with spaceflight are a concern to NASA. This has been particularly true during Shuttle flights where the primary concern is the crew's physical health, including the pilot's ability to land the Orbiter, and the crew's ability to quickly egress and move to safety should a dangerous condition arise. The study of astronauts during Shuttle activities is inherently more difficult than most human research. Consequently, sample sizes have been small and results have lacked consistency. Before the Extended Duration Orbiter Medical Project (EDOMP), there was a lack of normative data on changes in cardiovascular parameters during and after spaceflight. The EDOMP for the first time allowed studies on a large enough number of subjects to overcome some of these problems. There were three primary goals of the Cardiovascular EDOMP studies. The first was to establish, through descriptive studies, a normative data base of cardiovascular changes attributable to spaceflight. The second goal was to determine mechanisms of cardiovascular changes resulting from spaceflight (particularly orthostatic hypotension and cardiac rhythm disturbances). The third was to evaluate possible countermeasures. The Cardiovascular EDOMP studies involved parallel descriptive, mechanistic, and countermeasure evaluations.

  2. MicroRNAs in Human Diseases: From Cancer to Cardiovascular Disease

    PubMed Central

    2011-01-01

    The great discovery of microRNAs (miRNAs) has revolutionized current cell biology and medical science. miRNAs are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region of specific messenger RNAs for degradation or translational repression. New members of the miRNA family are being discovered on a daily basis and emerging evidence has demonstrated that miRNAs play a major role in a wide range of developmental process including cell proliferation, cell cycle, cell differentiation, metabolism, apoptosis, developmental timing, neuronal cell fate, neuronal gene expression, brain morphogenesis, muscle differentiation and stem cell division. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, psychiatric and neurological diseases, cardiovascular disease, and autoimmune disease. Interestingly, in addition, miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from cancer to myocardial infarction. miRNAs can repress the gene translation of hundreds of their targets and are therefore well-positioned to target a multitude of cellular mechanisms. As a consequence of extensive participation in normal functions, it is quite logical to ask the question if abnormalities in miRNAs should have importance in human diseases. Great discoveries and rapid progress in the past few years on miRNAs provide the hope that miRNAs will in the near future have a great potential in the diagnosis and treatment of many diseases. Currently, an explosive literature has focussed on the role of miRNA in human cancer and cardiovascular disease. In this review, I briefly summarize the explosive current studies about involvement of miRNA in various human cancers and cardiovascular disease. PMID:21860607

  3. Inhaled cellulosic and plastic fibers found in human lung tissue.

    PubMed

    Pauly, J L; Stegmeier, S J; Allaart, H A; Cheney, R T; Zhang, P J; Mayer, A G; Streck, R J

    1998-05-01

    We report the results of studies undertaken to determine whether inhaled plant (i.e., cellulosic; e.g., cotton) and plastic (e.g., polyester) fibers are present in human lungs and, if so, whether inhaled fibers are also present in human lung cancers. Specimens of lung cancer of different histological types and adjacent nonneoplastic lung tissue were obtained from patients undergoing a lung resection for removal of a tumor. With the protection of a laminar flow hood and safeguards to prevent contamination by extraneous fibers, fresh, nonfixed, and nonstained samples of lung tissue were compressed between two glass microscope slides. Specimens in these dual slide chambers were examined with a microscope configured to permit viewing with white light, fluorescent light, polarizing light, and phase-contrast illumination. Near-term fetal bovine lungs and nonlung human tumors were used as controls. In contrast to the observations of these control tissues, morphologically heterogeneous fibers were seen repetitively in freshly excised human lung tissue using polarized light. Inhaled fibers were present in 83% of nonneoplastic lung specimens (n = 67/81) and in 97% of malignant lung specimens (n = 32/33). Thus, of the 114 human lung specimens examined, fibers were observed in 99 (87%). Examination of histopathology slides of lung tissue with polarized light confirmed the presence of inhaled cellulosic and plastic fibers. Of 160 surgical histopathology lung tissue slides, 17 were selected for critical examination; of these, fibers were identified in 13 slides. The inhalation of mineral (e.g., asbestos) fibers has been described by many investigators; we believe, however, that this is the first report of inhaled nonmineral (e.g., plant and plastic) fibers. These bioresistant and biopersistent cellulosic and plastic fibers are candidate agents contributing to the risk of lung cancer.

  4. Formation of tissue factor activity following incubation of recombinant human tissue factor apoprotein with plasma lipoproteins

    SciTech Connect

    Sakai, T.; Kisiel, W. )

    1990-11-01

    Incubation of recombinant human tissue factor apoprotein (Apo-TF) with human plasma decreased the recalcified clotting time of this plasma in a time-and dose-dependent manner suggesting relipidation of the Apo-TF by plasma lipoproteins. Incubation of Apo-TF with purified preparations of human very low density, low density and high density lipoproteins resulted in tissue factor activity in a clotting assay. The order of effectiveness was VLDL greater than LDL much greater than HDL. Tissue factor activity generated by incubation of a fixed amount of Apo-TF with plasma lipoproteins was lipoprotein concentration-dependent and saturable. The association of Apo-TF with lipoprotein particles was supported by gel filtration studies in which {sup 125}I-Apo-TF coeluted with the plasma lipoprotein in the void volume of a Superose 6 column in the presence and absence of calcium ions. In addition, void-volume Apo-TF-lipoprotein fractions exhibited tissue factor activity. These results suggest that the factor VIII-bypassing activity of bovine Apo-TF observed in a canine hemophilic model may be due, in part, to its association with plasma lipoproteins and expression of functional tissue factor activity.

  5. The Circulatory and Metabolic Responses to Hypoxia in Humans – With Special Reference to Adipose Tissue Physiology and Obesity

    PubMed Central

    Heinonen, Ilkka H. A.; Boushel, Robert; Kalliokoski, Kari K.

    2016-01-01

    Adipose tissue metabolism and circulation play an important role in human health. It is well-known that adipose tissue mass is increased in response to excess caloric intake leading to obesity and further to local hypoxia and inflammatory signaling. Acute exercise increases blood supply to adipose tissue and mobilization of fat stores for energy. However, acute exercise during systemic hypoxia reduces subcutaneous blood flow in healthy young subjects, but the response in overweight or obese subjects remains to be investigated. Emerging evidence also indicates that exercise training during hypoxic exposure may provide additive benefits with respect to many traditional cardiovascular risk factors as compared to exercise performed in normoxia, but unfavorable effects of hypoxia have also been documented. These topics will be covered in this brief review dealing with hypoxia and adipose tissue physiology. PMID:27621722

  6. Magnetic studies of iron-entities in human tissues

    NASA Astrophysics Data System (ADS)

    Ślawska-Waniewska, A.; Mosiniewicz-Szablewska, E.; Nedelko, N.; Gałązka-Friedman, J.; Friedman, A.

    2004-05-01

    Iron-entities in the human liver, brain and blood tissues have been investigated by means of EPR spectroscopy and magnetization measurements over the temperature range 4-300 K. The identification of the most typical forms of iron in the human body (i.e. isolated Fe-ions bonded in hemoglobin and transferrin as well as exchange coupled Fe-ions in nanosized ferritin cores) is presented.

  7. Characterization of human arterial tissue affected by atherosclerosis using multimodal nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Baria, Enrico; Cicchi, Riccardo; Rotellini, Matteo; Nesi, Gabriella; Massi, Daniela; Pavone, Francesco S.

    2016-03-01

    Atherosclerosis is a widespread cardiovascular disease caused by the deposition of lipids (such as cholesterol and triglycerides) on the inner arterial wall. The rupture of an atherosclerotic plaque, resulting in a thrombus, is one of the leading causes of death in the Western World. Preventive assessment of plaque vulnerability is therefore extremely important and can be performed by studying collagen organization and lipid composition in atherosclerotic arterial tissues. Routinely used diagnostic methods, such as histopathological examination, are limited to morphological analysis of the examined tissues, whereas an exhaustive characterization requires immune-histochemical examination and a morpho-functional approach. Instead, a label-free and non-invasive alternative is provided by nonlinear microscopy. In this study, we combined SHG and FLIM microscopy in order to characterize collagen organization and lipids in human carotid ex vivo tissues affected by atherosclerosis. SHG and TPF images, acquired from different regions within atherosclerotic plaques, were processed through image pattern analysis methods (FFT, GLCM). The resulting information on collagen and cholesterol distribution and anisotropy, combined with collagen and lipids fluorescence lifetime measured from FLIM images, allowed characterization of carotid samples and discrimination of different tissue regions. The presented method can be applied for automated classification of atherosclerotic lesions and plaque vulnerability. Moreover, it lays the foundation for a potential in vivo diagnostic tool to be used in clinical setting.

  8. Translational neuropharmacology: the use of human isolated gastrointestinal tissues

    PubMed Central

    Sanger, GJ; Broad, J; Kung, V; Knowles, CH

    2013-01-01

    Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal (GI) tract. Tissues are obtained after informed consent, in collaboration with surgeons (surgical techniques help minimize variables) and pathologists. Given the difficulties of directly recording from human myenteric neurones (embedded between muscle layers), enteric motor nerve functions are studied by measuring muscle contractions/relaxations evoked by electrical stimulation of intrinsic nerves; responses are regionally dependent, often involving cholinergic and nitrergic phenotypes. Enteric sensory functions can be studied by evoking the peristaltic reflex, involving enteric sensory and motor nerves, but this has rarely been achieved. As submucosal neurones are more accessible (after removing the mucosa), direct neuronal recordings are possible. Neurosecretory functions are studied by measuring changes in short-circuit current across the mucosa. For all experiments, basic questions must be addressed. Because tissues are from patients, what are the controls and the influence of disease? How long does it take before function fully recovers? What is the impact of age- and gender-related differences? What is the optimal sample size? Addressing these and other questions minimizes variability and raises the scientific credibility of human tissue research. Such studies also reduce animal use. Further, the many differences between animal and human GI functions also means that human tissue research must question the ethical validity of using strains of animals with unproved translational significance. Linked Article BJP published a themed issue on Translational Neuropharmacology in 2011. To view the articles in this themed issue visit http://dx.doi.org/10

  9. Microimaging FT-IR of oral cavity tumours. Part III: Cells, inoculated tissues and human tissues

    NASA Astrophysics Data System (ADS)

    Conti, C.; Ferraris, P.; Giorgini, E.; Pieramici, T.; Possati, L.; Rocchetti, R.; Rubini, C.; Sabbatini, S.; Tosi, G.; Mariggiò, M. A.; Lo Muzio, L.

    2007-05-01

    The biochemistry of healthy and tumour cell cultures, inoculated tissues and oral cavity tissues have been studied by FT-IR Microscopy with the aim to relate spectral patterns with microbiological and histopathological findings. 'Supervised' and 'unsupervised' procedures of data handling afforded a satisfactory degree of accordance between spectroscopic and the other two techniques. In particular, changes in frequency and intensity of proteins, connective and nucleic acids vibrational modes as well as the visualization of biochemical single wave number or band ratio images, allowed an evaluation of the pathological changes. The spectroscopic patterns of inoculated tissues resulted quite similar to human tissues; differences of both types of sections with cellular lines could be explained by the influence of the environment.

  10. Collagen in Human Tissues: Structure, Function, and Biomedical Implications from a Tissue Engineering Perspective

    NASA Astrophysics Data System (ADS)

    Balasubramanian, Preethi; Prabhakaran, Molamma P.; Sireesha, Merum; Ramakrishna, Seeram

    The extracellular matrix is a complex biological structure encoded with various proteins, among which the collagen family is the most significant and abundant of all, contributing 30-35% of the whole-body protein. "Collagen" is a generic term for proteins that forms a triple-helical structure with three polypeptide chains, and around 29 types of collagen have been identified up to now. Although most of the members of the collagen family form such supramolecular structures, extensive diversity exists between each type of collagen. The diversity is not only based on the molecular assembly and supramolecular structures of collagen types but is also observed within its tissue distribution, function, and pathology. Collagens possess complex hierarchical structures and are present in various forms such as collagen fibrils (1.5-3.5 nm wide), collagen fibers (50-70 nm wide), and collagen bundles (150-250 nm wide), with distinct properties characteristic of each tissue providing elasticity to skin, softness of the cartilage, stiffness of the bone and tendon, transparency of the cornea, opaqueness of the sclera, etc. There exists an exclusive relation between the structural features of collagen in human tissues (such as the collagen composition, collagen fibril length and diameter, collagen distribution, and collagen fiber orientation) and its tissue-specific mechanical properties. In bone, a transverse collagen fiber orientation prevails in regions of higher compressive stress whereas longitudinally oriented collagen fibers correlate to higher tensile stress. The immense versatility of collagen compels a thorough understanding of the collagen types and this review discusses the major types of collagen found in different human tissues, highlighting their tissue-specific uniqueness based on their structure and mechanical function. The changes in collagen during a specific tissue damage or injury are discussed further, focusing on the many tissue engineering applications for

  11. Tissue distribution of human acetylcholinesterase and butyrylcholinesterase messenger RNA

    SciTech Connect

    Jbilo, O.; Barteles, C.F.; Chatonnet, A.; Toutant, J.P.; Lockridge, O.

    1994-12-31

    Tissue distribution of human acetyicholinesterase and butyryicholinesterase messenger RNA. 1 Cholinesterase inhibitors occur naturally in the calabar bean (eserine), green potatoes (solanine), insect-resistant crab apples, the coca plant (cocaine) and snake venom (fasciculin). There are also synthetic cholinesterase inhibitors, for example man-made insecticides. These inhibitors inactivate acetyicholinesterase and butyrylcholinesterase as well as other targets. From a study of the tissue distribution of acetylcholinesterase and butyrylcholinesterase mRNA by Northern blot analysis, we have found the highest levels of butyrylcholinesterase mRNA in the liver and lungs, tissues known as the principal detoxication sites of the human body. These results indicate that butyrylcholinesterase may be a first line of defense against poisons that are eaten or inhaled.

  12. Arrhenius parameters for primary thermal injury in human tonsillar tissue

    NASA Astrophysics Data System (ADS)

    McMillan, Kathleen; Radabaugh, Rebecca; Coad, James E.

    2011-03-01

    Clinical implementation of a thermal therapy requires the ability to predict tissue injury following exposures to specific thermal histories. As part of an effort to develop a nonexcisional alternative to tonsillectomy, the degree of primary hyperthermic tissue injury in human tonsil was characterized. Fifteen fresh pediatric hypertrophic tonsillectomy specimens were sectioned and treated in a NIST-calibrated saline bath at temperatures of 40 to 70°C with hold times of one to seven minutes. The treated tissues were subsequently nitroblue tetrazolium (NBT) stained to assess for thermal respiratory enzyme inactivation as a marker of cellular injury/death. The NBT stains were quantitatively image analyzed and used to calculate Arrhenius parameters for primary thermal injury in human tonsils.

  13. Engineering musculoskeletal tissues with human embryonic germ cell derivatives.

    PubMed

    Varghese, Shyni; Hwang, Nathaniel S; Ferran, Angela; Hillel, Alexander; Theprungsirikul, Parnduangjai; Canver, Adam C; Zhang, Zijun; Gearhart, John; Elisseeff, Jennifer

    2010-04-01

    The cells derived from differentiating embryoid bodies of human embryonic germ (hEG) cells express a broad spectrum of gene markers and have been induced toward ecto- and endodermal lineages. We describe here in vitro and in vivo differentiation of hEG-derived cells (LVEC line) toward mesenchymal tissues. The LVEC cells express many surface marker proteins characteristic of mesenchymal stem cells and differentiated into cartilage, bone, and fat. Homogenous hyaline cartilage was generated from cells after 63 population doublings. In vivo results demonstrate cell survival, differentiation, and tissue formation. The high proliferative capacity of hEG-derived cells and their ability to differentiate and form three-dimensional mesenchymal tissues without teratoma formation underscores their significant potential for regenerative medicine. The adopted coculture system also provides new insights into how a microenvironment comprised of extracellular and cellular components may be harnessed to generate hierarchically complex tissues from pluripotent cells.

  14. Human cancers overexpress genes that are specific to a variety of normal human tissues

    PubMed Central

    Lotem, Joseph; Netanely, Dvir; Domany, Eytan; Sachs, Leo

    2005-01-01

    We have analyzed gene expression data from three different kinds of samples: normal human tissues, human cancer cell lines, and leukemic cells from lymphoid and myeloid leukemia pediatric patients. We have searched for genes that are overexpressed in human cancer and also show specific patterns of tissue-dependent expression in normal tissues. Using the expression data of the normal tissues, we identified 4,346 genes with a high variability of expression and clustered these genes according to their relative expression level. Of 91 stable clusters obtained, 24 clusters included genes preferentially expressed either only in hematopoietic tissues or in hematopoietic and one to two other tissues; 28 clusters included genes preferentially expressed in various nonhematopoietic tissues such as neuronal, testis, liver, kidney, muscle, lung, pancreas, and placenta. Analysis of the expression levels of these two groups of genes in the human cancer cell lines and leukemias identified genes that were highly expressed in cancer cells but not in their normal counterparts and, thus, were overexpressed in the cancers. The different cancer cell lines and leukemias varied in the number and identity of these overexpressed genes. The results indicate that many genes that are overexpressed in human cancer cells are specific to a variety of normal tissues, including normal tissues other than those from which the cancer originated. It is suggested that this general property of cancer cells plays a major role in determining the behavior of the cancers, including their metastatic potential. PMID:16339305

  15. Functional Tissue Analysis Reveals Successful Cryopreservation of Human Osteoarthritic Synovium

    PubMed Central

    de Vries, Marieke; Bennink, Miranda B.; van Lent, Peter L. E. M.; van der Kraan, Peter M.; Koenders, Marije I.; Thurlings, Rogier M.; van de Loo, Fons A. J.

    2016-01-01

    Osteoarthritis (OA) is a degenerative joint disease affecting cartilage and is the most common form of arthritis worldwide. One third of OA patients have severe synovitis and less than 10% have no evidence of synovitis. Moreover, synovitis is predictive for more severe disease progression. This offers a target for therapy but more research on the pathophysiological processes in the synovial tissue of these patients is needed. Functional studies performed with synovial tissue will be more approachable when this material, that becomes available by joint replacement surgery, can be stored for later use. We set out to determine the consequences of slow-freezing of human OA synovial tissue. Therefore, we validated a method that can be applied in every routine laboratory and performed a comparative study of five cryoprotective agent (CPA) solutions. To determine possible deleterious cryopreservation-thaw effects on viability, the synovial tissue architecture, metabolic activity, RNA quality, expression of cryopreservation associated stress genes, and expression of OA characteristic disease genes was studied. Furthermore, the biological activity of the cryopreserved tissue was determined by measuring cytokine secretion induced by the TLR ligands lipopolysaccharides and Pam3Cys. Compared to non frozen synovium, no difference in cell and tissue morphology could be identified in the conditions using the CS10, standard and CryoSFM CPA solution for cryopreservation. However, we observed significantly lower preservation of tissue morphology with the Biofreeze and CS2 media. The other viability assays showed trends in the same direction but were not sensitive enough to detect significant differences between conditions. In all assays tested a clearly lower viability was detected in the condition in which synovium was frozen without CPA solution. This detailed analysis showed that OA synovial tissue explants can be cryopreserved while maintaining the morphology, viability and

  16. Patient-specific system for prognosis of surgical treatment outcomes of human cardiovascular system

    NASA Astrophysics Data System (ADS)

    Golyadkina, Anastasiya A.; Kalinin, Aleksey A.; Kirillova, Irina V.; Kossovich, Elena L.; Kossovich, Leonid Y.; Menishova, Liyana R.; Polienko, Asel V.

    2015-03-01

    Object of study: Improvement of life quality of patients with high stroke risk ia the main goal for development of system for patient-specific modeling of cardiovascular system. This work is dedicated at increase of safety outcomes for surgical treatment of brain blood supply alterations. The objects of study are common carotid artery, internal and external carotid arteries and bulb. Methods: We estimated mechanical properties of carotid arteries tissues and patching materials utilized at angioplasty. We studied angioarchitecture features of arteries. We developed and clinically adapted computer biomechanical models, which are characterized by geometrical, physical and mechanical similarity with carotid artery in norm and with pathology (atherosclerosis, pathological tortuosity, and their combination). Results: Collaboration of practicing cardiovascular surgeons and specialists in the area of Mathematics and Mechanics allowed to successfully conduct finite-element modeling of surgical treatment taking into account various features of operation techniques and patching materials for a specific patient. Numerical experiment allowed to reveal factors leading to brain blood supply decrease and atherosclerosis development. Modeling of carotid artery reconstruction surgery for a specific patient on the basis of the constructed biomechanical model demonstrated the possibility of its application in clinical practice at approximation of numerical experiment to the real conditions.

  17. Enabling research with human embryonic and fetal tissue resources.

    PubMed

    Gerrelli, Dianne; Lisgo, Steven; Copp, Andrew J; Lindsay, Susan

    2015-09-15

    Congenital anomalies are a significant burden on human health. Understanding the developmental origins of such anomalies is key to developing potential therapies. The Human Developmental Biology Resource (HDBR), based in London and Newcastle, UK, was established to provide embryonic and fetal material for a variety of human studies ranging from single gene expression analysis to large-scale genomic/transcriptomic studies. Increasingly, HDBR material is enabling the derivation of stem cell lines and contributing towards developments in tissue engineering. Use of the HDBR and other fetal tissue resources discussed here will contribute to the long-term aims of understanding the causation and pathogenesis of congenital anomalies, and developing new methods for their treatment and prevention.

  18. Enabling research with human embryonic and fetal tissue resources

    PubMed Central

    Gerrelli, Dianne; Lisgo, Steven; Copp, Andrew J.; Lindsay, Susan

    2015-01-01

    Summary Congenital anomalies are a significant burden on human health. Understanding the developmental origins of such anomalies is key to developing potential therapies. The Human Developmental Biology Resource (HDBR), based in London and Newcastle UK, was established to provide embryonic and fetal material for a variety of human studies ranging from single gene expression analysis to large scale genomic/transcriptomic studies. Increasingly HDBR material is enabling the derivation of stem cell lines and contributing towards developments in tissue engineering. Use of the HDBR and other fetal tissue resources discussed here will contribute to the long term aims of understanding the causation and pathogenesis of congenital anomalies, and developing new methods for their treatment and prevention. PMID:26395135

  19. Microwave dielectric measurements and tissue characteristics of the human brain: potential in localizing intracranial tissues.

    PubMed

    Axer, Hubertus; Grässel, David; Steinhauer, Matthias; Stöhr, Peter; John, Andreas; Coenen, Volker A; Jansen, Rolf H; von Keyserlingk, Diedrich Graf

    2002-05-21

    This study describes the measurements of dielectric properties in the microwave range to differentiate various human central nervous structures. Using a vector network analyser transmission and reflection coefficients were measured from 500 MHz to 18 GHz in four human formalin fixed human brains. The positions of the electrodes were marked, and the tissue was histologically stained to visualize the myelo- and the cytoarchitecture as well as the nerve fibre orientation at the electrodes. The profiles of the transmission coefficients showed a characteristic minimum peak. In order to describe this peak, a mathematical function was fitted. Parameters derived from digital image processing were used to characterize the myelo- and cytoarchitecure of the tissue at the electrodes. A multiple regression model, with the frequency at the transmission peak minimum as a dependent variable and two tissue characteristics at the two electrodes as independent variables, showed a multiple regression coefficient of 0.765. A neural network model was able to estimate the frequency at the transmission peak minimum from the tissue characteristics at the electrode. The measurements of dielectric properties are well suited to differentiate distinct intracerebral structures. The method could be used for online monitoring of the needle's position during a stereotactic intervention in neurosurgery.

  20. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct

    PubMed Central

    Valarmathi, Mani T.; Fuseler, John W.; Davis, Jeffrey M.; Price, Robert L.

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty. PMID:28194397

  1. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct.

    PubMed

    Valarmathi, Mani T; Fuseler, John W; Davis, Jeffrey M; Price, Robert L

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty.

  2. Preclinical humanized mouse model with ectopic ovarian tissues

    PubMed Central

    FU, SHILONG; WANG, JUE; SUN, WU; XU, YI; ZHOU, XIAOYU; CHENG, WENJUN

    2014-01-01

    The aim of the present study was to establish human ovarian stroma within the mouse subcutaneously, in order for the resulting stroma to serve as a useful preclinical tool to study the progression of human ovarian cancer in a humanized ovarian microenvironment. Normal human ovarian tissues were subcutaneously implanted into severe combined immunodeficient (SCID) mice and then the implants were identified by immunohistochemistry. The implants became vascularized and retained their original morphology for about 4 weeks following implantation. Immunohistochemical staining for cytokeratin-7 confirmed the ovarian origin of the epithelial cells. CD34 staining demonstrated human-derived vessels. Positive estrogen receptor and partially-positive progesterone receptor staining indicated the estrogen and progesterone dependence of the implants. Only vascular pericytes expressed α-smooth muscle actin, indicating the normal ovarian origin of the xenografts. Human ovarian tissue successfully survived in SCID mice and retained its original properties. This humanized mouse model may be used as preclinical tool to investigate ovarian cancer. PMID:25120592

  3. Human immunodeficiency virus type 1 nef quasispecies in pathological tissue.

    PubMed Central

    Blumberg, B M; Epstein, L G; Saito, Y; Chen, D; Sharer, L R; Anand, R

    1992-01-01

    The role of the nef gene in human immunodeficiency virus type 1 (HIV-1) infection is poorly understood. To provide a basis for studies on the role of nef in AIDS, we used targeted polymerase chain reaction amplification and DNA sequencing to determine the structure of nef genes in pathologic tissue from HIV-1-infected children and adults. We find that the nef reading frame is open in 92% of clones derived from both brain and lymphocytic tissue of children, suggesting that nef is expressed in these tissues. One HIV-1 clone, BRVA, obtained by coculture from the brain of an adult AIDS patient with progressive dementia, was previously shown to contain a duplicated region in nef. We show here that similar duplications are widespread in both adults and children with AIDS. However, coculture strongly selects against the broad spectrum of nef quasispecies found in tissue. These findings suggest functional selection for nef quasispecies in pathologic tissues during HIV-1 infection of the human host. Images PMID:1501274

  4. Modeling of human artery tissue with probabilistic approach.

    PubMed

    Xiong, Linfei; Chui, Chee-Kong; Fu, Yabo; Teo, Chee-Leong; Li, Yao

    2015-04-01

    Accurate modeling of biological soft tissue properties is vital for realistic medical simulation. Mechanical response of biological soft tissue always exhibits a strong variability due to the complex microstructure and different loading conditions. The inhomogeneity in human artery tissue is modeled with a computational probabilistic approach by assuming that the instantaneous stress at a specific strain varies according to normal distribution. Material parameters of the artery tissue which are modeled with a combined logarithmic and polynomial energy equation are represented by a statistical function with normal distribution. Mean and standard deviation of the material parameters are determined using genetic algorithm (GA) and inverse mean-value first-order second-moment (IMVFOSM) method, respectively. This nondeterministic approach was verified using computer simulation based on the Monte-Carlo (MC) method. Cumulative distribution function (CDF) of the MC simulation corresponds well with that of the experimental stress-strain data and the probabilistic approach is further validated using data from other studies. By taking into account the inhomogeneous mechanical properties of human biological tissue, the proposed method is suitable for realistic virtual simulation as well as an accurate computational approach for medical device validation.

  5. Injury Response of Resected Human Brain Tissue In Vitro.

    PubMed

    Verwer, Ronald W H; Sluiter, Arja A; Balesar, Rawien A; Baaijen, Johannes C; de Witt Hamer, Philip C; Speijer, Dave; Li, Yichen; Swaab, Dick F

    2015-07-01

    Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by resection (interruption of the circulation) and aggravated by the preparation of slices (severed neuronal and glial processes and blood vessels) reflect the reaction of human brain tissue to severe injury. We investigated this process using immunocytochemical markers, reverse transcriptase quantitative polymerase chain reaction and Western blot analysis. Essential features were rapid shrinkage of neurons, loss of neuronal marker expression and proliferation of reactive cells that expressed Nestin and Vimentin. Also, microglia generally responded strongly, whereas the response of glial fibrillary acidic protein-positive astrocytes appeared to be more variable. Importantly, some reactive cells also expressed both microglia and astrocytic markers, thus confounding their origin. Comparison with post-mortem human brain tissue obtained at rapid autopsies suggested that the reactive process is not a consequence of epilepsy.

  6. Identification of rheological properties of human body surface tissue.

    PubMed

    Benevicius, Vincas; Gaidys, Rimvydas; Ostasevicius, Vytautas; Marozas, Vaidotas

    2014-04-11

    According to World Health Organization obesity is one of the greatest public health challenges of the 21st century. It has tripled since the 1980s and the numbers of those affected continue to rise at an alarming rate, especially among children. There are number of devices that act as a prevention measure to boost person's motivation for physical activity and its levels. The placement of these devices is not restricted thus the measurement errors that appear because of the body rheology, clothes, etc. cannot be eliminated. The main objective of this work is to introduce a tool that can be applied directly to process measured accelerations so human body surface tissue induced errors can be reduced. Both the modeling and experimental techniques are proposed to identify body tissue rheological properties and prelate them to body mass index. Multi-level computational model composed from measurement device model and human body surface tissue rheological model is developed. Human body surface tissue induced inaccuracies can increase the magnitude of measured accelerations up to 34% when accelerations of the magnitude of up to 27 m/s(2) are measured. Although the timeframe of those disruptions are short - up to 0.2 s - they still result in increased overall measurement error.

  7. FT-Raman spectroscopy study of human breast tissue

    NASA Astrophysics Data System (ADS)

    Bitar Carter, Renata A.; Martin, Airton A.; Netto, Mario M.; Soares, Fernando A.

    2004-07-01

    Optical spectroscopy has been extensively studied as a potential in vivo diagnostic tool to provide information about the chemical and morphologic structure of tissue. Raman Spectroscpy is an inelastic scattering process that can provide a wealth of spectral features that can be related to the specific molecular structure of the sample. This article reports results of an in vitro study of the FT-Raman human breast tissue spectra. An Nd:YAG laser at 1064nm was used as the excitation source in the FT-Raman Spectrometer. The neoplastic human breast samples, both Fibroadenoma and ICD, were obtained during therapeutical routine medical procedures required by the primary disease, and the non-diseased human tissue was obtained in plastic surgery. No sample preparation was needed for the FT-Raman spectra collection. The FT-Raman spectra were recorded from normal, benign (Fibroadenomas) and malignant (IDC-Intraductal Carcinoma) samples, adding up 51 different areas. The main spectral differences of a typical FT-Raman spectra of a Normal (Non-diseased), Fibroadenoma, and Infiltrating Ductal Carcinoma (IDC) breast tissue at the interval of 600 to 1800cm-1, which may differentiate diagnostically the sample, were found in the bands of 1230 to 1295cm-1, 1440 to 1460 cm-1 and 1650 to 1680 cm-1, assigned to the vibrational bands of the carbohydrate-amide III, proteins and lipids, and carbohydrate-amide I, respectively.

  8. Spatial coherence in human tissue: implications for imaging and measurement

    PubMed Central

    Pinton, Gianmarco; Trahey, Gregg; Dahl, Jeremy

    2014-01-01

    The spatial coherence properties of the signal backscattered by human tissue and measured by an ultrasound transducer array are investigated. Fourier acoustics are used to describe the propagation of ultrasound through a model of tissue that includes reverberation and random scatterering in the imaging plane. The theoretical development describes how the near-field tissue layer, transducer aperture properties, and reflectivity function at the focus reduce the spatial coherence of the imaging wave measured at the transducer surface. Simulations are used to propagate the acoustic field through a histologically characterized sample of the human abdomen and to validate the theoretical predictions. In vivo measurements performed with a diagnostic ultrasound scanner demonstrate that simulations and theory closely match the measured spatial coherence characteristics in the human body across the transducer array’s entire spatial extent. The theoretical framework and simulations are then used to describe the physics of spatial coherence imaging, a type of ultrasound imaging that measures coherence properties instead of echo brightness. The same echo data from an F/2 transducer was used to generate B-mode and short lag spatial coherence images. For an anechoic lesion at the focus the contrast to noise ratio is 1.21 for conventional B-mode imaging and 1.95 for spatial coherence imaging. It is shown that the contrast in spatial coherence imaging depends on the properties of the near-field tissue layer and the backscattering function in the focal plane. PMID:25474774

  9. Human Research Program Human Health Countermeasures Element Cardiovascular Risks Standing Review Panel (SRP)

    NASA Technical Reports Server (NTRS)

    Joyner, Michael

    2009-01-01

    The Cardiovascular Risk Standing Review Panel (SRP) evaluated several cardiovascular risks associated with space flight along with the ongoing and emerging plans to study these issues and potentially propose and/or develop countermeasures. The areas of focus included: 1) The risk of cardiac rhythm problems during prolonged space flight, and 2) Issues related to the risk of orthostatic intolerance during re-exposure to gravity. An emerging area of concern is radiation associated vascular injury. The risk of cardiac rhythm disturbances has emerged based on case reports only. No systematic study of this risk has been published. However, concerns about this risk are heightened by the age range of astronauts, the structural changes in the heart that occur during space flight, and the potential shifts in fluids and electrolytes. The current plan is to use prolonged Holter monitor EKG records made as part of the "Integrated Cardiovascular SMO" in space to determine more about the frequency and magnitude of this problem and to link this data to complementary data from the nutrition group on electrolytes. The SRP was supportive of this approach. The SRP also felt that any data related to cardiovascular risk in space should be better coordinated with the medical screening data that all astronauts undergo at regular intervals. Additionally, while there are potential privacy issues related to this suggestion, many of the current barriers to better coordination of experimental and clinical data appear to reflect longstanding cultural traditions at NASA that need rethinking. The risk of orthostatic intolerance during re-exposure to gravity was seen by the SRP as an area supported by a wealth of published physiological evidence. The SRP also felt that moving forward with the planned approach to countermeasures was reasonable and that extensive additional hypothesis testing on the physiology of orthostatic intolerance was not needed at this time. There was support for developing

  10. Occurrence of human bocaviruses and parvovirus 4 in solid tissues.

    PubMed

    Norja, Päivi; Hedman, Lea; Kantola, Kalle; Kemppainen, Kaisa; Suvilehto, Jari; Pitkäranta, Anne; Aaltonen, Leena-Maija; Seppänen, Mikko; Hedman, Klaus; Söderlund-Venermo, Maria

    2012-08-01

    Human bocaviruses 1-4 (HBoV1-4) and parvovirus 4 (PARV4) are recently discovered human parvoviruses. HBoV1 is associated with respiratory infections of young children, while HBoV2-4 are enteric viruses. The clinical manifestations of PARV4 remain unknown. The objective of this study was to determine whether the DNAs of HBoV1-4 and PARV4 persist in human tissues long after primary infection. Biopsies of tonsillar tissue, skin, and synovia were examined for HBoV1-4 DNA and PARV4 DNA by PCR. Serum samples from the tissue donors were assayed for HBoV1 and PARV4 IgG and IgM antibodies. To obtain species-specific seroprevalences for HBoV1 and for HBoV2/3 combined, the sera were analyzed after virus-like particle (VLP) competition. While HBoV1 DNA was detected exclusively in the tonsillar tissues of 16/438 individuals (3.7%), all of them ≤8 years of age. HBoV2-4 and PARV4 DNAs were absent from all tissue types. HBoV1 IgG seroprevalence was 94.9%. No subject had HBoV1 or PARV4 IgM, nor did they have PARV4 IgG. The results indicate that HBoV1 DNA occurred in a small proportion of tonsils of young children after recent primary HBoV1 infection, but did not persist long in the other tissue types studied, unlike parvovirus B19 DNA. The results obtained by the PARV4 assays are in line with previous results on PARV4 epidemiology.

  11. Cross-spectral coherence between geomagnetic disturbance and human cardiovascular variables at non-societal frequencies.

    PubMed

    Watanabe, Y; Hillman, D C; Otsuka, K; Bingham, C; Breus, T K; Cornélissen, G; Halberg, F

    1994-01-01

    A 35-year-old cardiologist monitored himself with an automatic ABPM-630 (Colin Electronics) monitor, mostly at 15-minute intervals around-the-clock for three years with a few interruptions. In this subject with a family history of high blood pressure and stroke, a cross-spectral analysis revealed a statistically significant coherence at 27.7 days between systolic and diastolic blood pressure and heart rate vs. the geomagnetic disturbance index, Kp. A lesser peak in coherence was found for systolic blood pressure with Kp at a trial period of 4.16 days (P = 0.046). These results suggest that changes in geomagnetism may influence the human circulation, at least in the presence of familial cardiovascular disease risk, and they may do so at frequencies that have no precise human-made cyclic worldwide match.

  12. Structured illumination microscopy of autofluorescent aggregations in human tissue.

    PubMed

    Best, Gerrit; Amberger, Roman; Baddeley, David; Ach, Thomas; Dithmar, Stefan; Heintzmann, Rainer; Cremer, Christoph

    2011-06-01

    Sections from human eye tissue were analyzed with Structured Illumination Microscopy (SIM) using a specially designed microscope setup. In this microscope the structured illumination was generated with a Twyman-Green Interferometer. This SIM technique allowed us to acquire light-optical images of autofluorophore distributions in the tissue with previously unmatched optical resolution. In this work the unique setup of the microscope made possible the application of SIM with three different excitation wavelengths (488, 568 and 647 nm), thus enabling us to gather spectral information about the autofluorescence signal.

  13. Effects of laser interaction with living human tissues

    NASA Astrophysics Data System (ADS)

    Molchanova, O. E.; Protasov, E. A.; Protasov, D. E.; Smirnova, A. V.

    2016-09-01

    With the help of a highly sensitive laser device with the wavelength λ = 0.808 pm, which is optimal for deep penetration of the radiation into biological tissues, the effects associated with the appearance of uncontrolled human infrasonic vibrations of different frequencies were investigated. It was established that the observed fluctuations are associated with the vascular system which is characterized by its own respiratory movements, occurring synchronously with the movements of the respiratory muscles, the operation of the heart muscle, and the effect of compression ischemia. The effect of “enlightenment” of a tissue is observed with stopping of blood flow in vessels by applying a tourniquet on the wrist.

  14. Pan-FGFR inhibition leads to blockade of FGF23 signaling, soft tissue mineralization, and cardiovascular dysfunction.

    PubMed

    Yanochko, Gina M; Vitsky, Allison; Heyen, Jonathan R; Hirakawa, Brad; Lam, Justine L; May, Jeff; Nichols, Tim; Sace, Frederick; Trajkovic, Dusko; Blasi, Eileen

    2013-10-01

    The fibroblast growth factor receptors (FGFR) play a major role in angiogenesis and are desirable targets for the development of therapeutics. Groups of Wistar Han rats were dosed orally once daily for 4 days with a small molecule pan-FGFR inhibitor (5mg/kg) or once daily for 6 days with a small molecule MEK inhibitor (3mg/kg). Serum phosphorous and FGF23 levels increased in all rats during the course of the study. Histologically, rats dosed with either drug exhibited multifocal, multiorgan soft tissue mineralization. Expression levels of the sodium phosphate transporter Npt2a and the vitamin D-metabolizing enzymes Cyp24a1 and Cyp27b1 were modulated in kidneys of animals dosed with the pan-FGFR inhibitor. Both inhibitors decreased ERK phosphorylation in the kidneys and inhibited FGF23-induced ERK phosphorylation in vitro in a dose-dependent manner. A separate cardiovascular outcome study was performed to monitor hemodynamics and cardiac structure and function of telemetered rats dosed with either the pan-FGFR inhibitor or MEK inhibitor for 3 days. Both compounds increased blood pressure (~+ 17 mmHg), decreased heart rate (~-75 bpm), and modulated echocardiography parameters. Our data suggest that inhibition of FGFR signaling following administration of either pan-FGFR inhibitor or MEK inhibitor interferes with the FGF23 pathway, predisposing animals to hyperphosphatemia and a tumoral calcinosis-like syndrome in rodents.

  15. Natural killer cell distribution and trafficking in human tissues

    PubMed Central

    Carrega, Paolo; Ferlazzo, Guido

    2012-01-01

    Few data are available regarding the recirculation of natural killer (NK) cells among human organs. Earlier studies have been often impaired by the use of markers then proved to be either not sufficiently specific for NK cells (e.g., CD57, CD56) or expressed only by subsets of NK cells (e.g., CD16). At the present, available data confirmed that human NK cells populate blood, lymphoid organs, lung, liver, uterus (during pregnancy), and gut. Several studies showed that NK cell homing appears to be subset-specific, as secondary lymphoid organs and probably several solid tissues are preferentially inhabited by CD56brightCD16neg/dull non-cytotoxic NK cells. Similar studies performed in the mouse model showed that lymph node and bone marrow are preferentially populated by CD11bdull NK cells while blood, spleen, and lung by CD27dull NK cells. Therefore, an important topic to be addressed in the human system is the contribution of factors that regulate NK cell tissue homing and egress, such as chemotactic receptors or homeostatic mechanisms. Here, we review the current knowledge on NK cell distribution in peripheral tissues and, based on recent acquisitions, we propose our view regarding the recirculation of NK cells in the human body. PMID:23230434

  16. Engineering of human hepatic tissue with functional vascular networks.

    PubMed

    Takebe, Takanori; Koike, Naoto; Sekine, Keisuke; Fujiwara, Ryoji; Amiya, Takeru; Zheng, Yun-Wen; Taniguchi, Hideki

    2014-01-01

    Although absolute organ shortage highlights the needs of alternative organ sources for regenerative medicine, the generation of a three-dimensional (3D) and complex vital organ, such as well-vascularized liver, remains a challenge. To this end, tissue engineering holds great promise; however, this approach is significantly limited by the failure of early vascularization in vivo after implantation. Here, we established a stable 3D in vitro pre-vascularization platform to generate human hepatic tissue after implantation in vivo. Human fetal liver cells (hFLCs) were mixed with human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (hMSCs) and were implanted into a collagen/fibronectin matrix composite that was used as a 3-D carrier. After a couple of days, the fluorescent HUVECs developed premature vascular networks in vitro, which were stabilized by hMSCs. The establishment of functional vessels inside the pre-vascularized constructs was proven using dextran infusion studies after implantation under a transparency cranial window. Furthermore, dynamic morphological changes during embryonic liver cell maturation were intravitaly quantified with high-resolution confocal microscope analysis. The engineered human hepatic tissue demonstrated multiple liver-specific features, both structural and functional. Our new techniques discussed here can be implemented in future clinical uses and industrial uses, such as drug testing.

  17. Maresin conjugates in tissue regeneration biosynthesis enzymes in human macrophages

    PubMed Central

    Dalli, Jesmond; Vlasakov, Iliyan; Riley, Ian R.; Rodriguez, Ana R.; Spur, Bernd W.; Chiang, Nan; Serhan, Charles N.

    2016-01-01

    Macrophages are central in coordinating immune responses, tissue repair, and regeneration, with different subtypes being associated with inflammation-initiating and proresolving actions. We recently identified a family of macrophage-derived proresolving and tissue regenerative molecules coined maresin conjugates in tissue regeneration (MCTR). Herein, using lipid mediator profiling we identified MCTR in human serum, lymph nodes, and plasma and investigated MCTR biosynthetic pathways in human macrophages. With human recombinant enzymes, primary cells, and enantiomerically pure compounds we found that the synthetic maresin epoxide intermediate 13S,14S-eMaR (13S,14S-epoxy- 4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic acid) was converted to MCTR1 (13R-glutathionyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid) by LTC4S and GSTM4. Incubation of human macrophages with LTC4S inhibitors blocked LTC4 and increased resolvins and lipoxins. The conversion of MCTR1 to MCTR2 (13R-cysteinylglycinyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid) was catalyzed by γ-glutamyl transferase (GGT) in human macrophages. Biosynthesis of MCTR3 was mediated by dipeptidases that cleaved the cysteinyl-glycinyl bond of MCTR2 to give 13R-cysteinyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid. Of note, both GSTM4 and GGT enzymes displayed higher affinity to 13S,14S-eMaR and MCTR1 compared with their classic substrates in the cysteinyl leukotriene metabolome. Together these results establish the MCTR biosynthetic pathway and provide mechanisms in tissue repair and regeneration. PMID:27791009

  18. Soft tissues store and return mechanical energy in human running.

    PubMed

    Riddick, R C; Kuo, A D

    2016-02-08

    During human running, softer parts of the body may deform under load and dissipate mechanical energy. Although tissues such as the heel pad have been characterized individually, the aggregate work performed by all soft tissues during running is unknown. We therefore estimated the work performed by soft tissues (N=8 healthy adults) at running speeds ranging 2-5 m s(-1), computed as the difference between joint work performed on rigid segments, and whole-body estimates of work performed on the (non-rigid) body center of mass (COM) and peripheral to the COM. Soft tissues performed aggregate negative work, with magnitude increasing linearly with speed. The amount was about -19 J per stance phase at a nominal 3 m s(-1), accounting for more than 25% of stance phase negative work performed by the entire body. Fluctuations in soft tissue mechanical power over time resembled a damped oscillation starting at ground contact, with peak negative power comparable to that for the knee joint (about -500 W). Even the positive work from soft tissue rebound was significant, about 13 J per stance phase (about 17% of the positive work of the entire body). Assuming that the net dissipative work is offset by an equal amount of active, positive muscle work performed at 25% efficiency, soft tissue dissipation could account for about 29% of the net metabolic expenditure for running at 5 m s(-1). During running, soft tissue deformations dissipate mechanical energy that must be offset by active muscle work at non-negligible metabolic cost.

  19. An Introduction to The Royan Human Ovarian Tissue Bank

    PubMed Central

    Abtahi, Naeimeh Sadat; Ebrahimi, Bita; Fathi, Rouhollah; Khodaverdi, Sepideh; Mehdizadeh Kashi, Abolfazl; Valojerdi, Mojtaba Rezazadeh

    2016-01-01

    From December 2000 until 2010, the researchers at Royan Institute conducted a wide range of investigations on ovarian tissue cryopreservation with the intent to provide fertility pres- ervation to cancer patients that were considered to be candidates for these services. In 2010, Royan Institute established the Royan Human Ovarian Tissue Bank as a subgroup of the Embryology Department. Since its inception, approximately 180 patients between the ages of 747 years have undergone consultations. Ovarian samples were cryopreserved from 47 patients (age: 7-35 years) diagnosed with cervical adenocarcinoma (n=9); breast carcinoma (n=7), Ewing’s sarcoma (n=7), opposite side ovarian tumor (n=7), endometrial adenocarci- noma (n=4), malignant colon tumors (n=3), as well as Hodgkin’s lymphoma, major thalas- semia and acute lymphoblastic leukemia (n=1-2 patients for each disease). Additionally, two patients requested ovarian tissue transplantation after completion of their treatments. PMID:27441061

  20. A continuous fiber distribution material model for human cervical tissue.

    PubMed

    Myers, Kristin M; Hendon, Christine P; Gan, Yu; Yao, Wang; Yoshida, Kyoko; Fernandez, Michael; Vink, Joy; Wapner, Ronald J

    2015-06-25

    The uterine cervix during pregnancy is the vital mechanical barrier which resists compressive and tensile loads generated from a growing fetus. Premature cervical remodeling and softening is hypothesized to result in the shortening of the cervix, which is known to increase a woman׳s risk of preterm birth. To understand the role of cervical material properties in preventing preterm birth, we derive a cervical material model based on previous mechanical, biochemical and histological experiments conducted on nonpregnant and pregnant human hysterectomy cervical tissue samples. In this study we present a three-dimensional fiber composite model that captures the equilibrium material behavior of the tissue in tension and compression. Cervical tissue is modeled as a fibrous composite material, where a single family of preferentially aligned and continuously distributed collagen fibers are embedded in a compressible neo-Hookean ground substance. The total stress in the collagen solid network is calculated by integrating the fiber stresses. The shape of the fiber distribution is described by an ellipsoid where semi-principal axis lengths are fit to optical coherence tomography measurements. The composite material model is fit to averaged mechanical testing data from uni-axial compression and tension experiments, and averaged material parameters are reported for nonpregnant and term pregnant human cervical tissue. The model is then evaluated by investigating the stress and strain state of a uniform thick-walled cylinder under a compressive stress with collagen fibers preferentially aligned in the circumferential direction. This material modeling framework for the equilibrium behavior of human cervical tissue serves as a basis to determine the role of preferentially-aligned cervical collagen fibers in preventing cervical deformation during pregnancy.

  1. Adipose tissue macrophages impair preadipocyte differentiation in humans

    PubMed Central

    Liu, Li Fen; Craig, Colleen M.; Tolentino, Lorna L.; Choi, Okmi; Morton, John; Rivas, Homero; Cushman, Samuel W.; Engleman, Edgar G.; McLaughlin, Tracey

    2017-01-01

    Aim The physiologic mechanisms underlying the relationship between obesity and insulin resistance are not fully understood. Impaired adipocyte differentiation and localized inflammation characterize adipose tissue from obese, insulin-resistant humans. The directionality of this relationship is not known, however. The aim of the current study was to investigate whether adipose tissue inflammation is causally-related to impaired adipocyte differentiation. Methods Abdominal subcutaneous(SAT) and visceral(VAT) adipose tissue was obtained from 20 human participants undergoing bariatric surgery. Preadipocytes were isolated, and cultured in the presence or absence of CD14+ macrophages obtained from the same adipose tissue sample. Adipocyte differentiation was quantified after 14 days via immunofluorescence, Oil-Red O, and adipogenic gene expression. Cytokine secretion by mature adipocytes cultured with or without CD14+macrophages was quantified. Results Adipocyte differentiation was significantly lower in VAT than SAT by all measures (p<0.001). With macrophage removal, SAT preadipocyte differentiation increased significantly as measured by immunofluorescence and gene expression, whereas VAT preadipocyte differentiation was unchanged. Adipocyte-secreted proinflammatory cytokines were higher and adiponectin lower in media from VAT vs SAT: macrophage removal reduced inflammatory cytokine and increased adiponectin secretion from both SAT and VAT adipocytes. Differentiation of preadipocytes from SAT but not VAT correlated inversely with systemic insulin resistance. Conclusions The current results reveal that proinflammatory immune cells in human SAT are causally-related to impaired preadipocyte differentiation, which in turn is associated with systemic insulin resistance. In VAT, preadipocyte differentiation is poor even in the absence of tissue macrophages, pointing to inherent differences in fat storage potential between the two depots. PMID:28151993

  2. A double chamber rotating bioreactor for enhanced tubular tissue generation from human mesenchymal stem cells: a promising tool for vascular tissue regeneration.

    PubMed

    Stefani, I; Asnaghi, M A; Cooper-White, J J; Mantero, S

    2016-10-24

    Cardiovascular diseases represent a major global health burden, with high rates of mortality and morbidity. Autologous grafts are commonly used to replace damaged or failing blood vessels; however, such approaches are hampered by the scarcity of suitable graft tissue, donor site morbidity and poor long-term stability. Tissue engineering has been investigated as a means by which exogenous vessel grafts can be produced, with varying levels of success to date, a result of mismatched mechanical properties of these vessel substitutes and inadequate ex vivo vessel tissue genesis. In this work, we describe the development of a novel multifunctional dual-phase (air/aqueous) bioreactor, designed to both rotate and perfuse small-diameter tubular scaffolds and encourage enhanced tissue genesis throughout such scaffolds. Within this novel dynamic culture system, an elastomeric nanofibrous, microporous composite tubular scaffold, composed of poly(caprolactone) and acrylated poly(lactide-co-trimethylene-carbonate) and with mechanical properties approaching those of native vessels, was seeded with human mesenchymal stem cells (hMSCs) and cultured for up to 14 days in inductive (smooth muscle) media. This scaffold/bioreactor combination provided a dynamic culture environment that enhanced (compared with static controls) scaffold colonization, cell growth, extracellular matrix deposition and in situ differentiation of the hMSCs into mature smooth muscle cells, representing a concrete step towards our goal of creating a mature ex vivo vascular tissue for implantation. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Space Weather and a State of Cardiovascular System of Human Being with a Weakened Adaptation System

    NASA Astrophysics Data System (ADS)

    Samsonov, S. N.

    As has been shown in [Samsonov et al., 2013] even at the considerable disturbances of space weather parameters a healthy human being did not undergo painful symptoms although measurements of objective physiological indices showed their changes. At the same time the state of health of people with the weakened adaptation system under the same conditions can considerably be deteriorated up to fatal outcome. The analysis of results of the project "Heliomed" and the number of calls for the emergency medical care (EMC) around Yakutsk as to cardiovascular diseases (CVD) has shown:- the total number of calls for EMC concerning myocardial infarction (MI) per year near the geomagnetic disturbance maximum (1992) exceeds the number of calls per year near the geomagnetic activity minimum (1998) by a factor of 1,5 and concerning to strokes - by a factor of 1,8.- maxima of MI are observed during spring and autumn periods coinciding with maxima of geophysical disturbance;- the coincidence of 30-32 daily periods in a power spectrum of MI with the same periods in power spectra of space weather parameters (speeds and density of the solar wind, interplanetary magnetic field, geophysical disturbance);- the existence of 3 maxima of the number of calls for EMC: a) at the moment of disturbance on the Sun; during a geophysical disturbance (in 2-4 days after a disturbance on the Sun); in 2-4 days after a geophysical disturbance;- the availability of coincidence of insignificant disturbances of space weather parameters with changes of the functional state of cardiovascular system of a human being with the weakened adaptation system and the occurrence of MI and strokes at considerable values of such disturbances is explained by a quasi-logarithmic dependence of the response of human being organisms to the environment disturbance intensity.

  4. Ultra-trace analysis of platinum in human tissue samples.

    PubMed

    Rudolph, Elisabeth; Hann, Stephan; Stingeder, Gerhard; Reiter, Christian

    2005-08-01

    Background levels of platinum were determined in human autopsy tissues taken from five individuals. The investigated specimens were lung, liver and kidney. Sample preparation involved microwave digestion followed by an open vessel treatment. Inductively-coupled plasma sector field mass spectrometry (ICP-SFMS) was applied in combination with an ultrasonic nebulization/membrane desolvation system for sample introduction. Isotope dilution analysis was employed for accurate quantification of platinum. Excellent procedural detection limits (3 s validation) of 20, 20 and 34 pg g(-1) dry weight were obtained for lung, liver and kidney tissue, respectively. Due to the lack of appropriate biological reference material, road dust (BCR-723) was used for method validation. Platinum levels ranging between 0.03 and 1.42 ng g(-1) were determined in the investigated samples. The platinum concentrations observed in human lung tissue may reflect the increasing atmospheric background levels of platinum originating from car catalysts. The presence of platinum in kidney and liver tissue samples clearly indicates the bioavailability of the element.

  5. Two types of brown adipose tissue in humans

    PubMed Central

    Lidell, Martin E; Betz, Matthias J; Enerbäck, Sven

    2014-01-01

    During the last years the existence of metabolically active brown adipose tissue in adult humans has been widely accepted by the research community. Its unique ability to dissipate chemical energy stored in triglycerides as heat makes it an attractive target for new drugs against obesity and its related diseases. Hence the tissue is now subject to intense research, the hypothesis being that an expansion and/or activation of the tissue is associated with a healthy metabolic phenotype. Animal studies provide evidence for the existence of at least two types of brown adipocytes. Apart from the classical brown adipocyte that is found primarily in the interscapular region where it constitutes a thermogenic organ, a second type of brown adipocyte, the so-called beige adipocyte, can appear within white adipose tissue depots. The fact that the two cell types develop from different precursors suggests that they might be recruited and stimulated by different cues and therefore represent two distinct targets for therapeutic intervention. The aim of this commentary is to discuss recent work addressing the question whether also humans possess two types of brown adipocytes and to highlight some issues when looking for molecular markers for such cells. PMID:24575372

  6. Best Practice BioBanking of Human Heart Tissue.

    PubMed

    Lal, Sean; Li, Amy; Allen, David; Allen, Paul D; Bannon, Paul; Cartmill, Tim; Cooke, Roger; Farnsworth, Alan; Keogh, Anne; Dos Remedios, Cristobal

    2015-12-01

    This review provides a guide to researchers who wish to establish a biobank. It also gives practical advice to investigators seeking access to samples of healthy or diseased human hearts. We begin with a brief history of the Sydney Heart Bank (SHB) from when it began in 1989, including the pivotal role played by the late Victor Chang. We discuss our standard operating procedures for tissue collection which include cryopreservation and the quality assurance needed to maintain the long-term molecular and cellular integrity of the samples. The SHB now contains about 16,000 heart samples derived from over 450 patients who underwent isotopic heart transplant procedures and from over 100 healthy organ donors. These enable us to provide samples from a wide range of categories of heart failure. So far, we have delivered heart samples to more than 50 laboratories over two decades, and we answer their most frequently asked questions. Other SHB services include the development of tissue microarrays (TMA). These enable end users to perform preliminary examinations of the expression and localisation of target molecules in diseased or aging donor hearts, all in a single section of the TMA. Finally, the processes involved in managing tissue requests from external users and logistics considerations for the shipment of human tissue are discussed in detail.

  7. Human omental and subcutaneous adipose tissue exhibit specific lipidomic signatures.

    PubMed

    Jové, Mariona; Moreno-Navarrete, José María; Pamplona, Reinald; Ricart, Wifredo; Portero-Otín, Manuel; Fernández-Real, José Manuel

    2014-03-01

    Despite their differential effects on human metabolic pathophysiology, the differences in omental and subcutaneous lipidomes are largely unknown. To explore this field, liquid chromatography coupled with mass spectrometry was used for lipidome analyses of adipose tissue samples (visceral and subcutaneous) selected from a group of obese subjects (n=38). Transcriptomics and in vitro studies in adipocytes were used to confirm the pathways affected by location. The analyses revealed the existence of obesity-related specific lipidome signatures in each of these locations, attributed to selective enrichment of specific triglycerides, glycerophospholipids, and sphingolipids, because these were not observed in adipose tissues from nonobese individuals. The changes were compatible with subcutaneous enrichment in pathways involved in adipogenesis, triacylglyceride synthesis, and lipid droplet formation, as well as increased α-oxidation. Marked differences between omental and subcutaneous depots in obese individuals were seen in the association of lipid species with metabolic traits (body mass index and insulin sensitivity). Targeted studies also revealed increased cholesterol (Δ56%) and cholesterol epoxide (Δ34%) concentrations in omental adipose tissue. In view of the effects of cholesterol epoxide, which induced enhanced expression of adipocyte differentiation and α-oxidation genes in human omental adipocytes, a novel role for cholesterol epoxide as a signaling molecule for differentiation is proposed. In summary, in obesity, adipose tissue exhibits a location-specific differential lipid profile that may contribute to explaining part of its distinct pathogenic role.

  8. Expression of the Endocannabinoid Receptors in Human Fascial Tissue

    PubMed Central

    Fede, C.; Albertin, G.; Petrelli, L.; Sfriso, M.M.; Biz, C.; Caro, R. De; Stecco, C.

    2016-01-01

    Cannabinoid receptors have been localized in the central and peripheral nervous system as well as on cells of the immune system, but recent studies on animal tissue gave evidence for the presence of cannabinoid receptors in different types of tissues. Their presence was supposed also in myofascial tissue, suggesting that the endocannabinoid system may help resolve myofascial trigger points and relieve symptoms of fibromyalgia. However, until now the expression of CB1 (cannabinoid receptor 1) and CB2 (cannabinoid receptor 2) in fasciae has not yet been established. Small samples of fascia were collected from volunteers patients during orthopedic surgery. For each sample were done a cell isolation, immunohistochemical investigation (CB1 and CB2 antibodies) and real time RT-PCR to detect the expression of CB1 and CB2. Both cannabinoid receptors are expressed in human fascia and in human fascial fibroblasts culture cells, although to a lesser extent than the control gene. We can assume that the expression of mRNA and protein of CB1 and CB2 receptors in fascial tissue are concentrated into the fibroblasts. This is the first demonstration that the fibroblasts of the muscular fasciae express CB1 and CB2. The presence of these receptors could help to provide a description of cannabinoid receptors distribution and to better explain the role of fasciae as pain generator and the efficacy of some fascial treatments. Indeed the endocannabinoid receptors of fascial fibroblasts can contribute to modulate the fascial fibrosis and inflammation. PMID:27349320

  9. Best Practice BioBanking of Human Heart Tissue

    PubMed Central

    Lal, Sean; Li, Amy; Allen, David; Allen, Paul D; Bannon, Paul; Cartmill, Tim; Cooke, Roger; Farnsworth, Alan; Keogh, Anne; dos Remedios, Cristobal

    2015-01-01

    This review provides a guide to researchers who wish to establish a biobank. It also gives practical advice to investigators seeking access to samples of healthy or diseased human hearts. We begin with a brief history of the Sydney Heart Bank (SHB) from when it began in 1989, including the pivotal role played by the late Victor Chang. We discuss our standard operating procedures for tissue collection which include cryopreservation and the quality assurance needed to maintain the long-term molecular and cellular integrity of the samples. The SHB now contains about 16,000 heart samples derived from over 450 patients who underwent isotopic heart transplant procedures and from over 100 healthy organ donors. These enable us to provide samples from a wide range of categories of heart failure. So far, we have delivered heart samples to more than 50 laboratories over two decades, and we answer their most frequently asked questions. Other SHB services include the development of tissue microarrays (TMA). These enable end users to perform preliminary examinations of the expression and localisation of target molecules in diseased or aging donor hearts, all in a single section of the TMA. Finally, the processes involved in managing tissue requests from external users and logistics considerations for the shipment of human tissue are discussed in detail. PMID:26998172

  10. Numerical simulation of the blood flow in the human cardiovascular system.

    PubMed

    Zácek, M; Krause, E

    1996-01-01

    This paper describes a numerical model of the human cardiovascular system. The model is composed of 15 elements connected in series representing the main parts of the system. Each element is composed of a rigid connecting tube and an elastic reservoir. The blood flow is described by a one-dimensional time-dependent Bernoulli equation. The action of the ventricles is simulated with a Hill's three-element model, adapted for the left and right heart. The closing of the four heart valves is simulated with the aid of time-dependent drag coefficients. Closing is achieved by letting the drag coefficient approach infinity. The resulting system of 32 non-linear ordinary differential equations is solved numerically with the Runge-Kutta method. The results of the simulation (pressure-time and volume-time dependence for the atria and ventricles and pressure forms in the aorta at a heart rate of 70 beats per minute) agree with the physiological data given in the literature. The model's input aortic impedance is 31.5 dyn s cm-5 which agrees with literature data given for aortic input impedance in man 26-80 dyn s cm-5). Long-term stability of the system was achieved. The cardiovascular system presented here can also be simulated at higher and varying heart rates--up to 200 beats per minute. The results of calculations for some pathological changes (e.g. valvular abnormalities) are discussed.

  11. Nutritional Genomics and the Mediterranean Diet’s Effects on Human Cardiovascular Health

    PubMed Central

    Fitó, Montserrat; Konstantinidou, Valentini

    2016-01-01

    The synergies and cumulative effects among different foods and nutrients are what produce the benefits of a healthy dietary pattern. Diets and dietary patterns are a major environmental factor that we are exposed to several times a day. People can learn how to control this behavior in order to promote healthy living and aging, and to prevent diet-related diseases. To date, the traditional Mediterranean diet has been the only well-studied pattern. Stroke incidence, a number of classical risk factors including lipid profile and glycaemia, emergent risk factors such as the length of telomeres, and emotional eating behavior can be affected by genetic predisposition. Adherence to the Mediterranean diet could exert beneficial effects on these risk factors. Our individual genetic make-up should be taken into account to better prevent these traits and their subsequent consequences in cardiovascular disease development. In the present work, we review the results of nutritional genomics explaining the role of the Mediterranean diet in human cardiovascular disease. A multidisciplinary approach is necessary to extract knowledge from large-scale data. PMID:27089360

  12. A Large-Scale, Energetic Model of Cardiovascular Homeostasis Predicts Dynamics of Arterial Pressure in Humans

    PubMed Central

    Roytvarf, Alexander; Shusterman, Vladimir

    2008-01-01

    The energetic balance of forces in the cardiovascular system is vital to the stability of blood flow to all physiological systems in mammals. Yet, a large-scale, theoretical model, summarizing the energetic balance of major forces in a single, mathematically closed system has not been described. Although a number of computer simulations have been successfully performed with the use of analog models, the analysis of energetic balance of forces in such models is obscured by a big number of interacting elements. Hence, the goal of our study was to develop a theoretical model that represents large-scale, energetic balance in the cardiovascular system, including the energies of arterial pressure wave, blood flow, and the smooth muscle tone of arterial walls. Because the emphasis of our study was on tracking beat-to-beat changes in the balance of forces, we used a simplified representation of the blood pressure wave as a trapezoidal pressure-pulse with a strong-discontinuity leading front. This allowed significant reduction in the number of required parameters. Our approach has been validated using theoretical analysis, and its accuracy has been confirmed experimentally. The model predicted the dynamics of arterial pressure in human subjects undergoing physiological tests and provided insights into the relationships between arterial pressure and pressure wave velocity. PMID:18269976

  13. Terahertz spectroscopic investigation of human gastric normal and tumor tissues

    NASA Astrophysics Data System (ADS)

    Hou, Dibo; Li, Xian; Cai, Jinhui; Ma, Yehao; Kang, Xusheng; Huang, Pingjie; Zhang, Guangxin

    2014-09-01

    Human dehydrated normal and cancerous gastric tissues were measured using transmission time-domain terahertz spectroscopy. Based on the obtained terahertz absorption spectra, the contrasts between the two kinds of tissue were investigated and techniques for automatic identification of cancerous tissue were studied. Distinctive differences were demonstrated in both the shape and amplitude of the absorption spectra between normal and tumor tissue. Additionally, some spectral features in the range of 0.2~0.5 THz and 1~1.5 THz were revealed for all cancerous gastric tissues. To systematically achieve the identification of gastric cancer, principal component analysis combined with t-test was used to extract valuable information indicating the best distinction between the two types. Two clustering approaches, K-means and support vector machine (SVM), were then performed to classify the processed terahertz data into normal and cancerous groups. SVM presented a satisfactory result with less false classification cases. The results of this study implicate the potential of the terahertz technique to detect gastric cancer. The applied data analysis methodology provides a suggestion for automatic discrimination of terahertz spectra in other applications.

  14. FTIR protein secondary structure analysis of human ascending aortic tissues.

    PubMed

    Bonnier, Franck; Rubin, Sylvain; Debelle, Laurent; Ventéo, Lydie; Pluot, Michel; Baehrel, Bernard; Manfait, Michel; Sockalingum, Ganesh D

    2008-08-01

    The advent of moderate dilatations in ascending aortas is often accompanied by structural modifications of the main components of the aortic tissue, elastin and collagen. In this study, we have undertaken an approach based on FTIR microscopy coupled to a curve-fitting procedure to analyze secondary structure modifications in these proteins in human normal and pathological aortic tissues. We found that the outcome of the aortic pathology is strongly influenced by these proteins, which are abundant in the media of the aortic wall, and that the advent of an aortic dilatation is generally accompanied by a decrease of parallel beta-sheet structures. Elastin, essentially composed of beta-sheet structures, seems to be directly related to these changes and therefore indicative of the elastic alteration of the aortic wall. Conventional microscopy and confocal fluorescence microscopy were used to compare FTIR microscopy results with the organization of the elastic fibers present in the tissues. This in-vitro study on 6 patients (three normal and three pathologic), suggests that such a spectroscopic marker, specific to aneurismal tissue characterization, could be important information for surgeons who face the dilemma of moderate aortic tissue dilatation of the ascending aortas.

  15. Composition of MRI phantom equivalent to human tissues

    SciTech Connect

    Kato, Hirokazu; Kuroda, Masahiro; Yoshimura, Koichi; Yoshida, Atsushi; Hanamoto, Katsumi; Kawasaki, Shoji; Shibuya, Koichi; Kanazawa, Susumu

    2005-10-15

    We previously developed two new MRI phantoms (called the CAG phantom and the CAGN phantom), with T1 and T2 relaxation times equivalent to those of any human tissue at 1.5 T. The conductivity of the CAGN phantom is equivalent to that of most types of human tissue in the frequency range of 1 to 130 MHz. In this paper, the relaxation times of human tissues are summarized, and the composition of the corresponding phantoms are provided in table form. The ingredients of these phantoms are carrageenan as the gelling agent, GdCl{sub 3} as a T1 modifier, agarose as a T2 modifier, NaCl (CAGN phantom only) as a conductivity modifier, NaN{sub 3} as an antiseptic, and distilled water. The phantoms have T1 values of 202-1904 ms and T2 values of 38-423 ms when the concentrations of GdCl{sub 3} and agarose are varied from 0-140 {mu}mol/kg, and 0%-1.6%, respectively, and the CAGN phantom has a conductivity of 0.27-1.26 S/m when the NaCl concentration is varied from 0%-0.7%. These phantoms have sufficient strength to replicate a torso without the use of reinforcing agents, and can be cut by a knife into any shape. We anticipate the CAGN phantom to be highly useful and practical for MRI and hyperthermia-related research.

  16. Expression cartography of human tissues using self organizing maps

    PubMed Central

    2011-01-01

    Background Parallel high-throughput microarray and sequencing experiments produce vast quantities of multidimensional data which must be arranged and analyzed in a concerted way. One approach to addressing this challenge is the machine learning technique known as self organizing maps (SOMs). SOMs enable a parallel sample- and gene-centered view of genomic data combined with strong visualization and second-level analysis capabilities. The paper aims at bridging the gap between the potency of SOM-machine learning to reduce dimension of high-dimensional data on one hand and practical applications with special emphasis on gene expression analysis on the other hand. Results The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues). SOM mapping reduces the dimension of expression data from ten of thousands of genes to a few thousand metagenes, each representing a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of genes related to specific molecular processes in the respective tissue. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering are better represented and provide better signal-to-noise ratios if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues broadly into three clusters containing nervous, immune system and the remaining tissues. Conclusions The SOM technique

  17. Elastic, permeability and swelling properties of human intervertebral disc tissues: A benchmark for tissue engineering.

    PubMed

    Cortes, Daniel H; Jacobs, Nathan T; DeLucca, John F; Elliott, Dawn M

    2014-06-27

    The aim of functional tissue engineering is to repair and replace tissues that have a biomechanical function, i.e., connective orthopaedic tissues. To do this, it is necessary to have accurate benchmarks for the elastic, permeability, and swelling (i.e., biphasic-swelling) properties of native tissues. However, in the case of the intervertebral disc, the biphasic-swelling properties of individual tissues reported in the literature exhibit great variation and even span several orders of magnitude. This variation is probably caused by differences in the testing protocols and the constitutive models used to analyze the data. Therefore, the objective of this study was to measure the human lumbar disc annulus fibrosus (AF), nucleus pulposus (NP), and cartilaginous endplates (CEP) biphasic-swelling properties using a consistent experimental protocol and analyses. The testing protocol was composed of a swelling period followed by multiple confined compression ramps. To analyze the confined compression data, the tissues were modeled using a biphasic-swelling model, which augments the standard biphasic model through the addition of a deformation-dependent osmotic pressure term. This model allows considering the swelling deformations and the contribution of osmotic pressure in the analysis of the experimental data. The swelling stretch was not different between the disc regions (AF: 1.28±0.16; NP: 1.73±0.74; CEP: 1.29±0.26), with a total average of 1.42. The aggregate modulus (Ha) of the extra-fibrillar matrix was higher in the CEP (390kPa) compared to the NP (100kPa) or AF (30kPa). The permeability was very different across tissue regions, with the AF permeability (64 E(-16)m(4)/Ns) higher than the NP and CEP (~5.5 E(-16)m(4)/Ns). Additionally, a normalized time-constant (3000s) for the stress relaxation was similar for all the disc tissues. The properties measured in this study are important as benchmarks for tissue engineering and for modeling the disc's mechanical

  18. Human pyridoxal phosphatase. Molecular cloning, functional expression, and tissue distribution.

    PubMed

    Jang, Young Min; Kim, Dae Won; Kang, Tae-Cheon; Won, Moo Ho; Baek, Nam-In; Moon, Byung Jo; Choi, Soo Young; Kwon, Oh-Shin

    2003-12-12

    Pyridoxal phosphatase catalyzes the dephosphorylation of pyridoxal 5'-phosphate (PLP) and pyridoxine 5'-phosphate. A human brain cDNA clone was identified to the PLP phosphatase on the basis of peptide sequences obtained previously. The cDNA predicts a 296-amino acid protein with a calculated Mr of 31698. The open reading frame is encoded by two exons located on human chromosome 22q12.3, and the exon-intron junction contains the GT/AG consensus splice site. In addition, a full-length mouse PLP phosphatase cDNA of 1978 bp was also isolated. Mouse enzyme encodes a protein of 292 amino acids with Mr of 31512, and it is localized on chromosome 15.E1. Human and mouse PLP phosphatase share 93% identity in protein sequence. A BLAST search revealed the existence of putative proteins in organism ranging from bacteria to mammals. Catalytically active human PLP phosphatase was expressed in Escherichia coli, and characteristics of the recombinant enzyme were similar to those of erythrocyte enzyme. The recombinant enzyme displayed Km and kcat values for pyridoxal of 2.5 microM and 1.52 s(-1), respectively. Human PLP phosphatase mRNA is differentially expressed in a tissue-specific manner. A single mRNA transcript of 2.1 kb was detected in all human tissues examined and was highly abundant in the brain. Obtaining the molecular properties for the human PLP phosphatase may provide new direction for investigating metabolic pathway involving vitamin B6.

  19. Challenge or threat? Cardiovascular indexes of resilience and vulnerability to potential stress in humans.

    PubMed

    Seery, Mark D

    2011-06-01

    Humans continually face situations that require actions to achieve valued goals with meaningful consequences at stake. Although the pursuit of such goals can be a negatively "stressful" experience, it is not necessarily so. According to the biopsychosocial model of challenge and threat, evaluations of personal resources and situational demands determine to what extent individuals experience a relatively positive (challenge) versus negative (threat) psychological state in this context. Challenge occurs when evaluated resources meet or exceed demands, whereas threat occurs when demands exceed resources. The challenge response thus reflects resilience in the face of potential stress. Because challenge and threat reliably result in distinct patterns of physiological changes, assessing cardiovascular responses in particular can provide valuable insight into underlying psychological processes. Research applying this methodology to individual differences (e.g., self-esteem level and stability and cumulative lifetime exposure to adversity) has implications for understanding how early life experience could contribute to resilience versus vulnerability to potential stress in daily life.

  20. Evaluating Oxidative Stress in Human Cardiovascular Disease: Methodological Aspects and Considerations

    PubMed Central

    Lee, R; Margaritis, M; Channon, KM; Antoniades, C

    2012-01-01

    Oxidative stress is a key feature in atherogenesis, since reactive oxygen species (ROS) are involved in all stages of the disease, from endothelial dysfunction to atheromatic plaque formation and rupture. It is therefore important to identify reliable biomarkers allowing us to monitor vascular oxidative stress status. These may lead to improved understanding of disease pathogenesis and development of new therapeutic strategies. Measurement of circulating biomarkers of oxidative stress is challenging, since circulation usually behaves as a separate compartment to the individual structures of the vascular wall. However, measurement of stable products released by the reaction of ROS and vascular/circulating molecular structures is a particularly popular approach. Serum lipid hydroperoxides, plasma malondialdehyde or urine F2-isoprostanes are widely used and have a prognostic value in cardiovascular disease. Quantification of oxidative stress at a tissue level is much more accurate. Various chemiluminescence and high performance liquid chromatography assays have been developed over the last few years, and some of them are extremely accurate and specific. Electron spin resonance spectroscopy and micro-electrode assays able to detect ROS directly are also widely used. In conclusion, measurement of circulating biomarkers of oxidative stress is valuable, and some of them appear to have predictive value in cardiovascular disease. However, these biomarkers do not necessarily reflect intravascular oxidative stress and therefore cannot be used as therapeutic targets or markers to monitor pharmacological treatments in clinical settings. Measurement of vascular oxidative stress status is still the only reliable way to evaluate the involvement of oxidative stress in atherogenesis. PMID:22489713

  1. Relevance and safety of telomerase for human tissue engineering

    PubMed Central

    Klinger, Rebecca Y.; Blum, Juliana L.; Hearn, Bevin; Lebow, Benjamin; Niklason, Laura E.

    2006-01-01

    Tissue engineering holds the promise of replacing damaged or diseased tissues and organs. The use of autologous donor cells is often not feasible because of the limited replicative lifespan of cells, particularly those derived from elderly patients. Proliferative arrest can be overcome by the ectopic expression of telomerase via human telomerase reverse transcriptase (hTERT) gene transfection. To study the efficacy and safety of this potentially valuable technology, we used differentiated vascular smooth muscle cells (SMC) and vascular tissue engineering as a model system. Although we previously demonstrated that vessels engineered with telomerase-expressing SMC had improved mechanics over those grown with control cells, it is critical to assess the phenotypic impact of telomerase expression in donor cells, because telomerase up-regulation is observed in >95% of human malignancies. To study the impact of telomerase in tissue engineering, expression of hTERT was retrovirally induced in SMC from eight elderly patients and one young donor. In hTERT SMC, significant lifespan extension beyond that of control was achieved without population doubling time acceleration. Karyotype changes were seen in both control and hTERT SMC but were not clonal nor representative of cancerous change. hTERT cells also failed to show evidence of neoplastic transformation in functional assays of tumorigenicity. In addition, the impact of donor age on cellular behavior, particularly the synthetic capability of SMC, was not affected by hTERT expression. Hence, this tissue engineering model system highlights the impact of donor age on cellular synthetic function that appears to be independent of lifespan extension by hTERT. PMID:16477025

  2. The Transcriptome of Human Epicardial, Mediastinal and Subcutaneous Adipose Tissues in Men with Coronary Artery Disease

    PubMed Central

    Guauque-Olarte, Sandra; Gaudreault, Nathalie; Piché, Marie-Ève; Fournier, Dominique; Mauriège, Pascale; Mathieu, Patrick; Bossé, Yohan

    2011-01-01

    Background The biological functions of epicardial adipose tissue (EAT) remain largely unknown. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). The objectives of this study were to identify genes differentially regulated among three adipose tissues, namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases. Methods and Results Samples were collected from subjects undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in the three adipose depots of six men using the Illumina® HumanWG-6 v3.0 expression BeadChips. Twenty-three and 73 genes were differentially up-regulated in EAT compared to MAT and SAT, respectively. Ninety-four genes were down-regulated in EAT compared to SAT. However, none were significantly down-regulated in EAT compared to MAT. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (EAT>MAT>SAT). The results of ADORA1 and PTGDS were confirmed by quantitative real-time PCR in 25 independent subjects. Conclusions Overall, the transcriptional profiles of EAT and MAT were similar compared to the SAT. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were differentially up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD. PMID:21603615

  3. Multistructure index in revealing complexity of regulatory mechanisms of human cardiovascular system at rest and orthostatic stress in healthy humans

    NASA Astrophysics Data System (ADS)

    Makowiec, Danuta; Graff, Beata; Struzik, Zbigniew R.

    2017-02-01

    Biological regulation is sufficiently complex to pose an enduring challenge for characterization of both its equilibrium and transient non-equilibrium dynamics. Two univariate but coupled observables, heart rate and systolic blood pressure, are commonly characterized in the benchmark example of the human cardiovascular regulatory system. Asymmetric distributions of accelerations and decelerations of heart rate, as well as rises and falls in systolic blood pressure, recorded in humans during a head-up tilt test provide insights into the dynamics of cardiovascular response to a rapid, controlled deregulation of the system's homeostasis. The baroreflex feedback loop is assumed to be the fundamental physiological mechanism for ensuring homeostatic blood supply to distant organs at rest and during orthostatic stress, captured in a classical beat-to-beat autoregressive model of baroreflex by de Boer et al. (1987). For model corroboration, a multistructure index statistic is proposed, seamlessly evaluating the size spectrum of magnitudes of neural reflexes such as baroreflex, responsible for maintaining the homeostatic dynamics. The multistructure index exposes a distinctly different dynamics of multiscale asymmetry between results obtained from real-life signals recorded from healthy subjects and those simulated using both the classical and perturbed versions of the model. Nonlinear effects observed suggest the pronounced presence of complex mechanisms resulting from baroreflex regulation when a human is at rest, which is aggravated in the system's response to orthostatic stress. Using our methodology of multistructure index, we therefore show a marked difference between model and real-life scenarios, which we attribute to multiscale asymmetry of non-linear origin in real-life signals, which we are not reproducible by the classical model.

  4. Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues.

    PubMed

    Miyake, Masateru; Toguchi, Hajime; Nishibayashi, Toru; Higaki, Kazutaka; Sugita, Akira; Koganei, Kazutaka; Kamada, Nobuhiko; Kitazume, Mina T; Hisamatsu, Tadakazu; Sato, Toshiro; Okamoto, Susumu; Kanai, Takanori; Hibi, Toshifumi

    2013-08-01

    The objective of this study was to establish a novel prediction system of drug absorption in humans by utilizing human intestinal tissues. Based on the transport index (TI), a newly defined parameter, calculated by taking account of the change in drug concentrations because of precipitation on the apical side and the amounts accumulated in the tissue and transported to the basal side, the absorbability of drugs in rank order as well as the fraction of dose absorbed (Fa) in humans were estimated. Human intestinal tissues taken from ulcerative colitis or Crohn's disease patients were mounted in a mini-Ussing chamber and transport studies were performed to evaluate the permeation of drugs, including FD-4, a very low permeable marker, atenolol, a low permeable marker, and metoprolol, a high permeable marker. Although apparent permeability coefficients calculated by the conventional equation did not reflect human Fa values for FD-4, atenolol, and metoprolol, TI values were well correlated with Fa values, which are described by 100 · [1 - e (- f · (TI - α)) ]. Based on this equation, Fa values in humans for other test drugs were predicted successfully, indicating that our new system utilizing human intestinal tissues would be valuable for predicting oral drug absorption in humans.

  5. Brown adipose tissue in humans: therapeutic potential to combat obesity.

    PubMed

    Carey, Andrew L; Kingwell, Bronwyn A

    2013-10-01

    Harnessing the considerable capacity of brown adipose tissue (BAT) to consume energy was first proposed as a potential target to control obesity nearly 40years ago. The plausibility of this approach was, however, questioned due to the prevailing view that BAT was either not present or not functional in adult humans. Recent definitive identification of functional BAT in adult humans as well as a number of important advances in the understanding of BAT biology has reignited interest in BAT as an anti-obesity target. Proof-of-concept evidence demonstrating drug-induced BAT activation provides an important foundation for development of targeted pharmacological approaches with clinical application. This review considers evidence from both human and relevant animal studies to determine whether harnessing BAT for the treatment of obesity via pharmacological intervention is a realistic goal.

  6. Brown adipose tissue as a therapeutic target for human obesity.

    PubMed

    Saito, Masayuki

    2013-12-01

    Brown adipose tissue (BAT) is the major site of sympathetically activated adaptive thermogenesis during cold exposure and after spontaneous hyperphagia, thereby controlling whole-body energy expenditure and body fat. Recent radionuclide studies have demonstrated the existence of metabolically active BAT in healthy adult humans. Human BAT is activated by acute cold exposure, being positively correlated to cold-induced increases in energy expenditure. The metabolic activity of BAT is lower in older and obese individuals. The inverse relationship between the BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. In fact, either repeated cold exposure or daily ingestion of some food ingredients acting on transient receptor potential channels recruited BAT in association with increased energy expenditure and decreased body fat even in individuals with low BAT activities before the treatment. Thus, BAT is a promising therapeutic target for combating human obesity and related metabolic disorders.

  7. Human brown adipose tissue: regulation and anti-obesity potential.

    PubMed

    Saito, Masayuki

    2014-01-01

    Brown adipose tissue (BAT) is the site of sympathetically activated adaptive thermognenesis during cold exposure and after hyperphagia, thereby controlling whole-body energy expenditure (EE) and body fat. Radionuclide imaging studies have demonstrated that adult humans have metabolically active BAT composed of mainly beige/brite adipocytes, recently identified brown-like adipocytes. The inverse relationship between the BAT activity and body fatness suggests that BAT is, because of its energy dissipating activity, protective against body fat accumulation in humans as it is in small rodents. In fact, either repeated cold exposure or daily ingestion of some food ingredients acting on transient receptor potential channels recruits BAT in parallel with increased EE and decreased body fat. In addition to the sympathetic nervous system, several endocrine factors are also shown to recruit BAT. Thus, BAT is a promising therapeutic target for combating human obesity and related metabolic disorders.

  8. Semaphorin signaling in cardiovascular development.

    PubMed

    Epstein, Jonathan A; Aghajanian, Haig; Singh, Manvendra K

    2015-02-03

    Semaphorins were originally identified as neuronal guidance molecules mediating their attractive or repulsive signals by forming complexes with plexin and neuropilin receptors. Subsequent research has identified functions for semaphorin signaling in many organs and tissues outside of the nervous system. Vital roles for semaphorin signaling in vascular patterning and cardiac morphogenesis have been demonstrated, and impaired semaphorin signaling has been associated with various human cardiovascular disorders, including persistent truncus arteriosus, sinus bradycardia and anomalous pulmonary venous connections. Here, we review the functions of semaphorins and their receptors in cardiovascular development and disease and highlight important recent discoveries in the field.

  9. Fucosyltransferase activities in human pancreatic tissue: comparative study between cancer tissues and established tumoral cell lines.

    PubMed

    Mas, E; Pasqualini, E; Caillol, N; El Battari, A; Crotte, C; Lombardo, D; Sadoulet, M O

    1998-06-01

    Human pancreatic cancer is characterized by an alteration in fucose-containing surface blood group antigens such as H antigen, Lewis b, Lewis y, and sialyl-Lewis. These carbohydrate determinants can be synthesized by sequential action of alpha(2,3) sialyltransferases or alpha(1,2) fucosyltransferases (Fuc-T) and alpha(1,3/1,4) fucosyltransferases on (poly)N-acetyllactosamine chains. Therefore, the expression and the function of seven fucosyltransferases were investigated in normal and cancer pancreatic tissues and in four pancreatic carcinoma cell lines. Transcripts of FUT1, FUT2, FUT3, FUT4, FUT5, and FUT7 were detected by RT-PCR in carcinoma cell lines as well as in normal and tumoral tissues. Interestingly, the FUT6 message was only detected in tumoral tissues. Analysis of the acceptor substrate specificity for fucosyltransferases indicated that alpha(1,2) Fuc-T, alpha(1,3) Fuc-T, and alpha(1,4) Fuc-T were expressed in microsome preparations of all tissues as demonstrated by fucose incorporation into phenyl beta-d-galactoside, 2'-fucosyllactose, N-acetyllactosamine, 3'-sialyl-N-acetyllactosamine, and lacto-N-biose. However, these fucosyltransferase activities varied between tissues. A substantial decrease of alpha(1,2) Fuc-T activity was observed in tumoral tissues and cell lines compared to normal tissues. Conversely, the activity of alpha(1,4) Fuc-T, which generates Lewis a and sialyl-Lewis a structures, and that of alpha(1,3) Fuc-T, able to generate a lactodifucotetraose structure, were very important in SOJ-6 and BxPC-3 cell lines. These increases correlated with an enhanced expression of Lewis a, sialyl-Lewis a, and Lewis y on the cell surface. The activity of alpha(1,3) Fuc-T, which participates in the synthesis of the sialyl-Lewis x structure, was not significantly modified in cell lines compared to normal tissues. However, the sialyl-Lewis x antigen was expressed preferentially on the surface of SOJ-6 and BxPC-3 cell lines but was not detected on Panc-1

  10. A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue.

    PubMed

    Teraoka, S; Kyoizumi, S; Seyama, T; Yamakido, M; Akiyama, M

    1995-05-01

    We established a novel severe combined immunodeficient (SCID) mouse model for the study of human lung cancer metastasis to human lung. Implantation of both human fetal and adult lung tissue into mammary fat pads of SCID mice showed a 100% rate of engraftment, but only fetal lung implants revealed normal morphology of human lung tissue. Using these chimeric mice, we analyzed human lung cancer metastasis to both mouse and human lungs by subcutaneous inoculation of human squamous cell carcinoma and adenocarcinoma cell lines into the mice. In 60 to 70% of SCID mice injected with human-lung squamous-cell carcinoma, RERF-LC-AI, cancer cells were found to have metastasized to both mouse lungs and human fetal lung implants but not to human adult lung implants 80 days after cancer inoculation. Furthermore, human-lung adenocarcinoma cells, RERF-LC-KJ, metastasized to the human lung implants within 90 days in about 40% of SCID mice, whereas there were no metastases to the lungs of the mice. These results demonstrate the potential of this model for the in vivo study of human lung cancer metastasis.

  11. Characterization of human myoblast cultures for tissue engineering.

    PubMed

    Stern-Straeter, Jens; Bran, Gregor; Riedel, Frank; Sauter, Alexander; Hörmann, Karl; Goessler, Ulrich Reinhart

    2008-01-01

    Skeletal muscle tissue engineering, a promising specialty, aims at the reconstruction of skeletal muscle loss. In vitro tissue engineering attempts to achieve this goal by creating differentiated, functional muscle tissue through a process in which stem cells are extracted from the patient, e.g. by muscle biopsies, expanded and differentiated in a controlled environment, and subsequently re-implanted. A prerequisite for this undertaking is the ability to cultivate and differentiate human skeletal muscle cell cultures. Evidently, optimal culture conditions must be investigated for later clinical utilization. We therefore analysed the proliferation of human cells in different environments and evaluated the differentiation potential of different culture media. It was shown that human myoblasts have a higher rate of proliferation in the alamarBlue assay when cultured on gelatin-coated culture flasks rather than polystyrene-coated flasks. We also demonstrated that myoblasts treated with a culture medium with a high concentration of growth factors [growth medium (GM)] showed a higher proliferation compared to cultures treated with a culture medium with lower amounts of growth factors [differentiation medium (DM)]. Differentiation of human myoblast cell cultures treated with GM and DM was analysed until day 16 and myogenesis was verified by expression of MyoD, myogenin, alpha-sarcomeric actin and myosin heavy chain by semi-quantitative RT-PCR. Immunohistochemical staining for desmin, Myf-5 and alpha-sarcomeric actin was performed to verify the myogenic phenotype of extracted satellite cells and to prove the maturation of cells. Cultures treated with DM showed positive staining for alpha-sarcomeric actin. Notably, markers of differentiation were also detected in cultures treated with GM, but there was no formation of myotubes. In the enzymatic assay of creatine phosphokinase, cultures treated with DM showed a higher activity, evidencing a higher degree of differentiation

  12. Computational model of soft tissues in the human upper airway.

    PubMed

    Pelteret, J-P V; Reddy, B D

    2012-01-01

    This paper presents a three-dimensional finite element model of the tongue and surrounding soft tissues with potential application to the study of sleep apnoea and of linguistics and speech therapy. The anatomical data was obtained from the Visible Human Project, and the underlying histological data was also extracted and incorporated into the model. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus.

  13. Suggestive evidence of a multi-cytokine resistin pathway in humans and its role on cardiovascular events in high-risk individuals

    PubMed Central

    Menzaghi, Claudia; Marucci, Antonella; Antonucci, Alessandra; De Bonis, Concetta; Ortega Moreno, Lorena; Salvemini, Lucia; Copetti, Massimiliano; Trischitta, Vincenzo; Di Paola, Rosa

    2017-01-01

    In cells and tissues resistin affects IL-1β, IL-6, IL-8, IL-12 and TNF-α expression, thus suggesting the existence of a multi-cytokine “resistin pathway”. We investigated whether such pathway does exist in humans and, if so, if it is associated with cardiovascular risk factors and with major adverse cardiovascular events (MACE). Serum cytokines were measured in 280 healthy subjects from the Gargano Study 2 (GS2) whose BMI, waist circumference, HOMAIR, triglycerides, HDL-cholesterol, systolic and diastolic blood pressure data were available and in 353 patients with type 2 diabetes and coronary artery disease from the Gargano Heart Study (GHS)-prospective design (follow-up 5.4 ± 2.5 years; 71 MACE). In GS2, cytokines mRNA levels in white blood cells were also measured. In GS2, resistin mRNA was correlated with all cytokines expression (all p < 0.001), but IL-12B. Consistently, serum resistin was correlated with all serum cytokines (all p < 0.001), but IL-12. Expression (eRPS) and serum (sRPS) resistin pathway scores (excluding IL-12) were each other correlated (p < 0.001) and both associated with cardiovascular risk factors (all p < 0.01). In GHS, sRPS was independently associated with MACE (HR = 1.44, 95% CI = 1.10–1.90). Our data indicate the existence of a resistin pathway, which is associated with cardiovascular risk factors and which strongly and independently predicts MACE. PMID:28290549

  14. Polyethylene glycol enhanced refolding of the recombinant human tissue transglutaminase.

    PubMed

    Ambrus, A; Fésüs, L

    2001-02-01

    Tissue transglutaminase forms cross-links between lysine and glutamine side-chains of polypeptide chains in a Ca2+-dependent reaction; its structural basis is still not clarified. In this study, we demonstrate that the refolding of the human recombinant enzyme molecule to its catalytically active form from inclusion bodies needs the presence of a helper material with higher molecular mass, but only in the initiation phase. Ca2+ and nucleotides are ascribed as affector molecules also in the early phase of structural reconstitution. Two optimal concentrations of polyethylene glycol and a relatively long time scale for the evolution of the final structure were identified. The optimized refolding procedure is reported.

  15. A module of human peripheral blood mononuclear cell transcriptional network containing primitive and differentiation markers is related to specific cardiovascular health variables.

    PubMed

    Moldovan, Leni; Anghelina, Mirela; Kantor, Taylor; Jones, Desiree; Ramadan, Enass; Xiang, Yang; Huang, Kun; Kolipaka, Arunark; Malarkey, William; Ghasemzadeh, Nima; Mohler, Peter J; Quyyumi, Arshed; Moldovan, Nicanor I

    2014-01-01

    Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells (CSPCs), have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene), defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p<0.03) with age (R2 = -0.23), vascular stiffness (R2 = -0.24), and central aortic pressure (R2 = -0.19) and positively correlated with body mass index (R2 = 0.72, in women). The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72±22% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional network

  16. Calcium Sensing Receptor (CaSR) activation elevates proinflammatory factor expression in human adipose cells and adipose tissue

    PubMed Central

    Cifuentes, Mariana; Fuentes, Cecilia; Acevedo, Ingrid; Villalobos, Elisa; Hugo, Eric; Ben Jonathan, Nira; Reyes, Marcela

    2013-01-01

    We have previously established that human adipose cells and the human adipose cell line LS14 express the calcium sensing receptor (CaSR) and that its expression is elevated upon exposure to inflammatory cytokines that are typically elevated in obese humans. Research in recent years has established that an important part of the adverse metabolic and cardiovascular consequences of obesity derive from a dysfunction of the tissue, one of the mechanisms being a disordered secretion pattern leading to an excess of proinflammatory cytokines and chemokines. Given the reported association of the CaSR to inflammatory processes in other tissues, we sought to evaluate its role elevating the adipose expression of inflammatory factors. We exposed adipose tissue and in-vitro cultured LS14 preadipocytes and differentiated adipocytes to the calcimimetic cinacalcet and evaluated the expression or production of the proinflammatory cytokines IL6, IL1β and TNFα as well as the chemoattractant factor CCL2. CaSR activation elicited an elevation in the expression of the inflammatory factors, which was in part reverted by SN50, an inhibitor of the inflammatory mediator NFκB. Our observations suggest that CaSR activation elevates cytokine and chemokine production through a signaling pathway involving activation of NFκB nuclear translocation. These findings confirm the relevance of the CaSR in the pathophysiology of obesity-induced adipose tissue dysfunction, with an interesting potential for pharmacological manipulation in the fight against obesity- associated diseases. PMID:22449852

  17. 21 CFR 1270.43 - Retention, recall, and destruction of human tissue.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Retention, recall, and destruction of human tissue. 1270.43 Section 1270.43 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... HUMAN TISSUE INTENDED FOR TRANSPLANTATION Inspection of Tissue Establishments § 1270.43...

  18. 21 CFR 1270.43 - Retention, recall, and destruction of human tissue.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Retention, recall, and destruction of human tissue. 1270.43 Section 1270.43 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... HUMAN TISSUE INTENDED FOR TRANSPLANTATION Inspection of Tissue Establishments § 1270.43...

  19. 21 CFR 1270.43 - Retention, recall, and destruction of human tissue.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Retention, recall, and destruction of human tissue. 1270.43 Section 1270.43 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... HUMAN TISSUE INTENDED FOR TRANSPLANTATION Inspection of Tissue Establishments § 1270.43...

  20. 21 CFR 1270.43 - Retention, recall, and destruction of human tissue.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Retention, recall, and destruction of human tissue. 1270.43 Section 1270.43 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... HUMAN TISSUE INTENDED FOR TRANSPLANTATION Inspection of Tissue Establishments § 1270.43...

  1. 21 CFR 1270.43 - Retention, recall, and destruction of human tissue.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Retention, recall, and destruction of human tissue. 1270.43 Section 1270.43 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... HUMAN TISSUE INTENDED FOR TRANSPLANTATION Inspection of Tissue Establishments § 1270.43...

  2. Long Non-coding RNA ANRIL and Polycomb in Human Cancers and Cardiovascular Disease.

    PubMed

    Aguilo, Francesca; Di Cecilia, Serena; Walsh, Martin J

    2016-01-01

    The long non-coding RNA CDKN2B-AS1, commonly referred to as the A ntisense N on-coding R NA in the I NK4 L ocus (ANRIL), is a 3.8-kb-long RNA transcribed from the short arm of human chromosome 9 on p21.3 that overlaps a critical region encompassing three major tumor suppressor loci juxtaposed to the INK4b-ARF-INK4a gene cluster and the methyl-thioadenosine phosphorylase (MTAP) gene. Genome-wide association studies have identified this region with a remarkable and growing number of disease-associated DNA alterations and single nucleotide polymorphisms, which corresponds to increased susceptibility to human disease. Recent attention has been devoted on whether these alterations in the ANRIL sequence affect its expression levels and/or its splicing transcript variation, and in consequence, global cellular homeostasis. Moreover, recent evidence postulates that ANRIL not only can regulate their immediate genomic neighbors in cis, but also has the capacity to regulate additional loci in trans. This action would further increase the complexity for mechanisms imposed through ANRIL and furthering the scope of this lncRNA in disease pathogenesis. In this chapter, we summarize the most recent findings on the investigation of ANRIL and provide a perspective on the biological and clinical significance of ANRIL as a putative biomarker, specifically, its potential role in directing cellular fates leading to cancer and cardiovascular disease.

  3. Mathematical modelling and electrical analog equivalent of the human cardiovascular system.

    PubMed

    Abdolrazaghi, Mona; Navidbakhsh, Mahdi; Hassani, Kamran

    2010-06-01

    The objective of this study is to develop a model of the cardiovascular system capable of simulating the normal operation of the systemic and pulmonary circulation, starts from aorta, and follows by upper and lower extremities vessels, finally ends with pulmonary veins. The model consists of a closed loop lumped elements with 43 compartments representing the cardiovascular system. The model parameters have been extracted from the literature. Using MATLAB software, the mathematical model has been simulated for the cardiovascular system. Each compartment includes a Resistor-Inductor-Capacitor (RLC) segment. The normal cardiovascular operation is characterised by the pressure-volume curves in different parts of the system. Model verification is performed by comparing the simulation results with the clinical observation reported in the literature. The described model is a useful tool in studying the physiology of cardiovascular system, and the related diseases. Also, it could be a great tool to investigate the effects of the pathologies of the cardiovascular system.

  4. Tissue engineered humanized bone supports human hematopoiesis in vivo.

    PubMed

    Holzapfel, Boris M; Hutmacher, Dietmar W; Nowlan, Bianca; Barbier, Valerie; Thibaudeau, Laure; Theodoropoulos, Christina; Hooper, John D; Loessner, Daniela; Clements, Judith A; Russell, Pamela J; Pettit, Allison R; Winkler, Ingrid G; Levesque, Jean-Pierre

    2015-08-01

    Advances in tissue-engineering have resulted in a versatile tool-box to specifically design a tailored microenvironment for hematopoietic stem cells (HSCs) in order to study diseases that develop within this setting. However, most current in vivo models fail to recapitulate the biological processes seen in humans. Here we describe a highly reproducible method to engineer humanized bone constructs that are able to recapitulate the morphological features and biological functions of the HSC niches. Ectopic implantation of biodegradable composite scaffolds cultured for 4 weeks with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone organ including a large number of human mesenchymal cells which were shown to be metabolically active and capable of establishing a humanized microenvironment supportive of the homing and maintenance of human HSCs. A syngeneic mouse-to-mouse transplantation assay was used to prove the functionality of the tissue-engineered ossicles. We predict that the ability to tissue engineer a morphologically intact and functional large-volume bone organ with a humanized bone marrow compartment will help to further elucidate physiological or pathological interactions between human HSCs and their native niches.

  5. Cardiomyocyte clusters derived from human embryonic stem cells share similarities with human heart tissue.

    PubMed

    Asp, Julia; Steel, Daniella; Jonsson, Marianne; Améen, Caroline; Dahlenborg, Kerstin; Jeppsson, Anders; Lindahl, Anders; Sartipy, Peter

    2010-10-01

    Cardiotoxicity testing is a key activity in the pharmaceutical industry in order to detect detrimental effects of new drugs. A reliable human in vitro model would both be beneficial in selection of lead compounds and be important for reducing animal experimentation. However, the human heart is a complex organ composed of many distinct types of cardiomyocytes, but cardiomyocyte clusters (CMCs) derived from human embryonic stem cells could be an option for a cellular model. Data on functional properties of CMCs demonstrate similarities to their in vivo analogues in human. However, development of an in vitro model requires a more thorough comparison of CMCs to human heart tissue. Therefore, we directly compared individually isolated CMCs to human fetal, neonatal, adult atrial and ventricular heart tissues. Real-time qPCR analysis of mRNA levels and protein staining of ion channels and cardiac markers showed in general a similar expression pattern in CMCs and human heart. Moreover, a significant decrease in beat frequency was noted after addition of Zatebradine, a blocker to I(f) involved in regulation of spontaneous contraction in CMCs. The results underscore the similarities of CMCs to human cardiac tissue, and further support establishment of novel cardiotoxicity assays based on the CMCs in drug discovery.

  6. Effects of acute and chronic cigarette smoking on the expression of endothelin-1 mRNA of the cardiovascular tissues in rats.

    PubMed

    Adachi, C; Naruse, M; Ishihara, Y; Tanabe, A; Takagi, S; Yoshimoto, T; Naruse, K; Kagawa, J; Takano, K

    2000-11-01

    Although smoking has been suggested to be involved in the development of cardiovascular diseases, details of the mechanism still need to be revealed. We investigated the effects of cigarette smoking on the tissue mRNA expression of endothelin-1 (ET-1). Male Wistar rats of 4 weeks of age were exposed to smoke from six cigarettes for 30 min (acute exposure) and six cigarettes for 30 min/day, 5 days a week for 6 months (chronic exposure). Half of the rats exposed to 6 months smoking were kept in clean-air conditions for a further 3 months to clear the effects. Tissue expression of ET-1 mRNA in the kidney, aorta, heart and lung was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot analysis. There was no significant difference in body and organ weight of the heart and kidney between the control and smoking group in either the acute or chronic experiment. In the acute-exposure experiment, expression of ET-1 mRNA was increased in the heart and lung, while that in the kidney and aorta was unchanged. In the chronic-exposure experiment, however, there was no significant difference in the expression of ET-1 mRNA in all the tissues between the smoking and control groups. These results suggest that cigarette smoking could cause cardiovascular and pulmonary diseases by modulating ET-1 mRNA expression in the tissues.

  7. A Protocol for Collecting Human Cardiac Tissue for Research

    PubMed Central

    Blair, Cheavar A.; Haynes, Premi; Campbell, Stuart G.; Chung, Charles; Mitov, Mihail I.; Dennis, Donna; Bonnell, Mark R.; Hoopes, Charles W.; Guglin, Maya; Campbell, Kenneth S.

    2016-01-01

    This manuscript describes a protocol at the University of Kentucky that allows a translational research team to collect human myocardium that can be used for biological research. We have gained a great deal of practical experience since we started this protocol in 2008, and we hope that other groups might be able to learn from our endeavors. To date, we have procured ~4000 samples from ~230 patients. The tissue that we collect comes from organ donors and from patients who are receiving a heart transplant or a ventricular assist device because they have heart failure. We begin our manuscript by describing the importance of human samples in cardiac research. Subsequently, we describe the process for obtaining consent from patients, the cost of running the protocol, and some of the issues and practical difficulties that we have encountered. We conclude with some suggestions for other researchers who may be considering starting a similar protocol. PMID:28042604

  8. Fracture of Human Femur Tissue Monitored by Acoustic Emission Sensors

    PubMed Central

    Aggelis, Dimitrios. G.; Strantza, Maria; Louis, Olivia; Boulpaep, Frans; Polyzos, Demosthenes; van Hemelrijck, Danny

    2015-01-01

    The study describes the acoustic emission (AE) activity during human femur tissue fracture. The specimens were fractured in a bending-torsion loading pattern with concurrent monitoring by two AE sensors. The number of recorded signals correlates well with the applied load providing the onset of micro-fracture at approximately one sixth of the maximum load. Furthermore, waveform frequency content and rise time are related to the different modes of fracture (bending of femur neck or torsion of diaphysis). The importance of the study lies mainly in two disciplines. One is that, although femurs are typically subjects of surgical repair in humans, detailed monitoring of the fracture with AE will enrich the understanding of the process in ways that cannot be achieved using only the mechanical data. Additionally, from the point of view of monitoring techniques, applying sensors used for engineering materials and interpreting the obtained data pose additional difficulties due to the uniqueness of the bone structure. PMID:25763648

  9. Proteomic analysis in cardiovascular research.

    PubMed

    Oda, Teiji; Matsumoto, Ken-ichi

    2016-03-01

    Advances in mass spectrometry technology and bioinformatics using clinical human samples have expanded quantitative proteomics in cardiovascular research. There are two major proteomic strategies: namely, "gel-based" or "gel-free" proteomics coupled with either "top-down" or "bottom-up" mass spectrometry. Both are introduced into the proteomic analysis using plasma or serum sample targeting 'biomarker" searches of aortic aneurysm and tissue samples, such as from the aneurysmal wall, calcific aortic valve, or myocardial tissue, investigating pathophysiological protein interactions and post-translational modifications. We summarize the proteomic studies that analyzed human samples taken during cardiovascular surgery to investigate disease processes, in order to better understand the system-wide changes behind known molecular factors and specific signaling pathways.

  10. Epicardial Adipose Tissue (EAT) Thickness Is Associated with Cardiovascular and Liver Damage in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Pisano, Giuseppina; Consonni, Dario; Tiraboschi, Silvia; Baragetti, Andrea; Bertelli, Cristina; Norata, Giuseppe Danilo; Dongiovanni, Paola; Valenti, Luca; Grigore, Liliana; Tonella, Tatiana; Catapano, Alberico; Fargion, Silvia

    2016-01-01

    Background and Aims Epicardial adipose tissue (EAT) has been proposed as a cardiometabolic and hepatic fibrosis risk factor in patients with non alcoholic fatty liver disease (NAFLD). Aim of this study was to evaluate the role of EAT in NAFLD by analyzing 1) the association between EAT, the other metabolic parameters and the severity of steatosis 2) the relationship between cardiovascular (cIMT, cplaques, E/A), liver (presence of NASH and significant fibrosis) damage and metabolic risk factors including EAT 3) the relationship between EAT and genetic factors strongly influencing liver steatosis. Methods In a cross-sectional study, we considered 512 consecutive patients with NAFLD (confirmed by biopsy in 100). EAT, severity of steatosis, carotid intima-media thickness (cIMT) and plaques were evaluated by ultrasonography and results analysed by multiple linear and logistic regression models. Variables independently associated with EAT (mm) were female gender (p = 0.003), age (p = 0.001), BMI (p = 0.01), diastolic blood pressure (p = 0.009), steatosis grade 2 (p = 0.01) and 3 (p = 0.04), fatty liver index (p = 0.001) and statin use (p = 0.03). Variables independently associated with carotid IMT were age (p = 0.0001), hypertension (p = 0.009), diabetes (p = 0.04), smoking habits (p = 0.04) and fatty liver index (p = 0.02), with carotid plaques age (p = 0.0001), BMI (p = 0.03), EAT (p = 0.02),) and hypertension (p = 0.02), and with E/A age (p = 0.0001), diabetes (p = 0.005), hypertension (p = 0.04) and fatty liver index (p = 0.004). In the 100 patients with available liver histology non alcoholic steatohepatitis (NASH) was independently associated with EAT (p = 0.04) and diabetes (p = 0.054) while significant fibrosis with EAT (p = 0.02), diabetes (p = 0.01) and waist circumference (p = 0.05). No association between EAT and PNPLA3 and TM6SF2 polymorphisms was found. Conclusion In patients with NAFLD, EAT is associated with the severity of liver and vascular damage

  11. Developmental changes in purine phosphoribosyltransferases in human and rat tissues.

    PubMed Central

    Adams, A; Harkness, R A

    1976-01-01

    1. The hypoxanthine/guanine and adenine phosphoribosyltransferase activities in a wide variety of human tissues were studied during their growth and development from foetal life onward. A wide range of activities develop after birth, with especially high values in the central nervous system and testes. 2. Postnatal development of hypoxanthine/guanine phosphoribosyltransferase was also defined in the rat. Although there were increases in the central nervous system and testes, there was also a rise in activity in the liver, which was less marked in man. 3. A sensitive radiochemical assay method, using dTTP to inhibit 5'-nucleotidase activity, suitable for tissue extracts, was developed. 4. No definite evidence of the existence of tissue-specific isoenzymes of hypoxanthine/guanine or adenine phosphoribosyltransferase was found. Hypoxanthine/guanine phosphoribosyltransferase in testes, however, had a significantly different thermal-denaturation rate constant. 5. The findings are discussed in an attempt to relate activity of hypoxanthine/guanine phosphoribosyltransferase to biological function. Growth as well as some developmental changes appear to be related to increase in the activity of this enzyme. PMID:1016239

  12. Mechanical stimulation improves tissue-engineered human skeletal muscle.

    PubMed

    Powell, Courtney A; Smiley, Beth L; Mills, John; Vandenburgh, Herman H

    2002-11-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  13. Mechanical stimulation improves tissue-engineered human skeletal muscle

    NASA Technical Reports Server (NTRS)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  14. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

    PubMed

    Tanzi, Elisabetta; Bianchi, Silvia; Frati, Elena R; Amicizia, Daniela; Martinelli, Marianna; Bragazzi, Nicola L; Brisigotti, Maria Pia; Colzani, Daniela; Fasoli, Ester; Zehender, Gianguglielmo; Panatto, Donatella; Gasparini, Roberto

    2015-01-01

    Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.

  15. Proteogenomic Analysis of Human Chromosome 9-Encoded Genes from Human Samples and Lung Cancer Tissues

    PubMed Central

    Ahn, Jung-Mo; Kim, Min-Sik; Kim, Yong-In; Jeong, Seul-Ki; Lee, Hyoung-Joo; Lee, Sun Hee; Paik, Young-Ki; Pandey, Akhilesh; Cho, Je-Yoel

    2014-01-01

    The Chromosome-centric Human Proteome Project (C-HPP) was recently initiated as an international collaborative effort. Our team adopted chromosome 9 (Chr 9) and performed a bioinformatics and proteogenomic analysis to catalog Chr 9-encoded proteins from normal tissues, lung cancer cell lines and lung cancer tissues. Approximately 74.7% of the Chr 9 genes of the human genome were identified, which included approximately 28% of missing proteins (46 of 162) on Chr 9 compared with the list of missing proteins from the neXtProt master table (2013-09). In addition, we performed a comparative proteomics analysis between normal lung and lung cancer tissues. Based on the data analysis, 15 proteins from Chr 9 were detected only in lung cancer tissues. Finally, we conducted a proteogenomic analysis to discover Chr 9-residing single nucleotide polymorphisms (SNP) and mutations described in the COSMIC cancer mutation database. We identified 21 SNPs and 4 mutations containing peptides on Chr 9 from normal human cells/tissues and lung cancer cell lines, respectively. In summary, this study provides valuable information of the human proteome for the scientific community as part of C-HPP. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the data set identifier PXD. PMID:24274035

  16. Animal Models to Study Links between Cardiovascular Disease and Renal Failure and Their Relevance to Human Pathology

    PubMed Central

    Hewitson, Tim D.; Holt, Stephen G.; Smith, Edward R.

    2015-01-01

    The close association between cardiovascular pathology and renal dysfunction is well documented and significant. Patients with conventional risk factors for cardiovascular disease like diabetes and hypertension also suffer renal dysfunction. This is unsurprising if the kidney is simply regarded as a “modified blood vessel” and thus, traditional risk factors will affect both systems. Consistent with this, it is relatively easy to comprehend how patients with either sudden or gradual cardiac and or vascular compromise have changes in both renal hemodynamic and regulatory systems. However, patients with pure or primary renal dysfunction also have metabolic changes (e.g., oxidant stress, inflammation, nitric oxide, or endocrine changes) that affect the cardiovascular system. Thus, cardiovascular and renal systems are intimately, bidirectionally and inextricably linked. Whilst we understand several of these links, some of the mechanisms for these connections remain incompletely explained. Animal models of cardiovascular and renal disease allow us to explore such mechanisms, and more importantly, potential therapeutic strategies. In this article, we review various experimental models used, and examine critically how representative they are of the human condition. PMID:26441970

  17. The mirror RNA expression pattern in human tissues

    PubMed Central

    Bythwood, Tameka N.; Xu, Wei; Li, Wenzhi; Rao, Weinian; Li, Qiling; Xue, Xue; Richards, Jendai; Ma, Li; Song, Qing

    2017-01-01

    It has been realized in recent years that non-coding RNAs are playing important roles in genome functions and human diseases. Here we developed a new technology and observed a new pattern of gene expression. We observed that over 72% of RNAs in human genome are expressed in forward-reverse pairs, just like mirror images of each other between forward expression and reverse expression; the overview showed that it cannot be simply described as transcript overlapping, so we designated it as mirror expression. Furthermore, we found that the mirror expression is gene-specific and tissue-specific, and less common in the proximal promoter regions. The size of the shadows varies between different genes, different tissues and different classes. The shadow expression is most significant in the Alu element, it was also observed among L1, Simple Repeats and LTR elements, but rare in other repeats such as low-complexity, LINE/L2, DNA and MIRs. Although there is no evidence yet about the relationship of this mirror pattern and double-strand RNA (dsRNA), this new striking pattern provides a new clue and a new direction to unveil the role of RNAs in the genome functions and diseases.

  18. Tissue engineered human tracheas for in vivo implantation.

    PubMed

    Baiguera, Silvia; Jungebluth, Phillip; Burns, Alan; Mavilia, Carmelo; Haag, Johannes; De Coppi, Paolo; Macchiarini, Paolo

    2010-12-01

    Two years ago we performed the first clinical successful transplantation of a fully tissue engineered trachea. Despite the clinically positive outcome, the graft production took almost 3 months, a not feasible period of time for patients with the need of an urgent transplantation. We have then improved decellularization process and herein, for the first time, we completely describe and characterize the obtainment of human tracheal bioactive supports. Histological and molecular biology analysis demonstrated that all cellular components and nuclear material were removed and quantitative PCR confirmed it. SEM analysis revealed that the decellularized matrices retained the hierarchical structures of native trachea, and biomechanical tests showed that decellularization approach did not led to any influence on tracheal morphological and mechanical properties. Moreover immunohistological staining showed the preservation of angiogenic factors and angiogenic assays demonstrated that acellular human tracheal scaffolds exert an in vitro chemo-active action and induce strong in vivo angiogenic response (CAM analysis). We are now able to obtained, in a short and clinically useful time (approximately 3 weeks), a bioengineered trachea that is structurally and mechanically similar to native trachea, which exert chemotactive and pro-angiogenic properties and which could be successfully used for clinical tissue engineered airway clinical replacements.

  19. Distribution of adenosine deaminase complexing protein (ADCP) in human tissues.

    PubMed

    Dinjens, W N; ten Kate, J; van der Linden, E P; Wijnen, J T; Khan, P M; Bosman, F T

    1989-12-01

    The normal distribution of adenosine deaminase complexing protein (ADCP) in the human body was investigated quantitatively by ADCP-specific radioimmunoassay (RIA) and qualitatively by immunohistochemistry. In these studies we used a specific rabbit anti-human ADCP antiserum. In all 19 investigated tissues, except erythrocytes, ADCP was found by RIA in the soluble and membrane fractions. From all tissues the membrane fractions contained more ADCP (expressed per mg protein) than the soluble fractions. High membrane ADCP concentrations were found in skin, renal cortex, gastrointestinal tract, and prostate. Immunoperoxidase staining confirmed the predominant membrane-associated localization of the protein. In serous sweat glands, convoluted tubules of renal cortex, bile canaliculi, gastrointestinal tract, lung, pancreas, prostate gland, salivary gland, gallbladder, mammary gland, and uterus, ADCP immunoreactivity was found confined to the luminal membranes of the epithelial cells. These data demonstrate that ADCP is present predominantly in exocrine glands and absorptive epithelia. The localization of ADCP at the secretory or absorptive apex of the cells suggests that the function of ADCP is related to the secretory and/or absorptive process.

  20. Quantification of human body fat tissue percentage by MRI.

    PubMed

    Müller, Hans-Peter; Raudies, Florian; Unrath, Alexander; Neumann, Heiko; Ludolph, Albert C; Kassubek, Jan

    2011-01-01

    The MRI-based evaluation of the quantity and regional distribution of adipose tissue is one objective measure in the investigation of obesity. The aim of this article was to report a comprehensive and automatic analytical method for the determination of the volumes of subcutaneous fat tissue (SFT) and visceral fat tissue (VFT) in either the whole human body or selected slices or regions of interest. Using an MRI protocol in an examination position that was convenient for volunteers and patients with severe diseases, 22 healthy subjects were examined. The software platform was able to merge MRI scans of several body regions acquired in separate acquisitions. Through a cascade of image processing steps, SFT and VFT volumes were calculated. Whole-body SFT and VFT distributions, as well as fat distributions of defined body slices, were analysed in detail. Complete three-dimensional datasets were analysed in a reproducible manner with as few operator-dependent interventions as possible. In order to determine the SFT volume, the ARTIS (Adapted Rendering for Tissue Intensity Segmentation) algorithm was introduced. The advantage of the ARTIS algorithm was the delineation of SFT volumes in regions in which standard region grow techniques fail. Using the ARTIS algorithm, an automatic SFT volume detection was feasible. MRI data analysis was able to determine SFT and VFT volume percentages using new analytical strategies. With the techniques described, it was possible to detect changes in SFT and VFT percentages of the whole body and selected regions. The techniques presented in this study are likely to be of use in obesity-related investigations, as well as in the examination of longitudinal changes in weight during various medical conditions.

  1. Immunodetection of Human LINE-1 Expression in Cultured Cells and Human Tissues.

    PubMed

    Sharma, Reema; Rodić, Nemanja; Burns, Kathleen H; Taylor, Martin S

    2016-01-01

    Long interspersed element-1 (LINE-1) is the only active protein-coding retrotransposon in humans. It is not expressed in somatic tissue but is aberrantly expressed in a wide variety of human cancers. ORF1p protein is the most robust indicator of LINE-1 expression; the protein accumulates in large quantities in cellular cytoplasm. Recently, monoclonal antibodies have allowed more complete characterizations of ORF1p expression and indicated potential for developing ORF1p as a clinical biomarker. Here, we describe a mouse monoclonal antibody specific for human LINE-1 ORF1p and its application in immunofluorescence and immunohistochemistry of both cells and human tissues. We also describe detection of tagged LINE-1 ORF2p via immunofluorescence. These general methods may be readily adapted to use with many other proteins and antibodies.

  2. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.

    PubMed

    Carrasco-Benso, Maria P; Rivero-Gutierrez, Belen; Lopez-Minguez, Jesus; Anzola, Andrea; Diez-Noguera, Antoni; Madrid, Juan A; Lujan, Juan A; Martínez-Augustin, Olga; Scheer, Frank A J L; Garaulet, Marta

    2016-09-01

    In humans, insulin sensitivity varies according to time of day, with decreased values in the evening and at night. Mechanisms responsible for the diurnal variation in insulin sensitivity are unclear. We investigated whether human adipose tissue (AT) expresses intrinsic circadian rhythms in insulin sensitivity that could contribute to this phenomenon. Subcutaneous and visceral AT biopsies were obtained from extremely obese participants (body mass index, 41.8 ± 6.3 kg/m(2); 46 ± 11 y) during gastric-bypass surgery. To assess the rhythm in insulin signaling, AKT phosphorylation was determined every 4 h over 24 h in vitro in response to different insulin concentrations (0, 1, 10, and 100 nM). Data revealed that subcutaneous AT exhibited robust circadian rhythms in insulin signaling (P < 0.00001). Insulin sensitivity reached its maximum (acrophase) around noon, being 54% higher than during midnight (P = 0.009). The amplitude of the rhythm was positively correlated with in vivo sleep duration (r = 0.53; P = 0.023) and negatively correlated with in vivo bedtime (r = -0.54; P = 0.020). No circadian rhythms were detected in visceral AT (P = 0.643). Here, we demonstrate the relevance of the time of the day for how sensitive AT is to the effects of insulin. Subcutaneous AT shows an endogenous circadian rhythm in insulin sensitivity that could provide an underlying mechanism for the daily rhythm in systemic insulin sensitivity.-Carrasco-Benso, M. P., Rivero-Gutierrez, B., Lopez-Minguez, J., Anzola, A., Diez-Noguera, A., Madrid, J. A., Lujan, J. A., Martínez-Augustin, O., Scheer, F. A. J. L., Garaulet, M. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.

  3. Cardiac Structure and Function in Humans: A New Cardiovascular Physiology Laboratory

    ERIC Educational Resources Information Center

    Song, Su; Burleson, Paul D.; Passo, Stanley; Messina, Edward J.; Levine, Norman; Thompson, Carl I.; Belloni, Francis L.; Recchia, Fabio A.; Ojaimi, Caroline; Kaley, Gabor; Hintze, Thomas H.

    2009-01-01

    As the traditional cardiovascular control laboratory has disappeared from the first-year medical school curriculum, we have recognized the need to develop another "hands-on" experience as a vehicle for wide-ranging discussions of cardiovascular control mechanisms. Using an echocardiograph, an automatic blood pressure cuff, and a reclining bicycle,…

  4. Investigation of normal human skin tissue and acupuncture points of human skin tissue using fiberoptical FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Brooks, Angelique L.; Bruch, Reinhard F.; Afanasyeva, Natalia I.; Kolyakov, Sergei F.; Butvina, Leonid N.; Ma, Lixing

    1998-06-01

    An innovative spectroscopic diagnostic method has been developed for investigation of different regions of normal human skin tissue. This new method is a combination of Fourier transform IR fiberoptic evanescent wave (FTIR-FEW) spectroscopy and fiber optic techniques for the middle IR (MIR) wavelength range. The fiber optical sensors we have used are characterized by low optical losses and high flexibility for remote analysis. Our fiber optical accessories and method allows for direct interaction of the skin tissue with the fiber probe and can be utilized with a diversity of standard commercial Fourier transform spectrometers. The FTIR-FEW technique, using nontoxic unclad fibers in the attenuated total reflection regime, is suitable for noninvasive, fast, sensitive investigations of normal skin in vivo for various medical diagnostics applications including studies of acupuncture points. Here we present the first data on IR spectra of skin tissue in vivo for normal skin and several acupuncture points in the range of 1300 to 1800 cm-1 and 2600 to 4000 cm-1.

  5. Laser hard tissue interactions: energy transmission through human dental tissue using a holmium:YAG laser

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Holt, Raleigh A.; Nordquist, Robert E.

    1995-05-01

    Laser energy transmission through hard tissue was investigated using a pulsed Holmium:YAG laser (2.12 micrometers wavelength). The surface of extracted human dental tissue, 200 micrometers to 700 micrometers in thickness, was irradiated by a laser beam of various fluences between 3 J/cm2 to 28 J/cm2. The transmitted energy through different dentinal components of the tooth was measured. For the mature teeth, the region of the dentinoenamel junction showed the least transmission and the coronal the most; the difference between the two regions could be as large as 20%. The unerupted or young teeth revealed the opposite transmission characteristics. Repeated laser treatment revealed an enhanced transmissibility and the transmitted energy reached a plateau after certain irradiation exposure. Also studied were the effects of various media on the dental transmissibility. For example, surface application of a smear layer of unfilled resin did not change the transmissibility but appeared to slow down the temperature build-up. Visible surface damage -- a yellow or a white spot on the treatment site -- appeared when the fluence reached beyond 20 J/cm2. SEM samples revealed three different surface structural changes: melting with tubule closures, surface removal with tubule exposures, and surface cracking with crater formation, depending on the level of irradiation.

  6. Cardiovascular pharmacogenetics.

    PubMed

    Myburgh, Renier; Hochfeld, Warren E; Dodgen, Tyren M; Ker, James; Pepper, Michael S

    2012-03-01

    Human genetic variation in the form of single nucleotide polymorphisms as well as more complex structural variations such as insertions, deletions and copy number variants, is partially responsible for the clinical variation seen in response to pharmacotherapeutic drugs. This affects the likelihood of experiencing adverse drug reactions and also of achieving therapeutic success. In this paper, we review key studies in cardiovascular pharmacogenetics that reveal genetic variations underlying the outcomes of drug treatment in cardiovascular disease. Examples of genetic associations with drug efficacy and toxicity are described, including the roles of genetic variability in pharmacokinetics (e.g. drug metabolizing enzymes) and pharmacodynamics (e.g. drug targets). These findings have functional implications that could lead to the development of genetic tests aimed at minimizing drug toxicity and optimizing drug efficacy in cardiovascular medicine.

  7. Human thermal bioclimatic conditions associated with acute cardiovascular syndromes in Crete Island, Greece

    NASA Astrophysics Data System (ADS)

    Bleta, Anastasia G.; Nastos, Panagiotis T.

    2013-04-01

    The aim of this study is to quantify the association between bioclimatic conditions and daily counts of admissions for non-fatal acute cardiovascular (acute coronary syndrome, arrhythmia, decompensation of heart failure) syndromes (ACS) registered by the two main hospitals in Heraklion, Crete Island, during a five-year period 2008-2012. The bioclimatic conditions analyzed are based on human thermal bioclimatic indices such as the Physiological Equivalent Temperature (PET) and the Universal Thermal Climate Index (UTCI). Mean daily meteorological parameters, such as air temperature, relative humidity, wind speed and cloudiness, were acquired from the meteorological station of Heraklion (Hellenic National Meteorological Service). These parameters were used as input variables in modeling the aforementioned thermal indices, in order to interpret the grade of the thermo-physiological stress. The PET and UTCI analysis was performed by the use of the radiation and bioclimate model, "RayMan", which is well-suited to calculate radiation fluxes and human biometeorological indices. Generalized linear models (GLM) were applied to time series of daily numbers of outpatients with ACS against bioclimatic variations, after controlling for possible confounders and adjustment for season and trends. The interpretation of the results of this analysis suggests a significant association between cold weather and increased coronary heart disease incidence, especially in the elderly and males. Additionally, heat stress plays an important role in the configuration of daily ACS outpatients, even in temperate climate, as that in Crete Island. In this point it is worth mentioning that Crete Island is frequently affected by Saharan outbreaks, which are associated in many cases with miscellaneous phenomena, such as Föhn winds - hot and dry winds - causing extreme bioclimatic conditions (strong heat stress). Taking into consideration the projected increased ambient temperature in the future, ACS

  8. Cardiovascular regulation in humans in response to oscillatory lower body negative pressure

    NASA Technical Reports Server (NTRS)

    Levenhagen, D. K.; Evans, J. M.; Wang, M.; Knapp, C. F.

    1994-01-01

    The frequency response characteristics of human cardiovascular regulation during hypotensive stress have not been determined. We therefore exposed 10 male volunteers to seven frequencies (0.004-0.1 Hz) of oscillatory lower body negative pressure (OLBNP; 0-50 mmHg). Fourier spectra of arterial pressure (AP), central venous pressure (CVP), stroke volume (SV), cardiac output (CO), heart rate (HR), and total peripheral resistance (TPR) were determined and first harmonic mean, amplitude, and phase angles with respect to OLBNP are presented. AP was relatively well regulated as demonstrated by small oscillations in half amplitude (3.5 mmHg) that were independent of OLBNP frequency and similar to unstressed control spectra. Due to the biomechanics of the system, the magnitudes of oscillations in calf circumference (CC) and CVP decreased with increasing frequency; therefore, we normalized responses by these indexes of the fluid volume shifted. The ratios of oscillations in AP to oscillations in CC increased by an order of magnitude, whereas oscillations in CVP to oscillations in CC and oscillations in AP to oscillations in CVP both tripled between 0.004 and 0.1 Hz. Therefore, even though the amount of fluid shifted by OLBNP decreased with increasing frequency, the magnitude of both CVP and AP oscillations per volume of fluid shifted increased (peaking at 0.08 Hz). The phase relationships between variables, particularly the increasing lags in SV and TPR, but not CVP, indicated that efferent responses with lags of 5-6 s could account for the observed responses. We conclude that, at frequencies below 0.02 Hz, the neural system of humans functioned optimally in regulating AP; OLBNP-induced decreases in SV (by as much as 50%) were counteracted by appropriate oscillations in HR and TPR responses. As OLBNP frequency increased, SV, TPR, and HR oscillations increasingly lagged the input and became less optimally timed for AP regulation.

  9. New dimensions in tissue engineering: possible models for human physiology.

    PubMed

    Baar, Keith

    2005-11-01

    Tissue engineering is a discipline of great promise. In some areas, such as the cornea, tissues engineered in the laboratory are already in clinical use. In other areas, where the tissue architecture is more complex, there are a number of obstacles to manoeuvre before clinically relevant tissues can be produced. However, even in areas where clinically relevant tissues are decades away, the tissues being produced at the moment provide powerful new models to aid the understanding of complex physiological processes. This article provides a personal view of the role of tissue engineering in advancing our understanding of physiology, with specific attention being paid to musculoskeletal tissues.

  10. Characterization of proopiomelanocortin transcripts in human nonpituitary tissues

    SciTech Connect

    Lacaze-Masmonteil, T.; De Keyzer, Y.; Luton, J.P.; Kahn, A.; Bertagna, X.

    1987-10-01

    Proopiomelanocortin (POMC), the precursor to adrenocorticotropic hormone and other related peptides, was originally identified in the corticotropic cell. Recent evidence shows that POMC products are also normally present in a variety of nonpituitary tissues. To investigate this phenomenon in humans the authors looked for the presence and characteristics of POMC transcripts in various adult tissues. Blot hybridization analysis of normal adrenal, thymus, and testis RNAs revealed a small RNA species approximately 400 nucleotides shorter than the 1200-nucleotide pituitary species. Primer extension and S1 nuclease mapping studies showed that this small RNA lacked exon 1 and exon 2 of the gene, and it corresponded to a set of at least six molecules starting 41 to 162 nucleotides downstream from the 5' end of exon 3. These RNAs appear to result from heterogeneous transcription initiation sites presumably under the control of GC box promoter sequences located in the 3' end of intron 2. They cannot encode a complete POMC molecule, and the only truncated POMC molecules that could be translated would lack a signal peptide necessary for membrane translocation and precursor processing. The use of highly sensitive S1 nuclease mapping techniques with uniformly labeled single-stranded DNA probes allowed the detection of a small but definite amount of the normal, 1200-nucleotide, mRNA species. It is suggested that it is this POMC mRNA that is responsible for the local production of all the POMC peptides.

  11. Photobiomodulation in human muscle tissue: an advantage in sports performance?

    PubMed

    Ferraresi, Cleber; Huang, Ying-Ying; Hamblin, Michael R

    2016-12-01

    Photobiomodulation (PBM) describes the use of red or near-infrared (NIR) light to stimulate, heal, and regenerate damaged tissue. Both preconditioning (light delivered to muscles before exercise) and PBM applied after exercise can increase sports performance in athletes. This review covers the effects of PBM on human muscle tissue in clinical trials in volunteers related to sports performance and in athletes. The parameters used were categorized into those with positive effects or no effects on muscle performance and recovery. Randomized controlled trials and case-control studies in both healthy trained and untrained participants, and elite athletes were retrieved from MEDLINE up to 2016. Performance metrics included fatigue, number of repetitions, torque, hypertrophy; measures of muscle damage and recovery such as creatine kinase and delayed onset muscle soreness. Searches retrieved 533 studies, of which 46 were included in the review (n = 1045 participants). Studies used single laser probes, cluster of laser diodes, LED clusters, mixed clusters (lasers and LEDs), and flexible LED arrays. Both red, NIR, and red/NIR mixtures were used. PBM can increase muscle mass gained after training, and decrease inflammation and oxidative stress in muscle biopsies. We raise the question of whether PBM should be permitted in athletic competition by international regulatory authorities.

  12. Organochlorine pesticides and PCBs in human adipose tissues in Poland

    SciTech Connect

    Ludwicki, J.K.; Goralczyk, K. )

    1994-03-01

    Most of the persistent organochlorine (OC) pesticides, excluding lindane, were banned in Poland in 1975/76. The first restrictions concerning the use and marketing of lindane (gamma-HCH) became effective in 1980 and were gradually extended until it's agricultural use was ultimately banned in 1989. Unfortunately, there are no detailed data on the use and release of PCBs to the environment in Poland. The former studies showed that in the late seventies the concentrations of OC pesticides and their metabolites in men reached considerable high levels. Despite of the restrictions or bans of these pesticides in most of the countries of the temperate climate, they still circulate in various food chains and eventually concentrate in man. Many authors claim an uneven distribution of the OC compounds in the population and report different levels in men and women and also some relations between OC compounds levels in fat tissues and age. Environmental contamination also plays an important role in the magnitude of OC compounds levels in man. The aim of this paper is to present the actual concentrations of HCB, p,p[prime]-DDT, p,p[prime]-DDE, isomers of HCH (alpha, beta, gamma), and PCBs in human adipose tissues particularly regarding age and sex as possible factors influencing the levels of these compounds and to contribute to the general discussion on the distribution patterns of the organochlorine compounds in the population. 12 refs., 3 tabs.

  13. Engineering bone tissue substitutes from human induced pluripotent stem cells.

    PubMed

    de Peppo, Giuseppe Maria; Marcos-Campos, Iván; Kahler, David John; Alsalman, Dana; Shang, Linshan; Vunjak-Novakovic, Gordana; Marolt, Darja

    2013-05-21

    Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate the utility of human-induced pluripotent stem cells (hiPSCs) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. We then engineered functional bone substitutes by culturing hiPSC-derived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 wk. Molecular analysis confirmed that the maturation of bone substitutes in perfusion bioreactors results in global repression of cell proliferation and an increased expression of lineage-specific genes. These results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease.

  14. Magnesium degradation products: effects on tissue and human metabolism.

    PubMed

    Seitz, J-M; Eifler, R; Bach, Fr-W; Maier, H J

    2014-10-01

    Owing to their mechanical properties, metallic materials present a promising solution in the field of resorbable implants. The magnesium metabolism in humans differs depending on its introduction. The natural, oral administration of magnesium via, for example, food, essentially leads to an intracellular enrichment of Mg(2+) . In contrast, introducing magnesium-rich substances or implants into the tissue results in a different decomposition behavior. Here, exposing magnesium to artificial body electrolytes resulted in the formation of the following products: magnesium hydroxide, magnesium oxide, and magnesium chloride, as well as calcium and magnesium apatites. Moreover, it can be assumed that Mg(2+) , OH(-) ions, and gaseous hydrogen are also present and result from the reaction for magnesium in an aqueous environment. With the aid of physiological metabolic processes, the organism succeeds in either excreting the above mentioned products or integrating them into the natural metabolic process. Only a burst release of these products is to be considered a problem. A multitude of general tissue effects and responses from the Mg's degradation products is considered within this review, which is not targeting specific implant classes. Furthermore, common alloying elements of magnesium and their hazardous potential in vivo are taken into account.

  15. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

    PubMed Central

    Fukusumi, Hayato; Shofuda, Tomoko; Bamba, Yohei; Yamamoto, Atsuyo; Kanematsu, Daisuke; Handa, Yukako; Okita, Keisuke; Nakamura, Masaya; Yamanaka, Shinya; Okano, Hideyuki; Kanemura, Yonehiro

    2016-01-01

    Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes. PMID:27212953

  16. Volume Expansion of Tissue Engineered Human Nasal Septal Cartilage

    PubMed Central

    Reuther, Marsha S; Briggs, Kristen K; Neuman, Monica K; Masuda, Koichi; Sah, Robert L; Watson, Deborah

    2014-01-01

    Importance Cartilaginous craniofacial defects range in size and autologous cartilaginous tissue is preferred for repair of these defects. Therefore, it is important to have the ability to produce large size cartilaginous constructs for repair of cartilaginous abnormalities. Objectives To produce autologous human septal neocartilage constructs substantially larger in size than previously produced constructs To demonstrate that volume expanded neocartilage constructs possess comparable histological and biochemical properties to standard size constructs To show that volume expanded neocartilage constructs retain similar biomechanical properties to standard size constructs Design Prospective, basic science Setting Laboratory Participants The study used remnant human septal specimens removed during routine surgery at the University of California, San Diego Medical Center or San Diego Veterans Affairs Medical Center. Cartilage from a total of 8 donors was collected. Main Outcomes Measured Human septal chondrocytes from 8 donors were used to create 12mm and 24mm neocartilage constructs. These were cultured for a total of 10 weeks. Photo documentation, histological, biochemical, and biomechanical properties were measured and compared. Results The 24mm diameter constructs were qualitatively similar to the 12mm constructs. They possessed adequate strength and durability to be manually manipulated. Histological analysis of the constructs demonstrated similar staining patterns in standard and volume expanded constructs. Proliferation, as measured by DNA content, was similar in 24mm and 12mm constructs. Additionally, glycosaminoglycan (GAG) and total collagen content did not significantly differ between the two construct sizes. Biomechanical analysis of the 24mm and 12mm constructs demonstrated comparable compressive and tensile properties. Conclusion and Relevance Volume expanded human septal neocartilage constructs are qualitatively and histologically similar to standard 12mm

  17. Full-field bulge test for planar anisotropic tissues: part I--experimental methods applied to human skin tissue.

    PubMed

    Tonge, Theresa K; Atlan, Lorre S; Voo, Liming M; Nguyen, Thao D

    2013-04-01

    The nonlinear anisotropic properties of human skin tissue were investigated using bulge testing. Full-field displacement data were obtained during testing of human skin tissues procured from the lower back of post-mortem human subjects using 3-D digital image correlation. To measure anisotropy, the dominant fiber direction of the tissue was determined from the deformed geometry of the specimen. Local strains and stress resultants were calculated along both the dominant fiber direction and the perpendicular direction. Variation in anisotropy and stiffness was observed between specimens. The use of stress resultants rather than the membrane stress approximation accounted for bending effects, which are significant for a thick nonlinear tissue. Of the six specimens tested, it was observed that specimens from older donors exhibited a stiffer and more isotropic response than those from younger donors. It was seen that the mechanical response of the tissue was negligibly impacted by preconditioning or the ambient humidity. The methods presented in this work for skin tissue are sufficiently general to be applied to other planar tissues, such as pericardium, gastrointestinal tissue, and fetal membranes. The stress resultant-stretch relations will be used in a companion paper to obtain material parameters for a nonlinear anisotropic hyperelastic model.

  18. Viral inactivation of human bone tissue using supercritical fluid extraction.

    PubMed

    Fages, J; Poirier, B; Barbier, Y; Frayssinet, P; Joffret, M L; Majewski, W; Bonel, G; Larzul, D

    1998-01-01

    A new bone tissue process using supercritical carbon dioxide fluid extraction (SFE) has been evaluated for its ability to inactivate or eliminate viruses. Four viruses, human immunodeficiency virus type 1 (HIV-1), Sindbis virus, polio Sabin type I virus, and pseudorabies virus (PRV), were exposed to four different processing steps. In addition to supercritical CO2, hydrogen peroxide, sodium hydroxide, and ethanol treatments were evaluated. The mean cumulated reduction factors (log10) for the four viruses exposed to these four steps were > 14.2 for HIV-1, > 18.2 for Sindbis virus, > 24.4 for poliovirus, and > 17.6 for PRV. The mean reduction factors obtained by the supercritical fluid extraction alone were > 4.0, > 4.3, > 6.6, and > 4.0, respectively. These results demonstrate that the SFE process is effective in inactivating viruses on human femoral heads, and provides a level of inactivation similar to that obtained by traditional cleaning methods. It is proposed that CO2 SFE be incorporated as a routine step in the processing of bone allografts for transplantation either to replace or supplement existing procedures.

  19. Absorbed dose assessment of cardiac and other tissues around the cardiovascular system in brachytherapy with 90Sr/90Y source by Monte Carlo simulation.

    PubMed

    Saghamanesh, S; Karimian, A; Abdi, M

    2011-09-01

    Cardiac disease is one of the most important causes of death in the world. Coronary artery stenosis is a very common cardiac disease. Intravascular brachytherapy (IVBT) is one of the radiotherapy methods which have been used recently in coronary artery radiation therapy for the treatment of restenosis. (90)Sr/(90)Y, a beta-emitting source, is a proper option for cardiovascular brachytherapy. In this research, a Monte Carlo simulation was done to calculate dosimetry parameters and effective equivalent doses to the heart and its surrounding tissues during IVBT. The results of this study were compared with the published experimental data and other simulations performed by different programs but with the same source of radiation. A very good agreement was found between results of this work and the published data. An assessment of the risk for cardiac and other sensitive soft tissues surrounding the treated vessel during (90)Sr/(90)Y IVBT was also performed in the study.

  20. An LC-MS assay for the screening of cardiovascular medications in human samples

    PubMed Central

    Dias, Eduardo; Hachey, Brian; McNaughton, Candace; Nian, Hui; Yu, Chang; Straka, Britt; Brown, Nancy J.; Caprioli, Richard M.

    2013-01-01

    Cardiovascular drugs are the most commonly prescribed medications. Some prior assays successfully detect cardiovascular drugs among multiple classes using a single sample. Here, we develop an assay to detect a broad range of cardiovascular drug classes to include commonly used cardiovascular drugs and evaluate the assay’s analytical and statistical properties in a clinical setting. We describe a protocol for drug detection that encompasses 34 commonly prescribed cardiovascular drugs or drug metabolites with a single LC-MS/MS method using 100µl of serum or plasma. Drug classes monitored by this assay include: anticoagulants, angiotensin converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), beta blockers, calcium channel blockers, diuretics, statins, and vasodilators, as well as digoxin, fenofibrate, and niacin. Analytical accuracy and precision for each drug was evaluated by repeating the assay on spiked samples at low, medium, and high concentrations. In 294 clinical samples obtained from hospitalized patients for whom medication administration was recorded, we evaluated the assay’s statistical sensitivity, specificity, and accuracy. For the 34 drugs or drug metabolites, the assay was statistically sensitive (>0.90) for all drugs except captopril (0.25), isosorbide (0.81), and niacin (0.89). The assay was statistically specific for all drugs, with a minimum specificity of 0.94 (aspirin). To our knowledge, this method is the first method of simultaneous analysis of 34 cardiovascular drugs or drug metabolites from nine drug classes evaluated using clinical samples from hospitalized patients. PMID:24013190

  1. Brown Adipose Tissue and Seasonal Variation in Humans

    PubMed Central

    Au-Yong, Iain T.H.; Thorn, Natasha; Ganatra, Rakesh; Perkins, Alan C.; Symonds, Michael E.

    2009-01-01

    OBJECTIVE Brown adipose tissue (BAT) is present in adult humans where it may be important in the prevention of obesity, although the main factors regulating its abundance are not well established. BAT demonstrates seasonal variation relating to ambient temperature and photoperiod in mammals. The objective of our study was therefore to determine whether seasonal variation in BAT activity in humans was more closely related to the prevailing photoperiod or temperature. RESEARCH DESIGN AND METHODS We studied 3,614 consecutive patients who underwent positron emission tomography followed by computed tomography scans. The presence and location of BAT depots were documented and correlated with monthly changes in photoperiod and ambient temperature. RESULTS BAT activity was demonstrated in 167 (4.6%) scans. BAT was demonstrated in 52/724 scans (7.2%) in winter compared with 27/1,067 (2.5%) in summer months (P < 0.00001, χ2 test). Monthly changes in the occurrence of BAT were more closely related to differences in photoperiod (r2 = 0.876) rather than ambient temperature (r2 = 0.696). Individuals with serial scans also demonstrated strong seasonal variation in BAT activity (average standardized uptake value [SUVmax] 1.5 in July and 9.4 in January). BAT was also more common in female patients (female: n = 107, 7.2%; male: n = 60, 2.8%; P < 0.00001, χ2 test). CONCLUSIONS Our study demonstrates a very strong seasonal variation in the presence of BAT. This effect is more closely associated with photoperiod than ambient temperature, suggesting a previously undescribed mechanism for mediating BAT function in humans that could now potentially be recruited for the prevention or reversal of obesity. PMID:19696186

  2. [The features of adaptation and disadaptation of the human cardiovascular system in the space flight conditions].

    PubMed

    Kotovskaia, A R; Fomina, G A

    2010-01-01

    The work was aimed at analysis and generalization of the hemodynamic data collected over 20 years from 26 cosmonauts flown 8 to 438 days aboard orbital stations Salyut 7 and Mir. The paper presents the results of ultrasonic investigations of the heart, arterial and venous peripheral vessels in different parts of human body, and measurements of leg veins capacity with the use of occlusive plethysmograpy. It was shown that in the resting condition such prime hemodynamic parameters as the pumping function of the heart and blood supply of the brain, and integral parameters, i.e. arterial pressure and heat rate, were best "protected" as they demonstrated stability throughout long exposure in microgravity. In the absence of gravitational stimulation, arterial resistance went down in essentially all vascular regions below the heart level; to put it differently, the anti-gravity distribution of the vascular tone was annulled gradually as unneeded in microgravity. Compared with the data about arteries, venous hemodynamics was found to be particularly sensitive considering the early advent and significance of changes. Venous return slowed down, resistance of the lower body vessels declined and capacity of the leg venous net increased. Functional testing with the lower body negative pressure revealed degradation of the gravity-dependent reactions that became more conspicuous as flight duration extended further. Cardiovascular deconditioning showed itself clearly on return to Earth's gravity by decreased g-tolerance during re-entry and orthostatic instability post flight. These investigations provided objective evidence for multifactorial genesis of orthostatic instability during space flight including blood redistribution, altered tone regulation of leg's venous and arterial vessels and hypovolemia.

  3. Requirement of DLG1 for cardiovascular development and tissue elongation during cochlear, enteric, and skeletal development: possible role in convergent extension.

    PubMed

    Iizuka-Kogo, Akiko; Senda, Takao; Akiyama, Tetsu; Shimomura, Atsushi; Nomura, Ryuji; Hasegawa, Yoshimi; Yamamura, Ken-Ichi; Kogo, Hiroshi; Sawai, Nobuhiko; Matsuzaki, Toshiyuki

    2015-01-01

    The Dlg1 gene encodes a member of the MAGUK protein family involved in the polarization of epithelial cells. Null mutant mice for the Dlg1 gene (Dlg1-/- mice) exhibit respiratory failure and cyanosis, and die soon after birth. However, the cause of this neonatal lethality has not been determined. In the present study, we further examined Dlg1-/- mice and found severe defects in the cardiovascular system, including ventricular septal defect, persistent truncus arteriosus, and double outlet right ventricle, which would cause the neonatal lethality. These cardiovascular phenotypes resemble those of mutant mice lacking planar cell polarity (PCP) genes and support a recent notion that DLG1 is involved in the PCP pathway. We assessed the degree of involvement of DLG1 in the development of other organs, as the cochlea, intestine, and skeleton, in which PCP signaling has been suggested to play a role. In the organ of Corti, tissue elongation was inhibited accompanied by disorganized arrangement of the hair cell rows, while the orientation of the stereocilia bundle was normal. In the sternum, cleft sternum, abnormal calcification pattern of cartilage, and disorganization of chondrocytes were observed. Furthermore, shortening of the intestine, sternum, and long bones of the limbs was observed. These phenotypes of Dlg1-/- mice involving cellular disorganization and insufficient tissue elongation strongly suggest a defect in the convergent extension movements in these mice. Thus, our present results provide a possibility that DLG1 is particularly required for convergent extension among PCP signaling-dependent processes.

  4. A Comprehensive TALEN-Based Knockout Library for Generating Human Induced Pluripotent Stem Cell-Based Models for Cardiovascular Diseases.

    PubMed

    Karakikes, Ioannis; Termglinchan, Vittavat; Cepeda, Diana A; Lee, Jaecheol; Diecke, Sebastian; Hendel, Ayal; Itzhaki, Ilanit; Ameen, Mohamed; Shrestha, Rajani; Wu, Haodi; Ma, Ning; Shao, Ning-Yi; Seeger, Timon; Woo, Nicole A; Wilson, Kitchener D; Matsa, Elena; Porteus, Matthew H; Sebastiano, Vittorio; Wu, Joseph C

    2017-02-28

    Rationale: Targeted genetic engineering using programmable nucleases such as transcription activator-like effector nucleases (TALENs) is a valuable tool for precise, site-specific genetic modification in the human genome. Objective: The emergence of novel technologies such as human induced pluripotent stem cells (iPSCs) and nuclease-mediated genome editing represent a unique opportunity for studying cardiovascular diseases in vitro. Methods and Results: By incorporating extensive literature and database searches, we designed a collection of TALEN constructs to knockout (KO) eighty-eight human genes that are associated with cardiomyopathies and congenital heart diseases. The TALEN pairs were designed to induce double-strand DNA break near the starting codon of each gene that either disrupted the start codon or introduced a frameshift mutation in the early coding region, ensuring faithful gene KO. We observed that all the constructs were active and disrupted the target locus at high frequencies. To illustrate the general utility of the TALEN-mediated KO technique, six individual genes (TNNT2, LMNA/C, TBX5, MYH7, ANKRD1, and NKX2.5) were knocked out with high efficiency and specificity in human iPSCs. By selectively targeting a dilated cardiomyopathy (DCM)-causing mutation (TNNT2 p.R173W) in patient-specific iPSC-derived cardiac myocytes (iPSC-CMs), we demonstrated that the KO strategy ameliorates the DCM phenotype in vitro. In addition, we modeled the Holt-Oram syndrome (HOS) in iPSC-CMs in vitro and uncovered novel pathways regulated by TBX5 in human cardiac myocyte development. Conclusions: Collectively, our study illustrates the powerful combination of iPSCs and genome editing technology for understanding the biological function of genes and the pathological significance of genetic variants in human cardiovascular diseases. The methods, strategies, constructs and iPSC lines developed in this study provide a validated, readily available resource for cardiovascular

  5. 75 FR 34146 - Proposed Collection; Comment Request Resource for the Collection and Evaluation of Human Tissues...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-16

    ... HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request Resource for the Collection and Evaluation of Human Tissues and Cells From Donors With an Epidemiology Profile (NCI) SUMMARY... Collection: Title: Resource for the Collection and Evaluation of Human Tissues and Cells From Donors With...

  6. A computational physiology approach to personalized treatment models: the beneficial effects of slow breathing on the human cardiovascular system

    PubMed Central

    Fonoberova, Maria; Mezić, Igor; Buckman, Jennifer F.; Fonoberov, Vladimir A.; Mezić, Adriana; Vaschillo, Evgeny G.; Mun, Eun-Young; Vaschillo, Bronya

    2014-01-01

    Heart rate variability biofeedback intervention involves slow breathing at a rate of ∼6 breaths/min (resonance breathing) to maximize respiratory and baroreflex effects on heart period oscillations. This intervention has wide-ranging clinical benefits and is gaining empirical support as an adjunct therapy for biobehavioral disorders, including asthma and depression. Yet, little is known about the system-level cardiovascular changes that occur during resonance breathing or the extent to which individuals differ in cardiovascular benefit. This study used a computational physiology approach to dynamically model the human cardiovascular system at rest and during resonance breathing. Noninvasive measurements of heart period, beat-to-beat systolic and diastolic blood pressure, and respiration period were obtained from 24 healthy young men and women. A model with respiration as input was parameterized to better understand how the cardiovascular processes that control variability in heart period and blood pressure change from rest to resonance breathing. The cost function used in model calibration corresponded to the difference between the experimental data and model outputs. A good match was observed between the data and model outputs (heart period, blood pressure, and corresponding power spectral densities). Significant improvements in several modeled cardiovascular functions (e.g., blood flow to internal organs, sensitivity of the sympathetic component of the baroreflex, ventricular elastance) were observed during resonance breathing. Individual differences in the magnitude and nature of these dynamic responses suggest that computational physiology may be clinically useful for tailoring heart rate variability biofeedback interventions for the needs of individual patients. PMID:25063789

  7. Status quo of management of the human tissue banks in Taiwan.

    PubMed

    Chou, Ching-Pang; Chou, Szu-Cheng; Chen, Ying-Hua; Chen, Yu-Hsuan; Lee, Ming-Shin

    2017-03-01

    As the technologies associated with transplantation and biological tissue engineering continue to advance, human cells and tissues form an integral part to the practice of regenerative medicine. The patient's use of tissues entails the risk of introducing, transmitting and spreading communicable diseases. To prevent such risk and to ensure that the human organs, tissues and cells remain intact and functional after being handled and processed, the transplanted tissues must be subject to good management standards through all stages of collection, screening, processing, storage and distribution as the safety of the users is of the utmost importance. On February 2009, the government of Taiwan promulgated the Regulations for Administration on Human Organ Bank that requires all human tissues banks to adhere to the Good Tissue Practice for Human Organ, Tissue and Cell in terms of establishment and operation in order to cope with the international management trend and the development and management need of the domestic industry. Six years have passed since the law became effective. This article seeks to introduce the current management mechanism and status quo of management of human tissue banks in Taiwan. We also conducted statistical analysis of the data relating to the tissue banks to identify potential risks and the room for improvement. The study concludes that human tissue banks in Taiwan are on the right track with their management practice, leading to a state of steady development and progress.

  8. Impact of Statins on Gene Expression in Human Lung Tissues

    PubMed Central

    Lane, Jérôme; van Eeden, Stephan F.; Obeidat, Ma’en; Sin, Don D.; Tebbutt, Scott J.; Timens, Wim; Postma, Dirkje S.; Laviolette, Michel; Paré, Peter D.; Bossé, Yohan

    2015-01-01

    Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that alter the synthesis of cholesterol. Some studies have shown a significant association of statins with improved respiratory health outcomes of patients with asthma, chronic obstructive pulmonary disease and lung cancer. Here we hypothesize that statins impact gene expression in human lungs and may reveal the pleiotropic effects of statins that are taking place directly in lung tissues. Human lung tissues were obtained from patients who underwent lung resection or transplantation. Gene expression was measured on a custom Affymetrix array in a discovery cohort (n = 408) and two replication sets (n = 341 and 282). Gene expression was evaluated by linear regression between statin users and non-users, adjusting for age, gender, smoking status, and other covariables. The results of each cohort were combined in a meta-analysis and biological pathways were studied using Gene Set Enrichment Analysis. The discovery set included 141 statin users. The lung mRNA expression levels of eighteen and three genes were up-regulated and down-regulated in statin users (FDR < 0.05), respectively. Twelve of the up-regulated genes were replicated in the first replication set, but none in the second (p-value < 0.05). Combining the discovery and replication sets into a meta-analysis improved the significance of the 12 up-regulated genes, which includes genes encoding enzymes and membrane proteins involved in cholesterol biosynthesis. Canonical biological pathways altered by statins in the lung include cholesterol, steroid, and terpenoid backbone biosynthesis. No genes encoding inflammatory, proteases, pro-fibrotic or growth factors were altered by statins, suggesting that the direct effect of statin in the lung do not go beyond its antilipidemic action. Although more studies are needed with specific lung cell types and different classes and doses of statins, the improved health outcomes and survival observed in statin

  9. [Animal models of cardiovascular disease].

    PubMed

    Chorro, Francisco J; Such-Belenguer, Luis; López-Merino, Vicente

    2009-01-01

    The use of animal models to study cardiovascular disease has made a substantial contribution to increasing our understanding of disease pathogenesis, has led to the development of diagnostic techniques, and has made it possible to verify the effectiveness of different preventative and therapeutic approaches, whether pharmacological or interventional. The main limitations stem from differences between human and experimentally induced pathology, in terms of both genetic regulatory mechanisms and factors that influence cardiovascular function. The experimental models and preparations used in cardiovascular research include those based on isolated cells or tissues or structures immersed in organ baths. The Langendorff system enables isolated perfused hearts to be studied directly under conditions of either no load or controlled loading. In small mammals, a number of models have been developed of cardiovascular conditions that result from spontaneous genetic mutations or, alternatively, that may be induced by specific genomic modification. One of the techniques employed is gene transfer, which can involve the controlled induction of mutations that result in the expression of abnormalities associated with the development of a broad range of different types of cardiovascular disease. Larger animals are used in experimental models in which it is important that physiological regulatory and homeostatic mechanisms are present.

  10. Cell Therapy for Cardiovascular Regeneration

    PubMed Central

    2013-01-01

    A great numbers of cardiovascular disease patients all over the world are suffering in the poor outcomes. Under this situation, cardiac regeneration therapy to reorganize the postnatal heart that is defined as a terminal differentiated-organ is a very important theme and mission for human beings. However, the temporary success of several clinical trials using usual cell types with uncertain cell numbers has provided the transient effect of cell therapy to these patients. We therefore should redevelop the evidence of cell-based cardiovascular regeneration therapy, focusing on targets (disease, patient’s status, cardiac function), materials (cells, cytokines, genes), and methodology (transplantation route, implantation technology, tissue engineering). Meanwhile, establishment of the induced pluripotent stem (iPS) cells is an extremely innovative technology which should be proposed as embryonic stem (ES) cellularization of post natal somatic cells, and this application have also showed the milestones of the direct conversion to reconstruct cardiomyocyte from the various somatic cells, which does not need the acquisition of the re-pluripotency. This review discusses the new advance in cardiovascular regeneration therapy from cardiac regeneration to cardiac re-organization, which is involved in recent progress of on-going clinical trials, basic research in cardiovascular regeneration, and the possibility of tissue engineering technology. PMID:23825492

  11. Cardiac structure and function in humans: a new cardiovascular physiology laboratory

    PubMed Central

    Song, Su; Burleson, Paul D.; Passo, Stanley; Messina, Edward J.; Levine, Norman; Thompson, Carl I.; Belloni, Francis L.; Recchia, Fabio A.; Ojaimi, Caroline; Kaley, Gabor

    2009-01-01

    As the traditional cardiovascular control laboratory has disappeared from the first-year medical school curriculum, we have recognized the need to develop another “hands-on” experience as a vehicle for wide-ranging discussions of cardiovascular control mechanisms. Using an echocardiograph, an automatic blood pressure cuff, and a reclining bicycle, we developed protocols to illustrate the changes in cardiac and vascular function that occur with changes in posture, venous return, and graded exercise. We use medical student volunteers and a professional echocardiographer to generate and acquire data, respectively. In small-group sessions, we developed an interactive approach to discuss the data and to make a large number of calculations from a limited number of measurements. The sequence of cardiac events and cardiac structure in vivo were illustrated with the volunteers lying down, standing, and then with their legs raised passively above the heart to increase venous return. Volunteers were then asked to peddle the bicycle to achieve steady-state heart rates of 110 and 150 beats/min. Data were collected in all these states, and calculations were performed and used as the basis of a small-group discussion to illustrate physiological principles. Information related to a surprisingly large number of cardiovascular control mechanisms was derived, and its relevance to cardiovascular dysfunction was explored. This communication describes our experience in developing a new cardiovascular control laboratory to reinforce didactic material presented in lectures and small-group sessions. PMID:19745049

  12. Commodification of human tissue: implications for feminist and development ethics.

    PubMed

    Dickenson, Donna

    2002-05-01

    One effect of late capitalism--the commodification of practically everything--is to knock down the Chinese walls between the natural and productive realms, to use a Marxist framework. Women's labour in egg extraction and 'surrogate' motherhood might then be seen as what it is, labour which produces something of value. But this does not necessarily mean that women will benefit from the commodification of practically everything, in either North or South. In the newly developing biotechnologies involving stem cells, the reverse is more likely, particular given the the shortage in the North of the egg donors who will be increasingly necessary to therapeutic cloning. Although most of the ethical debate has focused on the status of the embryo, this is to define ethics with no reference to global or gender justice. There has been little or no debate about possible exploitation of women, particularly of ovum donors from the South. Countries of the South without national ethics committees or guidelines may be particularly vulnerable: although there is increasing awareness of the susceptibility of poorer countries to abuses in research ethics, very little has been written about how they might be affected by the enormously profitable new technologies exploiting human tissue. Even in the UK, although the new Medical Research Council guidelines make a good deal of the 'gift relationship', what they are actually about is commodification. If donors believe they are demonstrating altruism, but biotechnology firms and researchers use the discourse of commodity and profit, we have not 'incomplete commodification' but complete commodification with a plausibly human face.

  13. Evaluation of immunohistochemical staining for glucagon in human pancreatic tissue.

    PubMed

    Gurlo, Tatyana; Butler, Peter C; Butler, Alexandra E

    Immunohistochemistry (IHC) and immunofluorescence (IF) staining techniques are important diagnostic tools of anatomic pathology in the clinical setting and widely used analytical tools in research laboratories. In diabetes research, they are routinely used for the assessment of beta- and alpha-cell mass, for assessment of endocrine cell distribution within the pancreas, for evaluation of islet composition and islet morphology. Here, we present the evaluation of IHC techniques for the detection of alpha-cells in human pancreatic tissue. We compared the Horse Radish Peroxidase (HRP)-based method utilizing DAB Peroxidase Substrate to the Alkaline Phosphatase (AP)-based method utilizing Vector Red substrate. We conclude that HRP-DAB staining is a robust and reliable method for detection of alpha-cells using either rabbit polyclonal or mouse monoclonal anti-glucagon antibodies. However, AP-Vector Red staining should be used with caution, because it is affected by the dehydration with ethanol and toluene preceding the mounting of slides with Permount mounting medium. When AP-Vector Red is a preferable method for alpha-cell labeling, slides should be mounted using aqueous mounting medium or, alternatively, they could be air-dried before permanent mounting.

  14. Nattokinase-promoted tissue plasminogen activator release from human cells.

    PubMed

    Yatagai, Chieko; Maruyama, Masugi; Kawahara, Tomoko; Sumi, Hiroyuki

    2008-01-01

    When heated to a temperature of 70 degrees C or higher, the strong fibrinolytic activity of nattokinase in a solution was deactivated. Similar results were observed in the case of using Suc-Ala-Ala-Pro-Phe-pNA and H-D-Val-Leu-Lys-pNA, which are synthetic substrates of nattokinase. In the current study, tests were conducted on the indirect fibrinolytic effects of the substances containing nattokinase that had been deactivated through heating at 121 degrees C for 15 min. Bacillus subtilis natto culture solutions made from three types of bacteria strain were heat-treated and deactivated, and it was found that these culture solutions had the ability to generate tissue plasminogen activators (tPA) from vascular endothelial cells and HeLa cells at certain concentration levels. For example, it was found that the addition of heat-treated culture solution of the Naruse strain (undiluted solution) raises the tPA activity of HeLa cells to about 20 times that of the control. Under the same conditions, tPA activity was raised to a level about 5 times higher for human vascular endothelial cells (HUVEC), and to a level about 24 times higher for nattokinase sold on the market. No change in cell count was observed for HeLa cells and HUVEC in the culture solution at these concentrations, and the level of activity was found to vary with concentration.

  15. High-Resolution NMR Studies of Human Tissue Factor

    PubMed Central

    Nuzzio, Kristin M.; Watt, Eric D.; Boettcher, John M.; Gajsiewicz, Joshua M.; Morrissey, James H.; Rienstra, Chad M.

    2016-01-01

    In normal hemostasis, the blood clotting cascade is initiated when factor VIIa (fVIIa, other clotting factors are named similarly) binds to the integral membrane protein, human tissue factor (TF). The TF/fVIIa complex in turn activates fX and fIX, eventually concluding with clot formation. Several X-ray crystal structures of the soluble extracellular domain of TF (sTF) exist; however, these structures are missing electron density in functionally relevant regions of the protein. In this context, NMR can provide complementary structural information as well as dynamic insights into enzyme activity. The resolution and sensitivity for NMR studies are greatly enhanced by the ability to prepare multiple milligrams of protein with various isotopic labeling patterns. Here, we demonstrate high-yield production of several isotopically labeled forms of recombinant sTF, allowing for high-resolution NMR studies both in the solid and solution state. We also report solution NMR spectra at sub-mM concentrations of sTF, ensuring the presence of dispersed monomer, as well as the first solid-state NMR spectra of sTF. Our improved sample preparation and precipitation conditions have enabled the acquisition of multidimensional NMR data sets for TF chemical shift assignment and provide a benchmark for TF structure elucidation. PMID:27657719

  16. Measurement of elastic wave dispersion on human femur tissue

    NASA Astrophysics Data System (ADS)

    Strantza, M.; Louis, O.; Polyzos, D.; Boulpaep, F.; Van Hemelrijck, D.; Aggelis, D. G.

    2014-03-01

    Cortical bone is one of the most complex heterogeneous media exhibiting strong wave dispersion. In such media when a burst of energy goes into the formation of elastic waves the different modes tend to separate according to the velocities of the frequency components as usually occurs in waveguides. In this study human femur specimens were subjected to elastic wave measurements. The main objective of the study is using broadband acoustic emission sensors to measure parameters like wave velocity dispersion and attenuation. Additionally, waveform parameters like the duration, rise time and average frequency, are also examined relatively to the propagation distance as a preparation for acoustic emission monitoring during fracture. To do so, four sensors were placed at adjacent positions on the surface of the cortical bone in order to record the transient response after pencil lead break excitation. The results are compared to similar measurements on a bulk metal piece which does not exhibit heterogeneity at the scale of the propagating wave lengths. It is shown that the microstructure of the tissue imposes a dispersive behavior for frequencies below 1 MHz and care should be taken for interpretation of the signals.

  17. Low Energy Defibrillation in Human Cardiac Tissue: A Simulation Study

    PubMed Central

    Morgan, Stuart W.; Plank, Gernot; Biktasheva, Irina V.; Biktashev, Vadim N.

    2009-01-01

    We aim to assess the effectiveness of feedback-controlled resonant drift pacing as a method for low energy defibrillation. Antitachycardia pacing is the only low energy defibrillation approach to have gained clinical significance, but it is still suboptimal. Low energy defibrillation would avoid adverse side effects associated with high voltage shocks and allow the application of implantable cardioverter defibrillator (ICD) therapy, in cases where such therapy is not tolerated today. We present results of computer simulations of a bidomain model of cardiac tissue with human atrial ionic kinetics. Reentry was initiated and low energy shocks were applied with the same period as the reentry, using feedback to maintain resonance. We demonstrate that such stimulation can move the core of reentrant patterns, in the direction that depends on the location of the electrodes and the time delay in the feedback. Termination of reentry is achieved with shock strength one-order-of-magnitude weaker than in conventional single-shock defibrillation. We conclude that resonant drift pacing can terminate reentry at a fraction of the shock strength currently used for defibrillation and can potentially work where antitachycardia pacing fails, due to the feedback mechanisms. Success depends on a number of details that these numerical simulations have uncovered. PMID:19217854

  18. Characterization of RNA isolated from eighteen different human tissues: results from a rapid human autopsy program.

    PubMed

    Walker, Douglas G; Whetzel, Alexis M; Serrano, Geidy; Sue, Lucia I; Lue, Lih-Fen; Beach, Thomas G

    2016-09-01

    Many factors affect the integrity of messenger RNA from human autopsy tissues including postmortem interval (PMI) between death and tissue preservation and the pre-mortem agonal and disease states. In this communication, we describe RNA isolation and characterization of 389 samples from 18 different tissues from elderly donors who were participants in a rapid whole-body autopsy program located in Sun City, Arizona ( www.brainandbodydonationprogram.org ). Most tissues were collected within a PMI of 2-6 h (median 3.15 h; N = 455), but for this study, tissue from cases with longer PMIs (1.25-29.25 h) were included. RNA quality was assessed by RNA integrity number (RIN) and total yield (ng RNA/mg tissue). RIN correlated with PMI for heart (r = -0.531, p = 0.009) and liver (r = -558, p = 0.0017), while RNA yield correlated with PMI for colon (r = -485, p = 0.016) and skin (r = -0.460, p = 0.031). RNAs with the lowest integrity were from skin and cervix where 22.7 and 31.4 % of samples respectively failed to produce intact RNA; by contrast all samples from esophagus, lymph node, jejunum, lung, stomach, submandibular gland and kidney produced RNA with measurable RINs. Expression levels in heart RNA of 4 common housekeeping normalization genes showed significant correlations of Ct values with RIN, but only one gene, glyceraldehyde-3 phosphate dehydrogenase, showed a correlation of Ct with PMI. There were no correlations between RIN values obtained for liver, adrenal, cervix, esophagus and lymph node and those obtained from corresponding brain samples. We show that high quality RNA can be produced from most human autopsy tissues, though with significant differences between tissues and donors. The RNA stability and yield did not depend solely on PMI; other undetermined factors are involved, but these do not include the age of the donor.

  19. Fetal growth restriction and cardiovascular outcome in early human infancy: a prospective longitudinal study.

    PubMed

    Mäkikallio, Kaarin; Shah, Jyotsna; Slorach, Cameron; Qin, Hong; Kingdom, John; Keating, Sarah; Kelly, Ed; Manlhiot, Cedric; Redington, Andrew; Jaeggi, Edgar

    2016-09-01

    The association between low birth weight and premature cardiovascular disease has led to the "prenatal origin of adult disease-hypothesis". We postulated that fetal growth restriction is associated with cardiovascular changes detectable at birth and in early infancy. Fifty-two appropriately grown fetuses (AGA) and 60 growth-restricted fetuses (FGR) with (n = 20) or without (n = 40) absent or reversed end-diastolic umbilical artery blood flow were prospectively examined by echocardiography before birth, at 1 week and 6 months of life. The impact of growth restriction on postnatal blood pressure, heart rate, cardiovascular dimensions, and function, as well as on vascular morphology of umbilical cord vessels was studied. FGR fetuses displayed significant blood flow redistribution and were delivered earlier with lower birth weights than AGA fetuses. After adjustment for gender, gestational age, and weight at birth, there were no intergroup differences in blood pressure, heart rate, left ventricular morphology, mass, and performance, and in cord vessel morphology. During the first 6 months of life brachioradial pulse wave velocity increased more in FGR fetuses, while other parameters describing vascular stiffness remained comparable between the groups. Fetal growth restriction had no detectable adverse impact on cardiovascular dimensions and function at birth. Cardiovascular findings also remained comparable during the first 6 months of life between the groups except a higher increase in brachioradial pulse wave velocity in the FGR group. Our observations suggest that abnormalities that link reduced intrauterine growth with premature cardiovascular diseases may commence later in childhood, indicating a potential window for screening and prevention.

  20. Current Approaches to Quantifying Tonic and Reflex Autonomic Outflows Controlling Cardiovascular Function in Humans and Experimental Animals.

    PubMed

    Salman, Ibrahim M

    2015-11-01

    The role of the autonomic nervous system in the pathophysiology of human and experimental models of cardiovascular disease is well established. In the recent years, there have been some rapid developments in the diagnostic approaches used to assess and monitor autonomic functions. Although most of these methods are devoted for research purposes in laboratory animals, many have still found their way to routine clinical practice. To name a few, direct long-term telemetry recording of sympathetic nerve activity (SNA) in rodents, single-unit SNA recording using microneurography in human subjects and spectral analysis of blood pressure and heart rate in both humans and animals have recently received an overwhelming attention. In this article, we therefore provide an overview of the methods and techniques used to assess tonic and reflex autonomic functions in humans and experimental animals, highlighting current advances available and procedure description, limitations and usefulness for diagnostic purposes.

  1. Recombinant human activated protein C attenuates cardiovascular and microcirculatory dysfunction in acute lung injury and septic shock

    PubMed Central

    2010-01-01

    Introduction This prospective, randomized, controlled, experimental animal study looks at the effects of recombinant human activated protein C (rhAPC) on global hemodynamics and microcirculation in ovine acute lung injury (ALI) and septic shock, resulting from smoke inhalation injury. Methods Twenty-one sheep (37 ± 2 kg) were operatively prepared for chronic study and randomly allocated to either the sham, control, or rhAPC group (n = 7 each). The control and rhAPC groups were subjected to insufflation of four sets of 12 breaths of cotton smoke followed by instillation of live Pseudomonas aeruginosa into both lung lobes, according to an established protocol. Healthy sham animals were not subjected to the injury and received only four sets of 12 breaths of room air and instillation of the vehicle (normal saline). rhAPC (24 μg/kg/hour) was intravenously administered from 1 hour post injury until the end of the 24-hour experiment. Regional microvascular blood flow was analyzed using colored microspheres. All sheep were mechanically ventilated with 100% oxygen, and fluid resuscitated with lactated Ringer's solution to maintain hematocrit at baseline levels. Results The rhAPC-associated reduction in heart malondialdehyde (MDA) and heart 3-nitrotyrosine (a reliable indicator of tissue injury) levels occurred parallel to a significant increase in mean arterial pressure and to a significant reduction in heart rate and cardiac output compared with untreated controls that showed a typical hypotensive, hyperdynamic response to the injury (P < 0.05). In addition, rhAPC significantly attenuated the changes in microvascular blood flow to the trachea, kidney, and spleen compared with untreated controls (P < 0.05 each). Blood flow to the ileum and pancreas, however, remained similar between groups. The cerebral blood flow as measured in cerebral cortex, cerebellum, thalamus, pons, and hypothalamus, was significantly increased in untreated controls, due to a loss of cerebral

  2. Using a human cardiovascular-respiratory model to characterize cardiac tamponade and pulsus paradoxus

    PubMed Central

    Ramachandran, Deepa; Luo, Chuan; Ma, Tony S; Clark, John W

    2009-01-01

    Background Cardiac tamponade is a condition whereby fluid accumulation in the pericardial sac surrounding the heart causes elevation and equilibration of pericardial and cardiac chamber pressures, reduced cardiac output, changes in hemodynamics, partial chamber collapse, pulsus paradoxus, and arterio-venous acid-base disparity. Our large-scale model of the human cardiovascular-respiratory system (H-CRS) is employed to study mechanisms underlying cardiac tamponade and pulsus paradoxus. The model integrates hemodynamics, whole-body gas exchange, and autonomic nervous system control to simulate pressure, volume, and blood flow. Methods We integrate a new pericardial model into our previously developed H-CRS model based on a fit to patient pressure data. Virtual experiments are designed to simulate pericardial effusion and study mechanisms of pulsus paradoxus, focusing particularly on the role of the interventricular septum. Model differential equations programmed in C are solved using a 5th-order Runge-Kutta numerical integration scheme. MATLAB is employed for waveform analysis. Results The H-CRS model simulates hemodynamic and respiratory changes associated with tamponade clinically. Our model predicts effects of effusion-generated pericardial constraint on chamber and septal mechanics, such as altered right atrial filling, delayed leftward septal motion, and prolonged left ventricular pre-ejection period, causing atrioventricular interaction and ventricular desynchronization. We demonstrate pericardial constraint to markedly accentuate normal ventricular interactions associated with respiratory effort, which we show to be the distinct mechanisms of pulsus paradoxus, namely, series and parallel ventricular interaction. Series ventricular interaction represents respiratory variation in right ventricular stroke volume carried over to the left ventricle via the pulmonary vasculature, whereas parallel interaction (via the septum and pericardium) is a result of

  3. Terahertz pulsed imaging of freshly excised human colonic tissues

    NASA Astrophysics Data System (ADS)

    Reid, Caroline B.; Fitzgerald, Anthony; Reese, George; Goldin, Robert; Tekkis, Paris; O'Kelly, P. S.; Pickwell-MacPherson, Emma; Gibson, Adam P.; Wallace, Vincent P.

    2011-07-01

    We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption.

  4. The impact on histopathology practice of new human tissue legislation in the UK.

    PubMed

    Underwood, J C E

    2006-09-01

    The undisclosed or unauthorized retention of tissue from autopsies in the UK and elsewhere has caused considerable public concern and much distress to some families. Histopathologists involved in these cases have also been discomfited. These events have exposed deficiencies in prevailing legislation, principally in the Human Tissue Act 1961 and the Coroners Rules 1984. New human tissue legislation comes into force in the UK in September 2006. The Human Tissue Act 2004 and the Human Tissue (Scotland) Act 2006 make it unlawful to remove, store and use tissue from the dead without appropriate authority. The Human Tissue Act 2004, which does not apply in Scotland, also prohibits the removal, storage and use of tissue from living individuals for purposes specified in the Act unless appropriate consent has been obtained. The Coroners (Amendment) Rules 2005, which came into force in June 2005, introduced new arrangements for dealing with the retention of tissue from bodies undergoing coroner's autopsies. This new legislative regime is intended to create a climate in which pathologists, patients and the public can have confidence that tissue is used appropriately and, when necessary, with proper authority or valid consent. However, other than in Scotland, there may be unintended consequences arising from restrictions on archiving, for audit and diagnostic review, tissue samples from coronial autopsies.

  5. Effects and underlying mechanisms of human opiorphin on cardiovascular activity in anesthetized rats.

    PubMed

    Tian, Xiao-zhu; Chen, Yong; Bai, Lu; Luo, Pan; Du, Xue-jing; Chen, Qiang; Tian, Xin-min

    2015-02-15

    The present study was performed to investigate the peripheral cardiovascular effects of opiorphin in anesthetized rats. Intravenous (i.v.) injection of opiorphin (50-500nmol/kg) caused marked dose-dependent increase in blood pressure and heart rate. The pressor and tachycardic responses induced by opiorphin (300nmol/kg, i.v.) were significantly decreased by pretreatment with angiotensin-converting enzyme inhibitor captopril or angiotensin II type 1 (AT1) receptor antagonist valsartan, which suggested that endogenous angiotensin may be involved in the response to opiorphin. Pretreatment with α-adrenoreceptor antagonist phentolamine and β-adrenoceptor antagonist propranolol respectively attenuated the pressor response induced by opiorphin. Propranolol, but not phentolamine, inhibited the tachycardic response. Moreover, reserpine blocked both responses to opiorphin. These findings indicated that the effects of opiorphin to increase blood pressure and heart rate might be due to the stimulation of sympathetic ganglia. Additionally, studies with bilaterally adrenalectomized rats showed that adrenal medulla may be involved in the cardiovascular regulation of opiorphin. In addition, pretreatment with nonselective opioid receptor antagonist naloxone did not modify the cardiovascular responses to opiorphin, suggesting that the effects of opiorphin were not related to the opioid system. Furthermore, radioimmunoassay (RIA) showed that opiorphin significantly increased endogenous levels of angiotensin II and angiotensin III. In summary, all the results indicate that the cardiovascular effects induced by opiorphin are mediated through the renin-angiotensin system (RAS), the sympathetic ganglia and adrenal medulla, but not the opioid system.

  6. Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents.

    PubMed

    Murphy, M O; Cohn, D M; Loria, A S

    2017-03-01

    The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood.

  7. The effects of cardiovascular exercise on human memory: a review with meta-analysis.

    PubMed

    Roig, Marc; Nordbrandt, Sasja; Geertsen, Svend Sparre; Nielsen, Jens Bo

    2013-09-01

    We reviewed the evidence for the use of cardiovascular exercise to improve memory and explored potential mechanisms. Data from 29 and 21 studies including acute and long-term cardiovascular interventions were retrieved. Meta-analyses revealed that acute exercise had moderate (SMD=0.26; 95% CI=0.03, 0.49; p=0.03; N=22) whereas long-term had small (SMD=0.15; 95% CI=0.02, 0.27; p=0.02; N=37) effects on short-term memory. In contrast, acute exercise showed moderate to large (SMD=0.52; 95% CI=0.28, 0.75; p<0.0001; N=20) whereas long-term exercise had insignificant effects (SMD=0.07; 95% CI=-0.13, 0.26; p=0.51; N=22) on long-term memory. We argue that acute and long-term cardiovascular exercise represent two distinct but complementary strategies to improve memory. Acute exercise improves memory in a time-dependent fashion by priming the molecular processes involved in the encoding and consolidation of newly acquired information. Long-term exercise, in contrast, has negligible effects on memory but provides the necessary stimuli to optimize the responses of the molecular machinery responsible for memory processing. Strategically combined, acute and long-term interventions could maximize the benefits of cardiovascular exercise on memory.

  8. Controlled Exposure of Humans with Metabolic Syndrome to Concentrated Ultrafine Ambient Particulate Matter Causes Cardiovascular Effects

    EPA Science Inventory

    Background: Many studies have reported associations between PM2.5 and adverse cardiovascular effects. However there is increased concern that ultrafine PM (aerodynamic diameter less than 0.1 micron) may be disproportionately toxic relative to the 0.1 to 2.5 micron fraction of PM2...

  9. Estrogen receptor β actions in the female cardiovascular system: A systematic review of animal and human studies.

    PubMed

    Muka, Taulant; Vargas, Kris G; Jaspers, Loes; Wen, Ke-xin; Dhana, Klodian; Vitezova, Anna; Nano, Jana; Brahimaj, Adela; Colpani, Veronica; Bano, Arjola; Kraja, Bledar; Zaciragic, Asija; Bramer, Wichor M; van Dijk, Gaby M; Kavousi, Maryam; Franco, Oscar H

    2016-04-01

    Five medical databases were searched for studies that assessed the role of ERβ in the female cardiovascular system and the influence of age and menopause on ERβ functioning. Of 9472 references, 88 studies met our inclusion criteria (71 animal model experimental studies, 15 human model experimental studies and 2 population based studies). ERβ signaling was shown to possess vasodilator and antiangiogenic properties by regulating the activity of nitric oxide, altering membrane ionic permeability in vascular smooth muscle cells, inhibiting vascular smooth muscle cell migration and proliferation and by regulating adrenergic control of the arteries. Also, a possible protective effect of ERβ signaling against left ventricular hypertrophy and ischemia/reperfusion injury via genomic and non-genomic pathways was suggested in 27 studies. Moreover, 5 studies reported that the vascular effects of ERβ may be vessel specific and may differ by age and menopause status. ERβ seems to possess multiple functions in the female cardiovascular system. Further studies are needed to evaluate whether isoform-selective ERβ-ligands might contribute to cardiovascular disease prevention.

  10. Definition of human apolipoprotein A-I epitopes recognized by autoantibodies present in patients with cardiovascular diseases.

    PubMed

    Teixeira, Priscila Camillo; Ducret, Axel; Ferber, Philippe; Gaertner, Hubert; Hartley, Oliver; Pagano, Sabrina; Butterfield, Michelle; Langen, Hanno; Vuilleumier, Nicolas; Cutler, Paul

    2014-10-10

    Autoantibodies to apolipoprotein A-I (anti-apoA-I IgG) have been shown to be both markers and mediators of cardiovascular disease, promoting atherogenesis and unstable atherosclerotic plaque. Previous studies have shown that high levels of anti-apoA-I IgGs are independently associated with major adverse cardiovascular events in patients with myocardial infarction. Autoantibody responses to apoA-I can be polyclonal and it is likely that more than one epitope may exist. To identify the specific immunoreactive peptides in apoA-I, we have developed a set of methodologies and procedures to isolate, purify, and identify novel apoA-I endogenous epitopes. First, we generated high purity apoA-I from human plasma, using thiophilic interaction chromatography followed by enzymatic digestion specifically at lysine or arginine residues. Immunoreactivity to the different peptides generated was tested by ELISA using serum obtained from patients with acute myocardial infarction and high titers of autoantibodies to native apoA-I. The immunoreactive peptides were further sequenced by mass spectrometry. Our approach successfully identified two novel immunoreactive peptides, recognized by autoantibodies from patients suffering from myocardial infarction, who contain a high titer of anti-apoA-I IgG. The discovery of these epitopes may open innovative prognostic and therapeutic opportunities potentially suitable to improve current cardiovascular risk stratification.

  11. VEGF expression in human brain tissue after acute ischemic stroke.

    PubMed

    Mărgăritescu, Otilia; Pirici, D; Mărgăritescu, Cl

    2011-01-01

    Ischemic stroke is the third most common cause of death in humans, requiring further studies to elucidate its pathophysiological background. One potential mechanism to increase oxygen delivery to the affected tissue is induction of angiogenesis. The most potent proangiogenic factor is VEGF. For this reason, our study investigated immunohistochemically VEGF reactivity in different cellular brain compartments from 15 ischemic stroke patients, as well as from 2 age control cases. By enzymatic immunohistochemistry, we investigate VEGF expression in different brain cell compartments and then we quantified its signal intensity by assessing integrated optical densities (IOD). To establish the exact cellular brain topography of VEGF immunoreactivity we performed double fluorescent immunohistochemistry series (VEGF÷NeuN, GFAP, CD68, CD105). In control samples, VEGF reactivity was observed especially in neurons from the Brodmann cortical layers IV to VI and in protoplasmic astrocytes from the deeper layers of gray matter and in endothelial cells from normal blood vessels because of systemic hypoxia generated after death. In acute ischemic stroke samples, this reactivity was noticed in all brain cellular compartments but with different intensities. The most reactive compartment was the neurons, the intensity of VEGF reaction decreasing with the lesional age from the core infarct toward intact adjacent brain cortex. With a lower intensity, VEGF reaction was noticed in astrocytes compartments, especially in gemistocytic astrocytes adjacent to the liquefaction zone. We also noticed a weak reaction in activated non-phagocytic microglia from the periphery of liquefaction zones, and high VEGF-CD105 colocalization values at the level of microvessels that surround the infarcted brain area. In conclusion, this reactivity could suggest that VEGF might exhibit neuronal and glial protective effects and also a neoangiogenic property in acute ischemic stroke, facts that may have

  12. Analysis of mRNA from human heart tissue and putative applications in forensic molecular pathology.

    PubMed

    Partemi, Sara; Berne, Paola M; Batlle, Montserrat; Berruezo, Antonio; Mont, Luis; Riuró, Helena; Ortiz, José T; Roig, Eulalia; Pascali, Vincenzo L; Brugada, Ramon; Brugada, Josep; Oliva, Antonio

    2010-12-15

    The usefulness of post-mortem mRNA analysis and its potential applications in forensic casework is currently of interest, especially because of several factors affecting the quality of RNA samples that are not practically predictable. In fact, post-mortem RNA degradation is a complex process that has not been studied systematically. The purpose of this work is to establish whether RNA analysis from post-mortem heart tissue could be used as a forensic tool to investigate the cause of death, with special regard to those cases where a cardiac disease is suspected as the manner of death. We analysed heart tissue from 16 individuals with normal cardiac function, 9 with long post-mortem intervals (L-PMI) and 7 from organ donors with very short PMIs (S-PMIs). Right ventricle tissue was homogenised, and the RNA was isolated and reverse transcribed. The resulting cDNA was used in real-time PCR reactions to quantify the gene expression of beta-glucuronidase (GUSB), Nitric Oxide Synthase 3 (NOS3), Collagen 1 (COL1A1) and Collagen 3 (COL3A1). The percentage of samples with high-quality RNA was higher in samples with S-PMI (7 out of 7) than in samples with L-PMI (4 out of 9, p<0.05). No differences in PMI time or cause of exitus were found between samples with degraded or non-degraded RNA in the L-PMI group. When comparing mRNA levels in samples with non-degraded RNA, we found similar values between the L-PMI and S-PMI groups for GUSB, COL1A1 and COL3A1. The NOS3 gene expression in the L-PMI subgroup was less than half that in the S-PMI. These results suggest that high-quality mRNA can be extracted from post-mortem human hearts only in some cases. Moreover, our data show that mRNA levels are independent from the PMI, even though there are mRNAs in which the expression levels are very susceptible to ischemia times. Clear knowledge about the relationship between mRNA integrity and expression and PMI could allow the use of several mRNAs as forensic tools to contribute to the

  13. Quantification of Calcified Particles in Human Valve Tissue Reveals Asymmetry of Calcific Aortic Valve Disease Development

    PubMed Central

    Yabusaki, Katsumi; Hutcheson, Joshua D.; Vyas, Payal; Bertazzo, Sergio; Body, Simon C.; Aikawa, Masanori; Aikawa, Elena

    2016-01-01

    Recent studies indicated that small calcified particles observable by scanning electron microscopy (SEM) may initiate calcification in cardiovascular tissues. We hypothesized that if the calcified particles precede gross calcification observed in calcific aortic valve disease (CAVD), they would exhibit a regional asymmetric distribution associated with CAVD development, which always initiates at the base of aortic valve leaflets adjacent to the aortic outflow in a region known as the fibrosa. Testing this hypothesis required counting the calcified particles in histological sections of aortic valve leaflets. SEM images, however, do not provide high contrast between components within images, making the identification and quantification of particles buried within tissue extracellular matrix difficult. We designed a new unique pattern-matching based technique to allow for flexibility in recognizing particles by creating a gap zone in the detection criteria that decreased the influence of non-particle image clutter in determining whether a particle was identified. We developed this flexible pattern particle-labeling (FpPL) technique using synthetic test images and human carotid artery tissue sections. A conventional image particle counting method (preinstalled in ImageJ) did not properly recognize small calcified particles located in noisy images that include complex extracellular matrix structures and other commonly used pattern-matching methods failed to detect the wide variation in size, shape, and brightness exhibited by the particles. Comparative experiments with the ImageJ particle counting method demonstrated that our method detected significantly more (p < 2 × 10−7) particles than the conventional method with significantly fewer (p < 0.0003) false positives and false negatives (p < 0.0003). We then applied the FpPL technique to CAVD leaflets and showed a significant increase in detected particles in the fibrosa at the base of the leaflets (p

  14. Needle optical coherence elastography for the measurement of microscale mechanical contrast deep within human breast tissues

    NASA Astrophysics Data System (ADS)

    Kennedy, Kelsey M.; McLaughlin, Robert A.; Kennedy, Brendan F.; Tien, Alan; Latham, Bruce; Saunders, Christobel M.; Sampson, David D.

    2013-12-01

    Optical coherence elastography (OCE) is an emerging imaging technique that probes microscale mechanical contrast in tissues with the potential to differentiate healthy and malignant tissues. However, conventional OCE techniques are limited to imaging the first 1 to 2 mm of tissue in depth. We demonstrate, for the first time, OCE measurements deep within human tissues using needle OCE, extending the potential of OCE as a surgical guidance tool. We use needle OCE to detect tissue interfaces based on mechanical contrast in both normal and malignant breast tissues in freshly excised human mastectomy samples, as validated against histopathology. Further, we demonstrate the feasibility of in situ measurements >4 cm from the tissue surface using ultrasound guidance of the OCE needle probe. With further refinement, our method may potentially aid in accurate detection of the boundary of the tumor to help ensure full removal of all malignant tissues, which is critical to the success of breast-conserving surgery.

  15. The effects of exercise on blood flow with reference to the human cardiovascular system: a finite element study

    NASA Technical Reports Server (NTRS)

    Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.

    1992-01-01

    This paper reports on a theoretical investigation into the effects of vasomotion on blood through the human cardiovascular system. The finite element method has been used to analyse the model. Vasoconstriction and vasodilation may be effected either through the action of the central nervous system or autoregulation. One of the conditions responsible for vasomotion is exercise. The proposed model has been solved and quantitative results of flows and pressures due to changing the conductances of specific networks of arterioles, capillaries and venules comprising the arms, legs, stomach and their combinations have been obtained.

  16. Human stem cells and articular cartilage tissue engineering.

    PubMed

    Stoltz, J-F; Huselstein, C; Schiavi, J; Li, Y Y; Bensoussan, D; Decot, V; De Isla, N

    2012-12-01

    Injuries to articular cartilage are one of the most challenging issues of musculoskeletal medicine due to the poor intrinsic ability of this tissue for repair. Despite progress in orthopaedic surgery, cell-based surgical therapies such as autologous chondrocyte transplantation (ACT) have been in clinical use for cartilage repair for over a decade but this approach has shown mixed results. Moreover, the lack of efficient modalities of treatment for large chondral defects has prompted research on cartilage tissue engineering combining cells, scaffold materials and environmental factors. This paper focuses on the main parameters in tissue engineering and in particular, on the potential of mesenchymal stem cells (MSCs) as an alternative to cells derived from patient tissues in autologous transplantation and tissue engineering. We discussed the prospects of using autologous chondrocytes or MSCs in regenerative medicine and summarized the advantages and disadvantages of these cells in articular cartilage engineering.

  17. Evidence for Trypanosoma cruzi in adipose tissue in human chronic Chagas disease

    PubMed Central

    Ferreira, Adaliene Versiani Matos; Segatto, Marcela; Menezes, Zélia; Macedo, Andréa Mara; Gelape, Cláudio; de Oliveira Andrade, Luciana; Nagajyothi, Fnu; Scherer, Philipp E.; Teixeira, Mauro Martins; Tanowitz, Herbert B.

    2013-01-01

    Trypanosoma cruzi the cause of Chagas disease persists in tissues of infected experimental animals and humans. Here we demonstrate the persistence of the parasite in adipose tissue from of three of 10 elderly seropositive patients with chronic chagasic heart disease. Nine control patients had no parasites in the fat. We also demonstrate that T. cruzi parasitizes primary adipocytes in vitro. Thus, in humans as in mice the parasite may persist in adipose tissue for decades and become a reservoir of infection. PMID:21726660

  18. Evidence for Trypanosoma cruzi in adipose tissue in human chronic Chagas disease.

    PubMed

    Ferreira, Adaliene Versiani Matos; Segatto, Marcela; Menezes, Zélia; Macedo, Andréa Mara; Gelape, Cláudio; de Oliveira Andrade, Luciana; Nagajyothi, Fnu; Scherer, Philipp E; Teixeira, Mauro Martins; Tanowitz, Herbert B

    2011-11-01

    Trypanosoma cruzi the cause of Chagas disease persists in tissues of infected experimental animals and humans. Here we demonstrate the persistence of the parasite in adipose tissue from of three of 10 elderly seropositive patients with chronic chagasic heart disease. Nine control patients had no parasites in the fat. We also demonstrate that T. cruzi parasitizes primary adipocytes in vitro. Thus, in humans as in mice the parasite may persist in adipose tissue for decades and become a reservoir of infection.

  19. Characterization of human breast cancer tissues by infrared imaging.

    PubMed

    Verdonck, M; Denayer, A; Delvaux, B; Garaud, S; De Wind, R; Desmedt, C; Sotiriou, C; Willard-Gallo, K; Goormaghtigh, E

    2016-01-21

    Fourier Transform InfraRed (FTIR) spectroscopy coupled to microscopy (IR imaging) has shown unique advantages in detecting morphological and molecular pathologic alterations in biological tissues. The aim of this study was to evaluate the potential of IR imaging as a diagnostic tool to identify characteristics of breast epithelial cells and the stroma. In this study a total of 19 breast tissue samples were obtained from 13 patients. For 6 of the patients, we also obtained Non-Adjacent Non-Tumor tissue samples. Infrared images were recorded on the main cell/tissue types identified in all breast tissue samples. Unsupervised Principal Component Analyses and supervised Partial Least Square Discriminant Analyses (PLS-DA) were used to discriminate spectra. Leave-one-out cross-validation was used to evaluate the performance of PLS-DA models. Our results show that IR imaging coupled with PLS-DA can efficiently identify the main cell types present in FFPE breast tissue sections, i.e. epithelial cells, lymphocytes, connective tissue, vascular tissue and erythrocytes. A second PLS-DA model could distinguish normal and tumor breast epithelial cells in the breast tissue sections. A patient-specific model reached particularly high sensitivity, specificity and MCC rates. Finally, we showed that the stroma located close or at distance from the tumor exhibits distinct spectral characteristics. In conclusion FTIR imaging combined with computational algorithms could be an accurate, rapid and objective tool to identify/quantify breast epithelial cells and differentiate tumor from normal breast tissue as well as normal from tumor-associated stroma, paving the way to the establishment of a potential complementary tool to ensure safe tumor margins.

  20. Raman spectrosopic characterization of human malignant tissues: implications for a percutaneous optical biopsy technique for in-situ tissue diagnosis

    NASA Astrophysics Data System (ADS)

    Redd, Douglas C. B.; Frank, Christopher J.; Feng, Zhe Chuan; Gansler, Ted S.; McCreery, Richard L.

    1994-01-01

    Recent advancements in the technique of Raman spectroscopy now make it possible to achieve rapid, minimally invasive and non-destructive characterization of tissues. In order to evaluate the efficacy of this technique for diagnosis, the Raman spectra of normal and neoplastic human tissues (e.g., breast, kidney, liver and colon) were obtained utilizing visible and near-IR excitation. Normal breast tissue and colon adenocarcinoma showed major Raman features due to the presence of carotenoids and lipids. In breast carcinoma, the features due to lipids were attenuated and as fibrosis (desmoplasia) increased, new spectral features attributable to collagen were observed. Samples of normal and neoplastic liver and kidney show unique spectral differences sufficient to permit tissue differentiation.

  1. X-ray microscopy of soft and hard human tissues

    SciTech Connect

    Müller, Bert Schulz, Georg Deyhle, Hans Stalder, Anja K. Ilgenstein, Bernd Holme, Margaret N. Hieber, Simone E.; Beckmann, Felix

    2016-01-28

    The simultaneous post mortem visualization of soft and hard tissues using absorption-based CT remains a challenge. If the photon energy is optimized for the visualization of hard tissue, the surrounding soft tissue components are almost X-ray transparent. Therefore, the combination with other modalities such as phase-contrast CT, magnetic resonance microscopy, and histology is essential to detect the anatomical features. The combination of the 2D and 3D data sets using sophisticated segmentation and registration tools allows for conclusions about otherwise inaccessible anatomical features essential for improved patient treatments.

  2. X-ray microscopy of soft and hard human tissues

    NASA Astrophysics Data System (ADS)

    Müller, Bert; Schulz, Georg; Deyhle, Hans; Stalder, Anja K.; Ilgenstein, Bernd; Holme, Margaret N.; Weitkamp, Timm; Beckmann, Felix; Hieber, Simone E.

    2016-01-01

    The simultaneous post mortem visualization of soft and hard tissues using absorption-based CT remains a challenge. If the photon energy is optimized for the visualization of hard tissue, the surrounding soft tissue components are almost X-ray transparent. Therefore, the combination with other modalities such as phase-contrast CT, magnetic resonance microscopy, and histology is essential to detect the anatomical features. The combination of the 2D and 3D data sets using sophisticated segmentation and registration tools allows for conclusions about otherwise inaccessible anatomical features essential for improved patient treatments.

  3. The influence of the human microbiome and probiotics on cardiovascular health

    PubMed Central

    Ettinger, Grace; MacDonald, Kyle; Reid, Gregor; Burton, Jeremy P

    2014-01-01

    Cardiovascular disease (CVD) is a major cause of death worldwide. Of the many etiological factors, microorganisms constitute one. From the local impact of the gut microbiota on energy metabolism and obesity, to the distal association of periodontal disease with coronary heart disease, microbes have a significant impact on cardiovascular health. In terms of the ability to modulate or influence the microbes, probiotic applications have been considered. These are live microorganisms which when administered in adequate amounts confer a benefit on the host. While a number of reports have established the beneficial abilities of certain probiotic bacterial strains to reduce cholesterol and hypertension, recent research suggests that their use could be more widely applied. This review presents an up-to-date summary of the known associations of the microbiome with CVD, and potential applications of probiotic therapy. PMID:25529048

  4. Patterns of Senescence in Human Cardiovascular Fitness: VO2max in Subsistence and Industrialized Populations

    PubMed Central

    Pisor, Anne C.; Gurven, Michael; Blackwell, Aaron D.; Kaplan, Hillard; Yetish, Gandhi

    2014-01-01

    Objectives This study explores whether cardiovascular fitness levels and senescent decline are similar in the Tsimane of Bolivia and Canadians, as well as other subsistence and industrialized populations. Among Tsimane, we examine whether morbidity predicts lower levels and faster decline of cardiovascular fitness, or whether their lifestyle (e.g., high physical activity) promotes high levels and slow decline. Alternatively, high activity levels and morbidity might counterbalance such that Tsimane fitness levels and decline are similar to those in industrialized populations. Methods Maximal oxygen uptake (VO2max) was estimated using a step test heart rate method for 701 participants. We compared these estimates to the Canadian Health Measures Survey and previous studies in industrialized and subsistence populations. We evaluated whether health indicators and proxies for market integration were associated with VO2max levels and rate of decline for the Tsimane. Results The Tsimane have significantly higher levels of VO2max and slower rates of decline than Canadians; initial evidence suggests differences in VO2max levels between other subsistence and industrialized populations. Low hemoglobin predicts low VO2max for Tsimane women while helminth infection predicts high VO2max for Tsimane men, though results might be specific to the VO2max scaling parameter used. No variables tested interact with age to moderate decline. Conclusions The Tsimane demonstrate higher levels of cardiovascular fitness than industrialized populations, but levels similar to other subsistence populations. The high VO2max of Tsimane is consistent with their high physical activity and few indicators of cardiovascular disease, measured in previous studies. PMID:24022886

  5. Impact of the human circadian system, exercise, and their interaction on cardiovascular function.

    PubMed

    Scheer, Frank A J L; Hu, Kun; Evoniuk, Heather; Kelly, Erin E; Malhotra, Atul; Hilton, Michael F; Shea, Steven A

    2010-11-23

    The risk of adverse cardiovascular events peaks in the morning (≈9:00 AM) with a secondary peak in the evening (≈8:00 PM) and a trough at night. This pattern is generally believed to be caused by the day/night distribution of behavioral triggers, but it is unknown whether the endogenous circadian system contributes to these daily fluctuations. Thus, we tested the hypotheses that the circadian system modulates autonomic, hemodynamic, and hemostatic risk markers at rest, and that behavioral stressors have different effects when they occur at different internal circadian phases. Twelve healthy adults were each studied in a 240-h forced desynchrony protocol in dim light while standardized rest and exercise periods were uniformly distributed across the circadian cycle. At rest, there were large circadian variations in plasma cortisol (peak-to-trough ≈85% of mean, peaking at a circadian phase corresponding to ≈9:00 AM) and in circulating catecholamines (epinephrine, ≈70%; norepinephrine, ≈35%, peaking during the biological day). At ≈8:00 PM, there was a circadian peak in blood pressure and a trough in cardiac vagal modulation. Sympathetic variables were consistently lowest and vagal markers highest during the biological night. We detected no simple circadian effect on hemostasis, although platelet aggregability had two peaks: at ≈noon and ≈11:00 PM. There was circadian modulation of the cardiovascular reactivity to exercise, with greatest vagal withdrawal at ≈9:00 AM and peaks in catecholamine reactivity at ≈9:00 AM and ≈9:00 PM. Thus, the circadian system modulates numerous cardiovascular risk markers at rest as well as their reactivity to exercise, with resultant profiles that could potentially contribute to the day/night pattern of adverse cardiovascular events.

  6. Plasma and Dietary Antioxidant Status as Cardiovascular Disease Risk Factors: A Review of Human Studies

    PubMed Central

    Wang, Ying; Chun, Ock K.; Song, Won O.

    2013-01-01

    Extensive evidence has demonstrated that many antioxidants such as vitamin C, vitamin E, carotenoids and polyphenols have protective effects in preventing cardiovascular disease (CVD), a chronic disease that is mediated by oxidative stress and inflammation. This review focuses on evidence from prospective cohort studies and clinical trials in regard to the associations between plasma/dietary antioxidants and cardiovascular events. Long-term, large-scale, population-based cohort studies have found that higher levels of serum albumin, bilirubin, glutathione, vitamin E, vitamin C, and carotenoids were associated with a lower risk of CVD. Evidence from the cohort studies in regard to dietary antioxidants also supported the protective effects of dietary vitamin E, vitamin C, carotenoids, and polyphenols on CVD risk. However, results from large randomized controlled trials did not support long-term use of single antioxidant supplements for CVD prevention due to their null or even adverse effects on major cardiovascular events or cancer. Diet quality indexes that consider overall diet quality rather than single nutrients have been drawing increasing attention. Cohort studies and intervention studies that focused on diet patterns such as high total antioxidant capacity have documented protective effects on CVD risk. This review provides a perspective for future studies that investigate antioxidant intake and risk of CVD. PMID:23912327

  7. Creation of a Large Adipose Tissue Construct in Humans Using a Tissue-engineering Chamber: A Step Forward in the Clinical Application of Soft Tissue Engineering☆

    PubMed Central

    Morrison, Wayne A.; Marre, Diego; Grinsell, Damien; Batty, Andrew; Trost, Nicholas; O'Connor, Andrea J.

    2016-01-01

    Tissue engineering is currently exploring new and exciting avenues for the repair of soft tissue and organ defects. Adipose tissue engineering using the tissue engineering chamber (TEC) model has yielded promising results in animals; however, to date, there have been no reports on the use of this device in humans. Five female post mastectomy patients ranging from 35 to 49 years old were recruited and a pedicled thoracodorsal artery perforator fat flap ranging from 6 to 50 ml was harvested, transposed onto the chest wall and covered by an acrylic perforated dome-shaped chamber ranging from 140 to 350 cm3. Magnetic resonance evaluation was performed at three and six months after chamber implantation. Chambers were removed at six months and samples were obtained for histological analysis. In one patient, newly formed tissue to a volume of 210 ml was generated inside the chamber. One patient was unable to complete the trial and the other three failed to develop significant enlargement of the original fat flap, which, at the time of chamber explantation, was encased in a thick fibrous capsule. Our study provides evidence that generation of large well-vascularized tissue engineered constructs using the TEC is feasible in humans. PMID:27211566

  8. Creation of a Large Adipose Tissue Construct in Humans Using a Tissue-engineering Chamber: A Step Forward in the Clinical Application of Soft Tissue Engineering.

    PubMed

    Morrison, Wayne A; Marre, Diego; Grinsell, Damien; Batty, Andrew; Trost, Nicholas; O'Connor, Andrea J

    2016-04-01

    Tissue engineering is currently exploring new and exciting avenues for the repair of soft tissue and organ defects. Adipose tissue engineering using the tissue engineering chamber (TEC) model has yielded promising results in animals; however, to date, there have been no reports on the use of this device in humans. Five female post mastectomy patients ranging from 35 to 49years old were recruited and a pedicled thoracodorsal artery perforator fat flap ranging from 6 to 50ml was harvested, transposed onto the chest wall and covered by an acrylic perforated dome-shaped chamber ranging from 140 to 350cm(3). Magnetic resonance evaluation was performed at three and six months after chamber implantation. Chambers were removed at six months and samples were obtained for histological analysis. In one patient, newly formed tissue to a volume of 210ml was generated inside the chamber. One patient was unable to complete the trial and the other three failed to develop significant enlargement of the original fat flap, which, at the time of chamber explantation, was encased in a thick fibrous capsule. Our study provides evidence that generation of large well-vascularized tissue engineered constructs using the TEC is feasible in humans.

  9. Infarct tissue characterization in implantable cardioverter-defibrillator recipients for primary versus secondary prevention following myocardial infarction: a study with contrast-enhancement cardiovascular magnetic resonance imaging.

    PubMed

    Olimulder, Marlon A G M; Kraaier, Karin; Galjee, Michel A; Scholten, Marcoen F; van Es, Jan; Wagenaar, Lodewijk J; van der Palen, Job; von Birgelen, Clemens

    2013-01-01

    Knowledge about potential differences in infarct tissue characteristics between patients with prior life-threatening ventricular arrhythmia versus patients receiving prophylactic implantable cardioverter-defibrillator (ICD) might help to improve the current risk stratification in myocardial infarction (MI) patients who are considered for ICD implantation. In a consecutive series of (ICD) recipients for primary and secondary prevention following MI, we used contrast-enhanced (CE) cardiovascular magnetic resonance (CMR) imaging to evaluate differences in infarct tissue characteristics. Cine-CMR measurements included left ventricular end-diastolic and end-systolic volumes (EDV, ESV), left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and mass. CE-CMR images were analyzed for core, peri, and total infarct size, infarct localization (according to coronary artery territory), and transmural extent. In this study, 95 ICD recipients were included. In the primary prevention group (n = 66), LVEF was lower (23 ± 9% vs. 31 ± 14%; P < 0.01), ESV and WMSI were higher (223 ± 75 ml vs. 184 ± 97 ml, P = 0.04, and 1.89 ± 0.52 vs. 1.47 ± 0.68; P < 0.01), and anterior infarct localization was more frequent (P = 0.02) than in the secondary prevention group (n = 29). There were no differences in infarct tissue characteristics between patients treated for primary versus secondary prevention (P > 0.6 for all). During 21 ± 9 months of follow-up, 3 (5%) patients in the primary prevention group and 9 (31%) in the secondary prevention group experienced appropriate ICD therapy for treatment of ventricular arrhythmia (P < 0.01). There was no difference in infarct tissue characteristics between recipients of ICD for primary versus secondary prevention, while the secondary prevention group showed a higher frequency of applied ICD therapy for ventricular arrhythmia.

  10. Online quantitative analysis of multispectral images of human body tissues

    SciTech Connect

    Lisenko, S A

    2013-08-31

    A method is developed for online monitoring of structural and morphological parameters of biological tissues (haemoglobin concentration, degree of blood oxygenation, average diameter of capillaries and the parameter characterising the average size of tissue scatterers), which involves multispectral tissue imaging, image normalisation to one of its spectral layers and determination of unknown parameters based on their stable regression relation with the spectral characteristics of the normalised image. Regression is obtained by simulating numerically the diffuse reflectance spectrum of the tissue by the Monte Carlo method at a wide variation of model parameters. The correctness of the model calculations is confirmed by the good agreement with the experimental data. The error of the method is estimated under conditions of general variability of structural and morphological parameters of the tissue. The method developed is compared with the traditional methods of interpretation of multispectral images of biological tissues, based on the solution of the inverse problem for each pixel of the image in the approximation of different analytical models. (biomedical optics)

  11. The effects of corrosive substances on human bone, teeth, hair, nails, and soft tissue.

    PubMed

    Hartnett, Kristen M; Fulginiti, Laura C; Di Modica, Frank

    2011-07-01

    This research investigates the effects of household chemicals on human tissues. Five different human tissues (bone, tooth, hair, fingernails, and skin/muscle/fat) were immersed into six different corrosive agents. These agents consisted of hydrochloric acid, sulfuric acid, lye, bleach, organic septic cleaner, and Coca-Cola(®) soda. Tap water was used as a control. Tissue samples were cut to consistent sizes and submerged in the corrosive liquids. Over time, the appearance, consistency, and weight were documented. Hydrochloric acid was the most destructive agent in this study, consuming most tissues within 24 h. Sulfuric acid was the second most destructive agent in this study. Bleach, lye, and cola had no structural effects on the hard tissues of the body, but did alter the appearance or integrity of the hair, nails, or flesh in some way. The organic septic cleaner and tap water had no effect on any of the human tissue tested during the timeframe of the study.

  12. Determination of optical parameters of human breast tissue from spatially resolved fluorescence: a diffusion theory model

    NASA Astrophysics Data System (ADS)

    Nair, Maya S.; Ghosh, Nirmalya; Raju, Narisetti Sundar; Pradhan, Asima

    2002-07-01

    We report the measurement of optical transport parameters of pathologically characterized malignant tissues, normal tissues, and different types of benign tumors of the human breast in the visible wavelength region. A spatially resolved steady-state diffuse fluorescence reflectance technique was used to estimate the values for the reduced-scattering coefficient (mu's) and the absorption coefficient (mua) of human breast tissues at three wavelengths (530, 550, and 590 nm). Different breast tissues could be well differentiated from one another, and different benign tumors could also be distinguished by their measured transport parameters. A diffusion theory model was developed to describe fluorescence light energy distribution, especially its spatial variation in a turbid and multiply scattering medium such as human tissue. The validity of the model was checked with a Monte Carlo simulation and also with different tissue phantoms prepared with polystyrene microspheres as scatterers, riboflavin as fluorophores, and methylene blue as absorbers.

  13. Ethical issues surrounding the transplantation of human fetal tissues.

    PubMed

    Hurd, R E

    1992-12-01

    Organ transplants have been one of the greatest advances in medicine. However, organs from living relatives or cadavers are in short supply, and many people die awaiting a donor organ. Increasing the donor pool by using organs from aborted fetuses has been proposed to increase the supply. In addition, there are benefits of using fetal tissue including its particular usefulness in children, the fact that it is not readily rejected, and its potential for growth. Guidelines for fetal research were issued in 1975, but a research moratorium was imposed in 1988 to allow study of ethical and legal issues. While the federal government delays in lifting the ban, several states have written laws governing experimentation with fetuses. Ethical arguments against using fetal tissue for organ transplant include a concern that this would create a branch of biomedicine which depends on the continuation of induced abortions. This could lead to neglect of research for other therapies. The timing and type of abortion should continue to benefit the mother, rather than the organ recipient. Ethicists debate whether or not use of aborted tissue implies complicity in the abortion process beyond that which exists for all members of a society which permits abortion. They also wonder whether knowing that some good could come of an abortion would influence a woman's decision to have one. Proposals to keep the use of fetal tissue ethical include banning the commercial use of sale of tissues, forbidding designation of the tissue recipient (to prevent harvesting fetal tissue for a relative), separating abortion counseling and management from harvesting of the tissue, and obtaining informed consent (perhaps from a proxy surrogate rather than from the mother) for the use of fetal tissue. When the medical and ethical communities have reached some consensus on these issues, crafted safeguards, and precluded conflicts of interest, then restrictions on government funding should be lifted. Whereas it

  14. Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro

    PubMed Central

    2012-01-01

    Background Obesity is associated with prostate cancer aggressiveness and mortality. The contribution of periprostatic adipose tissue, which is often infiltrated by malignant cells, to cancer progression is largely unknown. Thus, this study aimed to determine if periprostatic adipose tissue is linked with aggressive tumor biology in prostate cancer. Methods Supernatants of whole adipose tissue (explants) or stromal vascular fraction (SVF) from paired fat samples of periprostatic (PP) and pre-peritoneal visceral (VIS) anatomic origin from different donors were prepared and analyzed for matrix metalloproteinases (MMPs) 2 and 9 activity. The effects of those conditioned media (CM) on growth and migration of hormone-refractory (PC-3) and hormone-sensitive (LNCaP) prostate cancer cells were measured. Results We show here that PP adipose tissue of overweight men has higher MMP9 activity in comparison with normal subjects. The observed increased activities of both MMP2 and MMP9 in PP whole adipose tissue explants, likely reveal the contribution of adipocytes plus stromal-vascular fraction (SVF) as opposed to SVF alone. MMP2 activity was higher for PP when compared to VIS adipose tissue. When PC-3 cells were stimulated with CM from PP adipose tissue explants, increased proliferative and migratory capacities were observed, but not in the presence of SVF. Conversely, when LNCaP cells were stimulated with PP explants CM, we found enhanced motility despite the inhibition of proliferation, whereas CM derived from SVF increased both cell proliferation and motility. Explants culture and using adipose tissue of PP origin are most effective in promoting proliferation and migration of PC-3 cells, as respectively compared with SVF culture and using adipose tissue of VIS origin. In LNCaP cells, while explants CM cause increased migration compared to SVF, the use of PP adipose tissue to generate CM result in the increase of both cellular proliferation and migration. Conclusions Our

  15. Scattering properties of normal and cancerous tissues from human stomach based on phase-contrast microscope

    NASA Astrophysics Data System (ADS)

    Zhang, Hui; Li, Zhifang; Li, Hui

    2012-12-01

    In order to study scattering properties of normal and cancerous tissues from human stomach, we collect images for human gastric specimens by using phase-contrast microscope. The images were processed by the way of mathematics morphology. The equivalent particle size distribution of tissues can be obtained. Combining with Mie scattering theory, the scattering properties of tissues can be calculated. Assume scattering of light in biological tissue can be seen as separate scattering events by different particles, total scattering properties can be equivalent to as scattering sum of particles with different diameters. The results suggest that scattering coefficient of the cancerous tissue is significantly higher than that of normal tissue. The scattering phase function is different especially in the backscattering area. Those are significant clinical benefits to diagnosis cancerous tissue

  16. In-Vivo Time Domain Measurement of Dielectric Properties of Human Body Tissue

    NASA Astrophysics Data System (ADS)

    Koyama, Kazunori; Hirata, Akimasa; Wang, Jianquing; Fujiwara, Osamu

    It is essential to measure dielectric properties of human tissues for the safety evaluation of electromagnetic field exposures. In this paper, towards developing an in-vivo measurement method for living human tissues, we employed an open-ended coaxial probe together with a time domain reflectometry (TDR) technique, which probably enables us to extract a reflected waveform from some specified tissues in the time domain. We compared the TDR-measured dielectric properties for human surface tissues with those derived from a conventional frequency-domain technique. As a result, we found a fair agreement between them in the frequency range from 300 MHz to 6 GHz. This result suggests the possibility of in-vivo dielectric property measurement for superficial human tissues by using the proposed TDR technique.

  17. Laser therapy in cardiovascular disease

    NASA Astrophysics Data System (ADS)

    Rindge, David

    2009-02-01

    Cardiovascular disease is the number one cause of death worldwide. It is broadly defined to include anything which adversely affects the heart or blood vessels. One-third of Americans have one or more forms of it. By one estimate, average human life expectancy would increase by seven years if it were eliminated. The mainstream medical model seeks mostly to "manage" cardiovascular disease with pharmaceuticals or to surgically bypass or reopen blocked vessels via angioplasty. These methods have proven highly useful and saved countless lives. Yet drug therapy may be costly and ongoing, and it carries the risk of side effects while often doing little or nothing to improve underlying health concerns. Similarly, angioplasty or surgery are invasive methods which entail risk. Laser therapy1 regenerates tissue, stimulates biological function, reduces inflammation and alleviates pain. Its efficacy and safety have been increasingly well documented in cardiovascular disease of many kinds. In this article we will explore the effects of laser therapy in angina, atherosclerosis, coronary artery disease, hypertension, hyperlipidemia, myocardial infarction, stroke and other conditions. The clinical application of various methods of laser therapy, including laserpuncture and transcutaneous, supravascular and intravenous irradiation of blood will be discussed. Implementing laser therapy in the treatment of cardiovascular disease offers the possibility of increasing the health and wellbeing of patients while reducing the costs and enhancing safety of medical care.

  18. A comparison of concentrations of lead in human tissues.

    PubMed Central

    Barry, P S

    1975-01-01

    This postmortem study of lead concentrations in the tissues of 129 subjects is an extension to a report by Barry and Mossman (1970). Lead concentrations in bone greatly exceeded the concentrations in soft tissues and were highest in the dense bones. Bone lead concentrations increased with age in both sexes, more especially in male subjects and in dense bone, varying between mean values of 2-16 ppm in the ribs of children to over 50 ppm in the dense petrous temporal bones of elderly male adults. Male adults contained over 30% more lead in their bones than females. Mean concentrations of lead in the soft tissues varied from less than 0-1 ppm in organs such as muscle and heart to over 2 ppm in the aorta. In most tissues with lead values in excess of 0-2 ppm the male concentrations exceeded female values by about 30%. With the exception of the aorta, spleen, lung, and prostate, lead concentrations did not increase with age in the soft tissues of either sex after about the second decade of life. Children showed concentrations of lead in their soft tissues comparable to female adults, but the concentrations in bone were much lower. It is suggested that children do not possess the same capacity as adults to retain lead in bone. In male adults occupationally exposed to lead the concentrations of lead in bone exceeded the concentrations in unexposed male adults within the same age group by two-to three-fold. Soft tissue lead concentrations between the two groups were less divergent. An assessment of the total body burden of lead revealed higher levels in adult male subjects than in females at mean values of 164-8 mg compared to 103-6 mg, respectively. Over 90% of the total body burden of lead in adults was in bone, of which over 70% was in dense bone. Male adults occupationally exposed to lead had mean total body burdens of 566-4 mg Pb, of which 97% was in bone. The release of lead from bone in conjunction with calcium was not considered to be of physiological significance

  19. Magnesium deficiency upregulates serine palmitoyl transferase (SPT 1 and SPT 2) in cardiovascular tissues: relationship to serum ionized Mg and cytochrome c.

    PubMed

    Altura, Burton M; Shah, Nilank C; Li, Zhiqiang; Jiang, Xian-Cheng; Perez-Albela, Jose Luis; Altura, Bella T

    2010-09-01

    The present work tested the hypothesis that a short-term dietary deficiency of magnesium (Mg) (21 days) in rats would result in the upregulation of the two major subunits of serine palmitoyl-CoA-transferase, serine palmitoyl transferase (SPT 1) and SPT 2 (the rate-limiting enzymes responsible for the de novo biosynthesis of ceramides) in left ventricular, right ventricular, and atrial heart muscle and abdominal aortic smooth muscle, as well as induce a reduction in serum sphingomyelin concomitant with the release of mitochondrial cytochrome c (Cyto c) in these tissues. Our data indicate that short-term Mg deficiency (MgD) resulted in an upregulation of SPT 1 and SPT 2, concomitant with a very significant release of Cyto c in left ventricular, right ventricular, atrial, and abdominal aortic smooth muscle. Short-term MgD also produced a lowering of serum sphingomyelin and ionized Mg. The greater the reduction in serum ionized Mg, the greater the upregulation of SPT 1 and 2 and the more the increase in free Cyto c. The data suggest that MgD, most likely, causes a biosynthesis of ceramides via two pathways in cardiovascular tissues, viz., via the activation of serine palmitoyl-CoA-transferase and sphingomyelinase, which lead to apoptotic events via intrinsic (present study) and extrinsic pathways (previous studies). Low levels of drinking water Mg were cardio- and vasculoprotective.

  20. KATP Channels in the Cardiovascular System.

    PubMed

    Foster, Monique N; Coetzee, William A

    2016-01-01

    KATP channels are integral to the functions of many cells and tissues. The use of electrophysiological methods has allowed for a detailed characterization of KATP channels in terms of their biophysical properties, nucleotide sensitivities, and modification by pharmacological compounds. However, even though they were first described almost 25 years ago (Noma 1983, Trube and Hescheler 1984), the physiological and pathophysiological roles of these channels, and their regulation by complex biological systems, are only now emerging for many tissues. Even in tissues where their roles have been best defined, there are still many unanswered questions. This review aims to summarize the properties, molecular composition, and pharmacology of KATP channels in various cardiovascular components (atria, specialized conduction system, ventricles, smooth muscle, endothelium, and mitochondria). We will summarize the lessons learned from available genetic mouse models and address the known roles of KATP channels in cardiovascular pathologies and how genetic variation in KATP channel genes contribute to human disease.

  1. KATP Channels in the Cardiovascular System

    PubMed Central

    Foster, Monique N.; Coetzee, William A.

    2015-01-01

    KATP channels are integral to the functions of many cells and tissues. The use of electrophysiological methods has allowed for a detailed characterization of KATP channels in terms of their biophysical properties, nucleotide sensitivities, and modification by pharmacological compounds. However, even though they were first described almost 25 years ago (Noma 1983, Trube and Hescheler 1984), the physiological and pathophysiological roles of these channels, and their regulation by complex biological systems, are only now emerging for many tissues. Even in tissues where their roles have been best defined, there are still many unanswered questions. This review aims to summarize the properties, molecular composition, and pharmacology of KATP channels in various cardiovascular components (atria, specialized conduction system, ventricles, smooth muscle, endothelium, and mitochondria). We will summarize the lessons learned from available genetic mouse models and address the known roles of KATP channels in cardiovascular pathologies and how genetic variation in KATP channel genes contribute to human disease. PMID:26660852

  2. KeyGenes, a Tool to Probe Tissue Differentiation Using a Human Fetal Transcriptional Atlas

    PubMed Central

    Roost, Matthias S.; van Iperen, Liesbeth; Ariyurek, Yavuz; Buermans, Henk P.; Arindrarto, Wibowo; Devalla, Harsha D.; Passier, Robert; Mummery, Christine L.; Carlotti, Françoise; de Koning, Eelco J.P.; van Zwet, Erik W.; Goeman, Jelle J.; Chuva de Sousa Lopes, Susana M.

    2015-01-01

    Summary Differentiated derivatives of human pluripotent stem cells in culture are generally phenotypically immature compared to their adult counterparts. Their identity is often difficult to determine with certainty because little is known about their human fetal equivalents in vivo. Cellular identity and signaling pathways directing differentiation are usually determined by extrapolating information from either human adult tissue or model organisms, assuming conservation with humans. To resolve this, we generated a collection of human fetal transcriptional profiles at different developmental stages. Moreover, we developed an algorithm, KeyGenes, which uses this dataset to quantify the extent to which next-generation sequencing or microarray data resemble specific cell or tissue types in the human fetus. Using KeyGenes combined with the human fetal atlas, we identified multiple cell and tissue samples unambiguously on a limited set of features. We thus provide a flexible and expandable platform to monitor and evaluate the efficiency of differentiation in vitro. PMID:26028532

  3. hPSC-derived lung and intestinal organoids as models of human fetal tissue.

    PubMed

    Aurora, Megan; Spence, Jason R

    2016-12-15

    In vitro human pluripotent stem cell (hPSC) derived tissues are excellent models to study certain aspects of normal human development. Current research in the field of hPSC derived tissues reveals these models to be inherently fetal-like on both a morphological and gene expression level. In this review we briefly discuss current methods for differentiating lung and intestinal tissue from hPSCs into individual 3-dimensional units called organoids. We discuss how these methods mirror what is known about in vivo signaling pathways of the developing embryo. Additionally, we will review how the inherent immaturity of these models lends them to be particularly valuable in the study of immature human tissues in the clinical setting of premature birth. Human lung organoids (HLOs) and human intestinal organoids (HIOs) not only model normal development, but can also be utilized to study several important diseases of prematurity such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC).

  4. Response patterns and cardiovascular effects during response sequence acquisition by humans.

    PubMed Central

    Kelly, T H; Fischman, M W; Foltin, R W; Brady, J V

    1991-01-01

    The effects of temporal delays imposed between successive responses and of vitamin C administration were examined on the acquisition of response sequences and on cardiovascular reactivity during sequence acquisition. Thirteen adult subjects (6 female, 7 male), in good health, gave written consent prior to participating in 12 weekly 45-min sessions. Points, exchanged for money after each session, were presented when subjects completed 15-response sequences on a touch-sensitive three-response keypad. A position counter increased from 0 to 14 as subjects emitted correct responses in the sequence. Four novel 15-response sequences were presented each session. No delays were imposed between successive responses during the acquisition of one sequence; delays were imposed immediately following each response during the acquisition of a second sequence, thereby delaying response feedback; delays were imposed following feedback during acquisition of a third sequence, resulting in the removal of the stimulus correlated with sequence position; and, as a control condition, delays were imposed following feedback, but stimuli correlated with sequence position were reinstated prior to the next response during acquisition of a fourth sequence. Subjects were exposed to one of two delay durations (0.2 and 0.5 or 0.5 and 1.0 s) each session, and delay durations alternated every session. During Weeks 5 to 8, subjects received 3 grams of vitamin C per day, whereas during Weeks 1 to 4 and 9 to 12, subjects received placebo under single-blind conditions. All subjects acquired the sequences, as evidenced by decreasing percentages of incorrect responses across trials. When temporal delays were imposed between successive responses during sequence acquisition, acquisition efficiency was enhanced. Examination of response latencies suggested that the status of preceding responses (i.e., correct or incorrect) rather than the status of the position counter influenced subsequent responding

  5. Exercise training and artery function in humans: nonresponse and its relationship to cardiovascular risk factors.

    PubMed

    Green, Daniel J; Eijsvogels, Thijs; Bouts, Yvette M; Maiorana, Andrew J; Naylor, Louise H; Scholten, Ralph R; Spaanderman, Marc E A; Pugh, Christopher J A; Sprung, Victoria S; Schreuder, Tim; Jones, Helen; Cable, Tim; Hopman, Maria T E; Thijssen, Dick H J

    2014-08-15

    The objectives of our study were to examine 1) the proportion of responders and nonresponders to exercise training in terms of vascular function; 2) a priori factors related to exercise training-induced changes in conduit artery function, and 3) the contribution of traditional cardiovascular risk factors to exercise-induced changes in artery function. We pooled data from our laboratories involving 182 subjects who underwent supervised, large-muscle group, endurance-type exercise training interventions with pre-/posttraining measures of flow-mediated dilation (FMD%) to assess artery function. All studies adopted an identical FMD protocol (5-min ischemia, distal cuff inflation), contemporary echo-Doppler methodology, and observer-independent automated analysis. Linear regression analysis was used to identify factors contributing to changes in FMD%. We found that cardiopulmonary fitness improved, and weight, body mass index (BMI), cholesterol, and mean arterial pressure (MAP) decreased after training, while FMD% increased in 76% of subjects (P < 0.001). Training-induced increase in FMD% was predicted by lower body weight (β = -0.212), lower baseline FMD% (β = -0.469), lower training frequency (β = -0.256), and longer training duration (β = 0.367) (combined: P < 0.001, r = 0.63). With the exception of a modest correlation with total cholesterol (r = -0.243, P < 0.01), changes in traditional cardiovascular risk factors were not significantly related to changes in FMD% (P > 0.05). In conclusion, we found that, while some subjects do not demonstrate increases following exercise training, improvement in FMD% is present in those with lower pretraining body weight and endothelial function. Moreover, exercise training-induced change in FMD% did not correlate with changes in traditional cardiovascular risk factors, indicating that some cardioprotective effects of exercise training are independent of improvement in risk factors.

  6. Measuring the local electrical conductivity of human brain tissue

    NASA Astrophysics Data System (ADS)

    Akhtari, M.; Emin, D.; Ellingson, B. M.; Woodworth, D.; Frew, A.; Mathern, G. W.

    2016-02-01

    The electrical conductivities of freshly excised brain tissues from 24 patients were measured. The diffusion-MRI of the hydrogen nuclei of water molecules from regions that were subsequently excised was also measured. Analysis of these measurements indicates that differences between samples' conductivities are primarily due to differences of their densities of solvated sodium cations. Concomitantly, the sample-to-sample variations of their diffusion constants are relatively small. This finding suggests that non-invasive in-vivo measurements of brain tissues' local sodium-cation density can be utilized to estimate its local electrical conductivity.

  7. 21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Determination of donor suitability for human..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE INTENDED FOR TRANSPLANTATION Donor Screening and...

  8. 21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Determination of donor suitability for human..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE INTENDED FOR TRANSPLANTATION Donor Screening and...

  9. Immunohistochemical localization of collagen type XI alpha1 and alpha2 chains in human colon tissue.

    PubMed

    Bowen, Kara B; Reimers, Aaron P; Luman, Sarah; Kronz, Joseph D; Fyffe, William E; Oxford, Julia Thom

    2008-03-01

    In previous studies, collagen XI mRNA has been detected in colon cancer, but its location in human colon tissue has not been determined. The heterotrimeric collagen XI consists of three alpha chains. While it is known that collagen XI plays a regulatory role in collagen fibril formation, its function in the colon is unknown. The characterization of normal human colon tissue will allow a better understanding of the variance of collagen XI in abnormal tissues. Grossly normal and malignant human colon tissue was obtained from pathology archives. Immunohistochemical staining with a 58K Golgi marker and alpha1(XI) and alpha2(XI) antisera was used to specifically locate their presence in normal colon tissue. A comparative bright field microscopic analysis showed the presence of collagen XI in human colon. The juxtanuclear, dot-like collagen XI staining in the Golgi apparatus of goblet cells in normal tissue paralleled the staining of the 58K Golgi marker. Ultra light microscopy verified these results. Staining was also confirmed in malignant colon tissue. This study is the first to show that collagen XI is present in the Golgi apparatus of normal human colon goblet cells and localizes collagen XI in both normal and malignant tissue. Although the function of collagen XI in the colon is unknown, our immunohistochemical characterization provides the foundation for future immunohistopathology studies of the colon.

  10. Environmental carcinogens in human target tissues in culture. Progress report

    SciTech Connect

    Hsu, I.C.

    1986-02-19

    Cells from different organ or animal species have shown diverse activities in activation and detoxification of chemical carcinogens. Based on the mutation assays, human hepatocytes were more effective than animal hepatocytes in detoxification of aromatic nitrogen compounds. The adduct formation was also different in human and rodent hepatocytes exposed to aminofluorene (AF) or acetylaminofluorene (AAF). Both AF and AAF adduct DNA were observed in rat liver cells exposed to AF or AAF. However, very little acetylation or deacetyl of the DNA adducts occurred in the human hepatocytes. Human hepatocytes treated with AF in primary culture produced mainly AF adducted DNA while AAF treated cells formed AAF adduct DNA. 2 figs., 1 tab.

  11. Computer-aided tissue engineering of a human vertebral body.

    PubMed

    Wettergreen, M A; Bucklen, B S; Sun, W; Liebschner, M A K

    2005-10-01

    Tissue engineering is developing into a less speculative science involving the careful interplay of numerous design parameters and multidisciplinary professionals. Problem solving abilities and state of the art research tools are required to develop solutions for a wide variety of clinical issues. One area of particular interest is orthopedic biomechanics, a field that is responsible for the treatment of over 700,000 vertebral fractures in the United States alone last year. Engineers are currently lacking the technology and knowledge required to govern the subsistence of cells in vivo, let alone the knowledge to create a functional tissue replacement for a whole organ. Despite this, advances in computer-aided tissue engineering are continually growing. Using a combinatory approach to scaffold design, patient-specific implants may be constructed. Computer-aided design, optimization of geometry using voxel finite element models or other optimization routines, creation of a library of architectures with specific material properties, rapid prototyping, and determination of a defect site using imaging modalities highlight the current availability of design resources. This study proposes a novel methodology from start to finish which could, in the future, be used to design a tissue-engineered construct for the replacement of an entire vertebral body.

  12. Multiple-Image Radiography for Human Soft Tissue

    SciTech Connect

    Muehleman,C.; Li, J.; Zhong, Z.; Brankov, J.; Wernick, M.

    2006-01-01

    Conventional radiography only provides a measure of the X-ray attenuation caused by an object; thus, it is insensitive to other inherent informative effects, such as refraction. Furthermore, conventional radiographs are degraded by X-ray scatter that can obscure important details of the object being imaged. The novel X-ray technology diffraction-enhanced imaging (DEI) has recently allowed the visualization of nearly scatter-free images displaying both attenuation and refraction properties. A new method termed multiple-image radiography (MIR) is a significant improvement over DEI, corrects errors in DEI, is more robust to noise and produces an additional image that is entirely new to medical imaging. This new image, which portrays ultra-small-angle X-ray scattering (USAXS) conveys the presence of microstructure in the object, thus differentiating homogeneous tissues from tissues that are irregular on a scale of micrometers. The aim of this study was to examine the use of MIR for evaluation of soft tissue, and in particular to conduct a preliminary investigation of the USAXS image, which has not previously been used in tissue imaging.

  13. Caspase Induction and BCL2 Inhibition in Human Adipose Tissue

    PubMed Central

    Tinahones, Francisco José; Coín Aragüez, Leticia; Murri, Mora; Oliva Olivera, Wilfredo; Mayas Torres, María Dolores; Barbarroja, Nuria; Gomez Huelgas, Ricardo; Malagón, Maria M.; El Bekay, Rajaa

    2013-01-01

    OBJECTIVE Cell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling. RESEARCH DESIGN AND METHODS The expression levels of initiator (CASP8/9) and effector (CASP3/7) caspases as well as antiapoptotic B-cell lymphoma (BCL)2 and inflammatory markers were assessed in visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with different degrees of obesity and without insulin resistance or diabetes. Adipose tissue explants from lean subjects were cultured with TNF-α or IL-6, and the expression of apoptotic and insulin signaling components was analyzed and compared with basal expression levels in morbidly obese subjects. RESULTS SAT and VAT exhibited increased CASP3/7 and CASP8/9 expression levels and decreased BCL2 expression with BMI increase. These changes were accompanied by increased inflammatory cytokine mRNA levels and macrophage infiltration markers. In obese subjects, CASP3/7 activation and BCL2 downregulation correlated with the IRS-1/2–expression levels. Expression levels of caspases, BCL2, p21, p53, IRS-1/2, GLUT4, protein tyrosine phosphatase 1B, and leukocyte antigen-related phosphatase in TNF-α– or IL-6–treated explants from lean subjects were comparable with those found in adipose tissue samples from morbidly obese subjects. These insulin component expression levels were reverted with CASP3/7 inhibition in these TNF-α– or IL-6–treated explants. CONCLUSIONS Body fat mass increase is associated with CASP3/7 and BCL2 expression in adipose tissue. Moreover, this proapoptotic state correlated with insulin signaling, suggesting its potential contribution to the development of insulin resistance. PMID:23193206

  14. Assessment of bioburden on human and animal tissues: part 2--results of testing of human tissue and qualification of a composite sample for routine bioburden determination.

    PubMed

    Kowalski, John B; Merritt, Karen; Gocke, David; Osborne, Joel

    2012-08-01

    A quantitative method was developed and validated to assess bioburden on tissue from human donors and to compare bioburden determination results to swab culture results from the same donor. An initial study with allograft tissue from 101 donors showed a wide range of bioburden levels; values from no colony-forming units (CFU) detected to >28,000 CFU were observed. Tissues from donors that had swab cultures negative for objectionable microorganisms generally had lower bioburden than tissues from donors where objectionable microorganisms were recovered by swab culturing. In a follow-up study with 1,445 donors, a wide range of bioburden levels was again observed on tissues from donors that were swab culture negative for objectionable microorganisms. Tissues from 885 (61%) of these donors had no recoverable bioburden (<2 CFU). Importantly, tissues from 560 (39%) of the donors had recoverable bioburden which ranged from 1 to >24,000 CFU. Identification of bioburden isolates showed a diversity of genera and species. In compliance with the recent revision of the American Association of Tissue Banks K2.210 Standard, the quantitative bioburden determination method was validated with a composite tissue sample that contains bone and soft tissue sections tested together in one extraction vessel. A recovery efficiency of 68% was validated and the composite sample was shown to be representative of all of the tissues recovered from a donor. The use of the composite sample in conjunction with the quantitative bioburden determination method will facilitate an accurate assessment of the numbers and types of contaminating microorganisms on allografts prior to disinfection/sterilization. This information will ensure that disinfection/sterilization processes are properly validated and the capability of the overall allograft process is understood on a donor by donor basis.

  15. Human auditory evoked potentials in the assessment of brain function during major cardiovascular surgery.

    PubMed

    Rodriguez, Rosendo A

    2004-06-01

    Focal neurologic and intellectual deficits or memory problems are relatively frequent after cardiac surgery. These complications have been associated with cerebral hypoperfusion, embolization, and inflammation that occur during or after surgery. Auditory evoked potentials, a neurophysiologic technique that evaluates the function of neural structures from the auditory nerve to the cortex, provide useful information about the functional status of the brain during major cardiovascular procedures. Skepticism regarding the presence of artifacts or difficulty in their interpretation has outweighed considerations of its potential utility and noninvasiveness. This paper reviews the evidence of their potential applications in several aspects of the management of cardiac surgery patients. The sensitivity of auditory evoked potentials to the effects of changes in brain temperature makes them useful for monitoring cerebral hypothermia and rewarming during cardiopulmonary bypass. The close relationship between evoked potential waveforms and specific anatomic structures facilitates the assessment of the functional integrity of the central nervous system in cardiac surgery patients. This feature may also be relevant in the management of critical patients under sedation and coma or in the evaluation of their prognosis during critical care. Their objectivity, reproducibility, and relative insensitivity to learning effects make auditory evoked potentials attractive for the cognitive assessment of cardiac surgery patients. From a clinical perspective, auditory evoked potentials represent an additional window for the study of underlying cerebral processes in healthy and diseased patients. From a research standpoint, this technology offers opportunities for a better understanding of the particular cerebral deficits associated with patients who are undergoing major cardiovascular procedures.

  16. Genes overexpressed in different human solid cancers exhibit different tissue-specific expression profiles

    PubMed Central

    Bock Axelsen, Jacob; Lotem, Joseph; Sachs, Leo; Domany, Eytan

    2007-01-01

    We have analyzed gene expression in different normal human tissues and different types of solid cancers derived from these tissues. The cancers analyzed include brain (astrocytoma and glioblastoma), breast, colon, endometrium, kidney, liver, lung, ovary, prostate, skin, and thyroid cancers. Comparing gene expression in each normal tissue to 12 other normal tissues, we identified 4,917 tissue-selective genes that were selectively expressed in different normal tissues. We also identified 2,929 genes that are overexpressed at least 4-fold in the cancers compared with the normal tissue from which these cancers were derived. The overlap between these two gene groups identified 1,340 tissue-selective genes that are overexpressed in cancers. Different types of cancers, including different brain cancers arising from the same lineage, showed differences in the tissue-selective genes they overexpressed. Melanomas overexpressed the highest number of brain-selective genes and this may contribute to melanoma metastasis to the brain. Of all of the genes with tissue-selective expression, those selectively expressed in testis showed the highest frequency of genes that are overexpressed in at least two types of cancer. However, colon and prostate cancers did not overexpress any testis-selective gene. Nearly all of the genes with tissue-selective expression that are overexpressed in cancers showed selective expression in tissues different from the cancers' tissue of origin. Cancers aberrantly expressing such genes may acquire phenotypic alterations that contribute to cancer cell viability, growth, and metastasis. PMID:17664417

  17. Design Principles for Engineering of Tissues from Human Pluripotent Stem Cells

    PubMed Central

    Matthys, Oriane B.; Hookway, Tracy A.; McDevitt, Todd C.

    2016-01-01

    Recent advances in human pluripotent stem cell (hPSC) technologies have enabled the engineering of human tissue constructs for developmental studies, disease modeling, and drug screening platforms. In vitro tissue formation can be generally described at three levels of cellular organization. Multicellular hPSC constructs are initially formed either with polymeric scaffold materials or simply via self-assembly, adhesive mechanisms. Heterotypic interactions within hPSC tissue constructs can be achieved by physically mixing independently differentiated cell populations or coaxed to simultaneously co-emerge from a common population of undifferentiated cells. Higher order tissue architecture can be engineered by imposing external spatial constraints, such as molds and scaffolds, or depend upon cell-driven organization that exploits endogenous innate developmental mechanisms. The multicellular, heterogeneous, and highly organized structure of hPSC constructs ultimately dictates the resulting form and function of in vitro engineered human tissue models. PMID:27330934

  18. The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans

    PubMed Central

    2015-01-01

    Understanding the functional consequences of genetic variation, and how it affects complex human disease and quantitative traits, remains a critical challenge for biomedicine. We present an analysis of RNA sequencing data from 1641 samples across 43 tissues from 175 individuals, generated as part of the pilot phase of the Genotype-Tissue Expression (GTEx) project. We describe the landscape of gene expression across tissues, catalog thousands of tissue-specific and shared regulatory expression quantitative trait loci (eQTL) variants, describe complex network relationships, and identify signals from genome-wide association studies explained by eQTLs. These findings provide a systematic understanding of the cellular and biological consequences of human genetic variation and of the heterogeneity of such effects among a diverse set of human tissues. PMID:25954001

  19. Epithelial-connective tissue boundary in the oral part of the human soft palate

    PubMed Central

    PAULSEN, FRIEDRICH; THALE, ANDREAS

    1998-01-01

    The papillary layer of the oral part of the human soft palate was studied in 31 subjects of different age by means of histological, immunohistochemical and scanning electron microscopical methods. For scanning electron microscopy a new maceration method was introduced. Results determine epithelial thickness, height and density of connective tissue papillae and their 3-dimensional architecture inside the lining epithelium as well as the collagenous arrangement of the openings of the glandular ducts. The individual connective tissue papillae of the soft palate are compared with the connective tissue boundary on the other side of the oral cavity. The connective tissue plateaux carrying a variable number of connective tissue papillae were found to be the basic structural units of the papillary body. The function of the epithelial-connective tissue interface and the extracellular matrix arrangement in the lamina propria are discussed in order to promote the comparability of normal with pathologically altered human soft palates. PMID:9877301

  20. Estimating head and neck tissue dose from x-ray scatter to physicians performing x-ray guided cardiovascular procedures: a phantom study.

    PubMed

    Fetterly, Kenneth A; Schueler, Beth A; Grams, Michael P; Sturchio, Glenn M

    2017-03-20

    Physicians performing x-ray guided interventional procedures have a keen interest in radiation safety. Radiation dose to tissues and organs of the head and neck are of particular interest because they are not routinely protected by wearable radiation safety devices. This study was conducted to facilitate estimation of radiation dose to tissues of the head and neck of interventional physicians based on the dose recorded by a personal dosimeter worn on the left collar. Scatter beam qualities maximum energy and HVL were measured for 40 scatter beams emitting from an anthropomorphic patient phantom. Variables of the scatter beams included scatter angle (35° and 90°), primary beam peak tube potential (60, 80, 100, and 120 kVp), and 5 Cu spectral filter thicknesses (0-0.9 mm). Four reference scatter beam qualities were selected to represent the range of scatter beams realized in a typical practice. A general radiographic x-ray tube was tuned to produce scatter-equivalent radiographic beams and used to simultaneously expose the head and neck of an anthropomorphic operator phantom and radiochromic film. The geometric relationship between the x-ray source of the scatter-equivalent beams and the operator phantom was set to mimic that between a patient and physician performing an invasive cardiovascular procedure. Dose to the exterior surface of the operator phantom was measured with both 3 × 3 cm(2) pieces of film and personal dosimeters positioned at the location of the left collar. All films were scanned with a calibrated flatbed scanner, which converted the film's reflective density to dose. Films from the transverse planes of the operator phantom provided 2D maps of the dose distribution within the phantom. These dose maps were normalized by the dose at the left collar, providing 2D percent of left collar dose (LCD) maps. The percent LCD maps were overlain with bony anatomy CT images of the operator phantom and estimates of percent LCD to the left, right and whole

  1. Cryopreservation, Culture, and Transplantation of Human Fetal Mesencephalic Tissue into Monkeys

    NASA Astrophysics Data System (ADS)

    Redmond, D. E.; Naftolin, F.; Collier, T. J.; Leranth, C.; Robbins, R. J.; Sladek, C. D.; Roth, R. H.; Sladek, J. R.

    1988-11-01

    Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases.

  2. LC-MS/MS method for the determination of several drugs used in combined cardiovascular therapy in human plasma.

    PubMed

    Gonzalez, Oskar; Iriarte, Gorka; Rico, Estitxu; Ferreirós, Nerea; Maguregui, Miren Itxaso; Alonso, Rosa Maria; Jiménez, Rosa Maria

    2010-10-15

    A simple, fast and validated method is reported for the simultaneous analysis, in human plasma, of several drugs usually combined in cardiovascular therapy (atenolol, bisoprolol, hydrochlorothiazide, chlorthalidone, salicylic acid, enalapril and its active metabolite enalaprilat, valsartan and fluvastatin) using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI), working in multiple reaction monitoring mode (MRM). Separation of analytes and internal standard (pravastatin) was performed on a Luna C18(2) (150mm×4.6mm, 3μm) column using a gradient elution mode with a run time of 15min. The mobile phase consisted of a mixture of acetonitrile and water containing 0.01% formic acid and 10mM ammonium formate at pH 4.1. Sample treatment consisted of a simple protein precipitation with acetonitrile, enabling a fast analysis. The method showed good linearity, precision (RSD% values between 0.7% and 12.7%) and accuracy (relative error values between 0.9% and 14.0%). Recoveries were within 68-106% range and the ion-suppression was not higher than 22% for any analyte. The method was successfully applied to plasma samples obtained from patients under combined cardiovascular treatment.

  3. START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection

    PubMed Central

    Siedner, Mark J.

    2016-01-01

    The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed. PMID:26989755

  4. Exercise aggravates cardiovascular risks and mortality in rats with disrupted nitric oxide pathway and treated with recombinant human erythropoietin.

    PubMed

    Meziri, Fayçal; Binda, Delphine; Touati, Sabeur; Pellegrin, Maxime; Berthelot, Alain; Touyz, Rhian M; Laurant, Pascal

    2011-08-01

    Chronic administration of recombinant human erythropoietin (rHuEPO) can generate serious cardiovascular side effects such as arterial hypertension (HTA) in clinical and sport fields. It is hypothesized that nitric oxide (NO) can protect from noxious cardiovascular effects induced by chronic administration of rHuEPO. On this base, we studied the cardiovascular effects of chronic administration of rHuEPO in exercise-trained rats treated with an inhibitor of NO synthesis (L-NAME). Rats were treated or not with rHuEPO and/or L-NAME during 6 weeks. During the same period, rats were subjected to treadmill exercise. The blood pressure was measured weekly. Endothelial function of isolated aorta and small mesenteric arteries were studied and the morphology of the latter was investigated. L-NAME induced hypertension (197 ± 6 mmHg, at the end of the protocol). Exercise prevented the rise in blood pressure induced by L-NAME (170 ± 5 mmHg). However, exercise-trained rats treated with both rHuEPO and L-NAME developed severe hypertension (228 ± 9 mmHg). Furthermore, in these exercise-trained rats treated with rHuEPO/L-NAME, the acetylcholine-induced relaxation was markedly impaired in isolated aorta (60% of maximal relaxation) and small mesenteric arteries (53%). L-NAME hypertension induced an internal remodeling of small mesenteric arteries that was not modified by exercise, rHuEPO or both. Vascular ET-1 production was not increased in rHuEPO/L-NAME/training hypertensive rats. Furthermore, we observed that rHuEPO/L-NAME/training hypertensive rats died during the exercise or the recovery period (mortality 51%). Our findings suggest that the use of rHuEPO in sport, in order to improve physical performance, represents a high and fatal risk factor, especially with pre-existing cardiovascular risk.

  5. Linking microstructure and nanochemistry in human dental tissues.

    PubMed

    Srot, Vesna; Bussmann, Birgit; Salzberger, Ute; Koch, Christoph T; van Aken, Peter A

    2012-06-01

    Mineralized dental tissues and dental pulp were characterized using advanced analytical transmission electron microscopy (TEM) methods. Quantitative X-ray energy dispersive spectroscopy was employed to determine the Ca/P and Mg/P concentration ratios. Significantly lower Ca/P concentration ratios were measured in peritubular dentine compared to intertubular dentine, which is accompanied by higher and variable Mg/P concentration ratios. There is strong evidence that magnesium is partially substituting calcium in the hydroxyapatite structure. Electron energy-loss near-edge structures (ELNES) of C-K and O-K from enamel and dentine are noticeably different. We observe a strong influence of beam damage on mineralized dental tissues and dental pulp, causing changes of the composition and consequently also differences in the ELNES. In this article, the importance of TEM sample preparation and specimen damage through electron irradiation is demonstrated.

  6. Analysis of variance in spectroscopic imaging data from human tissues.

    PubMed

    Kwak, Jin Tae; Reddy, Rohith; Sinha, Saurabh; Bhargava, Rohit

    2012-01-17

    The analysis of cell types and disease using Fourier transform infrared (FT-IR) spectroscopic imaging is promising. The approach lacks an appreciation of the limits of performance for the technology, however, which limits both researcher efforts in improving the approach and acceptance by practitioners. One factor limiting performance is the variance in data arising from biological diversity, measurement noise or from other sources. Here we identify the sources of variation by first employing a high throughout sampling platform of tissue microarrays (TMAs) to record a sufficiently large and diverse set data. Next, a comprehensive set of analysis of variance (ANOVA) models is employed to analyze the data. Estimating the portions of explained variation, we quantify the primary sources of variation, find the most discriminating spectral metrics, and recognize the aspects of the technology to improve. The study provides a framework for the development of protocols for clinical translation and provides guidelines to design statistically valid studies in the spectroscopic analysis of tissue.

  7. Legal requirements for donating and retaining organs: the Human Tissue Act.

    PubMed

    Griffith, Richard

    2006-10-01

    The Human Tissue Act 2004 came into force on 1 September 2006 and introduced significant changes in the way human body parts, tissue and organs are removed, stored and used. The Act seeks to remedy the poor availability of organs for transplant caused in part by laws that date back to the 17th Century and to right the concerns raised by the Liverpool Children's Inquiry that revealed widespread retention of organs by hospitals without permission. In this article Richard Griffith describes how consent is now the driving force underpinning such activity and how the wishes of the patient remain paramount even after death. He also outlines how the Human Tissue Authority will licence and inspect activities involving human tissue under the Act and discuss how the new law will affect district nurse practice.

  8. Production of tissue microarrays, immunohistochemistry staining and digitalization within the human protein atlas.

    PubMed

    Kampf, Caroline; Olsson, Ingmarie; Ryberg, Urban; Sjöstedt, Evelina; Pontén, Fredrik

    2012-05-31

    The tissue microarray (TMA) technology provides the means for high-throughput analysis of multiple tissues and cells. The technique is used within the Human Protein Atlas project for global analysis of protein expression patterns in normal human tissues, cancer and cell lines. Here we present the assembly of 1 mm cores, retrieved from microscopically selected representative tissues, into a single recipient TMA block. The number and size of cores in a TMA block can be varied from approximately forty 2 mm cores to hundreds of 0.6 mm cores. The advantage of using TMA technology is that large amount of data can rapidly be obtained using a single immunostaining protocol to avoid experimental variability. Importantly, only limited amount of scarce tissue is needed, which allows for the analysis of large patient cohorts (1 2). Approximately 250 consecutive sections (4 μm thick) can be cut from a TMA block and used for immunohistochemical staining to determine specific protein expression patterns for 250 different antibodies. In the Human Protein Atlas project, antibodies are generated towards all human proteins and used to acquire corresponding protein profiles in both normal human tissues from 144 individuals and cancer tissues from 216 different patients, representing the 20 most common forms of human cancer. Immunohistochemically stained TMA sections on glass slides are scanned to create high-resolution images from which pathologists can interpret and annotate the outcome of immunohistochemistry. Images together with corresponding pathology-based annotation data are made publically available for the research community through the Human Protein Atlas portal (www.proteinatlas.org) (Figure 1) (3 4). The Human Protein Atlas provides a map showing the distribution and relative abundance of proteins in the human body. The current version contains over 11 million images with protein expression data for 12.238 unique proteins, corresponding to more than 61% of all proteins

  9. Production of Tissue Microarrays, Immunohistochemistry Staining and Digitalization Within the Human Protein Atlas

    PubMed Central

    Kampf, Caroline; Olsson, IngMarie; Ryberg, Urban; Sjöstedt, Evelina; Pontén, Fredrik

    2012-01-01

    The tissue microarray (TMA) technology provides the means for high-throughput analysis of multiple tissues and cells. The technique is used within the Human Protein Atlas project for global analysis of protein expression patterns in normal human tissues, cancer and cell lines. Here we present the assembly of 1 mm cores, retrieved from microscopically selected representative tissues, into a single recipient TMA block. The number and size of cores in a TMA block can be varied from approximately forty 2 mm cores to hundreds of 0.6 mm cores. The advantage of using TMA technology is that large amount of data can rapidly be obtained using a single immunostaining protocol to avoid experimental variability. Importantly, only limited amount of scarce tissue is needed, which allows for the analysis of large patient cohorts 1 2. Approximately 250 consecutive sections (4 μm thick) can be cut from a TMA block and used for immunohistochemical staining to determine specific protein expression patterns for 250 different antibodies. In the Human Protein Atlas project, antibodies are generated towards all human proteins and used to acquire corresponding protein profiles in both normal human tissues from 144 individuals and cancer tissues from 216 different patients, representing the 20 most common forms of human cancer. Immunohistochemically stained TMA sections on glass slides are scanned to create high-resolution images from which pathologists can interpret and annotate the outcome of immunohistochemistry. Images together with corresponding pathology-based annotation data are made publically available for the research community through the Human Protein Atlas portal (www.proteinatlas.org) (Figure 1) 3 4. The Human Protein Atlas provides a map showing the distribution and relative abundance of proteins in the human body. The current version contains over 11 million images with protein expression data for 12.238 unique proteins, corresponding to more than 61% of all proteins

  10. Hard X-ray Microscopic Imaging Of Human Breast Tissues

    NASA Astrophysics Data System (ADS)

    Park, Sung H.; Kim, Hong T.; Kim, Jong K.; Jheon, Sang H.; Youn, Hwa S.

    2007-01-01

    X-ray microscopy with synchrotron radiation will be a useful tool for innovation of x-ray imaging in clinical and laboratory settings. It helps us observe detailed internal structure of material samples non-invasively in air. And, it also has the potential to solve some tough problems of conventional breast imaging if it could evaluate various conditions of breast tissue effectively. A new hard x-ray microscope with a spatial resolution better than 100 nm was installed at Pohang Light Source, a third generation synchrotron radiation facility in Pohang, Korea. The x-ray energy was set at 6.95 keV, and the x-ray beam was monochromatized by W/B4C monochromator. Condenser and objective zone plates were used as x-ray lenses. Zernike phase plate next to condenser zone plate was introduced for improved contrast imaging. The image of a sample was magnified 30 times by objective zone plate and 20 times by microscope objective, respectively. After additional 10 times digital magnification, the total magnifying power was up to 6000 times in the end. Phase contrast synchrotron images of 10-μm-thick female breast tissue of the normal, fibroadenoma, fibrocystic change and carcinoma cases were obtained. By phase contrast imaging, hard x-rays enable us to observe many structures of breast tissue without sample preparations such as staining or fixation.

  11. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

    PubMed

    Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

    2016-05-01

    High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

  12. Biomechanical Characterization of Human Soft Tissues Using Indentation and Tensile Testing

    PubMed Central

    Griffin, Michelle; Premakumar, Yaami; Seifalian, Alexander; Butler, Peter Edward; Szarko, Matthew

    2016-01-01

    Regenerative medicine aims to engineer materials to replace or restore damaged or diseased organs. The mechanical properties of such materials should mimic the human tissues they are aiming to replace; to provide the required anatomical shape, the materials must be able to sustain the mechanical forces they will experience when implanted at the defect site. Although the mechanical properties of tissue-engineered scaffolds are of great importance, many human tissues that undergo restoration with engineered materials have not been fully biomechanically characterized. Several compressive and tensile protocols are reported for evaluating materials, but with large variability it is difficult to compare results between studies. Further complicating the studies is the often destructive nature of mechanical testing. Whilst an understanding of tissue failure is important, it is also important to have knowledge of the elastic and viscoelastic properties under more physiological loading conditions. This report aims to provide a minimally destructive protocol to evaluate the compressive and tensile properties of human soft tissues. As examples of this technique, the tensile testing of skin and the compressive testing of cartilage are described. These protocols can also be directly applied to synthetic materials to ensure that the mechanical properties are similar to the native tissue. Protocols to assess the mechanical properties of human native tissue will allow a benchmark by which to create suitable tissue-engineered substitutes. PMID:28060331

  13. The effect of postmortem time on the RNA quality of human ocular tissues

    PubMed Central

    Kim, Byung-Jin; Sprehe, Nicholas; Morganti, Ashley; Wordinger, Robert J.

    2013-01-01

    Purpose Profiling gene expression in human ocular tissues provides invaluable information for understanding ocular biology and investigating numerous ocular diseases. Accurate measurement of gene expression requires high-quality RNA, which often is a challenge with postmortem ocular tissues. Methods We examined the effect of various death to preservation (DP) times on the RNA quality of ten different ocular tissues. We used 16 eyes from eight different human donors. The eyes were preserved immediately in RNAlater or preserved after initial storage at 4 °C to create a range of DP times from 2 to 48 h. Ten ocular tissues were dissected from each eye. After total RNA was extracted from each dissected ocular tissue, the RNA integrity number (RIN) was determined using an Agilent Bioanalyzer. Results The RIN values from corneal and trabecular meshwork tissues were significantly (p<0.05) higher than those from the ciliary body at an earlier DP time (<6 h), but were not different among all tissues after 8 h. Interestingly, the RIN values from non-vascularized tissues were significantly (p=0.0002) higher than those from vascularized ocular tissues at early DP times (<6 h). The RIN value from the cornea was significantly (p<0.05) higher at short DP times compared to longer DP times. The RIN values from corneal tissues were significantly correlated to DP time according to regression analysis (p<0.05). Conclusions In this study, we determined RNA quality from postmortem ocular tissues with various DP times. Our results emphasize the need for rapid preservation and processing of postmortem human donor eye tissues, especially for vascularized ocular tissues. PMID:23805035

  14. Generation of robust vascular networks from cardiovascular blast populations derived from human induced pluripotent stem cells in vivo and ex vivo organ culture system.

    PubMed

    Kawamoto, Tatsuya; Kobayashi, Yoshifumi; Nakajima, Hidenori; Yamagishi, Yukiko

    2013-11-08

    Vascular network formation is a key therapeutic event in regenerative medicine because it is essential for mitigating or ameliorating ischemic conditions implicated in various diseases and repair of tissues and organs. In this study, we induced human induced pluripotent stem cells (hiPSCs) to differentiate into heterogeneous cell populations which have abilities to form vascular vessel-like structures by recapitulating the embryonic process of vasculogenesis in vitro. These cell populations, named cardiovascular blast populations (CBPs) in this report, primarily consisted of CD31(+) and CD90(+) cells. By using cell-sheet technology, we observed that CBP with CD31(+) cells to CD90(+) cells in the ratio of 1:1.5 could reproducibly form robust vascular networks in vivo and ex vivo organ culture system. To our knowledge, this is the first report demonstrating the generation of vascular network from hiPSCs in ex vivo organ culture system that correlates closely with in vivo results. Our results suggest that CBP provides a promising approach for studying vasculogenesis and subsequently can be used in regenerative medicine.

  15. Three-dimensional tissues using human pluripotent stem cell spheroids as biofabrication building blocks.

    PubMed

    Lin, Haishuang; Li, Qiang; Lei, Yuguo

    2017-03-13

    A recently emerged approach for tissue engineering is to biofabricate tissues using cellular spheroids as building blocks. Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), can be cultured to generate large numbers of cells and presumably be differentiated into all the cell types of human body in vitro, thus are ideal cell source for biofabrication. We previously developed a hydrogel-based cell culture system that can economically produce large numbers of hPSC spheroids. With hPSCs and this culture system, there are two potential methods to biofabricate a desired tissue. In Method 1, hPSC spheroids are first utilized to biofabricate a hPSC tissue that is subsequently differentiated into the desired tissue. In Method 2, hPSC spheroids are first converted into tissue spheroids in the hydrogel-based culture system and the tissue spheroids are then utilized to biofabricate the desired tissue. In this paper, we systematically measured the fusion rates of hPSC spheroids without and with differentiation toward cortical and midbrain dopaminergic neurons and found spheroids' fusion rates dropped sharply as differentiation progressed. We found Method 1 was appropriated for biofabricating neural tissues.

  16. Current good tissue practice for human cell, tissue, and cellular and tissue-based product establishments; inspection and enforcement. Final rule.

    PubMed

    2004-11-24

    The Food and Drug Administration (FDA) is requiring human cell, tissue, and cellular and tissue-based product (HCT/P) establishments to follow current good tissue practice (CGTP), which governs the methods used in, and the facilities and controls used for, the manufacture of HCT/Ps; recordkeeping; and the establishment of a quality program. The agency is also issuing new regulations pertaining to labeling, reporting, inspections, and enforcement that will apply to manufacturers of those HCT/Ps regulated solely under the authority of the Public Health Service Act (PHS Act), and not as drugs, devices, and/or biological products. The agency's actions are intended to improve protection of the public health while keeping regulatory burden to a minimum, which in turn would encourage significant innovation.

  17. FTIR microscopic comparative study on normal, premalignant, and malignant tissues of human intenstine

    NASA Astrophysics Data System (ADS)

    Mordechai, Shaul; Argov, Shmuel; Salman, Ahmad O.; Cohen, Beny; Ramesh, Jagannathan; Erukhimovitch, Vitaly; Goldstein, Jed; Sinelnikov, Igor

    2000-07-01

    Fourier-Transform Infrared Spectroscopy (FTIR) employs a unique approach to optical diagnosis of tissue pathology based on the characteristic molecular vibrational spectra of the tissue. The architectural changes in the cellular and sub-cellular levels developing in abnormal tissue, including a majority of cancer forms, manifest themselves in different optical signatures, which can be detected in infrared spectroscopy. The biological systems we have studied include normal, premalignant (polyp) and malignant human colonic tissues from three patients. Our method is based on microscopic infrared study (FTIR-microscopy) of thin tissue specimens and a direct comparison with normal histopathological analysis, which serves as a `gold' reference. The normal intestine tissue has a stronger absorption than polyp and cancerous types over a wide region in all three cases. The detailed analysis showed that there is a significant decrease in total phosphate and creatine contents for polyp and cancerous tissue types in comparison to the controls.

  18. Multiscale model of the human cardiovascular system: Description of heart failure and comparison of contractility indices.

    PubMed

    Kosta, S; Negroni, J; Lascano, E; Dauby, P C

    2017-02-01

    A multiscale model of the cardiovascular system is presented. Hemodynamics is described by a lumped parameter model, while heart contraction is described at the cellular scale. An electrophysiological model and a mechanical model were coupled and adjusted so that the pressure and volume of both ventricles are linked to the force and length of a half-sarcomere. Particular attention was paid to the extreme values of the sarcomere length, which must keep physiological values. This model is able to reproduce healthy behavior, preload variations experiments, and ventricular failure. It also allows to compare the relevance of standard cardiac contractility indices. This study shows that the theoretical gold standard for assessing cardiac contractility, namely the end-systolic elastance, is actually load-dependent and therefore not a reliable index of cardiac contractility.

  19. Cardiovascular responses in humans to experimental chewing of gums of different consistencies.

    PubMed

    Farella, M; Bakke, M; Michelotti, A; Marotta, G; Martina, R

    1999-10-01

    Although the cardiovascular effects of exercise have been extensively investigated in man, little attention has been paid to such responses to jaw muscle activity. The aim here was to investigate the general cardiovascular effects of chewing activity in a single-blind, cross-over design. Ten healthy individuals performed one of the following chewing tasks in four separate sessions: chewing a very hard gum, chewing a moderately hard gum, chewing a soft gum, and "empty chewing" without a bolus. Unilateral chewing of gum or empty chewing was performed for 20 min on the participant's most convenient chewing side at a constant rate of 80 cycles/min. In each session, heart rate and arterial blood pressure were recorded together with electromyographic activity in the masseter and anterior temporalis muscles on the chewing side. Ratings of perceived masticatory fatigue were recorded with visual analogue scales. The heart rate and blood pressure were significantly increased (ANOVA; p < or= 0.01) during the chewing tasks and the increases were, in parallel with the muscle activity, more pronounced the harder the gum. With the very hard gum, heart rate increased by up to 11 beats/min, the systolic blood pressure was 14 mmHg (1.9kPa) higher, and the diastolic blood pressure was 11 mmHg (1.5kPa) higher. The perceived fatigue was proportional to the level of muscle activity. After 10 min of recovery from exercise, heart rate and arterial blood pressures were slightly but still significantly elevated. The results demonstrate that chewing is associated with general circulatory effects proportional to the bolus resistance.

  20. Raman spectroscopic analysis of human skin tissue sections ex-vivo: evaluation of the effects of tissue processing and dewaxing

    NASA Astrophysics Data System (ADS)

    Ali, Syed M.; Bonnier, Franck; Tfayli, Ali; Lambkin, Helen; Flynn, Kathleen; McDonagh, Vincent; Healy, Claragh; Clive Lee, T.; Lyng, Fiona M.; Byrne, Hugh J.

    2013-06-01

    Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections and the effects of tissue processing. Both hand and thigh sections of human cadavers were analyzed in their unprocessed and formalin-fixed, paraffin-processed (FFPP), and subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear differentiation of the stratum corneum (SC), intermediate underlying epithelium, and dermal layers for sections from both anatomical sites. The SC is seen to be relatively rich in lipidic content; the spectrum of the subjacent layers is strongly influenced by the presence of melanin, while that of the dermis is dominated by the characteristics of collagen. For a given anatomical site, little difference in layer structure and biochemistry is observed between samples from different cadavers. However, the hand and thigh sections are consistently differentiated for all cadavers, largely based on lipidic profiles. In dewaxed FFPP samples, while the SC, intermediate, and dermal layers are clearly differentiated by KMCA of Raman maps of tissue sections, the lipidic contributions to the spectra are significantly reduced, with the result that respective skin layers from different anatomical sites become indistinguishable. While efficient at removing the fixing wax, the tissue processing also efficiently removes the structurally similar lipidic components of the skin layers. In studies of dermatological processes in which lipids play an important role, such as wound healing, dewaxed samples are therefore not appropriate. Removal of the lipids does however accentuate the spectral features of the cellular and protein components, which may be more appropriate for retrospective analysis of disease progression and biochemical analysis using tissue banks.

  1. Effect of cocoa/chocolate ingestion on brachial artery flow-mediated dilation and its relevance to cardiovascular health and disease in humans.

    PubMed

    Monahan, Kevin D

    2012-11-15

    Prospective studies indicate that high intake of dietary flavanols, such as those contained in cocoa/chocolate, are associated with reduced rates of cardiovascular-related morbidity and mortality in humans. Numerous mechanisms may underlie these associations such as favorable effects of flavanols on blood pressure, platelet aggregation, thrombosis, inflammation, and the vascular endothelium. The brachial artery flow-mediated dilation (FMD) technique has emerged as a robust method to quantify endothelial function in humans. Collectively, the preponderance of evidence indicates that FMD is a powerful surrogate measure for firm cardiovascular endpoints, such as cardiovascular-related mortality, in humans. Thus, literally thousands of studies have utilized this technique to document group differences in FMD, as well as to assess the effects of various interventions on FMD. In regards to the latter, numerous studies indicate that both acute and chronic ingestion of cocoa/chocolate increases FMD in humans. Increases in FMD after cocoa/chocolate ingestion appear to be dose-dependent such that greater increases in FMD are observed after ingestion of larger quantities. The mechanisms underlying these responses are likely diverse, however most data suggest an effect of increased nitric oxide bioavailability. Thus, positive vascular effects of cocoa/chocolate on the endothelium may underlie (i.e., be linked mechanistically to) reductions in cardiovascular risk in humans.

  2. FADS2 genotype regulates delta-6 desaturase activity and inflammation in human adipose tissue[S

    PubMed Central

    Vaittinen, Maija; Walle, Paula; Kuosmanen, Emmi; Männistö, Ville; Käkelä, Pirjo; Ågren, Jyrki; Schwab, Ursula; Pihlajamäki, Jussi

    2016-01-01

    Obesity is associated with disturbed lipid metabolism and low-grade inflammation in tissues. The aim of this study was to investigate the association between FA metabolism and adipose tissue (AT) inflammation in the Kuopio Obesity Surgery study. We investigated the association of surgery-induced weight loss and FA desaturase (FADS)1/2 genotypes with serum and AT FA profile and with AT inflammation, measured as interleukin (IL)-1β and NFκB pathway gene expression, in order to find potential gene-environment interactions. We demonstrated an association between serum levels of saturated and polyunsaturated n-6 FAs, and estimated enzyme activities of FADS1/2 genes with IL-1β expression in AT both at baseline and at follow-up. Variation in the FADS1/2 genes associated with IL-1β and NFκB pathway gene expression in SAT after weight reduction, but not at baseline. In addition, the FA composition in subcutaneous and visceral fat correlated with serum FAs, and the associations between serum PUFAs and estimated D6D enzyme activity with AT inflammation were also replicated with corresponding AT FAs and AT inflammation. We conclude that the polymorphism in FADS1/2 genes associates with FA metabolism and AT inflammation, leading to an interaction between weight loss and FADS1/2 genes in the regulation of AT inflammation. PMID:26609056

  3. Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF-7 human breast cancer cells.

    PubMed

    Charles, Amelia K; Darbre, Philippa D

    2013-05-01

    The alkyl esters of p-hydroxybenzoic acid (parabens), which are used as preservatives in consumer products, possess oestrogenic activity and have been measured in human breast tissue. This has raised concerns for a potential involvement in the development of human breast cancer. In this paper, we have investigated the extent to which proliferation of MCF-7 human breast cancer cells can be increased by exposure to the five parabens either alone or in combination at concentrations as recently measured in 160 human breast tissue samples. Determination of no-observed-effect concentrations (NOEC), lowest-observed-effect concentrations (LOEC), EC50 and EC100 values for stimulation of proliferation of MCF-7 cells by five parabens revealed that 43/160 (27%) of the human breast tissue samples contained at least one paraben at a concentration ≥ LOEC and 64/160 (40%) > NOEC. Proliferation of MCF-7 cells could be increased by combining all five parabens at concentrations down to the 50(th) percentile (median) values measured in the tissues. For the 22 tissue samples taken at the site of ER + PR + primary cancers, 12 contained a sufficient concentration of one or more paraben to stimulate proliferation of MCF-7 cells. This demonstrates that parabens, either alone or in combination, are present in human breast tissue at concentrations sufficient to stimulate the proliferation of MCF-7 cells in vitro, and that functional consequences of the presence of paraben in human breast tissue should be assessed on the basis of all five parabens and not single parabens individually.

  4. Mineral Density Volume Gradients in Normal and Diseased Human Tissues

    PubMed Central

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.

    2015-01-01

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations. PMID:25856386

  5. Mineral density volume gradients in normal and diseased human tissues

    DOE PAGES

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; ...

    2015-04-09

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-raymore » fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.« less

  6. Mineral density volume gradients in normal and diseased human tissues

    SciTech Connect

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.; Aikawa, Elena

    2015-04-09

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  7. The influence of tissue procurement procedures on RNA integrity, gene expression, and morphology in porcine and human liver tissue.

    PubMed

    Kap, Marcel; Sieuwerts, Anieta M; Kubista, Mikael; Oomen, Monique; Arshad, Shazia; Riegman, Peter

    2015-06-01

    The advent of molecular characterization of tissues has brought an increasing emphasis on the quality of biospecimens, starting with the tissue procurement process. RNA levels are particularly affected by factors in the collection process, but the influence of different pre-analytical factors is not well understood. Here we present the influence of tissue specimen size, as well as the transport and freezing protocols, on RNA quality. Large, medium, and smaller porcine liver samples were stored either dry, on moist gauze, or in salt solution for various times, and then frozen in either liquid nitrogen or in pre-cooled isopentane. Large and small human liver samples were frozen in pre-cooled isopentane either immediately or after one hour at room temperature. The small samples were stored dry, on moist gauze, or in salt solution. RNA was isolated and RIN values were measured. The RNA for six standard reference genes from human liver was analyzed by RT-qPCR, and tissue morphology was assessed for artifacts of freezing. Experiments using porcine liver samples showed that RNA derived from smaller samples was more degraded after one hour of cold ischemia, and that cooled transport is preferable. Human liver samples showed significant RNA degradation after 1 h of cold ischemia, which was more pronounced in smaller samples. RNA integrity was not significantly influenced by the transport or freezing method, but changes in gene expression were observed in samples either transported on gauze or in salt solution. Based on observations in liver samples, smaller samples are more subject to gene expression variability introduced by post-excision sample handling than are larger samples. Small biopsies should be transported on ice and snap frozen as soon as possible after acquisition from the patient.

  8. [Analysis of human tissue samples for volatile fire accelerants].

    PubMed

    Treibs, Rudolf

    2014-01-01

    In police investigations of fires, the cause of a fire and the fire debris analysis regarding traces of fire accelerants are important aspects for forensic scientists. Established analytical procedures were recently applied to the remains of fire victims. When examining lung tissue samples, vapors inhaled from volatile ignitable liquids could be identified and differentiated from products of pyrolysis caused by the fire. In addition to the medico-legal results this evidence allowed to draw conclusions as to whether the fire victim was still alive when the fire started.

  9. Elemental composition of some essential cations in human ocular tissue

    SciTech Connect

    Panessa-Warren, B.J.; Kraner, H.W.; Warren, J.B.

    1983-01-01

    To obtain data on the baseline elemental content in normal adult sensory retina, RPE and iris, normal non-diabetic eyes were analyzed and these results were used for comparison to similarly prepared samples from diabetic donor eyes. To determine if the concentrations of the cations, Ca, Ba and Zn were altered by the age, alimentation and exposure to light of the donor, tissue from children (from 25 weeks gestation to 8-1/2 years old) was also analyzed by x-ray fluorescence spectroscopy, proton induced x-ray emission spectroscopy, and light and electron (scanning and transmission) microscopy.

  10. Communication channel modeling of human forearm with muscle fiber tissue characteristics.

    PubMed

    Zhang, Shuang; Pun, Sio Hang; Mak, Peng Un; Qin, Yu-Ping; Liu, Yi-He; Vai, Mang I

    2016-09-14

    Human-Body Communication (HBC) is a wireless communication method using the human body tissue as a transmission medium for signals. This paper on the basis of human muscle fiber tissues' characteristics, it is first proposed to establish the analytical model of galvanic coupling human-body communication channel. In this model, the parallel and the transverse electrical characteristics of muscular tissue are fully considered, and the model accurately presents the transmission mechanism of galvanic coupling human-body communication signals in the channel. At last, through compare with the experimental results and calculation results, the maximum error of the model is 22.4% and the average error is 14.2% within the frequency range.

  11. From cell lines to tissues: extrapolation of transcriptional effects to human tissues (SOT)

    EPA Science Inventory

    A new suite of assays in the metabolically-competent, human hepatocyte-derived HepaRG cell line has been added to the ToxCast screening suite. For 1066 chemicals we have evaluated the chemical treatment-induced changes in expression for a diverse set of 93 genes representative of...

  12. Role of endotoxemia in cardiovascular dysfunction and mortality. Escherichia coli and Staphylococcus aureus challenges in a canine model of human septic shock.

    PubMed Central

    Natanson, C; Danner, R L; Elin, R J; Hosseini, J M; Peart, K W; Banks, S M; MacVittie, T J; Walker, R I; Parrillo, J E

    1989-01-01

    Using different types of bacteria and a canine model simulating human septic shock, we investigated the role of endotoxin in cardiovascular dysfunction and mortality. Either Escherichia coli (a microorganism with endotoxin) or Staphylococcus aureus (a microorganism without endotoxin) were placed in an intraperitoneal clot in doses of viable or formalin-killed bacteria. Cardiovascular function of conscious animals was studied using simultaneous radionuclide heart scans and thermodilution cardiac outputs. Serial plasma endotoxin levels were measured. S. aureus produced a pattern of reversible cardiovascular dysfunction over 7-10 d that was concordant (P less than 0.01) with that of E. coli. Although this cardiovascular pattern was not altered by formalin killing (S. aureus and E. coli), formalin-killed organisms produced a lower mortality and less myocardial depression (P less than 0.01). S. aureus, compared to E. coli, produced higher postmortem concentrations of microorganisms and higher mortality (P less than 0.025). E. coli produced significant endotoxemia (P less than 0.01), though viable organisms (versus nonviable) resulted in higher endotoxin blood concentrations (P less than 0.05). Significant endotoxemia did not occur with S. aureus. Thus, in the absence of endotoxemia, S. aureus induced the same cardiovascular abnormalities of septic shock as E. coli. These findings indicate that structurally and functionally distinct microorganisms, with or without endotoxin, can activate a common pathway resulting in similar cardiovascular injury and mortality. PMID:2642920

  13. Swelling of Erectile Nasal Tissue Induced by Human Sexual Pheromone.

    PubMed

    Mazzatenta, Andrea; De Luca, C; Di Tano, A; Cacchio, M; Di Giulio, C; Pokorski, Mieczyslaw

    2016-01-01

    Most chemically mediated sexual communication in humans remains uncharacterized. Yet the study of sexual communication is decisive for understanding sexual behavior and evolutive mechanisms in our species. Here we provide the evidence to consider 4,16-androstadien-3-one (AND) as a man's sexual pheromone. Our experiment provides support for the physiological effect of AND on nasal airway resistance (Rna) in women, as assessed by anterior rhinomanometry. We found that AND administration increased the area of turbinate during the ovulatory phase, resulting in an increase of Rna. Thus, we discovered that minute amounts of AND, acting through neuroendocrine brain control, regulate Rna and consequently affect the sexual physiology and behavior. Fascinatingly, this finding provides the evidence of the preservation of chemosexual communication in humans, which it has been largely neglected due to its unconscious perception and concealed nature. Therefore, chemical communication is a plesiomorphic evolutive phenomenon in humans.

  14. Flow Cytometric Analysis of Myeloid Cells in Human Blood, Bronchoalveolar Lavage, and Lung Tissues

    PubMed Central

    Yu, Yen-Rei A.; Hotten, Danielle F.; Malakhau, Yuryi; Volker, Ellen; Ghio, Andrew J.; Noble, Paul W.; Kraft, Monica; Hollingsworth, John W.; Gunn, Michael D.

    2016-01-01

    Clear identification of specific cell populations by flow cytometry is important to understand functional roles. A well-defined flow cytometry panel for myeloid cells in human bronchoalveolar lavage (BAL) and lung tissue is currently lacking. The objective of this study was to develop a flow cytometry–based panel for human BAL and lung tissue. We obtained and performed flow cytometry/sorting on human BAL cells and lung tissue. Confocal images were obtained from lung tissue using antibodies for cluster of differentiation (CD)206, CD169, and E cadherin. We defined a multicolor flow panel for human BAL and lung tissue that identifies major leukocyte populations. These include macrophage (CD206+) subsets and other CD206− leukocytes. The CD206− cells include: (1) three monocyte (CD14+) subsets, (2) CD11c+ dendritic cells (CD14−, CD11c+, HLA-DR+), (3) plasmacytoid dendritic cells (CD14−, CD11c−, HLA-DR+, CD123+), and (4) other granulocytes (neutrophils, mast cells, eosinophils, and basophils). Using this panel on human lung tissue, we defined two populations of pulmonary macrophages: CD169+ and CD169− macrophages. In lung tissue, CD169− macrophages were a prominent cell type. Using confocal microscopy, CD169+ macrophages were located in the alveolar space/airway, defining them as alveolar macrophages. In contrast, CD169− macrophages were associated with airway/alveolar epithelium, consistent with interstitial-associated macrophages. We defined a flow cytometry panel in human BAL and lung tissue that allows identification of multiple immune cell types and delineates alveolar from interstitial-associated macrophages. This study has important implications for defining myeloid cells in human lung samples. PMID:26267148

  15. PIXE measurement applied to trace elemental analysis of human tissues

    NASA Astrophysics Data System (ADS)

    Tanaka, M.; Matsugi, E.; Miyasaki, K.; Yamagata, T.; Inoue, M.; Ogata, H.; Shimoura, S.

    1987-03-01

    PIXE measurement was applied for trace elemental analyses of 40 autoptic human kidneys. To investigate the reproducibility of the PIXE data, 9 targets obtained from one human liver were examined. The targets were prepared by wet-digestion using nitric and sulfuric acid. Yttrium was used as an internal standard. The extracted elemental concentrations for K, Fe, Cu, Zn, and Cd were in reasonable agreement with those obtained by atomic absorption spectrometry (AAS) and flame photometry (FP). Various correlations among the elements K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Rb, and Cd were examined individually for the renal cortex and renal medulla.

  16. Human tissue color as viewed in high dynamic range optical spectral transmission measurements.

    PubMed

    Petrov, Georgi I; Doronin, Alexander; Whelan, Harry T; Meglinski, Igor; Yakovlev, Vladislav V

    2012-09-01

    High dynamic range optical-to-near-infrared transmission measurements for different parts of human body in the spectral range from 650 to 950 nm have been performed. Experimentally measured spectra are correlated with Monte Carlo simulations using chromaticity coordinates in CIE 1976 L*a*b* color space. Both a qualitative and a quantitative agreement have been found, paving a new way of characterizing human tissues in vivo. The newly developed experimental and computational platform for assessing tissue transmission spectra is anticipated to have a considerable impact on identifying favorable conditions for laser surgery and optical diagnostics, while providing supplementary information about tissue properties.

  17. Infarct tissue characteristics of patients with versus without early revascularization for acute myocardial infarction: a contrast-enhancement cardiovascular magnetic resonance imaging study.

    PubMed

    Olimulder, M A G M; Kraaier, K; Galjee, M A; Scholten, M F; van Es, J; Wagenaar, L J; van der Palen, J; von Birgelen, C

    2012-05-01

    Histopathological studies have suggested that early revascularization for acute myocardial infarction (MI) limits the size, transmural extent, and homogeneity of myocardial necrosis. However, the long-term effect of early revascularization on infarct tissue characteristics is largely unknown. Cardiovascular magnetic resonance (CMR) imaging with contrast enhancement (CE) allows non-invasive examination of infarct tissue characteristics and left ventricular (LV) dimensions and function in one examination. A total of 69 patients, referred for cardiac evaluation for various clinical reasons, were examined with CE-CMR >1 month (median 6, range 1-213) post-acute MI. We compared patients with (n = 33) versus without (n = 36) successful early revascularization for acute MI. Cine-CMR measurements included the LV end-diastolic and end-systolic volumes (ESV), LV ejection fraction (LVEF, %), and wall motion score index (WMSI). CE images were analyzed for core, peri, and total infarct size (%), and for the number of transmural segments. In our population, patients with successful early revascularization had better LVEFs (46 ± 16 vs. 34 ± 14%; P < 0.01), superior WMSIs (0.53, range 0.00-2.29 vs. 1.42, range 0.00-2.59; P < 0.01), and smaller ESVs (121 ± 70 vs. 166 ± 82; P = 0.02). However, there was no difference in core (9 ± 6 vs. 11 ± 6%), peri (9 ± 4 vs. 10 ± 4%), and total infarct size (18 ± 9 vs. 21 ± 9%; P > 0.05 for all comparisons); only transmural extent (P = 0.07) and infarct age (P = 0.06) tended to be larger in patients without early revascularization. CMR wall motion abnormalities are significantly better after revascularization; these differences are particularly marked later after infarction. The difference in scar size is more subtle and does not reach significance in this study.

  18. Computational reconstruction of tissue-specific metabolic models: application to human liver metabolism

    PubMed Central

    Jerby, Livnat; Shlomi, Tomer; Ruppin, Eytan

    2010-01-01

    The computational study of human metabolism has been advanced with the advent of the first generic (non-tissue specific) stoichiometric model of human metabolism. In this study, we present a new algorithm for rapid reconstruction of tissue-specific genome-scale models of human metabolism. The algorithm generates a tissue-specific model from the generic human model by integrating a variety of tissue-specific molecular data sources, including literature-based knowledge, transcriptomic, proteomic, metabolomic and phenotypic data. Applying the algorithm, we constructed the first genome-scale stoichiometric model of hepatic metabolism. The model is verified using standard cross-validation procedures, and through its ability to carry out hepatic metabolic functions. The model's flux predictions correlate with flux measurements across a variety of hormonal and dietary conditions, and improve upon the predictive performance obtained using the original, generic human model (prediction accuracy of 0.67 versus 0.46). Finally, the model better predicts biomarker changes in genetic metabolic disorders than the generic human model (accuracy of 0.67 versus 0.59). The approach presented can be used to construct other human tissue-specific models, and be applied to other organisms. PMID:20823844

  19. Microwave irradiation of human brain tissue: production of microscopic slides within one day.

    PubMed Central

    Boon, M E; Marani, E; Adriolo, P J; Steffelaar, J W; Bots, G T; Kok, L P

    1988-01-01

    A three step method using microwave irradiation enabled microscopic slides of human brain tissue to be obtained within one working day: steps 1 and 2 hardened and solidified brain tissue; step 3 completed formalin fixation. The efficacy and precision of the method was compared with slides of conventionally processed brain tissue that had been fixed in formalin for six weeks. The microscopic quality of the sections was excellent with good presentation of brain tissue and equalled that of conventionally processed slides. Images Fig 1 Fig 2 Fig 3 PMID:3290268

  20. Human ex-vivo oral tissue imaging using spectral domain polarization sensitive optical coherence tomography.

    PubMed

    Sharma, Priyanka; Verma, Yogesh; Sahu, Khageswar; Kumar, Sudhir; Varma, Amit V; Kumawat, Jyoti; Gupta, Pradeep Kumar

    2017-01-01

    We report the use of spectral domain polarization sensitive optical coherence tomography for ex-vivo imaging of human oral mandibular tissue samples. Our results show that compared to the changes observed in the epithelium thickness and the decay constant of A-scan intensity profile, a much larger degree of change was observed in the phase retardation for tissue sites progressing from normal to the malignant state. These results suggest that monitoring of tissue retardance can help in better differentiation of normal and cancerous oral tissue sites.

  1. Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets

    PubMed Central

    Sathaliyawala, Taheri; Kubota, Masaru; Yudanin, Naomi; Turner, Damian; Camp, Philip; Thome, Joseph J. C.; Bickham, Kara L.; Lerner, Harvey; Goldstein, Michael; Sykes, Megan; Kato, Tomoaki; Farber, Donna L.

    2012-01-01

    SUMMARY Knowledge of human T cells derives chiefly from studies of peripheral blood, whereas their distribution and function in tissues remains largely unknown. Here, we present a unique analysis of human T cells in lymphoid and mucosal tissues obtained from individual organ donors, revealing tissue-intrinsic compartmentalization of naive, effector and memory subsets conserved between diverse individuals. Effector-memory CD4+ T cells producing IL-2 predominated in mucosal tissues and accumulated as central-memory subsets in lymphoid tissue, whereas CD8+ T cells were maintained as naïve subsets in lymphoid tissues and IFN-γ-producing effector-memory CD8+ T cells in mucosal sites. The T cell activation marker, CD69, was constitutively expressed by memory T cells in all tissues, distinguishing them from circulating subsets, with mucosal memory T cells exhibiting additional distinct phenotypic and functional properties. Our results provide an assessment of human T cell compartmentalization as a new baseline for understanding human adaptive immunity. PMID:23260195

  2. Atlas of tissue renin-angiotensin-aldosterone system in human: A transcriptomic meta-analysis

    PubMed Central

    Nehme, Ali; Cerutti, Catherine; Dhaouadi, Nedra; Gustin, Marie Paule; Courand, Pierre-Yves; Zibara, Kazem; Bricca, Giampiero

    2015-01-01

    Tissue renin-angiotensin-aldosterone system (RAAS) has attracted much attention because of its physiological and pharmacological implications; however, a clear definition of tissue RAAS is still missing. We aimed to establish a preliminary atlas for the organization of RAAS across 23 different normal human tissues. A set of 37 genes encoding classical and novel RAAS participants including gluco- and mineralo-corticoids were defined as extended RAAS (extRAAS) system. Microarray data sets containing more than 10 normal tissues were downloaded from the GEO database. R software was used to extract expression levels and construct dendrograms of extRAAS genes within each data set. Tissue co-expression modules were then extracted from reproducible gene clusters across data sets. An atlas of the maps of tissue-specific organization of extRAAS was constructed from gene expression and coordination data. Our analysis included 143 data sets containing 4933 samples representing 23 different tissues. Expression data provided an insight on the favored pathways in a given tissue. Gene coordination indicated the existence of tissue-specific modules organized or not around conserved core groups of transcripts. The atlas of tissue-specific organization of extRAAS will help better understand tissue-specific effects of RAAS. This will provide a frame for developing more effective and selective pharmaceuticals targeting extRAAS. PMID:25992767

  3. Tissue Metabonomic Phenotyping for Diagnosis and Prognosis of Human Colorectal Cancer

    PubMed Central

    Tian, Yuan; Xu, Tangpeng; Huang, Jia; Zhang, Limin; Xu, Shan; Xiong, Bin; Wang, Yulan; Tang, Huiru

    2016-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide and prognosis based on the conventional histological grading method for CRC remains poor. To better the situation, we analyzed the metabonomic signatures of 50 human CRC tissues and their adjacent non-involved tissues (ANIT) using high-resolution magic-angle spinning (HRMAS) 1H NMR spectroscopy together with the fatty acid compositions of these tissues using GC-FID/MS. We showed that tissue metabolic phenotypes not only discriminated CRC tissues from ANIT, but also distinguished low-grade tumor tissues (stages I-II) from the high-grade ones (stages III-IV) with high sensitivity and specificity in both cases. Metabonomic phenotypes of CRC tissues differed significantly from that of ANIT in energy metabolism, membrane biosynthesis and degradations, osmotic regulations together with the metabolism of proteins and nucleotides. Amongst all CRC tissues, the stage I tumors exhibited largest differentiations from ANIT. The combination of the differentiating metabolites showed outstanding collective power for differentiating cancer from ANIT and for distinguishing CRC tissues at different stages. These findings revealed details in the typical metabonomic phenotypes associated with CRC tissues nondestructively and demonstrated tissue metabonomic phenotyping as an important molecular pathology tool for diagnosis and prognosis of cancerous solid tumors. PMID:26876567

  4. Tissue Metabonomic Phenotyping for Diagnosis and Prognosis of Human Colorectal Cancer.

    PubMed

    Tian, Yuan; Xu, Tangpeng; Huang, Jia; Zhang, Limin; Xu, Shan; Xiong, Bin; Wang, Yulan; Tang, Huiru

    2016-02-15

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide and prognosis based on the conventional histological grading method for CRC remains poor. To better the situation, we analyzed the metabonomic signatures of 50 human CRC tissues and their adjacent non-involved tissues (ANIT) using high-resolution magic-angle spinning (HRMAS) (1)H NMR spectroscopy together with the fatty acid compositions of these tissues using GC-FID/MS. We showed that tissue metabolic phenotypes not only discriminated CRC tissues from ANIT, but also distinguished low-grade tumor tissues (stages I-II) from the high-grade ones (stages III-IV) with high sensitivity and specificity in both cases. Metabonomic phenotypes of CRC tissues differed significantly from that of ANIT in energy metabolism, membrane biosynthesis and degradations, osmotic regulations together with the metabolism of proteins and nucleotides. Amongst all CRC tissues, the stage I tumors exhibited largest differentiations from ANIT. The combination of the differentiating metabolites showed outstanding collective power for differentiating cancer from ANIT and for distinguishing CRC tissues at different stages. These findings revealed details in the typical metabonomic phenotypes associated with CRC tissues nondestructively and demonstrated tissue metabonomic phenotyping as an important molecular pathology tool for diagnosis and prognosis of cancerous solid tumors.

  5. Cardiovascular Adjustments to Gravitational Stress

    NASA Technical Reports Server (NTRS)

    Blomqvist, C. Gunnar; Stone, H. Lowell

    1991-01-01

    The effects of gravity on the cardiovascular system must be taken into account whenever a hemodynamic assessment is made. All intravascular pressure have a gravity-dependent hydrostatic component. The interaction between the gravitational field, the position of the body, and the functional characteristics of the blood vessels determines the distribution of intravascular volume. In turn this distribution largely determines cardiac pump function. Multiple control mechanisms are activated to preserve optimal tissue perfusion when the magnitude of the gravitational field or its direction relative to the body changes. Humans are particularly sensitive to such changes because of the combination of their normally erect posture and the large body mass and blood volume below the level of the heart. Current aerospace technology also exposes human subjects to extreme variations in the gravitational forces that range from zero during space travel to as much an nine-times normal during operation of high-performance military aircraft. This chapter therefore emphasizes human physiology.

  6. Effect of green tea extract microencapsulation on hypertriglyceridemia and cardiovascular tissues in high fructose-fed rats.

    PubMed

    Jung, Moon Hee; Seong, Pil Nam; Kim, Myung Hwan; Myong, Na-Hye; Chang, Moon-Jeong

    2013-10-01

    The application of polyphenols has attracted great interest in the field of functional foods and nutraceuticals due to their potential health benefits in humans. However, the effectiveness of polyphenols depends on their bioactivity and bioavailability. In the present study, the bioactive component from green tea extract (GTE) was administrated orally (50 mg/kg body weight/day) as free or in a microencapsulated form with maltodextrin in rats fed a high fructose diet. High fructose diet induced features of metabolic syndrome including hypertriglyceridemia, hyperuricemia, increased serum total cholesterol, and retroperitoneal obesity. In addition, myocardial fibrosis was increased. In rats receiving high fructose diet, the lowering of blood triglycerides, total cholesterol, non esterified fatty acid (NEFA) and uric acid, as well as the reduction in final body weight and retroperitoneal fat weight associated with the administration of GTE, led to a reversal of the features of metabolic syndrome (P < 0.05). In particular, the administration of microencapsulated GTE decreased myocardial fibrosis and increased liver catalase activity consistent with a further alleviation of serum NEFA, and hyperuricemia compared to administration of GTE. Taken together, our results suggest that microencapsulation of the bioactive components of GTE might have a protective effect on cardiovasucular system by attenuating the adverse features of myocardial fibrosis, decreasing uric acid levels and increasing hepatic catalase activity effectively by protecting their bioactivities.

  7. The Identification of Aluminum in Human Brain Tissue Using Lumogallion and Fluorescence Microscopy

    PubMed Central

    Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

    2016-01-01

    Aluminum in human brain tissue is implicated in the etiologies of neurodegenerative diseases including Alzheimer’s disease. While methods for the accurate and precise measurement of aluminum in human brain tissue are widely acknowledged, the same cannot be said for the visualization of aluminum. Herein we have used transversely-heated graphite furnace atomic absorption spectrometry to measure aluminum in the brain of a donor with Alzheimer’s disease, and we have developed and validated fluorescence microscopy and the fluor lumogallion to show the presence of aluminum in the same tissue. Aluminum is observed as characteristic orange fluorescence that is neither reproduced by other metals nor explained by autofluorescence. This new and relatively simple method to visualize aluminum in human brain tissue should enable more rigorous testing of the aluminum hypothesis of Alzheimer’s disease (and other neurological conditions) in the future. PMID:27472886

  8. Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells

    PubMed Central

    Månsson-Broberg, Agneta; Rodin, Sergey; Bulatovic, Ivana; Ibarra, Cristián; Löfling, Marie; Genead, Rami; Wärdell, Eva; Felldin, Ulrika; Granath, Carl; Alici, Evren; Le Blanc, Katarina; Smith, C.I. Edvard; Salašová, Alena; Westgren, Magnus; Sundström, Erik; Uhlén, Per; Arenas, Ernest; Sylvén, Christer; Tryggvason, Karl; Corbascio, Matthias; Simonson, Oscar E.; Österholm, Cecilia; Grinnemo, Karl-Henrik

    2016-01-01

    Summary The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs) has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN)-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.5. The majority of cells stained positive for PDGFR-α, ISL1, and NKX2.5, and subpopulations also expressed the progenitor markers TBX18, KDR, c-KIT, and SSEA-1. Upon culture of the cardiac MSCs in differentiation media and on relevant LNs, portions of the cells differentiated into spontaneously beating cardiomyocytes, and endothelial and smooth muscle-like cells. Our protocol for large-scale culture of human fetal cardiac MSCs enables future exploration of the regenerative functions of these cells in the context of myocardial injury in vitro and in vivo. PMID:27052314

  9. Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells.

    PubMed

    Månsson-Broberg, Agneta; Rodin, Sergey; Bulatovic, Ivana; Ibarra, Cristián; Löfling, Marie; Genead, Rami; Wärdell, Eva; Felldin, Ulrika; Granath, Carl; Alici, Evren; Le Blanc, Katarina; Smith, C I Edvard; Salašová, Alena; Westgren, Magnus; Sundström, Erik; Uhlén, Per; Arenas, Ernest; Sylvén, Christer; Tryggvason, Karl; Corbascio, Matthias; Simonson, Oscar E; Österholm, Cecilia; Grinnemo, Karl-Henrik

    2016-04-12

    The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs) has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN)-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.5. The majority of cells stained positive for PDGFR-α, ISL1, and NKX2.5, and subpopulations also expressed the progenitor markers TBX18, KDR, c-KIT, and SSEA-1. Upon culture of the cardiac MSCs in differentiation media and on relevant LNs, portions of the cells differentiated into spontaneously beating cardiomyocytes, and endothelial and smooth muscle-like cells. Our protocol for large-scale culture of human fetal cardiac MSCs enables future exploration of the regenerative functions of these cells in the context of myocardial injury in vitro and in vivo.

  10. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

    NASA Technical Reports Server (NTRS)

    Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

    1997-01-01

    The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

  11. Three-dimensional functional human myocardial tissues fabricated from induced pluripotent stem cells.

    PubMed

    Komae, Hyoe; Sekine, Hidekazu; Dobashi, Izumi; Matsuura, Katsuhisa; Ono, Minoru; Okano, Teruo; Shimizu, Tatsuya

    2017-03-01

    The most radical treatment currently available for severe heart failure is heart transplantation; however, the number of donor hearts is limited. A better approach is to make human cardiac tissues. We developed an original cell sheet-based tissue-engineering technology to fabricate human cardiac tissue by layering myocardial cell sheets. Human induced pluripotent stem (iPS) cells were differentiated into cardiomyocytes to fabricate cardiomyocyte sheets. Initially, three-layer human iPS cardiomyocyte (hiPSCM) sheets were transplanted on subcutaneous tissues of nude rats. Next, to fabricate thicker tissue, three-layer sheets were transplanted on one day, then additional three-layer sheets were transplanted onto them the following day, after the first sheets were vascularized. On day 3, the final three-layer sheets were again transplanted, creating a nine-layer graft (multi-step transplantation procedure). In the last step, six-layer sheets were transplanted on fat tissues of the inguinal portion, which were subsequently resected together with the femoral arteries and veins to make transplantable grafts with connectable vessels. They were then transplanted ectopically to the neck portion of other rats by anastomosing vessels with the host's jugular arteries and veins. Transplanted three-layer hiPSCMs were beating and, histologically, showed a cardiac muscle-like structure with vascular systems. Moreover, transplanted hiPSCMs proliferated and matured in vivo. Significantly thicker tissues were fabricated by a multi-step transplantation procedure. The ectopically transplanted graft survived and continued to beat. We succeeded in fabricating functional human cardiac tissue with cell sheet technology. Transplanting this cardiac tissue may become a new treatment option for severe heart failure. Copyright © 2015 John Wiley & Sons, Ltd.

  12. The evolution of human periodontal tissues with ageing.

    PubMed

    Craca, R; Romagnoli, P; Cambi, S; Orlando, S

    1991-01-01

    In this research, the structural modifications with ageing of clinically healthy periodontal tissues were analyzed by means of polarization microscopy and morphometrical methods for light microscopy. The new findings may be summarized as follows. The periodontal ligament was found to be widened in the cervical and apical regions. The thickening of cementum with ageing was shown to be accompanied by a modification in the shape of Sharpey's fibres, which in the elderlies were wavy instead of straight as in the control. Lamellar bone, forming an osteone, was found to substitute in part for cementum in one tooth. These results are interpreted as indicating that: (1) late active eruption occurs in man, causing the observed modification in the thickness of periodontal ligament and cementum in the apical region and in the direction of Sharpey's fibres within cementum; (2) cementum may undergo renewal during lifetime and in this case bone may be deposited in contact with dentin.

  13. Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis

    PubMed Central

    Margan, Madalin Marius; Jitariu, Andreea Adriana; Nica, Cristian; Raica, Marius

    2016-01-01

    Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1α and HIF-2α that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis. PMID:27382385

  14. 78 FR 41403 - Agency Information Collection Activities; Proposed Collection; Comment Request; Human Tissue...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-10

    ... transmission of human immunodeficiency virus, hepatitis B, and hepatitis C, through the use of human tissue for... 1270.31(a) and (b) also requires recording and justification of any deviation from the written... (5 CFR 1320.3(b)(2)). The recordkeeping burden, thus, is estimated for the remaining...

  15. Detection of DNA Adducts in Human Breast Tissues

    DTIC Science & Technology

    1997-07-01

    techniques employed are kept simple, which in turn limits the resolution and characterization. Fourth, the limited resolution can make it difficult to...PROCEDURES Our basic scheme for detecting DNA adducts in human samples consists of three general steps. In step I, standard techniques are used to isolate...this adjustment was done without changing the pH. Buffer A was added to part B to keep the volume the same. The samples were stored at room temperature

  16. [Organochlorine pesticide residues in human adipose tissue in Costa Rica].

    PubMed

    Barquero, M; Constenla, M A

    1986-06-01

    Organochlorine pesticide residues were found in 82 samples of human adipose material from 82 surgical cases in 16 Costa Rica hospitals. Identification was made by gas-liquid chromatography. The highest pesticide concentration was that of DDT and its metabolites (33.16 micrograms/g). Residues of almost all commercial pesticides were also found. Concentrations of alpha-chlordane. Aldrin and Polychlorinated biphenyls were not significant.

  17. Using human factors engineering to improve patient safety in the cardiovascular operating room.

    PubMed

    Gurses, Ayse P; Martinez, Elizabeth A; Bauer, Laura; Kim, George; Lubomski, Lisa H; Marsteller, Jill A; Pennathur, Priyadarshini R; Goeschel, Chris; Pronovost, Peter J; Thompson, David

    2012-01-01

    Despite significant medical advances, cardiac surgery remains a high risk procedure. Sub-optimal work system design characteristics can contribute to the risks associated with cardiac surgery. However, hazards due to work system characteristics have not been identified in the cardiovascular operating room (CVOR) in sufficient detail to guide improvement efforts. The purpose of this study was to identify and categorize hazards (anything that has the potential to cause a preventable adverse patient safety event) in the CVOR. An interdisciplinary research team used prospective hazard identification methods including direct observations, contextual inquiry, and photographing to collect data in 5 hospitals for a total 22 cardiac surgeries. We performed thematic analysis of the qualitative data guided by a work system model. 60 categories of hazards such as practice variations, high workload, non-compliance with evidence-based guidelines, not including clinicians' in medical device purchasing decisions were found. Results indicated that hazards are common in cardiac surgery and should be eliminated or mitigated to improve patient safety. To improve patient safety in the CVOR, efforts should focus on creating a culture of safety, increasing compliance with evidence based infection control practices, improving communication and teamwork, and designing better tools and technologies through partnership among all stakeholders.

  18. Acute effects of 50 Hz magnetic field exposure on human visual task and cardiovascular performance

    SciTech Connect

    Whittington, C.J.; Podd, J.V.; Rapley, B.R.

    1996-05-01

    One hundred subjects, males and females with ages ranging between 18 and 48 years, were studied under both field-exposed and sham-exposed conditions. A 50 Hz, 100 {micro}T magnetic field (MF) was used. To examine the effect of field exposure on performance, a two-alternative, forced-choice, duration-discrimination task with three levels of difficulty was used. The subject`s task was to decide which of two sequentially presented light flashes had the longer duration. The standard duration was 50 ms, and the alternative durations were 65, 100, or 125 ms. Both reaction time and percentage of correct responses were recorded for each subject. MF and sham exposure were for 9 min each. Blood pressure and heart rate were also measured before and following MF exposure and sham-exposure trials. The study was performed double blind, with the exposure order counterbalanced. Compared to sham exposure, MF exposure significantly decreased reaction time on the hardest level of the performance task. MF exposure did not reliably affect percentage correct or cardiovascular performance. It was demonstrated that a relatively high level of statistical power was the basis for the observed MF effect, and the need to pay closer attention to power levels in future research is discussed.

  19. Conditional symbolic analysis detects nonlinear influences of respiration on cardiovascular control in humans

    PubMed Central

    Porta, Alberto; Marchi, Andrea; Bari, Vlasta; Heusser, Karsten; Tank, Jens; Jordan, Jens; Barbic, Franca; Furlan, Raffaello

    2015-01-01

    We propose a symbolic analysis framework for the quantitative characterization of complex dynamical systems. It allows the description of the time course of a single variable, the assessment of joint interactions and an analysis triggered by a conditioning input. The framework was applied to spontaneous variability of heart period (HP), systolic arterial pressure (SAP) and integrated muscle sympathetic nerve activity (MSNA) with the aim of characterizing cardiovascular control and nonlinear influences of respiration at rest in supine position, during orthostatic challenge induced by 80° head-up tilt (TILT) and about 3 min before evoked pre-syncope signs (PRESY). The approach detected (i) the exaggerated sympathetic modulation and vagal withdrawal from HP variability and the increased presence of fast MSNA variability components during PRESY compared with TILT; (ii) the increase of the SAP–HP coordination occurring at slow temporal scales and a decrease of that occurring at faster time scales during PRESY compared with TILT; (iii) the reduction of the coordination between fast MSNA and SAP patterns during TILT and PRESY; (iv) the nonlinear influences of respiration leading to an increased likelihood to observe the abovementioned findings during expiration compared with inspiration one. The framework provided simple, quantitative indexes able to distinguish experimental conditions characterized by different states of the autonomic nervous system and to detect the early signs of a life threatening situation such as postural syncope. PMID:25548269

  20. Acknowledging tissue donation: Human cadaveric specimens in musculoskeletal research.

    PubMed

    Winkelmann, Andreas; Heinze, Anne-Kathrin; Hendrix, Sven

    2016-01-01

    Human cadaveric specimens are an important resource for research, particularly in biomechanical studies, but their use also raises ethical questions and cannot simply be taken for granted. It was asked how much information authors publishing musculoskeletal research actually give about such specimens and about how they were acquired. The aim was to formulate recommendations on how this reporting might be improved. Relevant articles published between 2009 and 2012 in four North American or European journals were scanned for information regarding the characteristics of the human specimens used, their institutional source and the ethical or legal context of their acquisition. While the majority of articles report biological characteristics of specimens (sex, age at death, preservation method), only 40% of articles refer to body donation, only 23% report the institution that provided specimens, and only 17% refer to some kind of formalized approval of their research. There were regional and journal-to-journal differences. No standard for reporting studies involving human specimens could be detected. It is suggested that such a standard be developed by researchers and editors. Information on the source of specimens and on the ethical or legal basis should be regularly reported to acknowledge this unique research resource and to preserve the good relationship between researchers and the communities, that provide the required specimens by body donation and upon which researchers depend.

  1. Genome-wide quantification of rare somatic mutations in normal human tissues using massively parallel sequencing

    PubMed Central

    Hoang, Margaret L.; Kinde, Isaac; Tomasetti, Cristian; McMahon, K. Wyatt; Rosenquist, Thomas A.; Grollman, Arthur P.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas

    2016-01-01

    We present the bottleneck sequencing system (BotSeqS), a next-generation sequencing method that simultaneously quantifies rare somatic point mutations across the mitochondrial and nuclear genomes. BotSeqS combines molecular barcoding with a simple dilution step immediately before library amplification. We use BotSeqS to show age- and tissue-dependent accumulations of rare mutations and demonstrate that somatic mutational burden in normal human tissues can vary by several orders of magnitude, depending on biologic and environmental factors. We further show major differences between the mutational patterns of the mitochondrial and nuclear genomes in normal tissues. Lastly, the mutation spectra of normal tissues were different from each other, but similar to those of the cancers that arose in them. This technology can provide insights into the number and nature of genetic alterations in normal tissues and can be used to address a variety of fundamental questions about the genomes of diseased tissues. PMID:27528664

  2. The Case for Applying Tissue Engineering Methodologies to Instruct Human Organoid Morphogenesis.

    PubMed

    Marti-Figueroa, Carlos R; Ashton, Randolph S

    2017-03-15

    Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100's of microns to millimeters), the organoids' morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology's potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology.

  3. Cardiovascular and Cerebrovascular Disease Associated microRNAs Are Dysregulated in Placental Tissues Affected with Gestational Hypertension, Preeclampsia and Intrauterine Growth Restriction

    PubMed Central

    Hromadnikova, Ilona; Kotlabova, Katerina; Hympanova, Lucie; Krofta, Ladislav

    2015-01-01

    Aims To demonstrate that pregnancy-related complications are associated with alterations in cardiovascular and cerebrovascular microRNA expression. Gene expression of 32 microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-33a-5p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-208a-3p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p) was assessed in placental tissues, compared between groups (35 gestational hypertension, 80 preeclampsia, 35 intrauterine growth restriction and 20 normal pregnancies) and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. Initially, selection and validation of endogenous controls for microRNA expression studies in placental tissues affected by pregnancy-related complications have been carried out. Results The expression profile of microRNAs was different between pregnancy-related complications and controls. The up-regulation of miR-499a-5p was a common phenomenon shared between gestational hypertension, preeclampsia, and intrauterine growth restriction. Preeclamptic pregnancies delivering after 34 weeks of gestation and IUGR with abnormal values of flow rate in the umbilical artery demonstrated up-regulation of miR-1-3b. Preeclampsia and IUGR requiring termination of gestation before 34 weeks of gestation were associated with down-regulation of miR-26a-5p, miR-103a-3p and miR-145-5p. On the other hand, some of microRNAs (miR-16-5p, miR-100-5p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-143-3p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, and miR-574-3p) were only down-regulated or showed a trend to down-regulation just in intrauterine growth restriction pregnancies requiring the delivery before 34 weeks of gestation. Conclusion

  4. Tissue motion and strain in the human brain assessed by intraoperative ultrasound in glioma patients.

    PubMed

    Selbekk, Tormod; Brekken, Reidar; Solheim, Ole; Lydersen, Stian; Hernes, Toril A N; Unsgaard, Geirmund

    2010-01-01

    The objective of the study was to investigate tissue motion and strain imposed by cardiovascular pulsation in pathologic and normal brain parenchyma, as quantified from in vivo ultrasound data. Ultrasound acquired during surgery of 16 patients with glial tumors was retrospectively processed and analyzed. The tissue velocity was quantified at depths of 1cm, 2cm and 3cm from brain cortex to investigate spatial dependency with depth. Comparison of strain and velocity in tumor and adjacent normal parenchyma was performed by selecting two regions-of-interest in the hyperechoic tumor and two regions in the low-echogenic areas interpreted as mainly normal tissue with some degree of tumor cell infiltration. The absolute maximum tissue velocity is seen to increase with increasing depths in 14 of 16 cases (87.5%). The maximum tissue velocities in the four regions close to the ultrasound visible tumor border are not statistically different (p=0.163 to p=0.975). The strain magnitudes are significantly higher in the regions with expected normal brain parenchyma than in regions with expected glial tumor tissue, both for the two regions being closest to the tumor border (p=0.0004) and for the two regions further away from the tumor border (p=0.0009). We conclude that the velocity of the brain parenchyma imposed by arterial pulsation during a cardiac cycle is generally increasing with increasing depth from cortex. The maximum velocity appears to be similar in regions with expected normal brain and tumor tissue, thus, does not seem to be affected by pathology. Strain magnitude is, however, a suitable parameter for discrimination of glial tumor and normal brain parenchyma. (E-mail: Tormod.Selbekk@sintef.no).

  5. Approaches to in vitro tissue regeneration with application for human disease modeling and drug development

    PubMed Central

    Ebrahimkhani, Mohammad R.; Young, Carissa L.; Lauffenburger, Douglas A.; Griffith, Linda G.; Borenstein, Jeffrey T.

    2014-01-01

    Reliable in vitro human disease models that capture the complexity of in vivo tissue behaviors are crucial to gain mechanistic insights into human disease and enable the development of treatments that are effective across broad patient populations. The integration of stem cell technologies, tissue engineering, emerging biomaterials strategies and microfabrication processes, as well as computational and systems biology approaches, is enabling new tools to generate reliable in vitro systems to study the molecular basis of human disease and facilitate drug development. In this review, we discuss these recently developed tools and emphasize opportunities and challenges involved in combining these technologies toward regenerative science. PMID:24793141

  6. Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans

    PubMed Central

    Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Annamalai, Palam; Enerbäck, Sven; Lidell, Martin E.; Saraf, Manish K.; Labbe, Sebastien M.; Hurren, Nicholas M.; Yfanti, Christina; Chao, Tony; Andersen, Clark R.; Cesani, Fernando; Hawkins, Hal

    2014-01-01

    Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT+) men and five BAT-negative (BAT−) men under thermoneutral conditions and after prolonged (5–8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT+ group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans. PMID:25056438

  7. Methods of Assessing Human Tendon Metabolism and Tissue Properties in Response to Changes in Mechanical Loading.

    PubMed

    Heinemeier, Katja M; Kjaer, Michael; Magnusson, S Peter

    2016-01-01

    In recent years a number of methodological developments have improved the opportunities to study human tendon. Microdialysis enables sampling of interstitial fluid in the peritendon tissue, while sampling of human tendon biopsies allows direct analysis of tendon tissue for gene- and protein expression as well as protein synthesis rate. Further the (14)C bomb-pulse method has provided data on long-term tissue turnover in human tendon. Non-invasive techniques allow measurement of tendon metabolism (positron emission tomography (PET)), tendon morphology (magnetic resonance imaging (MRI)), and tendon mechanical properties (ultrasonography combined with force measurement during movement). Finally, 3D cell cultures of human tendon cells provide the opportunity to investigate cell-matrix interactions in response to various interventions.

  8. Species-Specific Metastasis of Human Tumor Cells in the Severe Combined Immunodeficiency Mouse Engrafted with Human Tissue

    NASA Astrophysics Data System (ADS)

    Shtivelman, Emma; Namikawa, Reiko

    1995-05-01

    We have attempted to model human metastatic disease by implanting human target organs into the immunodeficient C.B-17 scid/scid (severe combined immunodeficiency; SCID) mouse, creating SCID-hu mice. Preferential metastasis to implants of human fetal lung and human fetal bone marrow occurred after i.v. injection of human small cell lung cancer (SCLC) cells into SCID-hu mice; the homologous mouse organs were spared. Clinically more aggressive variant SCLC cells metastasized more efficiently to human fetal lung implants than did cells from classic SCLC. Metastasis of variant SCLC to human fetal bone marrow was enhanced in SCID-hu mice exposed to γ-irradiation or to interleukin 1α. These data indicate that the SCID-hu mice may provide a model in which to study species- and tissue-specific steps of the human metastatic process.

  9. Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue

    PubMed Central

    Santos, Carlos F.; Morandini, Ana C.; Dionísio, Thiago J.; Faria, Flávio A.; Lima, Marta C.; Figueiredo, Caio M.; Colombini-Ishikiriama, Bella L.; Sipert, Carla R.; Maciel, Rubens P.; Akashi, Ana P.; Souza, Gabriela P.; Garlet, Gustavo P.; Rodini, Camila O.; Amaral, Sandra L.; Becari, Christiane; Salgado, Maria C.; Oliveira, Eduardo B.; Matus, Isaac; Didier, Daniela N.; Greene, Andrew S.

    2015-01-01

    The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats. PMID:26244896

  10. Integrated interactions database: tissue-specific view of the human and model organism interactomes.

    PubMed

    Kotlyar, Max; Pastrello, Chiara; Sheahan, Nicholas; Jurisica, Igor

    2016-01-04

    IID (Integrated Interactions Database) is the first database providing tissue-specific protein-protein interactions (PPIs) for model organisms and human. IID covers six species (S. cerevisiae (yeast), C. elegans (worm), D. melonogaster (fly), R. norvegicus (rat), M. musculus (mouse) and H. sapiens (human)) and up to 30 tissues per species. Users query IID by providing a set of proteins or PPIs from any of these organisms, and specifying species and tissues where IID should search for interactions. If query proteins are not from the selected species, IID enables searches across species and tissues automatically by using their orthologs; for example, retrieving interactions in a given tissue, conserved in human and mouse. Interaction data in IID comprises three types of PPI networks: experimentally detected PPIs from major databases, orthologous PPIs and high-confidence computationally predicted PPIs. Interactions are assigned to tissues where their proteins pairs or encoding genes are expressed. IID is a major replacement of the I2D interaction database, with larger PPI networks (a total of 1,566,043 PPIs among 68,831 proteins), tissue annotations for interactions, and new query, analysis and data visualization capabilities. IID is available at http://ophid.utoronto.ca/iid.

  11. Development of human nervous tissue upon differentiation of embryonic stem cells in three-dimensional culture.

    PubMed

    Preynat-Seauve, Olivier; Suter, David M; Tirefort, Diderik; Turchi, Laurent; Virolle, Thierry; Chneiweiss, Herve; Foti, Michelangelo; Lobrinus, Johannes-Alexander; Stoppini, Luc; Feki, Anis; Dubois-Dauphin, Michel; Krause, Karl Heinz

    2009-03-01

    Researches on neural differentiation using embryonic stem cells (ESC) require analysis of neurogenesis in conditions mimicking physiological cellular interactions as closely as possible. In this study, we report an air-liquid interface-based culture of human ESC. This culture system allows three-dimensional cell expansion and neural differentiation in the absence of added growth factors. Over a 3-month period, a macroscopically visible, compact tissue developed. Histological coloration revealed a dense neural-like neural tissue including immature tubular structures. Electron microscopy, immunochemistry, and electrophysiological recordings demonstrated a dense network of neurons, astrocytes, and oligodendrocytes able to propagate signals. Within this tissue, tubular structures were niches of cells resembling germinal layers of human fetal brain. Indeed, the tissue contained abundant proliferating cells expressing markers of neural progenitors. Finally, the capacity to generate neural tissues on air-liquid interface differed for different ESC lines, confirming variations of their neurogenic potential. In conclusion, this study demonstrates in vitro engineering of a human neural-like tissue with an organization that bears resemblance to early developing brain. As opposed to previously described methods, this differentiation (a) allows three-dimensional organization, (b) yields dense interconnected neural tissue with structurally and functionally distinct areas, and (c) is spontaneously guided by endogenous developmental cues.

  12. Mesenchymal Stromal Cells Derived from Human Umbilical Cord Tissues: Primitive Cells with Potential for Clinical and Tissue Engineering Applications

    NASA Astrophysics Data System (ADS)

    Moretti, Pierre; Hatlapatka, Tim; Marten, Dana; Lavrentieva, Antonina; Majore, Ingrida; Hass, Ralf; Kasper, Cornelia

    Mesenchymal stem or stromal cells (MSCs) have a high potential for cell-based therapies as well as for tissue engineering applications. Since Friedenstein first isolated stem or precursor cells from the human bone marrow (BM) stroma that were capable of osteogenesis, BM is currently the most common source for MSCs. However, BM presents several disadvantages, namely low frequency of MSCs, high donor-dependent variations in quality, and painful invasive intervention. Thus, tremendous research efforts have been observed during recent years to find alternative sources for MSCs.

  13. Prolactin suppresses malonyl-CoA concentration in human adipose tissue.

    PubMed

    Nilsson, L A; Roepstorff, C; Kiens, B; Billig, H; Ling, C

    2009-10-01

    Prolactin is best known for its involvement in lactation, where it regulates mechanisms that supply nutrients for milk production. In individuals with pathological hyperprolactinemia, glucose and fat homeostasis have been reported to be negatively influenced. It is not previously known, however, whether prolactin regulates lipogenesis in human adipose tissue. The aim of this study was to investigate the effect of prolactin on lipogenesis in human adipose tissue in vitro. Prolactin decreased the concentration of malonyl-CoA, the product of the first committed step in lipogenesis, to 77+/-6% compared to control 100+/-5% (p=0.022) in cultured human adipose tissue. In addition, prolactin was found to decrease glucose transporter 4 ( GLUT4) mRNA expression, which may cause decreased glucose uptake. In conclusion, we propose that prolactin decreases lipogenesis in human adipose tissue as a consequence of suppressed malonyl-CoA concentration in parallel with decreased GLUT-4 expression. In the lactating woman, this regulation in adipose tissue may enhance the provision of nutrients for the infant instead of nutrients being stored in adipose tissue. In hyperprolactinemic individuals, a suppressed lipogenesis could contribute to an insulin resistant state with consequences for the health.

  14. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics.

    PubMed

    Riba, Jordi; Valle, Marta; Urbano, Gloria; Yritia, Mercedes; Morte, Adelaida; Barbanoj, Manel J

    2003-07-01

    The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting beta-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.

  15. Aging alters muscle reflex control of autonomic cardiovascular responses to rhythmic contractions in humans.

    PubMed

    Sidhu, Simranjit K; Weavil, Joshua C; Venturelli, Massimo; Rossman, Matthew J; Gmelch, Benjamin S; Bledsoe, Amber D; Richardson, Russell S; Amann, Markus

    2015-11-01

    We investigated the influence of aging on the group III/IV muscle afferents in the exercise pressor reflex-mediated cardiovascular response to rhythmic exercise. Nine old (OLD; 68 ± 2 yr) and nine young (YNG; 24 ± 2 yr) males performed single-leg knee extensor exercise (15 W, 30 W, 80% max) under control conditions and with lumbar intrathecal fentanyl impairing feedback from group III/IV leg muscle afferents. Mean arterial pressure (MAP), cardiac output, leg blood flow (QL), systemic (SVC) and leg vascular conductance (LVC) were continuously determined. With no hemodynamic effect at rest, fentanyl blockade during exercise attenuated both cardiac output and QL ∼17% in YNG, while the decrease in cardiac output in OLD (∼5%) was significantly smaller with no impact on QL (P = 0.8). Therefore, in the face of similar significant ∼7% reduction in MAP during exercise with fentanyl blockade in both groups, LVC significantly increased ∼11% in OLD, but decreased ∼8% in YNG. The opposing direction of change was reflected in SVC with a significant ∼5% increase in OLD and a ∼12% decrease in YNG. Thus while cardiac output seems to account for the majority of group III/IV-mediated MAP responses in YNG, the impact of neural feedback on the heart may decrease with age and alterations in SVC become more prominent in mediating the similar exercise pressor reflex in OLD. In